Tight versus standard blood pressure control on the incidence of myocardial infarction and stroke: An observational retrospective cohort study in the general ambulatory setting

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This change raised much controversy. We conducted this study to compare the impact of tight (TBPC) versus standard BP control (SBPC) on the incidence of myocardial infarction (MI) and stroke. Methods: We retrospectively identified all hypertensive patients in an ambulatory setting based on the diagnostic code for 1 year at our institution who were classified by the range of BP across 3 years into 2 groups of TBPC (< 130 mmHg) and SBPC (130-139 mmHg). We compared the incidence of new MI and stroke between the 2 groups across a 2-year follow-up. Multivariate analysis was done to identify independent predictors for the incidence of new MI and stroke. Results: Of 5640 study patients, the TBPC group showed significantly less incidence of stroke compared to the SBPC group (1.5% vs. 2.7%, P < 0.010). No differences were found in MI incidence between the 2 groups (0.6% vs. 0.8%, P = 0.476). Multivariate analysis showed that increased age independently increased the incidence of both MI (OR 1.518, 95% CI 1.038-2.219) and stroke (OR 1.876, 95% CI 1.474-2.387), and TBPC independently decreased the incidence of stroke (OR 0.583, 95% CI 0.374-0.910) but not of MI. Conclusions: Our observational study suggests that TBPC may be beneficial in less stroke incidence compared to SBPC but it didn’t seem to affect the incidence of MI. Our study is limited by its retrospective design with potential confounders. General Practice Blood pressure Myocardial infarction Stroke Figures Figure 1 Introduction As one of the most common chronic health conditions, hypertension affects more than 1.3 billion adults worldwide [1] and about 75 million adults in the United States [2]. Hypertension can affect major body organs such as heart, brain, kidneys, and eyes and can lead to serious complications such as myocardial infarction (MI), stroke, end-stage renal disease, or visual impairment. For almost three decades hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg [3]. Recently, the American College of Cardiology (ACC) and American Heart Association (AHA) published a new guideline defining hypertension as blood pressure (BP) ≥ 130/80 mmHg, and set the BP treatment goal as < 130/80 mmHg [4]. This new guideline was based on the Systolic Blood Pressure Intervention Trial (SPRINT), which in 2015 showed lower rates of fatal and nonfatal major cardiovascular events and all-cause mortality when targeting SBP < 120 mmHg [5]. There have been clinical trials and meta-analyses showing that intensive blood pressure control significantly lowers the stroke risk [6-8]. Regarding the association of MI and BP control, there have been mixed results. A meta-analysis by Reboldi et al showed no benefit in the incidence of MI compared to stroke [8]. The ONTARGET trial by Mancia et al also found no significant benefit of intensive BP control on the MI outcome [9]. On the other hand, there have been studies that showed tight BP control might potentially increase the risk of MI [10, 11]. The new ACC/AHA guideline has raised controversies and the American Academy of Family Physicians recently decided to not endorse it due to the lack of sufficient data in systematic reviews, the lack of quality assessments for the studies, and giving considerable weight on the SPRINT trial while minimizing results from other trials [12]. Because of the controversy over the benefit of tight (TBPC) versus standard BP control (SBPC), we analyzed the incidences of MI and stroke in these two patient populations at our large health system. Methods Study Design and Patient Population This single-center, retrospective cohort study aimed to assess the occurrence of new MI or stroke in patients with TBPC (SBP < 130 mmHg) versus SBPC (SBP 130-139 mmHg). We addressed only SBP rather than both SBP and DBP based on similar previous studies including the SPRINT trial [5]. The data were collected and analyzed in 2018. We accessed the health system’s data stores (for medical records) to identify all outpatient encounters regardless of specialties (not limited to Family Medicine department) with ICD-10 diagnostic codes for hypertension in 2013. This resulted in 233,622 encounters in 88,456 patients. From this group we then applied inclusion and exclusion criteria to identify our study patients. BPs have been measured by healthcare professionals manually with using a sphygmomanometer and a stethoscope in a typical outpatient setting in the same health system. We included patients with SBP < 140 mmHg between ages 40 and 79 years. The age range was based on the recent Centers for Disease Control and Prevention report showing that adults between ages 18 and 44 years mostly had hypertension under control and used antihypertensive medications less often [13]. We excluded the population greater than or equal to age 80 due to limited life expectancy. We averaged each patient’s SBPs measured in the same year between 2013 and 2015, so that one individual should have one averaged SBP reading per year. We excluded patients if the annual SBP measure was absent or if the averaged SBP fluctuated between TBPC and SBPC during the 3 years for BP characterization (2013-2015). We excluded patients with diabetes mellitus because the disease is a significant risk factor and a confounder in MI or stroke outcome. We excluded patients with a history of MI or stroke before 2013 because these are the highest risk factors for recurrent MI or stroke and we cannot assess a true incidence of new MI and stroke if we include these patients. We also excluded patients with MI or stroke events between 2013 and 2015. The attrition diagram (Figure 1) summarizes the enrollment process. Outcome Measures The main outcome measures compared between the TBPC and SBPC groups were any new incidence of MI or stroke which occurred within 2 years (2016-2017). Clinical settings of the cardiovascular outcomes included outpatient, emergency department, and inpatient. For ICD-10 coding, we included MI including “late effect” codes, but we did not include angina pectoris. For stroke we counted both ischemic and hemorrhagic strokes and “late effect” codes. “Late effect” means residual sequelae after the initial acute phase of the illness has resolved [14]. We did not include transient ischemic attacks given its potential diagnostic uncertainty. We also excluded traumatic hemorrhages or vascular syndromes (e.g., vertebrobasilar artery syndrome). Variables All the variables were collected through the database sorting system on Epi Info 7 provided by the Centers for Disease Control and Prevention (Atlanta, GA) per statistician (LL). We obtained baseline demographic data such as age, gender, race, and body mass index (BMI). We noted smoking status, serum low-density lipoprotein (LDL) levels, glomerular filtration rate, aspirin use, antihypertensive use, and statins use. Age was categorized by decade (40-49, 50-59, 60-69, and 70-79 years old). Race/ethnicity was categorized as African American, Asian, Hispanic, white, and other/unknown. For analysis, we further dichotomized race into 2 groups of African American and non-African American based on the recent Centers for Disease Control and Prevention report showing a relatively low percentage of hypertension visits among African Americans compared to other races [13]. BMI was categorized as underweight (BMI < 18.5 kg/m 2 ), normal (BMI 18.5-24.9 kg/m 2 ), overweight (BMI 25.0-29.9 kg/m 2 ), obese (BMI 30.0-39.9 kg/m 2 ), and morbidly obese (BMI ≥ 40.0 kg/m 2 ) based on World Health Organization criteria [15]. Smoking status was categorized as “never” or “ever.” Serum LDL was categorized as ≥ 190 mg/dl or < 190 mg/dl; the former is one of the absolute indications of statin use based on 2013 ACC/AHA guidelines [16]. Glomerular filtration rate was categorized as ≥ 30 ml/min/1.73 m 2 and < 30 ml/min/1.73 m 2 ; the latter is the cutoff value where primary care physicians are recommended to refer patients to nephrology [17]. Use of aspirin, statins, and antihypertensives was determined from medication orders and defined as yes or no. In terms of counting antihypertensives, authors sorted it into major category of antihypertensives, for example, thiazide diuretic or calcium channel blockers, and then counted each medication that falls into each category of the antihypertensives per each patient during the enrollment period. This sorting process was done by statistician (LL). Adverse Events Authors believed it is important to evaluate hypotension-related adverse events in the TBPC group. However, given the retrospective nature of the study with using a large cohort, we were unable to collect data on the adverse events such as lightheadedness, dizziness, syncope, or falls in the TBPC group. However, we addressed and counted SBP < 90 mmHg in the TBPC group to find out the incidence of significant hypotension. Statistical Analysis Sample characteristics were described using means and standard deviations for continuous variables (SBP) and frequencies (number and percentage) for categorical variables (gender, race, smoking, BMI categories, use of statin, and use of aspirin). To compare the baseline variables between TBPC and SBPC groups, we conducted chi-square tests. For multivariate analysis to determine independent predictors for MI or stroke incidence, we performed binary logistic regression entering only those variables that showed significant difference between TBPC and SBPC groups with the only exception of the variable ‘antihypertensive use versus no use’ as this variable was considered to be relevant for the outcomes because antihypertensive use can modify the cardiovascular outcomes. We additionally included ‘the number of antihypertensives’ to build a different regression model to predict outcomes with excluding ‘antihypertensive use versus no use’. All statistical analyses were performed using Epi Info 7 provided by the Centers for Disease Control and Prevention (Atlanta, GA). A P value < 0.05 was considered statistically significant. Results Baseline Data We identified 5640 patients as a final cohort for our study (Figure 1). Significant differences were noted in age, race, BMI, statin use, and the number of antihypertensives between the 2 groups (Table 1). More patients aged 50 to 69 years were in the TBPC group whereas the SBPC group had significantly more patients between 70 and 79 years ( P < 0.001). African Americans were less likely to have TBPC compared to other races ( P < 0.001). The TBPC group had more normal weight and overweight patients whereas the SBPC group had significantly more obese and morbidly obese patients ( P < 0.001). The TBPC group had higher statin use than the SBPC group ( P < 0.05). More patients in the SBPC group used 3 or more antihypertensive medications than those in the TBPC group. No differences were noted in gender, smoking status, serum LDL, glomerular filtration rate, and aspirin use between the 2 groups. Incidence Outcomes The TBPC and SBPC groups showed no difference in incidence of new MI in the 2-year follow-up (Table 2). The SBPC group had a significantly higher incidence of stroke compared to the TBPC group (2.7% vs. 1.5%, P < 0.010) (Table 2). This gave an absolute risk reduction of 1.2%, and the number needed to treat of approximately 83. Multivariate Analysis In the logistic regression model, only increased age was an independent predictor of MI incidence (OR 1.518, 95% CI 1.038-2.219) when ‘antihypertensive use versus no use’ was included as one of the variables (Table 3). However, when ‘the number of antihypertensives’ was included in the model, increased number of antihypertensives was an independent predictor of MI (OR 2.272, 95% CI 1.441-3.581) (Table 4). In terms of stroke incidence, both increased age (OR 1.876, 95% CI 1.474-2.387) and TBPC (OR 0.583, 95% CI 0.374-0.910) were significantly associated with stroke incidence when ‘antihypertensive use versus no use’ was included as one of the variables (Table 3). When ‘the number of antihypertensives’ was included in the model, increased age (OR 1.792, 95% CI 1.406-2.284), increased number of antihypertensives (OR 1.282, 95% CI 1.011-1.627), and TBPC (OR 0.589, 95% CI 0.377-0.919) were independent predictors of stroke (Table 4). Adverse Events Among the 4530 patients in the TBPC group, only 5 patients (0.001%) had SBP < 90 mmHg per BP readings in the outpatient setting. Discussion This single-center cohort study of more than 5000 hypertensive patients evaluated the impact of TBPC (SBP < 130 mmHg) on the incidence of new MI and stroke. We suggest that TBPC independently decreased the incidence of stroke compared to SBPC, but did not have an impact on MI incidence. A retrospective study using the ACTION trial database found the greatest difference between SBP < 130 mmHg (2.5% incidence rate) and SBP < 140 mmHg (3.8% incidence rate) groups in the risk of stroke [18]. The cohort in the ACTION trial was different from ours in that their patients had stable coronary heart disease [19]. A meta-analysis performed by Lee et al demonstrated that SBP < 130 mmHg compared to SBP 130-139 mmHg showed additional protective effect on stroke in patients with cardiovascular risk factors but no previously established cardiovascular disease [7]. In another meta-analysis, Reboldi et al found that more-tight SBP control (< 120 mmHg), compared to less-tight SBP control (< 140 mmHg), significantly reduced stroke risk by 31%, but no significant risk reduction was noted in MI [8]. While these results are similar to ours, Reboldi et al’s analysis included diabetic patients and a different BP cutoff for the 2 groups. The ONTARGET trial provided further evidence on the significant impact of BP control on stroke but not on MI [9]. The trial found that more frequent achievement of target BPs (< 130/90 mmHg or < 140/90 mmHg) resulted in significant cerebrovascular protection but not cardiac protection [9]. More recent large European meta-analyses further strengthen the evidence that more intense blood pressure control reduces cardiovascular events [6, 20]. Why TBPC decreases the risk of stroke but not MI remains unclear. Several long-term prospective population-based studies have shown that hypertension increased the relative risk of stroke to a greater degree than MI [21-24]. One possible hypothesis is different blood flow physiology between the brain and heart. The brain receives a larger fraction of cardiac output by nearly 3-fold than the heart [25]. While most of the coronary blood flow occurs during diastole, the cerebral blood flow occurs during systole [26]. Therefore, cerebral blood flow might be more sensitive to a change in SBP than coronary blood flow, and coronary blood flow might be more sensitive to a change in DBP than SBP. A recent multinational study supports this hypothesis in that results showed increased risk of MI with increased DBP whereas increased SBP did not increase the risk of MI [11]. Other studies have reported different results. Verdecchia et al performed an open-label randomized trial and found no difference in the incidence of MI or stroke between TBPC (< 130 mmHg) and SBPC (< 140 mmHg) [27]. Their population was similar to ours in the exclusion of diabetic patients. Another large randomized study using the database of the Hypertension Optimal Treatment trial showed that TBPC (< 130 mmHg) in patients with diabetes and coronary artery disease did not improve cardiovascular outcomes compared to SBPC (< 140 mmHg) [28]. The ACCORD study conducted in 2010 also showed no difference in fatal and nonfatal cardiovascular events between TBPC (< 120 mmHg) and SBPC (< 140 mmHg) groups in diabetic patients. More importantly, the TBPC group demonstrated significantly higher rates of serious adverse events attributed to antihypertensive therapy [29]. Furthermore, a post hoc analysis using the Irbesartan Diabetic Nephropathy Trial database concluded that BP ≤ 120/85 mmHg may be associated with increased cardiovascular events [30]. Our study and the majority of cohort and prospective studies have shown that TBPC is associated with decreased risk of stroke. Nevertheless, the issue of TBPC must be addressed carefully in the clinical setting. Even though cerebral blood flow has an autoregulation mechanism, the mechanism can be lost if the mean arterial BP drops below 60 mmHg [31]. A study that targeted BP < 130/80 mmHg for diabetic patients found intensive BP control caused progressive reduction of cerebral blood flow velocity [32]. According to the meta-analysis by Thomopoulos et al, the BP-lowering treatment reduced cardiovascular events by 24% whereas it increased the risk of discontinuation attributed to adverse events by 89% [33]. Ferreira et al recently demonstrated significantly increased rates of cardiovascular death, heart failure hospitalization, MI, and stroke when SBP decreased below 125 mmHg [11]. In our study, only 0.001% (5/4530) in the TBPC group showed SBP < 90 mmHg. An interesting finding in our study is that statin use did not independently affect MI or stroke incidence. Based on the 2013 ACC/AHA guidelines, absolute indications for statin use include clinical atherosclerotic cardiovascular disease, type 2 diabetes mellitus, and serum LDL ≥ 190 mg/dl [16]. Perhaps statin use did not affect the MI or stroke incidence in our study because we excluded patients with diabetes and those with a history of MI or stroke. Very few patients in our study had a serum LDL ≥ 190 mg/dl (Table 1). Another interesting finding is that increased number of antihypertensive medications significantly predicted both MI and stroke incidence while the usage of antihypertensive medication itself did not predict either MI or stroke incidence in the multivariate model. This can suggest that requiring more antihypertensive medications rather than taking the medications itself could predict higher cardiovascular risk, or those who were prescribed many antihypertensive medications would have not been adherent to the medications. Limitations The major limitation of our study is that this is an observational retrospective study. Given the fact that authors did not do any interventional measures for the patients, strictly speaking, it might not be very appropriate to use the terms “tight control” and “standard control”. However, as all the patients were formally diagnosed with hypertension, authors assumed that they had received some type of BP control intervention including lifestyle counseling from their providers. And this would have justified our using the terms “control.” Our study also has several other limitations. Because of the retrospective design, we were not able to completely address and remove all potential confounders. For example, excluding patients whose BP showed fluctuating levels between TBPC and SBPC could otherwise have affected the outcome. There were significant differences in age, race, BMI, statin use, and the number of antihypertensives between TBPC and SBPC groups. The TBPC group was younger and had statins prescribed more often than the SBPC group. Although these variables were adjusted at multivariate analysis, these differences might still have affected our findings, and we admit that this is potentially the most major limitation of our study, which should be criticized. Also, as we excluded other significant risk factors of MI and stroke, such as diabetes and history of MI or stroke, our study population was different from actual patients commonly seen in clinical practice, which might have resulted in the relatively rare outcome events in our study. Also, as we were not able to review each patient’s medical record given the large, retrospective, and electronic-based data analysis, we were unable to collect information on the adverse events that can potentially occur from TBPC such as dizziness, syncope, falls, acute kidney injury, or cerebral hypo-perfusion. However, given that only 0.001% of the TBPC patients had SBP less than 90 mmHg, it is less likely that many of our TBPC patients developed significant hypotension-related complications. Also, we were unable to assess each patient’s medication adherence data as we only counted the numbers of the medication prescriptions which can potentially be significantly confounding. It also would have been more informative if we could include the mortality and quality of life outcomes in either group, which should be considered for future research. Conclusion Our observational retrospective cohort study showed that TBPC had a significant benefit in less stroke incidence compared to SBPC, although it did not affect the incidence of MI. Our study could help aid in the discussion regarding the association of BP control and stroke in actual clinical practice. Even though the American Academy of Family Physicians decided to not endorse the ACC/AHA guideline, our study shows more favorable result towards the SPRINT trial in terms of less stroke incidence. Abbreviations ACC: American College of Cardiology; AHA: American Heart Association; BMI: Body mass index; BP: Blood pressure; DBP: Diastolic blood pressure; LDL: Low-density lipoprotein; MI: Myocardial infarction; SBP: Systolic blood pressure; SBPC: Standard blood pressure control; SPRINT: Systolic Blood Pressure Intervention Trial; TBPC: Tight blood pressure control Declarations Ethics approval and consent to participate The study protocol was approved by the Institutional Review Board of Henry Ford Health System (IRB No. 11950) under expedited review with waiver of informed consent. Consent for publication Not applicable. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Competing interests All authors declare no competing interests for this study. Funding There was no funding support applicable to the study. Authors’ contributions All authors designed and conceived of the study as a group project. BP drafted the manuscript. BP, NA, SI, FA, RC, BEA, PACC, and LL collected and analyzed the data. LL performed a statistical analysis. KB, MES, DAR, and LL supervised overall study process, and revised the manuscript. All authors read and approved the final manuscript. Acknowledgements This study was conducted as an annual scholarly project of the family medicine residency program at Henry Ford Health System in 2018. This study was presented at Family Medicine Experience (FMX) 2018 in New Orleans, Louisiana. References Bloch MJ. Worldwide prevalence of hypertension exceeds 1.3 billion. J Am Soc Hypertens. 2016;10(10):753-4. https://doi.org/10.1016/j.jash.2016.08.006. Merai R , Siegel C , Rakotz M , et al. 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Effects of blood pressure lowering treatment in hypertension: 8. Outcome reductions vs. discontinuations because of adverse drug events – meta-analyses of randomized trials. J Hypertens. 2016;34(8):1451-63. Tables Table 1. Baseline data for patients with tight versus standard blood pressure control Variables TBPC (SBP <130 mmHg) (n=4530) N (%) SBPC (SBP 130-139 mmHg) (n=1110) N (%) P value a Age category 40 to 49 years 50 to 59 years 60 to 69 years 70 to 79 years 778 (17.2) 1533 (33.8) 1466 (32.4) 753 (16.6) 183 (16.5) 330 (29.7) 339 (30.5) 258 (23.2) <0.001 Gender Male Female 1917 (42.3) 2613 (57.7) 482 (43.4) 628 (56.6) 0.504 Race African American Asian Hispanic White Other/unknown 1235 (27.3) 152 (3.4) 58 (1.3) 2588 (57.1) 497 (11.1) 406 (36.6) 26 (2.3) 13 (1.2) 550 (49.5) 115 (10.4) <0.001 BMI category Underweight Normal Overweight Obese Morbidly obese 50 (1.1) 805 (18.4) 1602 (36.6) 1624 (37.1) 293 (6.7) 10 (0.9) 149 (13.8) 341 (31.7) 467 (43.4) 109 (10.1) <0.001 Smoking Ever Never 2195 (48.5) 2333 (51.5) 521 (47.1) 586 (52.9) 0.399 Serum LDL level ≥190 mg/dl <190 mg/dl 22 (0.6) 3652 (99.4) 9 (1.0) 894 (99.0) 0.182 EGFR (race-adjusted) ≥30 ml/min/1.73m 2 <30 ml/min/1.73m 2 3653 (99.3) 27 (0.7) 905 (99.6) 4 (0.4) 0.333 Aspirin use Yes No 1073 (23.7) 3457 (76.3) 253 (22.8) 857 (77.2) 0.529 Statin use Yes No 2008 (44.3) 2522 (55.7) 450 (40.5) 660 (59.5) <0.05 Antihypertensive use 0.646 Yes 4328 (95.5) 1064 (95.9) No 202 (4.5) 46 (4.1) No. Antihypertensives <0.001 0 202 (4.5) 46 (4.1) 1 1711 (37.8) 347 (31.3) 2 1376 (30.4) 321 (28.9) 3 or more 1241 (27.4) 396 (35.7) a Chi-square test. Boldface indicates statistical significance (p <0.05). Table 2. Two-year cardiovascular incidence in tight versus standard blood pressure control Variables TBPC (SBP <130 mmHg) (n=4530) N (%) SBPC (SBP 130-139 mmHG) (n=1110) N (%) P value a Myocardial infarction Yes No 28 (0.6) 4502 (99.4) 9 (0.8) 1101 (99.2) 0.476 Stroke Yes No 68 (1.5) 4462 (98.5) 30 (2.7) 1080 (97.3) <0.010 a Chi-square test. Boldface indicates statistical significance (p <0.05). Table 3. Multivariate analysis to predict myocardial infarction and stroke Variables OR (95% CI) P value a Myocardial infarction Age 1.518 (1.038-2.219) 0.032 African American (vs. other races) 1.010 (0.464-2.199) 0.981 Body mass index 0.828 (0.562-1.219) 0.338 Statin use (vs. no use) 1.408 (0.701-2.829) 0.314 Antihypertensive use (vs. no use) 140232.7426 (0.000->1.0E12) 0.969 Tight (vs. standard) BP control 0.734 (0.339-1.588) 0.432 Stroke Age 1.876 (1.474-2.387) <0.001 African American (vs. other races) 1.080 (0.677-1.722) 0.748 Body mass index 0.940 (0.742-1.192) 0.610 Statin use (vs. no use) 1.338 (0.876-2.044) 0.178 Antihypertensive use (vs. no use) 1.911 (0.466-7.838) 0.369 Tight (vs. standard) BP control 0.583 (0.374-0.910) 0.018 a Binary logistic regression test. Boldface indicates statistical significance (p <0.05). Table 4. Multivariate analysis to predict myocardial infarction and stroke (Number of antihypertensives as one of the variables) Variables OR (95% CI) P value a Myocardial infarction Age 1.358 (0.929-1.986) 0.115 African American (vs. other races) 0.910 (0.416-1.991) 0.814 Body mass index 0.960 (0.904-1.019) 0.176 Statin use (vs. no use) 1.269 (0.630-2.557) 0.504 Number of antihypertensives 2.272 (1.441-3.581) <0.001 Tight (vs. standard) BP control 0.788 (0.363-1.707) 0.545 Stroke Age 1.792 (1.406-2.284) <0.001 African American (vs. other races) 1.059 (0.663-1.690) 0.812 Body mass index 0.979 (0.944-1.015) 0.243 Statin use (vs. no use) 1.300 (0.849-1.990) 0.227 Number of antihypertensives 1.282 (1.011-1.627) 0.040 Tight (vs. standard) BP control 0.589 (0.377-0.919) 0.020 a Binary logistic regression test. Boldface indicates statistical significance (p <0.05). Supplementary Files AppendixforSTROBEchecklist.doc Cite Share Download PDF Status: Published Journal Publication published 16 May, 2020 Read the published version in BMC Primary Care → Version 4 posted Editorial decision: Accept 08 May, 2020 Editor assigned by journal 04 May, 2020 Editor invited by journal 03 May, 2020 Submission checks completed at journal 27 Nov, 2019 You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8701","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":545187,"identity":"58742f2e-3989-4147-bb6b-f47ee61a8a00","order_by":1,"name":"Bumsoo Park","email":"","orcid":"https://orcid.org/0000-0003-4505-2368","institution":"University of Michigan","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Bumsoo","middleName":"","lastName":"Park","suffix":""},{"id":545188,"identity":"8803f3d8-f2b8-4d01-9bec-d183b5675183","order_by":2,"name":"Katarzyna Budzynska","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0ElEQVRIiWNgGAWjYBACCQkgBtI8/BKMz0jTIiM5g9mMNC02BjeI1SI5u8fw5s+2OzzGt5vZHv5gsMmXdyCgRVrmjLGFZNszHrM7h9mNeRjSLDceIKBFTiLHTMKw7TCP2Y38Y9IMDIcNDBuI0ZII1GI8I5lN8gcxWqRBWg4CtRhIJLNJ8AC1yBPQwSA551ixZcO5wzwSN5LZpHkM0gwMCGmRuN288eaPssP2/GCHVdgYyBNyGBgwssFYQCsMDhCjheEPEps4W0bBKBgFo2AkAQDTBDlMxFdYUAAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0001-6640-7207","institution":"\tHenry Ford Health System","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Katarzyna","middleName":"","lastName":"Budzynska","suffix":""},{"id":545189,"identity":"01426106-7e78-4bbd-8ec2-2912fb75e0cd","order_by":3,"name":"Nada Almasri","email":"","orcid":"","institution":"Henry Ford Health System","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Nada","middleName":"","lastName":"Almasri","suffix":""},{"id":545190,"identity":"ae9e20b0-8831-49e3-8425-901b5fc7486a","order_by":4,"name":"Sumaiya Islam","email":"","orcid":"","institution":"Henry Ford Health System","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Sumaiya","middleName":"","lastName":"Islam","suffix":""},{"id":545191,"identity":"ea5aae46-79ce-4551-8a15-dac9f91fbac8","order_by":5,"name":"Fanar Alyas","email":"","orcid":"","institution":"ProMedica Monroe Regional Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Fanar","middleName":"","lastName":"Alyas","suffix":""},{"id":545192,"identity":"98a8d5ed-59e6-4e52-b1cf-649db7f4c723","order_by":6,"name":"Rachel L. 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Rees","email":"","orcid":"","institution":"Henry Ford Health System","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Della","middleName":"A.","lastName":"Rees","suffix":""},{"id":545197,"identity":"97a45023-1b79-4d16-856e-ec431027e84a","order_by":11,"name":"Lois Lamerato","email":"","orcid":"","institution":"Henry Ford Health System","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Lois","middleName":"","lastName":"Lamerato","suffix":""}],"badges":[],"createdAt":"2019-11-29 13:45:36","currentVersionCode":4,"declarations":"","doi":"10.21203/rs.2.18073/v4","doiUrl":"https://doi.org/10.21203/rs.2.18073/v4","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12875-020-01163-4","type":"published","date":"2020-05-16T20:31:52+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":1116715,"identity":"7bbe80c6-8a36-4efe-aea4-642b1ff11428","added_by":"auto","created_at":"2020-05-18 01:12:39","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":206774,"visible":true,"origin":"","legend":"Attrition diagram of the study population.","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8701/v4/1.png"},{"id":13503988,"identity":"656e31b8-6ae1-4d4a-8549-a003a9a93866","added_by":"auto","created_at":"2021-09-16 23:21:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":806209,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8701/v4/38632b84-0b12-46a7-aa28-390996ce3b03.pdf"},{"id":1116716,"identity":"41cda431-3d0a-4644-b5c9-d3b6a5c21e0a","added_by":"auto","created_at":"2020-05-18 01:12:40","extension":"doc","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":87040,"visible":true,"origin":"","legend":"","description":"","filename":"AppendixforSTROBEchecklist.doc","url":"https://assets-eu.researchsquare.com/files/rs-8701/v4/AppendixforSTROBEchecklist.doc"}],"financialInterests":"","formattedTitle":"Tight versus standard blood pressure control on the incidence of myocardial infarction and stroke: An observational retrospective cohort study in the general ambulatory setting","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAs one of the most common chronic health conditions, hypertension affects more than 1.3 billion adults worldwide [1] and about 75 million adults in the United States [2]. Hypertension can affect major body organs such as heart, brain, kidneys, and eyes and can lead to serious complications such as myocardial infarction (MI), stroke, end-stage renal disease, or visual impairment.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFor almost three decades hypertension was defined as systolic blood pressure (SBP) \u0026ge; 140 mmHg or diastolic blood pressure (DBP) \u0026ge; 90 mmHg [3]. Recently, the American College of Cardiology (ACC) and American Heart Association (AHA) published a new guideline defining hypertension as blood pressure (BP) \u0026ge; 130/80 mmHg, and set the BP treatment goal as \u0026lt; 130/80 mmHg [4]. This new guideline was based on the Systolic Blood Pressure Intervention Trial (SPRINT), which in 2015 showed lower rates of fatal and nonfatal major cardiovascular events and all-cause mortality when targeting SBP \u0026lt; 120 mmHg [5]. There have been clinical trials and meta-analyses showing that intensive blood pressure control significantly lowers the stroke risk [6-8]. Regarding the association of MI and BP control, there have been mixed results. A meta-analysis by Reboldi et al showed no benefit in the incidence of MI compared to stroke [8]. The ONTARGET trial by Mancia et al also found no significant benefit of intensive BP control on the MI outcome [9]. On the other hand, there have been studies that showed tight BP control might potentially increase the risk of MI [10, 11].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe new ACC/AHA guideline has raised controversies and the American Academy of Family Physicians recently decided to not endorse it due to the lack of sufficient data in systematic reviews, the lack of quality assessments for the studies, and giving considerable weight on the SPRINT trial while minimizing results from other trials [12]. Because of the controversy over the benefit of tight (TBPC) versus standard BP control (SBPC), we analyzed the incidences of MI and stroke in these two patient populations at our large health system.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cem\u003eStudy Design and Patient Population\u0026nbsp; \u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis single-center, retrospective cohort study aimed to assess the occurrence of new MI or stroke in patients with TBPC (SBP \u0026lt; 130 mmHg) versus SBPC (SBP 130-139 mmHg). We addressed only SBP rather than both SBP and DBP based on similar previous studies including the SPRINT trial [5].\u003c/p\u003e\n\u003cp\u003eThe data were collected and analyzed in 2018. We accessed the health system\u0026rsquo;s data stores (for medical records) to identify all outpatient encounters regardless of specialties (not limited to Family Medicine department) with ICD-10 diagnostic codes for hypertension in 2013. This resulted in 233,622 encounters in 88,456 patients. From this group we then applied inclusion and exclusion criteria to identify our study patients.\u003c/p\u003e\n\u003cp\u003eBPs have been measured by healthcare professionals manually with using a sphygmomanometer and a stethoscope in a typical outpatient setting in the same health system. We included patients with SBP \u0026lt; 140 mmHg between ages 40 and 79 years. The age range was based on the recent Centers for Disease Control and Prevention report showing that adults between ages 18 and 44 years mostly had hypertension under control and used antihypertensive medications less often [13]. We excluded the population greater than or equal to age 80 due to limited life expectancy. We averaged each patient\u0026rsquo;s SBPs measured in the same year between 2013 and 2015, so that one individual should have one averaged SBP reading per year. We excluded patients if the annual SBP measure was absent or if the averaged SBP fluctuated between TBPC and SBPC during the 3 years for BP characterization (2013-2015). We excluded patients with diabetes mellitus because the disease is a significant risk factor and a confounder in MI or stroke outcome. We excluded patients with a history of MI or stroke before 2013 because these are the highest risk factors for recurrent MI or stroke and we cannot assess a true incidence of new MI and stroke if we include these patients. We also excluded patients with MI or stroke events between 2013 and 2015. The attrition diagram (Figure 1) summarizes the enrollment process.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eOutcome Measures\u0026nbsp;\u0026nbsp; \u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe main outcome measures compared between the TBPC and SBPC groups were any new incidence of MI or stroke which occurred within 2 years (2016-2017). Clinical settings of the cardiovascular outcomes included outpatient, emergency department, and inpatient. For ICD-10 coding, we included MI including \u0026ldquo;late effect\u0026rdquo; codes, but we did not include angina pectoris. For stroke we counted both ischemic and hemorrhagic strokes and \u0026ldquo;late effect\u0026rdquo; codes. \u0026ldquo;Late effect\u0026rdquo; means residual sequelae after the initial acute phase of the illness has resolved [14]. We did not include transient ischemic attacks given its potential diagnostic uncertainty. We also excluded traumatic hemorrhages or vascular syndromes (e.g., vertebrobasilar artery syndrome).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eVariables\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAll the variables were collected through the database sorting system on Epi Info 7 provided by the Centers for Disease Control and Prevention (Atlanta, GA) per statistician (LL). We obtained baseline demographic data such as age, gender, race, and body mass index (BMI). We noted smoking status, serum low-density lipoprotein (LDL) levels, glomerular filtration rate, aspirin use, antihypertensive use, and statins use. Age was categorized by decade (40-49, 50-59, 60-69, and 70-79 years old). Race/ethnicity was categorized as African American, Asian, Hispanic, white, and other/unknown. For analysis, we further dichotomized race into 2 groups of African American and non-African American based on the recent Centers for Disease Control and Prevention report showing a relatively low percentage of hypertension visits among African Americans compared to other races [13]. BMI was categorized as underweight (BMI \u0026lt; 18.5 kg/m\u003csup\u003e2\u003c/sup\u003e), normal (BMI 18.5-24.9 kg/m\u003csup\u003e2\u003c/sup\u003e), overweight (BMI 25.0-29.9 kg/m\u003csup\u003e2\u003c/sup\u003e), obese (BMI 30.0-39.9 kg/m\u003csup\u003e2\u003c/sup\u003e), and morbidly obese (BMI \u0026ge; 40.0 kg/m\u003csup\u003e2\u003c/sup\u003e) based on World Health Organization criteria [15]. Smoking status was categorized as \u0026ldquo;never\u0026rdquo; or \u0026ldquo;ever.\u0026rdquo; Serum LDL was categorized as \u0026ge; 190 mg/dl or \u0026lt; 190 mg/dl; the former is one of the absolute indications of statin use based on 2013 ACC/AHA guidelines [16]. Glomerular filtration rate was categorized as \u0026ge; 30 ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e and \u0026lt; 30 ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e; the latter is the cutoff value where primary care physicians are recommended to refer patients to nephrology [17]. Use of aspirin, statins, and antihypertensives was determined from medication orders and defined as yes or no. In terms of counting antihypertensives, authors sorted it into major category of antihypertensives, for example, thiazide diuretic or calcium channel blockers, and then counted each medication that falls into each category of the antihypertensives per each patient during the enrollment period. This sorting process was done by statistician (LL).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAdverse Events\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAuthors believed it is important to evaluate hypotension-related adverse events in the TBPC group. However, given the retrospective nature of the study with using a large cohort, we were unable to collect data on the adverse events such as lightheadedness, dizziness, syncope, or falls in the TBPC group. However, we addressed and counted SBP \u0026lt; 90 mmHg in the TBPC group to find out the incidence of significant hypotension.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eStatistical Analysis \u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eSample characteristics were described using means and standard deviations for continuous variables (SBP) and frequencies (number and percentage) for categorical variables (gender, race, smoking, BMI categories, use of statin, and use of aspirin). To compare the baseline variables between TBPC and SBPC groups, we conducted chi-square tests. For multivariate analysis to determine independent predictors for MI or stroke incidence, we performed binary logistic regression entering only those variables that showed significant difference between TBPC and SBPC groups with the only exception of the variable \u0026lsquo;antihypertensive use versus no use\u0026rsquo; as this variable was considered to be relevant for the outcomes because antihypertensive use can modify the cardiovascular outcomes. We additionally included \u0026lsquo;the number of antihypertensives\u0026rsquo; to build a different regression model to predict outcomes with excluding \u0026lsquo;antihypertensive use versus no use\u0026rsquo;. All statistical analyses were performed using Epi Info 7 provided by the Centers for Disease Control and Prevention (Atlanta, GA). A \u003cem\u003eP\u003c/em\u003e value \u0026lt; 0.05 was considered statistically significant.\u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cem\u003eBaseline Data\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe identified 5640 patients as a final cohort for our study (Figure 1). Significant differences were noted in age, race, BMI, statin use, and the number of antihypertensives between the 2 groups (Table 1). More patients aged 50 to 69 years were in the TBPC group whereas the SBPC group had significantly more patients between 70 and 79 years (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001). African Americans were less likely to have TBPC compared to other races (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001). The TBPC group had more normal weight and overweight patients whereas the SBPC group had significantly more obese and morbidly obese patients (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001). The TBPC group had higher statin use than the SBPC group (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05). More patients in the SBPC group used 3 or more antihypertensive medications than those in the TBPC group. No differences were noted in gender, smoking status, serum LDL, glomerular filtration rate, and aspirin use between the 2 groups.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eIncidence Outcomes\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe TBPC and SBPC groups showed no difference in incidence of new MI in the 2-year follow-up (Table 2). The SBPC group had a significantly higher incidence of stroke compared to the TBPC group (2.7% vs. 1.5%, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.010) (Table 2). This gave an absolute risk reduction of 1.2%, and the number needed to treat of approximately 83.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eMultivariate Analysis \u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eIn the logistic regression model, only increased age was an independent predictor of MI incidence (OR 1.518, 95% CI 1.038-2.219) when \u0026lsquo;antihypertensive use versus no use\u0026rsquo; was included as one of the variables (Table 3). However, when \u0026lsquo;the number of antihypertensives\u0026rsquo; was included in the model, increased number of antihypertensives was an independent predictor of MI (OR 2.272, 95% CI 1.441-3.581) (Table 4). In terms of stroke incidence, both increased age (OR 1.876, 95% CI 1.474-2.387) and TBPC (OR 0.583, 95% CI 0.374-0.910) were significantly associated with stroke incidence when \u0026lsquo;antihypertensive use versus no use\u0026rsquo; was included as one of the variables (Table 3). When \u0026lsquo;the number of antihypertensives\u0026rsquo; was included in the model, increased age (OR 1.792, 95% CI 1.406-2.284), increased number of antihypertensives (OR 1.282, 95% CI 1.011-1.627), and TBPC (OR 0.589, 95% CI 0.377-0.919) were independent predictors of stroke (Table 4).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAdverse Events\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAmong the 4530 patients in the TBPC group, only 5 patients (0.001%) had SBP \u0026lt; 90 mmHg per BP readings in the outpatient setting. \u0026nbsp;\u003c/p\u003e"},{"header":"Discussion ","content":"\u003cp\u003eThis single-center cohort study of more than 5000 hypertensive patients evaluated the impact of TBPC (SBP \u0026lt; 130 mmHg) on the incidence of new MI and stroke. We suggest that TBPC independently decreased the incidence of stroke compared to SBPC, but did not have an impact on MI incidence.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA retrospective study using the ACTION trial database found the greatest difference between SBP \u0026lt; 130 mmHg (2.5% incidence rate) and SBP \u0026lt; 140 mmHg (3.8% incidence rate) groups in the risk of stroke [18]. The cohort in the ACTION trial was different from ours in that their patients had stable coronary heart disease [19]. A meta-analysis performed by Lee et al demonstrated that SBP \u0026lt; 130 mmHg compared to SBP 130-139 mmHg showed additional protective effect on stroke in patients with cardiovascular risk factors but no previously established cardiovascular disease [7]. In another meta-analysis, Reboldi et al found that more-tight SBP control (\u0026lt; 120 mmHg), compared to less-tight SBP control (\u0026lt; 140 mmHg), significantly reduced stroke risk by 31%, but no significant risk reduction was noted in MI [8]. While these results are similar to ours, Reboldi et al\u0026rsquo;s analysis included diabetic patients and a different BP cutoff for the 2 groups. The ONTARGET trial provided further evidence on the significant impact of BP control on stroke but not on MI [9]. The trial found that more frequent achievement of target BPs (\u0026lt; 130/90 mmHg or \u0026lt; 140/90 mmHg) resulted in significant cerebrovascular protection but not cardiac protection [9]. More recent large European meta-analyses further strengthen the evidence that more intense blood pressure control reduces cardiovascular events [6, 20].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWhy TBPC decreases the risk of stroke but not MI remains unclear. Several long-term prospective population-based studies have shown that hypertension increased the relative risk of stroke to a greater degree than MI [21-24]. One possible hypothesis is different blood flow physiology between the brain and heart. The brain receives a larger fraction of cardiac output by nearly 3-fold than the heart [25]. While most of the coronary blood flow occurs during diastole, the cerebral blood flow occurs during systole [26]. Therefore, cerebral blood flow might be more sensitive to a change in SBP than coronary blood flow, and coronary blood flow might be more sensitive to a change in DBP than SBP. A recent multinational study supports this hypothesis in that results showed increased risk of MI with increased DBP whereas increased SBP did not increase the risk of MI [11].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOther studies have reported different results. Verdecchia et al performed an open-label randomized trial and found no difference in the incidence of MI or stroke between TBPC (\u0026lt; 130 mmHg) and SBPC (\u0026lt; 140 mmHg) [27]. Their population was similar to ours in the exclusion of diabetic patients. Another large randomized study using the database of the Hypertension Optimal Treatment trial showed that TBPC (\u0026lt; 130 mmHg) in patients with diabetes and coronary artery disease did not improve cardiovascular outcomes compared to SBPC (\u0026lt; 140 mmHg) [28]. The ACCORD study conducted in 2010 also showed no difference in fatal and nonfatal cardiovascular events between TBPC (\u0026lt; 120 mmHg) and SBPC (\u0026lt; 140 mmHg) groups in diabetic patients. More importantly, the TBPC group demonstrated significantly higher rates of serious adverse events attributed to antihypertensive therapy [29]. Furthermore, a post hoc analysis using the Irbesartan Diabetic Nephropathy Trial database concluded that BP \u0026le; 120/85 mmHg may be associated with increased cardiovascular events [30].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOur study and the majority of cohort and prospective studies have shown that TBPC is associated with decreased risk of stroke. Nevertheless, the issue of TBPC must be addressed carefully in the clinical setting. Even though cerebral blood flow has an autoregulation mechanism, the mechanism can be lost if the mean arterial BP drops below 60 mmHg [31]. A study that targeted BP \u0026lt; 130/80 mmHg for diabetic patients found intensive BP control caused progressive reduction of cerebral blood flow velocity [32]. According to the meta-analysis by Thomopoulos et al, the BP-lowering treatment reduced cardiovascular events by 24% whereas it increased the risk of discontinuation attributed to adverse events by 89% [33]. Ferreira et al recently demonstrated significantly increased rates of cardiovascular death, heart failure hospitalization, MI, and stroke when SBP decreased below 125 mmHg [11]. In our study, only 0.001% (5/4530) in the TBPC group showed SBP \u0026lt; 90 mmHg.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAn interesting finding in our study is that statin use did not independently affect MI or stroke incidence. Based on the 2013 ACC/AHA guidelines, absolute indications for statin use include clinical atherosclerotic cardiovascular disease, type 2 diabetes mellitus, and serum LDL \u0026ge; 190 mg/dl [16]. Perhaps statin use did not affect the MI or stroke incidence in our study because we excluded patients with diabetes and those with a history of MI or stroke. Very few patients in our study had a serum LDL \u0026ge; 190 mg/dl (Table 1). Another interesting finding is that increased number of antihypertensive medications significantly predicted both MI and stroke incidence while the usage of antihypertensive medication itself did not predict either MI or stroke incidence in the multivariate model. This can suggest that requiring more antihypertensive medications rather than taking the medications itself could predict higher cardiovascular risk, or those who were prescribed many antihypertensive medications would have not been adherent to the medications.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eLimitations\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe major limitation of our study is that this is an observational retrospective study. Given the fact that authors did not do any interventional measures for the patients, strictly speaking, it might not be very appropriate to use the terms \u0026ldquo;tight control\u0026rdquo; and \u0026ldquo;standard control\u0026rdquo;. However, as all the patients were formally diagnosed with hypertension, authors assumed that they had received some type of BP control intervention including lifestyle counseling from their providers. And this would have justified our using the terms \u0026ldquo;control.\u0026rdquo; Our study also has several other limitations. Because of the retrospective design, we were not able to completely address and remove all potential confounders. For example, excluding patients whose BP showed fluctuating levels between TBPC and SBPC could otherwise have affected the outcome. There were significant differences in age, race, BMI, statin use, and the number of antihypertensives between TBPC and SBPC groups. The TBPC group was younger and had statins prescribed more often than the SBPC group. Although these variables were adjusted at multivariate analysis, these differences might still have affected our findings, and we admit that this is potentially the most major limitation of our study, which should be criticized. Also, as we excluded other significant risk factors of MI and stroke, such as diabetes and history of MI or stroke, our study population was different from actual patients commonly seen in clinical practice, which might have resulted in the relatively rare outcome events in our study. Also, as we were not able to review each patient\u0026rsquo;s medical record given the large, retrospective, and electronic-based data analysis, we were unable to collect information on the adverse events that can potentially occur from TBPC such as dizziness, syncope, falls, acute kidney injury, or cerebral hypo-perfusion. However, given that only 0.001% of the TBPC patients had SBP less than 90 mmHg, it is less likely that many of our TBPC patients developed significant hypotension-related complications. Also, we were unable to assess each patient\u0026rsquo;s medication adherence data as we only counted the numbers of the medication prescriptions which can potentially be significantly confounding. It also would have been more informative if we could include the mortality and quality of life outcomes in either group, which should be considered for future research. \u0026nbsp;\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur observational retrospective cohort study showed that TBPC had a significant benefit in less stroke incidence compared to SBPC, although it did not affect the incidence of MI. Our study could help aid in the discussion regarding the association of BP control and stroke in actual clinical practice. Even though the American Academy of Family Physicians decided to not endorse the ACC/AHA guideline, our study shows more favorable result towards the SPRINT trial in terms of less stroke incidence.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eACC: American College of Cardiology; AHA: American Heart Association; BMI: Body mass index; BP: Blood pressure; DBP: Diastolic blood pressure; LDL: Low-density lipoprotein; MI: Myocardial infarction; SBP: Systolic blood pressure; SBPC: Standard blood pressure control; SPRINT: Systolic Blood Pressure Intervention Trial; TBPC: Tight blood pressure control\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was approved by the Institutional Review Board of Henry Ford Health System (IRB No. 11950) under expedited review with waiver of informed consent.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare no competing interests for this study.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere was no funding support applicable to the study.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors designed and conceived of the study as a group project. BP drafted the manuscript. BP, NA, SI, FA, RC, BEA, PACC, and LL collected and analyzed the data. LL performed a statistical analysis. KB, MES, DAR, and LL supervised overall study process, and revised the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted as an annual scholarly project of the family medicine residency program at Henry Ford Health System in 2018. This study was presented at Family Medicine Experience (FMX) 2018 in New Orleans, Louisiana.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBloch MJ. Worldwide prevalence of hypertension exceeds 1.3 billion. 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J Hypertens. 2016;34(8):1451-63.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003eTable 1. Baseline data for patients with tight versus standard blood pressure control\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"width: 446.55pt; margin-left: 5.4pt; border-collapse: collapse; border: none;\" width=\"595\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 134.7pt; border-top: solid black 1.0pt; border-left: none; border-bottom: solid black 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"180\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eVariables\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 120.45pt; border-top: solid black 1.0pt; border-left: none; border-bottom: solid black 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"161\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003eTBPC\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e(SBP \u0026lt;130 mmHg)\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e(n=4530)\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003eN (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 136.35pt; border-top: solid black 1.0pt; border-left: none; border-bottom: solid black 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"182\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003eSBPC\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e(SBP 130-139 mmHg)\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e(n=1110)\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003eN (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.05pt; border-top: solid black 1.0pt; border-left: none; border-bottom: solid black 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"73\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cem\u003eP \u003c/em\u003evalue\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 134.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"180\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003eAge category\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp; 40 to 49 years\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp; 50 to 59 years\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp; 60 to 69 years\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp; 70 to 79 years\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 120.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"161\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e778 (17.2)\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e1533 (33.8)\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e1466 (32.4)\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e753 (16.6)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 136.35pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"182\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e183 (16.5)\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e330 (29.7)\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e339 (30.5)\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e258 (23.2)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"73\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 134.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"180\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eGender\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp; Male\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp; Female\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 120.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"161\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e1917 (42.3)\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e2613 (57.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 136.35pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"182\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e482 (43.4)\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e628 (56.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"73\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; word-break: normal;\"\u003e0.504\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 134.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"180\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003eRace\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp; African American\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp; Asian\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp; Hispanic\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp; White\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp; Other/unknown\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 120.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"161\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e1235 (27.3)\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e152 (3.4)\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e58 (1.3)\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e2588 (57.1)\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e497 (11.1)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 136.35pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"182\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e406 (36.6)\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e26 (2.3)\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e13 (1.2)\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e550 (49.5)\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e115 (10.4)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"73\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 134.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"180\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003eBMI category \u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp; Underweight\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp; Normal \u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp; Overweight\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp; Obese\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp; Morbidly obese\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 120.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"161\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e50 (1.1)\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e805 (18.4)\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e1602 (36.6)\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e1624 (37.1)\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e293 (6.7)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 136.35pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"182\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e10 (0.9)\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e149 (13.8)\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e341 (31.7)\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e467 (43.4)\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e109 (10.1)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"73\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 134.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"180\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eSmoking\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp; Ever\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp; Never\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 120.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"161\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e2195 (48.5)\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e2333 (51.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 136.35pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"182\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e521 (47.1)\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e586 (52.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"73\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; word-break: normal;\"\u003e0.399\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 134.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"180\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eSerum LDL level\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp; \u0026ge;190 mg/dl\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp; \u0026lt;190 mg/dl\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 120.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"161\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e22 (0.6)\u003c/p\u003e\n\u003cp style=\"text-indent: 24.0pt; line-height: 200%; word-break: normal;\"\u003e3652 (99.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 136.35pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"182\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;9 (1.0)\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e894 (99.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"73\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; word-break: normal;\"\u003e0.182\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 134.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"180\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eEGFR (race-adjusted)\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp; \u0026ge;30 ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp; \u0026lt;30 ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 120.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"161\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e3653 (99.3)\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e27 (0.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 136.35pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"182\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e905 (99.6)\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e4 (0.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"73\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; word-break: normal;\"\u003e0.333\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 134.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"180\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eAspirin use\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp; Yes\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp; No\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 120.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"161\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e1073 (23.7)\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e3457 (76.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 136.35pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"182\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e253 (22.8)\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e857 (77.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"73\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; word-break: normal;\"\u003e0.529\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 134.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"180\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003eStatin use\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp; Yes\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp; No\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 120.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"161\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e2008 (44.3)\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e2522 (55.7)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 136.35pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"182\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e450 (40.5)\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e660 (59.5)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"73\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026lt;0.05\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 134.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"180\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eAntihypertensive use\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 120.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"161\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 136.35pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"182\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"73\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; word-break: normal;\"\u003e0.646\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 134.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"180\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp; Yes\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 120.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"161\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e4328 (95.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 136.35pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"182\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e1064 (95.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"73\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 134.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"180\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp; No\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 120.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"161\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e202 (4.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 136.35pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"182\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e46 (4.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"73\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 134.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"180\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003eNo. Antihypertensives\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 120.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"161\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 136.35pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"182\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"73\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 134.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"180\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp; 0\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 120.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"161\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e202 (4.5)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 136.35pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"182\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e46 (4.1)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"73\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 134.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"180\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp; 1\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 120.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"161\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e1711 (37.8)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 136.35pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"182\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e347 (31.3)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"73\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 134.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"180\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp; 2\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 120.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"161\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e1376 (30.4)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 136.35pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"182\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e321 (28.9)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"73\"\u003e\n\u003cp style=\"text-align: right; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 134.7pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"180\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp; 3 or more\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 120.45pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"161\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e1241 (27.4)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 136.35pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"182\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e396 (35.7)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.05pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"73\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"line-height: 200%; word-break: normal;\"\u003e\u003csup\u003ea\u003c/sup\u003eChi-square test.\u003c/p\u003e\n\u003cp style=\"line-height: 200%; word-break: normal;\"\u003eBoldface indicates statistical significance (p \u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 200%; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003eTable 2. Two-year cardiovascular incidence in tight versus standard blood pressure control\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"width: 446.55pt; margin-left: 5.4pt; border-collapse: collapse; border: none;\" width=\"595\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 134.7pt; border-top: solid black 1.0pt; border-left: none; border-bottom: solid black 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"180\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eVariables\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 120.45pt; border-top: solid black 1.0pt; border-left: none; border-bottom: solid black 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"161\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003eTBPC\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e(SBP \u0026lt;130 mmHg)\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e(n=4530)\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003eN (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 136.35pt; border-top: solid black 1.0pt; border-left: none; border-bottom: solid black 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"182\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003eSBPC\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e(SBP 130-139 mmHG)\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e(n=1110)\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003eN (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.05pt; border-top: solid black 1.0pt; border-left: none; border-bottom: solid black 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"73\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cem\u003eP \u003c/em\u003evalue\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 134.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"180\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eMyocardial infarction\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u0026nbsp; Yes\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u0026nbsp; No\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 120.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"161\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e28 (0.6)\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e4502 (99.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 136.35pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"182\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e9 (0.8)\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e1101 (99.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"73\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;0.476\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 134.7pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"180\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003eStroke\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp;\u0026nbsp; Yes\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp;\u0026nbsp; No\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 120.45pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"161\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e68 (1.5)\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e4462 (98.5)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 136.35pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"182\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e30 (2.7)\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e1080 (97.3)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 55.05pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"73\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp;\u0026lt;0.010\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"line-height: 200%; word-break: normal;\"\u003e\u003csup\u003ea\u003c/sup\u003eChi-square test.\u003c/p\u003e\n\u003cp style=\"line-height: 200%; word-break: normal;\"\u003eBoldface indicates statistical significance (p \u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 200%; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003eTable 3. Multivariate analysis to predict myocardial infarction and stroke\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"width: 446.55pt; margin-left: 5.4pt; border-collapse: collapse; border: none;\" width=\"595\"\u003e\n\u003ctbody\u003e\n\u003ctr style=\"height: 11.9pt;\"\u003e\n\u003ctd style=\"width: 184.3pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt; height: 11.9pt;\" width=\"246\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eVariables\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 35.45pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt; height: 11.9pt;\" width=\"47\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 162.75pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt; height: 11.9pt;\" width=\"217\"\u003e\n\u003cp style=\"text-align: left; text-indent: 12.0pt; line-height: 200%; word-break: normal;\"\u003eOR (95% CI)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 64.05pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt; height: 11.9pt;\" width=\"85\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cem\u003eP \u003c/em\u003evalue\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 184.3pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"246\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eMyocardial infarction\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 35.45pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"47\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 162.75pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"217\"\u003e\n\u003cp style=\"text-align: left; text-indent: 12.0pt; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 64.05pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"85\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 184.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"246\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003eAge \u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 35.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"47\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 162.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"217\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e1.518 (1.038-2.219)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 64.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"85\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e0.032\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 184.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"246\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eAfrican American (vs. other races)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 35.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"47\"\u003e\n\u003cp style=\"text-align: center; text-indent: 6.0pt; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 162.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"217\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e1.010 (0.464-2.199)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 64.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"85\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e0.981\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 184.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"246\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eBody mass index\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 35.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"47\"\u003e\n\u003cp style=\"text-align: center; text-indent: 6.0pt; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 162.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"217\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e0.828 (0.562-1.219)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 64.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"85\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e0.338\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 184.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"246\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eStatin use (vs. no use)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 35.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"47\"\u003e\n\u003cp style=\"text-align: center; text-indent: 6.0pt; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 162.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"217\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e1.408 (0.701-2.829)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 64.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"85\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e0.314\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 184.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"246\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eAntihypertensive use (vs. no use)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 35.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"47\"\u003e\n\u003cp style=\"text-align: center; text-indent: 6.0pt; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 162.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"217\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e140232.7426 (0.000-\u0026gt;1.0E12)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 64.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"85\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e0.969\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 184.3pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"246\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eTight (vs. standard) BP control\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 35.45pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"47\"\u003e\n\u003cp style=\"text-align: center; text-indent: 6.0pt; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 162.75pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"217\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e0.734 (0.339-1.588)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 64.05pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"85\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e0.432\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 184.3pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"246\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eStroke\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 35.45pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"47\"\u003e\n\u003cp style=\"text-align: center; text-indent: 6.0pt; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 162.75pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"217\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 64.05pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"85\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 184.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"246\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003eAge \u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 35.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"47\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 162.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"217\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e1.876 (1.474-2.387)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 64.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"85\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 184.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"246\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eAfrican American (vs. other races)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 35.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"47\"\u003e\n\u003cp style=\"text-align: center; text-indent: 6.0pt; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 162.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"217\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e1.080 (0.677-1.722)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 64.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"85\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e0.748\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 184.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"246\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eBody mass index\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 35.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"47\"\u003e\n\u003cp style=\"text-align: center; text-indent: 6.0pt; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 162.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"217\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e0.940 (0.742-1.192)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 64.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"85\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e0.610\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 184.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"246\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eStatin use (vs. no use)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 35.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"47\"\u003e\n\u003cp style=\"text-align: center; text-indent: 6.0pt; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 162.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"217\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e1.338 (0.876-2.044)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 64.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"85\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e0.178\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 184.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"246\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eAntihypertensive use (vs. no use)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 35.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"47\"\u003e\n\u003cp style=\"text-align: center; text-indent: 6.0pt; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 162.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"217\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e1.911 (0.466-7.838)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 64.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"85\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e0.369\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 184.3pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"246\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003eTight (vs. standard) BP control\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 35.45pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"47\"\u003e\n\u003cp style=\"text-align: center; text-indent: 5.9pt; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 162.75pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"217\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e0.583 (0.374-0.910)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 64.05pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"85\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e0.018\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003csup\u003ea\u003c/sup\u003eBinary logistic regression test.\u003c/p\u003e\n\u003cp style=\"line-height: 200%; word-break: normal;\"\u003eBoldface indicates statistical significance (p \u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 200%; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003eTable 4. Multivariate analysis to predict myocardial infarction and stroke (Number of antihypertensives as one of the variables)\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"width: 446.55pt; margin-left: 5.4pt; border-collapse: collapse; border: none;\" width=\"595\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 184.3pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"246\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eVariables\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 35.45pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"47\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 162.75pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"217\"\u003e\n\u003cp style=\"text-indent: 12.0pt; line-height: 200%; word-break: normal;\"\u003eOR (95% CI)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 64.05pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"85\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cem\u003eP \u003c/em\u003evalue\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 184.3pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"246\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eMyocardial infarction\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 35.45pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"47\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 162.75pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"217\"\u003e\n\u003cp style=\"text-indent: 12.0pt; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 64.05pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"85\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 184.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"246\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eAge\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 35.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"47\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 162.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"217\"\u003e\n\u003cp style=\"line-height: 200%; word-break: normal;\"\u003e1.358 (0.929-1.986)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 64.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"85\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e0.115\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 184.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"246\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eAfrican American (vs. other races)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 35.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"47\"\u003e\n\u003cp style=\"text-align: center; text-indent: 6.0pt; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 162.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"217\"\u003e\n\u003cp style=\"line-height: 200%; word-break: normal;\"\u003e0.910 (0.416-1.991)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 64.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"85\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e0.814\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 184.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"246\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eBody mass index\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 35.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"47\"\u003e\n\u003cp style=\"text-align: center; text-indent: 6.0pt; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 162.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"217\"\u003e\n\u003cp style=\"line-height: 200%; word-break: normal;\"\u003e0.960 (0.904-1.019)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 64.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"85\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e0.176\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 184.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"246\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eStatin use (vs. no use)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 35.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"47\"\u003e\n\u003cp style=\"text-align: center; text-indent: 6.0pt; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 162.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"217\"\u003e\n\u003cp style=\"line-height: 200%; word-break: normal;\"\u003e1.269 (0.630-2.557)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 64.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"85\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e0.504\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 184.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"246\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003eNumber of antihypertensives\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 35.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"47\"\u003e\n\u003cp style=\"text-align: center; text-indent: 5.9pt; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 162.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"217\"\u003e\n\u003cp style=\"line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e2.272 (1.441-3.581)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 64.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"85\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 184.3pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"246\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eTight (vs. standard) BP control\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 35.45pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"47\"\u003e\n\u003cp style=\"text-align: center; text-indent: 6.0pt; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 162.75pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"217\"\u003e\n\u003cp style=\"line-height: 200%; word-break: normal;\"\u003e0.788 (0.363-1.707)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 64.05pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"85\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;0.545\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 184.3pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"246\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eStroke\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 35.45pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"47\"\u003e\n\u003cp style=\"text-align: center; text-indent: 6.0pt; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 162.75pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"217\"\u003e\n\u003cp style=\"line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 64.05pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"85\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 184.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"246\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003eAge \u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 35.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"47\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 162.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"217\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e1.792 (1.406-2.284)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 64.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"85\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026lt;0.001\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 184.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"246\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eAfrican American (vs. other races)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 35.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"47\"\u003e\n\u003cp style=\"text-align: center; text-indent: 6.0pt; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 162.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"217\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e1.059 (0.663-1.690)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 64.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"85\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e0.812\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 184.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"246\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eBody mass index\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 35.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"47\"\u003e\n\u003cp style=\"text-align: center; text-indent: 6.0pt; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 162.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"217\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e0.979 (0.944-1.015)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 64.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"85\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e0.243\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 184.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"246\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003eStatin use (vs. no use)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 35.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"47\"\u003e\n\u003cp style=\"text-align: center; text-indent: 6.0pt; line-height: 200%; word-break: normal;\"\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 162.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"217\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e1.300 (0.849-1.990)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 64.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"85\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e0.227\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 184.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"246\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003eNumber of antihypertensives\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 35.45pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"47\"\u003e\n\u003cp style=\"text-align: center; text-indent: 5.9pt; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 162.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"217\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e1.282 (1.011-1.627)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 64.05pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"85\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e0.040\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 184.3pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"246\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003eTight (vs. standard) BP control\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 35.45pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"47\"\u003e\n\u003cp style=\"text-align: center; text-indent: 5.9pt; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 162.75pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"217\"\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e0.589 (0.377-0.919)\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 64.05pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"85\"\u003e\n\u003cp style=\"text-align: center; line-height: 200%; word-break: normal;\"\u003e\u003cstrong\u003e0.020\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"text-align: left; line-height: 200%; word-break: normal;\"\u003e\u003csup\u003ea\u003c/sup\u003eBinary logistic regression test.\u003c/p\u003e\n\u003cp style=\"line-height: 200%; word-break: normal;\"\u003eBoldface indicates statistical significance (p \u0026lt;0.05).\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-primary-care","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"famp","sideBox":"Learn more about [BMC Primary Care](https://bmcprimcare.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12875","title":"BMC Primary Care","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Blood pressure, Myocardial infarction, Stroke ","lastPublishedDoi":"10.21203/rs.2.18073/v4","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.2.18073/v4","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: The 2017 American College of Cardiology and American Heart Association guideline defined hypertension as blood pressure (BP) ≥ 130/80 mmHg compared to the traditional definition of ≥ 140/90 mmHg. This change raised much controversy. We conducted this study to compare the impact of tight (TBPC) versus standard BP control (SBPC) on the incidence of myocardial infarction (MI) and stroke.\u0026nbsp;\u003c/p\u003e\u003cp\u003eMethods: We retrospectively identified all hypertensive patients in an ambulatory setting based on the diagnostic code for 1 year at our institution who were classified by the range of BP across 3 years into 2 groups of TBPC (\u0026lt; 130 mmHg) and SBPC (130-139 mmHg). We compared the incidence of new MI and stroke between the 2 groups across a 2-year follow-up. Multivariate analysis was done to identify independent predictors for the incidence of new MI and stroke.\u003c/p\u003e\u003cp\u003eResults: Of 5640 study patients, the TBPC group showed significantly less incidence of stroke compared to the SBPC group (1.5% vs. 2.7%, P \u0026lt; 0.010). No differences were found in MI incidence between the 2 groups (0.6% vs. 0.8%, P = 0.476). Multivariate analysis showed that increased age independently increased the incidence of both MI (OR 1.518, 95% CI 1.038-2.219) and stroke (OR 1.876, 95% CI 1.474-2.387), and TBPC independently decreased the incidence of stroke (OR 0.583, 95% CI 0.374-0.910) but not of MI.\u0026nbsp;\u0026nbsp;\u003c/p\u003e\u003cp\u003eConclusions: Our observational study suggests that TBPC may be beneficial in less stroke incidence compared to SBPC but it didn’t seem to affect the incidence of MI. Our study is limited by its retrospective design with potential confounders.\u003c/p\u003e","manuscriptTitle":"Tight versus standard blood pressure control on the incidence of myocardial infarction and stroke: An observational retrospective cohort study in the general ambulatory setting","msid":"","msnumber":"","nonDraftVersions":[{"code":4,"date":"2020-05-18 01:12:39","doi":"10.21203/rs.2.18073/v4","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Accept","date":"2020-05-08T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-05-04T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-05-03T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2019-11-27T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-primary-care","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"famp","sideBox":"Learn more about [BMC Primary Care](https://bmcprimcare.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12875","title":"BMC Primary Care","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":3,"date":"2020-03-04 21:17:33","doi":"10.21203/rs.2.18073/v3","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revision","date":"2020-04-21T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-04-20T12:00:00+00:00","index":1,"fulltext":"Recommendation: Accept after minor essential revisions\nForm responses:\n---\n\nComments to Author:\n---\nThank you very much for the opportunity to review your interesting study. I note that this paper has been through two rounds of revision already with thorough scrutiny from the other reviewers and careful and constructive consideration of the comments and suggestions by yourselves. Your paper is very clearly written and you have been open about discussing the limitations of your study. It is right that the limitations of studies such as this one are acknowledged. However, studies like this fulfil an important role in adding to the evidence base and given the ongoing question around \"what is the optimum blood pressure target?\" it is entirely appropriate that we make use of all data.\n\nGiven the revisions and reviews that have already been carried out I do not feel that I have much more that would meaningfully add to this paper. There are two minor points below:\n\nI think that the actual numbers should be reported in the results section of the abstract as this is common practice. For example, the incidence should be included after \"the TBPC group showed significantly less incidence of stroke compared to the SBPC group (2.7% vs. 1.5%, P \u003c 0.010)\". The same should be done for the other reported results.\n\nI note that you have included the STROBE checklist in your supplementary material, which is an excellent addition, and you have covered the criteria well. However you have not included anything about funding or ethics. I understand that this study might not have received specific funding, but the researchers carrying out the work will be funded in some way which should be included. The analysis was also carried out on a database containing patient data. Presumably this must have needed some level of approval to access this. If this was not the case, you should justify why it was not necessary.* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests.**\n* I agree to the open peer review policy of the journal. I understand that my name will be included on my report to the authors and, if the manuscript is accepted for publication, my named report including any attachments I upload will be posted on the website along with the authors' responses. I agree for my report to be made available under an Open Access Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any comments which I do not wish to be included in my named report can be included as confidential comments to the editors, which will not be published.: ** I agree to the open peer review policy of the journal**\n"},{"type":"editorInvitedReview","content":"","date":"2020-04-19T12:00:00+00:00","index":2,"fulltext":"Recommendation: Major revisions required\nForm responses:\n---\n\nComments to Author:\n---\nAbstract\n* Introduction does not relate clearly to the aim in the background\n* When the data were analysed is usually not reported.\n* What is BP rate?\n* Unclear how patients were identified. Methods need clearer explanation.\n* Unclear what the multivariate analysis was conducted for in the methods section. Risk factors for what?\n* Studies do not suggest\n* Conclusion has informal English.\n\nIntroduction\nTypographical error - 'evidences'\n'2' needs to be spelt out in full\n\nMethods\nParagraph 2 - What is the relevance of when the data were analysed?\nParagraph 2 - further information about where the data comes from is required. What is the 'health system's data stores' that is being referred to? I am guessing that this is routinely collected hospital administrative data? More details about the datasets interrogated for this research are required.\nParagraph 2 - How reliable are the ICD-10 diagnostic codes for hypertension?\nParagraph 2 - What are the inclusion and exclusion criteria? Is there something extra to what is discussed in the following paragraph? Or are the authors referring to the following paragraph?\nParagraph 3 - What is the rationale for excluding patients whose average SBP fluctuated between TBPC and SBPC? There is some evidence that blood pressure variability is associated with cardiovascular disease.\nParagraph 3 - Justification for excluding patients with a history of stroke and MI should be revised. Without making this exclusion, the outcome you would be looking at wouldn't be 'incidence'.\nOutcome measures - 'new' MI or stroke event is ambiguous.\nOutcome measures - What are the 'late effect' codes? Please provide further explanation and reference.\nVariables - how were these collected?\nVariables - further information is required for how medication utilisation was categorised. For example, was one script over the three years considered as 'use'? How was the 'number of antihypertensives' calculated (number of different medications? Which medications?)?\nAdverse events - revise first sentence.\nAdverse events - first time adverse events are mentioned. Authors should clarify the point of collecting these data prior to this section\nStatistical analysis - seems that 'antihypertensive use versus no use' was included irrespective of significance. Why use is insignificant should be discussed.\n\nResults\nIncidence outcomes - Is the reporting of the NNT relevant here? This is not a RCT. Also, what is the 'treatment' that is referred to here?\n\nDiscussion\nThe authors state that it was interesting that statin use was not associated with incidence in this cohort - I disagree that the analysis set-up in an appropriate way to determine this.\nThe authors need to provide a summary of the 'cohort and prospective studies have shown that TBPC is associated with decreased risk of stroke'. How is this study different? What does this study add to the literature?\n* Are the methods appropriate and well described?: **No**\n* Does the work include the necessary controls?: **No**\n* Are the conclusions drawn adequately supported by the data shown?: **No**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests**\n* I agree to the open peer review policy of the journal. I understand that my name will be included on my report to the authors and, if the manuscript is accepted for publication, my named report including any attachments I upload will be posted on the website along with the authors' responses. I agree for my report to be made available under an Open Access Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/). I understand that any comments which I do not wish to be included in my named report can be included as confidential comments to the editors, which will not be published.: ** I agree to the open peer review policy of the journal**\n"},{"type":"reviewerAgreed","content":"","date":"2020-04-05T12:00:00+00:00","index":2,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-04-01T12:00:00+00:00","index":1,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-03-11T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2020-03-02T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-03-01T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-03-01T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-primary-care","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"famp","sideBox":"Learn more about [BMC Primary Care](https://bmcprimcare.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12875","title":"BMC Primary Care","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":2,"date":"2020-02-05 17:56:31","doi":"10.21203/rs.2.18073/v2","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revision","date":"2020-02-24T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewersInvited","content":"","date":"2020-02-07T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-02-07T12:00:00+00:00","index":1,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2020-02-07T12:00:00+00:00","index":2,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-02-07T12:00:00+00:00","index":1,"fulltext":"Recommendation: Accept after minor essential revisions\nForm responses:\n---\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Needs some language corrections before being published**\n* Declaration of competing interests: **I declare that I have no competing interests'**\n\nComments to Author:\n---\nI congratulate the authors on a comprehensive and thoughtful response to the comments of myself and fellow Reviewer.\n\nMy only remaining concern is that is still unclear to me as what the setting of the study is. Reference is made to a single centre 'out patient setting'; further details are required as to whether this is a family practice setting or not. If not, the setting should be specified i believe in the paper title to alert readers of BMC Family Practice."},{"type":"editorInvitedReview","content":"","date":"2020-02-07T12:00:00+00:00","index":2,"fulltext":"Recommendation: Accept without revision\nForm responses:\n---\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **No**\n\nComments to Author:\n---\nThanks you for addressing the issues I had outlined."},{"type":"editorAssigned","content":"","date":"2020-02-04T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2020-02-03T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2020-02-03T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-primary-care","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"famp","sideBox":"Learn more about [BMC Primary Care](https://bmcprimcare.biomedcentral.com/)","snPcode":"","submissionUrl":"https://author-welcome.nature.com/12875","title":"BMC Primary Care","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":1,"date":"2019-12-04 21:16:02","doi":"10.21203/rs.2.18073/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2020-01-06T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2020-01-03T12:00:00+00:00","index":1,"fulltext":"Recommendation: Major revisions required\nForm responses:\n---\n* Are the methods appropriate and well described?: **No**\n* Does the work include the necessary controls?: **No**\n* Are the conclusions drawn adequately supported by the data shown?: **No**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests'**\n\nComments to Author:\n---\nThis is a well written and topical article researching the important question of whether family physicians should have, for patients with hypertension, a target systolic blood pressure of lower than 130 mmHg as compared to 140mmHg. The 2017 American College of Cardiology and American Heart Association guidelines now recommend the lower target; the 2018 European Society of Cardiology and European Society of Hypertension guidelines are more ambivalent. The authors retrospectively reviewed the electronic records of 88, 456 patients diagnosed with hypertension in 2013. After applying exclusion criteria, the incidence of stroke and myocardial infarction (MI) in 4, 530 patients with 'Tight Blood Pressure Control' and 1, 110 patients with 'Standard Blood Pressure Control' were compared.\n\nThe authors are to be congratulated for considering this important question in an apparent primary care population where most management of hypertension occurs - the 'real world'. They have clearly expended a lot of effort and thought in conducting and reporting this study.\nHowever I have a number of critical comments which may be worth consideration:\n\nThe most fundamental is the basic premise of the study - the categorisation of patients according to recorded blood pressure as 'tight' or 'standard' BP control. This suggests that practitioners adopted different treatment strategies for a similar population. This is not, I believe, the case. The blood pressure levels reflect, as I understand it, historical blood pressure over the passage of time in a cohort of patients. Lower blood pressure levels may indeed reflect a decision by a practitioner to aggressively target a lower blood pressure for that individual patient; however, it may well simply reflect a patient with a lower blood pressure level. The fact that more patients in the 'Standard' group were on more hypertensive medications (Table 1), supports the latter interpretation. The study could be simply considered as a confirmation that patients with naturally lower blood pressure levels have fewer adverse outcomes. Certainly, this key issue needs to be explicitly considered and clarified by the authors in the paper.\n\nWithout randomisation, separate patient groups may, and indeed more often than not, differ in basic characteristics. Table 1 illustrates significant and very striking differences between the two groups. 'Standard' patients were older, less likely to be white, more obese, less likely to be on a statin, and on more hypertensive medications. Apart from statin use, these all suggest an increased likelihood of experiencing the outcomes of interest - stroke or MI. The authors acknowledge this issue of potential confounding; however, Table 1 really highlights its import. Multivariate analysis is the expected but somewhat limited response. And, as ever, additional unknown confounders are likely to be similarly distributed. The somewhat circumspect acknowledgement in the discussion of confounding needs to be emboldened.\n\nThe authors rightly highlight the importance of the SPRINT trial. A major issue of contention regarding SPRINT is the method of BP measurement - unattended automatic measurement. The authors do not describe the BP measurement method for their study - presumably, it is routine office measurement? If so, without the exclusion of white coat hypertension, the reported values in this study may in reality actually represent 'lower' BP values. This clearly complicates the categorisation of patients as 'tight' or 'standard'. Did many patients have 24 hour ABPM's? If, so this would be an interesting sub study.\n\nA description of the patients and setting is not provided - I have presumed it is primary care based on the author affiliations. It would be good to confirm this in more detail.\n\nMore minor comments follow:\nPg 2 Abstract Lines 34-43\nNo actual figures are provided in the Abstract. The inevitable and significant limitations of a retrospective study design, merit some acknowledgement in the Conclusion of the Abstract.\n\nPg4 Lines 44-46\nPresumably to be included in the 'Tight' group - patients were required to have all BP readings below 130mmHg in 2014 and 2015? And similarly for the standard group above 140 mmHg? What was the minimum number of readings required? The patient group whose BP fluctuated is both interesting and large - 6, 062 patients. Would they not be an interesting third comparator group to include?\n\nPg 4 Lines 51-2\nPatients with previous MI or stroke were excluded. In a retrospective study like this, where Figure 1 highlights significant attrition - would inclusion of such patients not be an interesting sub-study with much higher event rates? Only a total of 136 outcomes were reported in this paper resulting in quite wide confidence intervals?\n\nPg 5 Lines 9-24 Outcome measures\nIt seems a pity, in an electronic retrospective study, not to expand the outcomes to include death and/ or indeed the SPRINT primary outcome of:\nnon-fatal myocardial infarction (MI), acute coronary syndrome not resulting in MI, non-fatal stroke, non-fatal acute decompensated heart failure, and CVD death.\n'Late effect codes' could be clarified.\n\nPg 6 Adverse events\nA recent meta-analysis has highlighted a concern that 'tighter' BP targets result in higher levels of treatment discontinuation due to treatment-related adverse events. It would be good to report medication adherence rates - if only for prescription refills.\nThomopoulos C, Parati G, Zanchetti A. Effects of blood pressure lowering treatment in hypertension: 8. Outcome reductions vs. discontinuations because of adverse drug events - meta-analyses of randomized trials.\nJ Hypertens 2016; 34:1451-1463\n\nPg 6 Statistical analysis\nTable 4, which includes the variable number of anti-hypertensives, is not included in these pre-specified analyses.\n\nPg 9 Discussion |Lines 19-48\nThis crucial paragraph places the findings of the current study in the context of existent literature. It is not very clear from the text what exactly the current study contributes. Section 7.3 of the ESC/ ESH Guidelines succinctly summarises this debate. The key finding of the current paper - that tight control results in lower incidences of stroke and not MI - is congruent with this literature. This finding should not be glossed over - confirmation of findings from RCT's and meta-analyses in real world data is a major strength of this paper. Two more recent meta-analyses, than those quoted by the authors, may be of interest:\n\nEttehad D, Emdin CA, Kiran A, Anderson SG, Callender T, Emberson J, Chalmers J, Rodgers A, Rahimi K. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis Lancet 2016; 387: 957-967.\n\nThomopoulos C, Parati G, Zanchetti A. Effects of blood pressure lowering on outcome incidence in hypertension: 7. Effects of more vs. less intensive blood pressure lowering and different achieved blood pressure levels - updated overview and meta-analyses of randomized trials. J Hypertens 2016; 34: 613-622.\n\n"},{"type":"reviewerAgreed","content":"","date":"2019-12-09T12:00:00+00:00","index":2,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2019-12-09T12:00:00+00:00","index":2,"fulltext":"Recommendation: Accept after minor essential revisions\nForm responses:\n---\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **'I declare that I have no competing interests'**\n\nComments to Author:\n---\nOriginality:\n1. This is an original paper. It is an important research question, which in my view has not yet been answered. This is clear when the AHA/ESH/NICE(UK) all differ to some degree. The research question is not best answered with a retrospective observational study, but this is a reasonable approach, and given time and funding restraints, this can point to the truth.\n\nScientific Quality:\n1. The design was appropriate. One group exposed to a factor (tight control), the other not. The authors tried to determine the chosen factors influence on the incidence of developing disease (MI/CVA). The chi squared tests was used to test whether the groups (exposed and non-exposed) were similar or not, and multivariate logistic regression then tried to pick out risk factors.\n\nRelevance to this Journal:\n1. BMC Family Practice is a suitable journal for this research paper.\n\nGeneral Comment:\n1. Thank you. The paper was carefully written. Some small areas exist where further explanation may be needed- as outlined below.\n\nAbstract:\n1. Thank you. I would weaken the wording of the conclusion slightly-line 43, page 2, as observational studies cannot show causality. Our study suggests….\n\nIntroduction:\n1. In the introduction- the reader wants to know why the AAFP has not endorsed this-maybe expand on this a little to stir up the controversy (line 46, page 3).\n\nLiterature Review:\n1. I think you also need a brief paragraph added to the introduction. This would be based on the literature showing that most RCT's looking at stroke showed a reduction in stroke rates with regard to lower blood pressure (example-see the comprehensive meta-analysis by world-leading hypertension experts Thomopoulos, Parati, and Zanchetti, of all BP lowering RCTs which showed that only patients with a previous stroke benefit from reductions in BP \u003c 130/80mm Hg). Also your refs 11, 12 ,13.\n\n2. And also add that the evidence with regard to MI is mixed. Some trials suggest that coronary artery heart disease worsened with lower BP's( INVEST (Pepine et al., 2003), ON-TARGET (Redon et al., 2012) TNT (Bangalore et al., 2010) and SYST-EUR (Staessen et al., 1997) ). You discussed this later but maybe you need some discussion upfront. The guidelines/BPs were adequately described\n\nMethodology\n1. I would add a comment- why did you leave out the over eighties? -line 43,page 4. You justify leaving out the under 40s etc.\n\n2. Please qualify what 'late effects codes' means for the reader-I can imagine, but I do not know fully. Line 19, page 5.\n\n3. I think you need a paragraph saying how Blood pressure was likely measured in the clinics ( I accept you may not know for sure), but was this a manual, blood pressure reading, taken by a healthcare professional in the clinic, in a typical fashion via sphygmomanometer or automated BP device -or was it taken in fashion similar to that in SPRINT. Add to methods.\n\n4. I do think the project is weaker because you were not able to collect data on dizziness/quality of life/ syncope etc. Data on anti-hypertensive induced acute kidney injury or cerebral hypo-perfusion or coronary artery disease would also have added additional value. This is the 'worry-zone' when physicians opt to pursue much lower BP targets.\n\n5. Could all cause death/CVD death also have been recorded as an outcome- even if only a small number. If this data is not easily available-proceed as is (not mandatory).\n\n\nResults:\n1. Thank you. The result were clear to me. I can see why you presented both versions of the multivariate analysis and seems sensible to do so.\n\n2. Line 31,page 8.-re SBP \u003c 90 mm Hg……ADD ..based on clinic manual BP readings - not ABPM. We don't know if patients had low BP outside of the clinic.\n\nDiscussions:\n1. Thank you. On line 9, page 9, I would use the word 'suggests'.\n\n2. Line 24, page 9-you need to describe the results of this research in numbers. Re Ref 10.\n\n3. Line 56, page 9 - query add RCT's to the list also.\n\n4. Line 36 - page 11-starting with 'Another issue…'. You have not mentioned adherence before. I see the table deals with number of medications and meds (yes/ no) but you have not to this point mentioned adherence. I wonder should you re phrase, add a paragraph on adherence, or omit.\n\n5. Line 50 Page 11- a different hypothesis, would say that perhaps some of those who are prescribed more medications are not taking any of them. - adherence might be the issue for many.\n\n\n6. I am glad you spoke about the differences between the two observed groups. As they are quite different, it does make generalization more complex. I am glad also you spoke about the elimination of those with multi morbidity from research- seeing as many of those in primary care have hypertension and diabetes and also perhaps COPD / CKD. Thank you.\n\n7. Maybe add to weaknesses-that you were unable to assess if there were any medical or quality of life issues in either group- not just TBPC\n\n\nConclusions:\n1. I would suggest the findings to the reader as this is an observational research piece.\n\nReferences / Bibliography:\n1. Appropriate\n\nFigures:\n1. Flow diagram helped greatly,\n\nTables:\n1. Tables were clear to me-lengthy but necessary.\n\nOthers:\n1. 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