Effect of Statin use on Patients with Hypertension: A Systematic Review and Meta-analysis

Effect of Statin use on Patients with Hypertension: A Systematic Review and Meta-analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effect of Statin use on Patients with Hypertension: A Systematic Review and Meta-analysis Ping Ding, Zhaohan Chu, Zili Xu, Qingqing Mu, Dong Xu, Xiaofeng Guo This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3503243/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction This meta-analysis focused on the effects of statin use (either alone or in combination with antihypertensive drugs) on hypertension-related outcome measures, including systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein-cholesterol (LDL-C), low-density lipoprotein- cholesterol (HDL-C), triglyceride (TG), total cholesterol, TG and total cholesterol. Methods We searched the PubMed, EMBASE, and Cochrane databases before October1 2023.Studies designed as cohort study or randomized controlled trials and investigating the effects of statin use or combined with antihypertensive therapy versus no statin use or antihypertensive therapy alone were included. Authors extracted the data independently; differences were decided to discussion. we use random-effects models to evaluate the merged outcomes. Due to the high heterogeneity of HDL-C group, we performed subgroup analysis according to the type of statin. We use sensitivity analysis, Egger’s test and Funnel plots to evaluate the stability and publication bias of our study. Results 23 trials were included in this meta-analysis. The primary outcomes revealed that (1) administering statins did not significantly impact the SBP of hypertensive patients (MD,-1.77; 95% CI, -4.82 to 1.27). Subgroup analyses revealed a decrease in SBP in patients who received rosuvastatin (MD,-1.70; 95% CI,-2.75 to -0.65) and pravastatin (MD,-8.00; 95% CI,-10.79 to -5.21); (2) no significant effect of statin treatment on DBP in hypertensive patients (MD,-2.04; 95% CI,-4.11 to 0.02). However, subgroup analyses suggest that simvastatin (MD,-2.49; 95% CI, -4.91 to -0.07) and pravastatin (MD,-5.00; 95% CI, -6.60 to -3.40) significantly reduced DBP in hypertensive patients. The secondary outcomes revealed that (1) the use of statins resulted in a significant reduction in LDL-C in hypertensive patients (MD, -0.95; 95% CI, -1.32 to -0.65), while significantly increasing HDL-C (MD, 0.39; 95% CI, 0.15 to 0.64); (2) statins were shown to significantly reduce TG levels in hypertensive patients (MD -0.14, 95% CI -0.23 to -0.05); (3) statins significantly reduced total cholesterol in those hypertensive patients (MD, -1.75; 95% CI, -2.66 to -0.83); (4) statins significantly reduced the incidence of cardiovascular events (HR, 0.73; 95% CI, 0.62 to 0.85) and mortality (HR, 0.47; 95% CI, 0.33 to 0.60). Conclusion Statin use did not modulate SBP and DBP of patients with hypertension, but SBP was decreased in rosuvastatin or pravastatin subgroup and DBP was decreased in simvastatin or pravastatin subgroup. Statin treatment reduced LDL-C, increased HDL-C, reduced TG and total cholesterol, reduced the incidence of cardiovascular events and mortality compared to control groups. Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Introduction Hypertension, also known as high blood pressure, is one of the most common diseases in adults and is considered as the leading risk for death globally. Over the past few decades, the incidence rates of hypertension have been increasing largely in low- and middle-income countries. A meta-analysis in 2020 reported that Europe has the highest prevalence of hypertension(61.09%), and followed by Africa(55.87%) and Asia(54.96%)[ 1 ]. Hypertension is the strongest evidence for causes of cardiovascular disease and it also has a high prevalence of exposure for cardiovascular disease[ 2 – 4 ]. Large cohort studies have also demonstrated that hypertension is an important risk factor to contribute to heart failure, chronic kidney disease, atrial fibrillation, heart valve diseases, aortic syndromes, coronary heart disease, dementia and stroke[ 2 ]. The definition of hypertension is that SBP values ≥ 140 mmHg and/or DBP values ≥ 90 mmHg[ 5 ].In addition to controlling blood pressure through lifestyle, many patients also need to control blood pressure through drug treatment, and there are five major drug classes to lower blood pressure: angiotensin converting enzyme inhibitors, betablockers, calcium channel blockers, angiotensin receptor blockers, and diuretics[ 5 ]. However, even with the use of various treatment modalities, it is still hard to control the blood pressure to guideline-recommended target levels[ 4 ], and there are possible contraindications for each class of drug[ 5 ]. Statins are the inhibitors of the hydroxymethylglutaryl-CoA (HMG-CoA) reductase enzyme. Statins effectively lower cholesterol by inhibiting a key step in the sterol biosynthetic pathway and have made a great achievements to the prevention of cardiovascular disease[ 6 ]. In addition to lowering blood lipids, statins can also improve endothelial function by retaining endothelial nitric oxide synthase, leading to vasodilation, and then prevent artery disease. The effect of statins on blood vessels may lead to improved cardiovascular outcomes after Percutaneous transluminal coronary angioplasty[ 6 ]. A study has shown that statins can prevent the progression of arterial stiffness when used in combination with recommended antihypertensive treatment[ 7 ]. Previous studies have reported a reduction in blood pressure in hypertensive patients also treated with statins[ 8 , 9 ]. Among the meta-analyses now published, there was a meta-analysis that studied the effects of combination statin use on the cardiology cardiovascular risk[ 10 ], and our study focused on the effects of statin use (either alone or in combination with antihypertensive drugs) on hypertension-related outcome measures, including SBP, DBP, LDL-C, HDL-C, TG, total cholesterol, cardiovascular event and mortality,. Methods This study was conducted according to the 2020 preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. Search strategy and inclusion criteria We searched the PubMed, EMBASE, and Cochrane databases for keywords: (rosuvastatin OR simvastatin OR atorvastatin OR pitavastatin OR pravastatin OR fluvastatin OR lovastatin OR cerivastatin OR "statin therapy" OR statins OR statin) AND (hypertension or high blood pressure). English articles and studies on humans were adopted. We searched the studies before October 1 2023. The original studies were included according to the following criteria: (1) involved adult patients with confirmed hypertension; (2) comparative group containing no statin use; (4) assessed the relationship between statins and hypertension-related outcome measures; (5) provide one or more of the following data: SBP, DBP, LDL-C, HDL-C,, TG, total cholesterol, cardiovascular event and mortality provide 95% confidence interval (CI) including (cardiovascular and mortality), standard deviation including (SBP, DBP, LDL-C, HDL-C, TG and total cholesterol) to assess outcomes; (6) were cohort study or randomized controlled design. (Study search flowchart for searching to Oct 2023 in Fig. 1 ) Data extraction Relevant information was collected from qualified studies, including the first author and year of publication, study design, Single/Multi Center, Study period, sample size, Mean Age or y, Female/ Male of Patients, experimental interventions, and outcomes. Authors extracted the data independently; differences were decided to discussion. Statistical analysis Meta-analysis data were analyzed by using STATA 12.0 software. We use the Q test and I2 to assess the heterogeneities among studies. When P 50%, it will be defined as high heterogeneity. Therefore, we use random-effects models to evaluate the merged outcomes. Due to the high heterogeneity of HDL-C group, we performed subgroup analysis according to the type of statin. We use sensitivity analysis, Egger’s test and Funnel plots to evaluate the stability and publication bias of our study. Results Characteristics of Eligible Studies A total of 30,212 records were initially retrieved from the database, with 23,091 duplicates being eliminated. Further, 22,990 records were excluded by screening the abstracts and titles, leaving only 101 pieces of literature for initial eligibility screening. Subsequently, 78 articles were excluded from these 101 documents, and eventually, 23 trials were included in this meta-analysis. There is a detailed overview of the characteristics of these 23 trials in Table 1 . Among the reviewed literature, 15 studies[11-25] and 14 studies[11-23, 25] assessed the impact of statins on the SBP and DBP of hypertensive patients respectively. whereas 11 studies[11, 13, 15, 18-21, 25-28] examined the effect of statins on HDL-C levels in hypertensive patients. Additionally, 8 studies[11, 12, 15, 19, 26-29] investigated the effect of statins on LDL-C levels in hypertensive patients, 8 studies[11, 15, 18-20, 25, 26, 28] examined the effect of statins on TG levels in hypertensive patients, 7 studies[18-21, 25, 26, 29] evaluated the effect of statins on total cholesterol levels in hypertensive patients, while 2 studies reported mortality outcomes and another 2 studies focused on cardiovascular events. Five types of statins, namely Pravastatin, Simvastatin, Fluvastatin, Rosuvastatin, and Atorvastatin, were administered at a maximum dose of 80 mg per day in these trials. Table 1. Characteristic of the Included Studies in the Meta-analysis of Statin Vs Placebo or Standard Supportive Care in Adults With hypertension Study Study type Single/Multi Center Study period Total Patients / Patients in Statins No. Mean Age, y Female/ Male of Patients No. Experimental Intervention Reported Outcomes AATeixeira, et al (2011) RCT SC NA 39/19 Fluvastatin:51 PC:51 31/8 Fluvastatin (20mg) HDL-C; LDL-C; TG Ichihara, et al (2005) RCT SC NA 85/65 Pravastatin:60 Simvastatin:60 Fluvastatin:60 PC:60 57/28 Pravastatin (10mg/d); Simvastatin (5mg/d); Fluvastatin (10mg/d); DBP; SBP Beck,et al (2012) RCT SC NA 54/26 Statin:54.2 PC:54 26/28 Simvastatin (26±2mg/d) DBP; SBP; HDL-C; LDL-C; TG Williams, et al (2009) RCT SC NA 891/434 Atorvastatin:62.6 PC: 62.8 128/763 Atorvastatin (10mg/d) SBP Table 1. (Continued) Study Study type Single/Multi Center Study period Total Patients / Patients in Statins No. Mean Age, y Female/ Male of Patients No. Experimental Intervention Reported Outcomes Broghi, et al (2000) RCT SC NA 85/41 Statins:61.5 PC:59.1 24/61 Fluvastatin (10-40mg/d) / Simvastatin (10-40mg/d) DBP; SBP; HDL-C Chen, et al (2020) Retrospective Cohort Study MC 01/2002-12/2017 2650/1325 Statin:72.64 PC:72.67 1144/1506 Statin Mortality; Borghi,et al (2004) RCT SC 1998-1993 1356/264 Statin:56.3 Lipid-lowering therapy:56.6 Lipid-lowering diet:53.8 580/776 Simvastatin (20-40mg/d)/ Gemfibrozil(400-800mg/d)/ cholestyramine(4-24g/d) DBP; SBP; LDL-C Table 1. (Continued) Study Study type Single/Multi Center Study period Total Patients / Patients in Statins No. Mean Age, y Female/ Male of Patients No. Experimental Intervention Reported Outcomes Dong, et al (2021) RCT SC 08/2008-11/2010 1133/581 Rosuvastatins:77.05 PC:77.13 560/573 Rosuvastatins (10mg/d) DBP; SBP; LDL-C; HDL-C;TG; Cardiovascular events; Mortality Kanaki, et al (2012) RCT SC NA 50/25 Atorvastatin:59.7PC:58.8 26/24 Atorvastatin (10mg/d) HDL-C; LDL-C;TG;Total Cholesterol Koh, et al (2015) RCT SC NA 102/51 Simvastatin:57 PC:57 48/54 Simvastatin（20mg/d） DBP; SBP; HDL-C; TG; Total Cholesterol V Correa,et al (2014) RCT SC NA 79/39 Simvastatin:57.7 PC:55.9 61/18 Simvastatin (40mg/d) DBP; SBP; Table 1. (Continued) Study Study type Single/Multi Center Study period Total Patients / Patients in Statins No. Mean Age, y Female/ Male of Patients No. Experimental Intervention Reported Outcomes Messerli, et al (2006) RCT MC NA 439/200 Atorvastatins:55.1 PC:55.3 177/262 Atorvastatins (10mg/d) HDL-C; LDL-C Glorioso, et al (1999) RCT SC NA 49/25 Pravastatin:53 PC:53 14/11 Pravastatin (20mg/d) DBP; SBP Koh, et al (2011) RCT SC NA 42/NA Atorvastatins:53 PC:53 20/22 atorvastatin 20 mg/day and amlodipine 10 mg/day DBP; SBP; HDL-C; LDL-C;TG; Total Cholesterol Holzhauser,et al (2017) Retrospective Cojort Study MC 01/2002-01/2012 762/138 Statin:72 PC:72 488/274 Statin DBP; SBP; Table 1. (Continued) Study Study type Single/Multi Center Study period Total Patients / Patients in Statins No. Mean Age, y Female/ Male of Patients No. Experimental Intervention Reported Outcomes Alves-Cabratosa, et al (2015) Retrospective Cohort Study SC 07/2006-12/2015 100276/90462 Statins:68.2 PC:68.1 60518/39758 Statins Cardiovascular events; Liu, et al (2014) RCT SC NA 79/39 Rosuvastatins:67.85 PC:65.9 40/39 Rosuvastatins (20mg/d) DBP; SBP; HDL-C; TG; Total Cholesterol Nazzaro,et al (1999) RCT SC NA 30/15 Simvastatin:42 PC:44 NA Simvastatin (10mg/d) DBP; SBP; HDL-C; Total Cholesterol Ruszkowski,et al (2019) RCT SC NA 30/20 Fluvastatin:56.5 PC:53.1 12/18 Fluvastatin (80mg/d) DBP; SBP Table 1. (Continued) Study Study type Single/Multi Center Study period Total Patients / Patients in Statins No. Mean Age, y Female/ Male of Patients No. Experimental Intervention Reported Outcomes Sirenko, et al (2023) RCT SC NA 99/59 Atorvastatin:58.02 PC:50.05 41/56 Atorvastatin (20-40mg/d) LDL-C; Office DBP; Office-SBP; Total Cholesterol Sirenko, et al (2017) RCT SC NA 587/226 Statins:58.2 PC:55.9 305/282 Statins DBP; SBP; Spannella,et al (2020) Retrospective Cohort Study SC NA 738/369 Statin:65.8 PC:65.3 355/383 Statins Office DBP; Office-SBP; Danaoğlu,et al (2003) RCT SC NA 39/21 Simvastatin:52 PC:54 29/10 Simvastatin (20mg/d) DBP; SBP；HDL-C; TG; Abbreviations: RCT, Randomized Controlled Trial; MC, Multi-center; SC, Single-center; PC, Placebo or control; NA, Not acquired; SBP, systolic blood pressure; DBP, diastolic blood pressure; TG,triglycerides; HDL-c, high-density lipoprotein cholesterol; LDL-c, low-density lipoprotein cholesterol; Primary Outcome We illustrated the alterations in SBP in hypertensive patients after being subjected to statin treatment in Figure2 . Notably, outcomes revealed that administering statins did not significantly impact the SBP of hypertensive patients (MD,-1.77; 95% CI, -4.82 to 1.27). Subgroup analyses revealed a decrease in SBP in patients who received rosuvastatin (MD,-1.70; 95% CI,-2.75 to -0.65) and pravastatin (MD,-8.00; 95% CI,-10.79 to -5.21) in Figure 3 . Outcome indicates changes in DBP following statin therapy in hypertensive subjects in Figure 4. The results indicate no significant effect of statin treatment on DBP in hypertensive patients (MD,-2.04; 95% CI,-4.11 to 0.02). However, subgroup analyses suggest that simvastatin (MD,-2.49; 95% CI, -4.91 to -0.07) and pravastatin (MD,-5.00; 95% CI, -6.60 to -3.40) significantly reduced DBP in hypertensive patients in Figure5 . Statin therapy did not have a significant effect on office SBP (MD,-0.09;95%CI,-2.72 to 2.54; Figure 6 ) and had only a minor effect on office DBP (MD,-0.14; 95%,-5.05 to 4.77; Figure 7 ). No evidence of publication bias was found for SBP (P=0.688) and DBP (P=0.989) based on the results of the funnel plot and Egger test ( Supplementary Figure. 1-4) . Supplementary Figures 5-6 suggest that the SBP and DBP models were not particularly reliable, as shown by sensitivity analyses. Secondary Outcomes Figures 8 to 13 demonstrate the evaluation of secondary outcomes. Abbreviations for technical terms were explained upon first use. Common academic sections were included, and author and institution formatting was maintained. The language was formal, objective, and value-neutral. Causal connections were established between statements and the structure had a logical progression. The text was precise, free from grammatical errors, and followed consistent footnote style and formatting features. Biases were avoided, and positions were made clear through hedging. The use of statins resulted in a significant reduction in LDL-C in hypertensive patients (MD, -0.95; 95% CI, -1.32 to -0.65; Figure 8 ), while significantly increasing HDL-C (MD, 0.39; 95% CI, 0.15 to 0.64; Figure 9 ). According to the subgroup analysis, atorvastatin (mean difference (MD) -1.27; 95% confidence interval (CI) -1.61 to -0.94), rosuvastatin (MD -0.62; 95% CI -0.69 to -0.55), and fluvastatin (MD -0.56; 95% CI -1.05 to -0.07) were associated with a reduction in LDL-C in Supplementary Figure 7 , whilst simvastatin (MD -0.69; 95% CI -1.89 to 0.50) did not demonstrate a significant decrease. In terms of its effect on HDL-C in Supplementary Figure 8 , pravastatin (MD 0.33, 95% CI 0.15 to 0.51) was found to have no effect when compared with rosuvastatin (MD 0.01, 95% CI -0.11 to 0.14), simvastatin (MD 0.05, 95% CI -0.19 to 0.30), and fluvastatin (MD -0.33, 95% CI -0.80 to 0.14). On the other hand, atorvastatin (MD 1.30, 95% CI -1.66 to 4.27) was found to be more effective. Moreover, statins were shown to significantly reduce TG levels in hypertensive patients (MD -0.14, 95% CI -0.23 to -0.05 in Figure 10 ). In the subgroup analyses in Supplementary Figure 9 , simvastatin (mean difference [MD], -0.17; 95% confidence interval [CI], -0.24 to -0.11) demonstrated greater efficacy compared to rosuvastatin (MD, -0.01; 95% CI, -0.25 to 0.23), fluvastatin (MD, 0.23; 95% CI, -0.78 to 1.24), and atorvastatin (MD, -0.19; 95% CI, -0.43 to 0.05). Moreover, statins significantly reduced total cholesterol in those hypertensive patients (MD, -1.75; 95% CI, -2.66 to -0.83 in Figure 11 ). Based on the subgroup analysis findings, simvastatin (MD,-1.30; 95% CI,-1.51 to -1.09) and atorvastatin (MD,-2.69; 95% CI,-4.68 to -0.70) were more effective than rosuvastatin (MD,0.00; 95% CI,-0.36 to 0.36) in treating hypertensive patients. Additionally, the results indicate that statins significantly reduced the incidence of cardiovascular events (HR, 0.71; 95% CI, 0.45 to 0.98 in Figure 12 ) and mortality (HR, 0.47; 95% CI, 0.33 to 0.60 in Figure 13 ). Funnel plots and Egger's test indicate no publication bias for LDL-C (P=0.472), HDL-C (P=0.430), TG (P=0.583), and total cholesterol (P=0.643) ( Supplementary Figures 11-18 ). Supplementary Figures 19-22 show that the models for LDL-C, HDL-C, TG, and total cholesterol were less plausible in the sensitivity analyses. Discussion This meta-analysis comprehensively comprised 23 studies (109,694patients), revealing the administration of statin use did not diminish SBP, DBP, office-SBP, office-DBP of patients with hypertension compared with control group. Nevertheless, it was disclosed that statin use contributed to a reduction of LDL-C and elevation of HDL-C, respectively. At the same time, statin use decreased the TG and total cholesterol, related with the lower risk of cardiovascular events and mortality. There are controversial outcomes about effect of statin use on lowering blood pressure. Aligning with our results, a study[30] reported that blood pressure lowering was not affected by statin use plus antihypertensive drugs compared with antihypertensive drug alone. However, previous study[31] reported the efficacy of statin use was associated with reduction of SBP and DBP on patients with blood pressure in normotensive or hypertensive. These results of article included a larger scope of patients. Besides, the addition of statin was associated with a significantly greater reduction of SBP compared with amlodipine monotherapy[32]. A meta-analysis conducted by Ying Wang et al.[33] showed that statin group reduced the risk of cardiovascular events compared with non-statin group, similar with our relevant results. With the efficacy of elevating nitric oxide bioavailability, statin use is also reported improving arterial compliance so that potentially lower blood pressure.[34, 35]. The effects of statin about potentially reduction in blood pressure may profit from anti-inflammatory properties on hypercholesterolemic patients[36]. Combination of and statin and drugs affecting renin-angiotensin-aldosterone system (RAAS) exerts a positive effect since stains use influences RAAS system. Statin inhibit the synthesis of Ang II and aldosterone from following ways, including downregulating the expression of receptors for angiotensin II (Ang II), inhibiting relevant signalling, oxidative stress and inflammation.[37]However there remains little documented the clinical mechanism of it. There is discrepancy from experimental trials and clinical outcomes of statin effect on blood pressure, lack of further exploration. The drug pharmacokinetics and effect of statins use lowering lipid may differ among ethnicities [38, 39]. The researchers reported statin treatment resulted in significant reductions in cardiovascular events. Patients in the highest tertile of SBP benefited most from intervention.[40] Rosuvastatin therapy reduces incidence of major cardiovascular events regardless of baseline LDL-C level[41].The positive effect of statins may trace back to potential effect of the central or peripheral homeostasis of blood pressure, inhibiting target organ damage, since statin use mediate endothelial vasoactive, downregulating oxidant stress, or inflammation Furthermore, there is also no evidence that statin therapy reducing cardiovascular event morbidity and mortality differ from patients with hypertension and normal blood pressure[42]. This meta-analysis has certain strengths. This study comprehensively assesses the efficacy of statin on patients with hypertension by a thorough literature search. Besides, the results are reliable shown on outcomes of sensitivity analysis. We also have several limitations. Firstly, the ages and complication of patients differ from included studies. Secondly, there is discrepancy on endpoint of administration of drugs. Lastly, high heterogeneity occurs in our results. Conclusion Statin use did not modulate SBP and DBP of patients with hypertension, but SBP was decreased in rosuvastatin or pravastatin subgroup and DBP was decreased in simvastatin or pravastatin subgroup. Statin treatment reduced LDL-C, increased HDL-C, reduced TG and total cholesterol, reduced the risk of cardiovascular events and mortality compared to control groups. Declarations Author contributions PD and XG provided the idea for the meta-analysis. DX contributed to the data extraction. QM and ZX prepared all pictures. PD and ZC wrote the article. All authors reviewed the manuscript. Funding No funding. Ethics approval and consent to participate Not applicable. 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Am J Cardiol 101(3):319–325 Additional Declarations No competing interests reported. Supplementary Files SFig1.tif SFig2.tif SFig3.tif SFig4.tif SFig5.tif SFig6.tif SFig7.tif SFig8.tif SFig9.tif SFig10.tif SFig11.tif SFig12.tif SFig13.tif SFig14.tif SFig15.tif SFig16.tif SFig17.tif SFig18.tif SFig19.tif SFig20.tif SFig21.tif SFig22.tif Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version 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-3503243","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":244788948,"identity":"73d9b4b6-d015-467a-b0f5-074e153de2d8","order_by":0,"name":"Ping Ding","email":"","orcid":"","institution":"Department of Critical Care Medicine, No. 988 hospital of The PLA Joint Logistic Support Force (PLAJLSF)","correspondingAuthor":false,"prefix":"","firstName":"Ping","middleName":"","lastName":"Ding","suffix":""},{"id":244788949,"identity":"5bbef738-dc59-477e-b2e9-b65472897859","order_by":1,"name":"Zhaohan 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diseases in adults and is considered as the leading risk for death globally. Over the past few decades, the incidence rates of hypertension have been increasing largely in low- and middle-income countries. A meta-analysis in 2020 reported that Europe has the highest prevalence of hypertension(61.09%), and followed by Africa(55.87%) and Asia(54.96%)[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Hypertension is the strongest evidence for causes of cardiovascular disease and it also has a high prevalence of exposure for cardiovascular disease[\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Large cohort studies have also demonstrated that hypertension is an important risk factor to contribute to heart failure, chronic kidney disease, atrial fibrillation, heart valve diseases, aortic syndromes, coronary heart disease, dementia and stroke[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The definition of hypertension is that SBP values\u0026thinsp;\u0026ge;\u0026thinsp;140 mmHg and/or DBP values\u0026thinsp;\u0026ge;\u0026thinsp;90 mmHg[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].In addition to controlling blood pressure through lifestyle, many patients also need to control blood pressure through drug treatment, and there are five major drug classes to lower blood pressure: angiotensin converting enzyme inhibitors, betablockers, calcium channel blockers, angiotensin receptor blockers, and diuretics[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, even with the use of various treatment modalities, it is still hard to control the blood pressure to guideline-recommended target levels[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], and there are possible contraindications for each class of drug[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eStatins are the inhibitors of the hydroxymethylglutaryl-CoA (HMG-CoA) reductase enzyme. Statins effectively lower cholesterol by inhibiting a key step in the sterol biosynthetic pathway and have made a great achievements to the prevention of cardiovascular disease[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In addition to lowering blood lipids, statins can also improve endothelial function by retaining endothelial nitric oxide synthase, leading to vasodilation, and then prevent artery disease. The effect of statins on blood vessels may lead to improved cardiovascular outcomes after Percutaneous transluminal coronary angioplasty[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. A study has shown that statins can prevent the progression of arterial stiffness when used in combination with recommended antihypertensive treatment[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Previous studies have reported a reduction in blood pressure in hypertensive patients also treated with statins[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAmong the meta-analyses now published, there was a meta-analysis that studied the effects of combination statin use on the cardiology cardiovascular risk[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], and our study focused on the effects of statin use (either alone or in combination with antihypertensive drugs) on hypertension-related outcome measures, including SBP, DBP, LDL-C, HDL-C, TG, total cholesterol, cardiovascular event and mortality,.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis study was conducted according to the 2020 preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSearch strategy and inclusion criteria\u003c/h2\u003e \u003cp\u003eWe searched the PubMed, EMBASE, and Cochrane databases for keywords: (rosuvastatin OR simvastatin OR atorvastatin OR pitavastatin OR pravastatin OR fluvastatin OR lovastatin OR cerivastatin OR \"statin therapy\" OR statins OR statin) AND (hypertension or high blood pressure). English articles and studies on humans were adopted. We searched the studies before October 1 2023.\u003c/p\u003e \u003cp\u003eThe original studies were included according to the following criteria: (1) involved adult patients with confirmed hypertension; (2) comparative group containing no statin use; (4) assessed the relationship between statins and hypertension-related outcome measures; (5) provide one or more of the following data: SBP, DBP, LDL-C, HDL-C,, TG, total cholesterol, cardiovascular event and mortality provide 95% confidence interval (CI) including (cardiovascular and mortality), standard deviation including (SBP, DBP, LDL-C, HDL-C, TG and total cholesterol) to assess outcomes; (6) were cohort study or randomized controlled design. (Study search flowchart for searching to Oct 2023 in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eData extraction\u003c/h2\u003e \u003cp\u003eRelevant information was collected from qualified studies, including the first author and year of publication, study design, Single/Multi Center, Study period, sample size, Mean Age or y, Female/ Male of Patients, experimental interventions, and outcomes. Authors extracted the data independently; differences were decided to discussion.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eMeta-analysis data were analyzed by using STATA 12.0 software. We use the Q test and I2 to assess the heterogeneities among studies. When P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 and I2\u0026thinsp;\u0026gt;\u0026thinsp;50%, it will be defined as high heterogeneity. Therefore, we use random-effects models to evaluate the merged outcomes. Due to the high heterogeneity of HDL-C group, we performed subgroup analysis according to the type of statin. We use sensitivity analysis, Egger\u0026rsquo;s test and Funnel plots to evaluate the stability and publication bias of our study.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eCharacteristics of Eligible Studies\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 30,212 records were initially retrieved from the database, with 23,091 duplicates being eliminated. Further, 22,990 records were excluded by screening the abstracts and titles, leaving only 101 pieces of literature for initial eligibility screening. Subsequently, 78 articles were excluded from these 101 documents, and eventually, 23 trials were included in this meta-analysis. There is a detailed overview of the characteristics of these 23 trials in \u003cstrong\u003eTable 1\u003c/strong\u003e. Among the reviewed literature, 15 studies[11-25] and 14 studies[11-23, 25] assessed the impact of statins on the SBP and DBP of hypertensive patients respectively. whereas 11 studies[11, 13, 15, 18-21, 25-28] examined the effect of statins on HDL-C levels in hypertensive patients. Additionally, 8 studies[11, 12, 15, 19, 26-29] investigated the effect of statins on LDL-C levels in hypertensive patients, 8 studies[11, 15, 18-20, 25, 26, 28] examined the effect of statins on TG levels in hypertensive patients, 7 studies[18-21, 25, 26, 29] evaluated the effect of statins on total cholesterol levels in hypertensive patients, while 2 studies reported mortality outcomes and another 2 studies focused on cardiovascular events. Five types of statins, namely Pravastatin, Simvastatin, Fluvastatin, Rosuvastatin, and Atorvastatin, were administered at a maximum dose of 80 mg per day in these trials.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e \u003cstrong\u003eCharacteristic of the Included Studies in the Meta-analysis of Statin Vs Placebo or Standard Supportive Care in Adults With hypertension\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"873\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.077981651376147%\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy type\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.51834862385321%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSingle/Multi Center\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy period\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.977064220183486%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal Patients\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e/ Patients in\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eStatins\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.798165137614679%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean Age, y\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale/ Male of Patients\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.853211009174313%\"\u003e\n \u003cp\u003e\u003cstrong\u003eExperimental Intervention\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.756880733944953%\"\u003e\n \u003cp\u003e\u003cstrong\u003eReported Outcomes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003eAATeixeira, et al (2011)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.077981651376147%\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.51834862385321%\"\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.977064220183486%\"\u003e\n \u003cp\u003e39/19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.798165137614679%\"\u003e\n \u003cp\u003eFluvastatin:51\u003c/p\u003e\n \u003cp\u003ePC:51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003e31/8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.853211009174313%\"\u003e\n \u003cp\u003eFluvastatin (20mg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.756880733944953%\"\u003e\n \u003cp\u003eHDL-C; LDL-C; TG\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.077981651376147%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.51834862385321%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.977064220183486%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.798165137614679%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.853211009174313%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.756880733944953%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003eIchihara, et al (2005)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.077981651376147%\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.51834862385321%\"\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.977064220183486%\"\u003e\n \u003cp\u003e85/65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.798165137614679%\"\u003e\n \u003cp\u003ePravastatin:60\u003c/p\u003e\n \u003cp\u003eSimvastatin:60\u003c/p\u003e\n \u003cp\u003eFluvastatin:60 PC:60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003e57/28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.853211009174313%\"\u003e\n \u003cp\u003ePravastatin (10mg/d);\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eSimvastatin (5mg/d);\u003c/p\u003e\n \u003cp\u003eFluvastatin (10mg/d);\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.756880733944953%\"\u003e\n \u003cp\u003eDBP; SBP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.077981651376147%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.51834862385321%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.977064220183486%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.798165137614679%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.853211009174313%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.756880733944953%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003eBeck,et al (2012)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.077981651376147%\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.51834862385321%\"\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.977064220183486%\"\u003e\n \u003cp\u003e54/26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.798165137614679%\"\u003e\n \u003cp\u003eStatin:54.2\u003c/p\u003e\n \u003cp\u003ePC:54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003e26/28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.853211009174313%\"\u003e\n \u003cp\u003eSimvastatin (26\u0026plusmn;2mg/d)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.756880733944953%\"\u003e\n \u003cp\u003eDBP; SBP; HDL-C; LDL-C; TG\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.077981651376147%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.51834862385321%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.977064220183486%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.798165137614679%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.853211009174313%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.756880733944953%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003eWilliams, et al (2009)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.077981651376147%\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.51834862385321%\"\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.977064220183486%\"\u003e\n \u003cp\u003e891/434\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.798165137614679%\"\u003e\n \u003cp\u003eAtorvastatin:62.6\u003c/p\u003e\n \u003cp\u003ePC: 62.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003e128/763\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.853211009174313%\"\u003e\n \u003cp\u003e\u0026nbsp;Atorvastatin (10mg/d)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.756880733944953%\"\u003e\n \u003cp\u003eSBP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003e(Continued)\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"917\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"6.986899563318778%\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.786026200873362%\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy type\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.06113537117904%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSingle/Multi Center\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.986899563318778%\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy period\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.497816593886462%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal Patients\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e/ Patients in\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eStatins\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.06113537117904%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean Age, y\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale/ Male of Patients\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.633187772925766%\"\u003e\n \u003cp\u003e\u003cstrong\u003eExperimental Intervention\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.689956331877728%\"\u003e\n \u003cp\u003e\u003cstrong\u003eReported Outcomes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"6.986899563318778%\"\u003e\n \u003cp\u003eBroghi, et al (2000)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.786026200873362%\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.06113537117904%\"\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.986899563318778%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.497816593886462%\"\u003e\n \u003cp\u003e85/41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.06113537117904%\"\u003e\n \u003cp\u003eStatins:61.5\u003c/p\u003e\n \u003cp\u003ePC:59.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\"\u003e\n \u003cp\u003e24/61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.633187772925766%\"\u003e\n \u003cp\u003eFluvastatin (10-40mg/d) / Simvastatin (10-40mg/d)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.689956331877728%\"\u003e\n \u003cp\u003eDBP; SBP; HDL-C\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"6.986899563318778%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.786026200873362%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.06113537117904%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.986899563318778%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.497816593886462%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.06113537117904%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.633187772925766%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.689956331877728%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"6.986899563318778%\"\u003e\n \u003cp\u003eChen, et al (2020)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.786026200873362%\"\u003e\n \u003cp\u003eRetrospective Cohort Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.06113537117904%\"\u003e\n \u003cp\u003eMC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.986899563318778%\"\u003e\n \u003cp\u003e01/2002-12/2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.497816593886462%\"\u003e\n \u003cp\u003e2650/1325\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.06113537117904%\"\u003e\n \u003cp\u003eStatin:72.64\u003c/p\u003e\n \u003cp\u003ePC:72.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\"\u003e\n \u003cp\u003e1144/1506\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.633187772925766%\"\u003e\n \u003cp\u003eStatin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.689956331877728%\"\u003e\n \u003cp\u003eMortality;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"6.986899563318778%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.786026200873362%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.06113537117904%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.986899563318778%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.497816593886462%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.06113537117904%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.633187772925766%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.689956331877728%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"6.986899563318778%\"\u003e\n \u003cp\u003eBorghi,et al (2004)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.786026200873362%\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.06113537117904%\"\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.986899563318778%\"\u003e\n \u003cp\u003e1998-1993\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.497816593886462%\"\u003e\n \u003cp\u003e1356/264\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.06113537117904%\"\u003e\n \u003cp\u003eStatin:56.3\u003c/p\u003e\n \u003cp\u003eLipid-lowering therapy:56.6\u003c/p\u003e\n \u003cp\u003eLipid-lowering diet:53.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.296943231441048%\"\u003e\n \u003cp\u003e580/776\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.633187772925766%\"\u003e\n \u003cp\u003eSimvastatin (20-40mg/d)/\u003c/p\u003e\n \u003cp\u003eGemfibrozil(400-800mg/d)/\u003c/p\u003e\n \u003cp\u003echolestyramine(4-24g/d)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.689956331877728%\"\u003e\n \u003cp\u003eDBP; SBP; LDL-C\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003e(Continued)\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"873\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.077981651376147%\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy type\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.51834862385321%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSingle/Multi Center\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy period\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.977064220183486%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal Patients\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e/ Patients in\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eStatins\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.798165137614679%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean Age, y\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale/ Male of Patients\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.853211009174313%\"\u003e\n \u003cp\u003e\u003cstrong\u003eExperimental Intervention\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.756880733944953%\"\u003e\n \u003cp\u003e\u003cstrong\u003eReported Outcomes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003eDong, et al (2021)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.077981651376147%\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.51834862385321%\"\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003e08/2008-11/2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.977064220183486%\"\u003e\n \u003cp\u003e1133/581\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.798165137614679%\"\u003e\n \u003cp\u003eRosuvastatins:77.05\u003c/p\u003e\n \u003cp\u003ePC:77.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003e560/573\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.853211009174313%\"\u003e\n \u003cp\u003eRosuvastatins (10mg/d)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.756880733944953%\"\u003e\n \u003cp\u003eDBP; SBP; LDL-C; HDL-C;TG; Cardiovascular events; Mortality\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.077981651376147%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.51834862385321%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.977064220183486%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.798165137614679%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.853211009174313%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.756880733944953%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003eKanaki, et al (2012)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.077981651376147%\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.51834862385321%\"\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.977064220183486%\"\u003e\n \u003cp\u003e50/25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.798165137614679%\"\u003e\n \u003cp\u003eAtorvastatin:59.7PC:58.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003e26/24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.853211009174313%\"\u003e\n \u003cp\u003eAtorvastatin (10mg/d)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.756880733944953%\"\u003e\n \u003cp\u003eHDL-C; LDL-C;TG;Total Cholesterol\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eKoh, et al (2015)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.077981651376147%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.51834862385321%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.977064220183486%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e102/51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.798165137614679%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eSimvastatin:57\u003c/p\u003e\n \u003cp\u003ePC:57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e48/54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.853211009174313%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eSimvastatin（20mg/d）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.756880733944953%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eDBP; SBP; HDL-C; TG;\u0026nbsp;Total Cholesterol\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003eV Correa,et al (2014)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.077981651376147%\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.51834862385321%\"\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.977064220183486%\"\u003e\n \u003cp\u003e79/39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.798165137614679%\"\u003e\n \u003cp\u003eSimvastatin:57.7\u003c/p\u003e\n \u003cp\u003ePC:55.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.339449541284404%\"\u003e\n \u003cp\u003e61/18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.853211009174313%\"\u003e\n \u003cp\u003eSimvastatin (40mg/d)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.756880733944953%\"\u003e\n \u003cp\u003eDBP; SBP;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003e(Continued)\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"907\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.056229327453142%\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.504961411245866%\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy type\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.489525909592063%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSingle/Multi Center\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.063947078280044%\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy period\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.584343991179713%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal Patients\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e/ Patients in\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eStatins\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.151047409040794%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean Age, y\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.474090407938258%\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale/ Male of Patients\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.861080485115767%\"\u003e\n \u003cp\u003e\u003cstrong\u003eExperimental Intervention\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814773980154357%\"\u003e\n \u003cp\u003e\u003cstrong\u003eReported Outcomes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.056229327453142%\"\u003e\n \u003cp\u003eMesserli, et al (2006)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.504961411245866%\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.489525909592063%\"\u003e\n \u003cp\u003eMC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.063947078280044%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.584343991179713%\"\u003e\n \u003cp\u003e439/200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.151047409040794%\"\u003e\n \u003cp\u003eAtorvastatins:55.1\u003c/p\u003e\n \u003cp\u003ePC:55.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.474090407938258%\"\u003e\n \u003cp\u003e177/262\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.861080485115767%\"\u003e\n \u003cp\u003eAtorvastatins (10mg/d)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814773980154357%\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;HDL-C; LDL-C\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.056229327453142%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.504961411245866%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.489525909592063%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.063947078280044%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.584343991179713%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.151047409040794%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.474090407938258%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.861080485115767%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814773980154357%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.056229327453142%\"\u003e\n \u003cp\u003eGlorioso, et al (1999)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.504961411245866%\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.489525909592063%\"\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.063947078280044%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.584343991179713%\"\u003e\n \u003cp\u003e49/25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.151047409040794%\"\u003e\n \u003cp\u003ePravastatin:53\u003c/p\u003e\n \u003cp\u003ePC:53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.474090407938258%\"\u003e\n \u003cp\u003e14/11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.861080485115767%\"\u003e\n \u003cp\u003ePravastatin (20mg/d)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814773980154357%\"\u003e\n \u003cp\u003eDBP; SBP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.056229327453142%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.504961411245866%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.489525909592063%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.063947078280044%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.584343991179713%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.151047409040794%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.474090407938258%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.861080485115767%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814773980154357%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.056229327453142%\"\u003e\n \u003cp\u003eKoh, et al (2011)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.504961411245866%\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.489525909592063%\"\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.063947078280044%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.584343991179713%\"\u003e\n \u003cp\u003e42/NA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.151047409040794%\"\u003e\n \u003cp\u003eAtorvastatins:53\u003c/p\u003e\n \u003cp\u003ePC:53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.474090407938258%\"\u003e\n \u003cp\u003e20/22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.861080485115767%\"\u003e\n \u003cp\u003eatorvastatin 20 mg/day and amlodipine 10 mg/day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814773980154357%\"\u003e\n \u003cp\u003eDBP; SBP; HDL-C; LDL-C;TG;\u0026nbsp;Total Cholesterol\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"7.056229327453142%\"\u003e\n \u003cp\u003eHolzhauser,et al (2017)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.504961411245866%\"\u003e\n \u003cp\u003eRetrospective Cojort Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.489525909592063%\"\u003e\n \u003cp\u003eMC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.063947078280044%\"\u003e\n \u003cp\u003e01/2002-01/2012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.584343991179713%\"\u003e\n \u003cp\u003e762/138\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.151047409040794%\"\u003e\n \u003cp\u003eStatin:72\u003c/p\u003e\n \u003cp\u003ePC:72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.474090407938258%\"\u003e\n \u003cp\u003e488/274\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.861080485115767%\"\u003e\n \u003cp\u003eStatin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.814773980154357%\"\u003e\n \u003cp\u003eDBP; SBP;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003e(Continued)\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"917\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.051254089422029%\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.415485278080698%\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy type\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.415485278080698%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSingle/Multi Center\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.97928026172301%\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy period\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.487459105779717%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal Patients\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e/ Patients in\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eStatins\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.14176663031625%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean Age, y\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.359869138495092%\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale/ Male of Patients\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.610687022900763%\"\u003e\n \u003cp\u003e\u003cstrong\u003eExperimental Intervention\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.538713195201744%\"\u003e\n \u003cp\u003e\u003cstrong\u003eReported Outcomes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.051254089422029%\"\u003e\n \u003cp\u003eAlves-Cabratosa, et al (2015)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.415485278080698%\"\u003e\n \u003cp\u003eRetrospective Cohort Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.415485278080698%\"\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.97928026172301%\"\u003e\n \u003cp\u003e07/2006-12/2015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.487459105779717%\"\u003e\n \u003cp\u003e100276/90462\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.14176663031625%\"\u003e\n \u003cp\u003eStatins:68.2\u003c/p\u003e\n \u003cp\u003ePC:68.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.359869138495092%\"\u003e\n \u003cp\u003e60518/39758\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.610687022900763%\"\u003e\n \u003cp\u003eStatins\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.538713195201744%\"\u003e\n \u003cp\u003e\u0026nbsp;Cardiovascular events;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.051254089422029%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.415485278080698%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.415485278080698%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.97928026172301%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.487459105779717%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.14176663031625%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.359869138495092%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.610687022900763%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.538713195201744%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.051254089422029%\"\u003e\n \u003cp\u003eLiu, et al (2014)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.415485278080698%\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.415485278080698%\"\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.97928026172301%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.487459105779717%\"\u003e\n \u003cp\u003e79/39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.14176663031625%\"\u003e\n \u003cp\u003eRosuvastatins:67.85\u003c/p\u003e\n \u003cp\u003ePC:65.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.359869138495092%\"\u003e\n \u003cp\u003e40/39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.610687022900763%\"\u003e\n \u003cp\u003eRosuvastatins (20mg/d)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.538713195201744%\"\u003e\n \u003cp\u003eDBP; SBP; HDL-C; TG; Total Cholesterol\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.051254089422029%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.415485278080698%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.415485278080698%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.97928026172301%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.487459105779717%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.14176663031625%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.359869138495092%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.610687022900763%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.538713195201744%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.051254089422029%\"\u003e\n \u003cp\u003eNazzaro,et al (1999)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.415485278080698%\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.415485278080698%\"\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.97928026172301%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.487459105779717%\"\u003e\n \u003cp\u003e30/15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.14176663031625%\"\u003e\n \u003cp\u003eSimvastatin:42\u003c/p\u003e\n \u003cp\u003ePC:44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.359869138495092%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.610687022900763%\"\u003e\n \u003cp\u003eSimvastatin (10mg/d)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.538713195201744%\"\u003e\n \u003cp\u003eDBP; SBP; HDL-C; Total Cholesterol\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.051254089422029%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.415485278080698%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.415485278080698%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.97928026172301%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.487459105779717%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.14176663031625%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.359869138495092%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.610687022900763%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.538713195201744%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.051254089422029%\"\u003e\n \u003cp\u003eRuszkowski,et al (2019)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.415485278080698%\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.415485278080698%\"\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.97928026172301%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.487459105779717%\"\u003e\n \u003cp\u003e30/20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.14176663031625%\"\u003e\n \u003cp\u003eFluvastatin:56.5\u003c/p\u003e\n \u003cp\u003ePC:53.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.359869138495092%\"\u003e\n \u003cp\u003e12/18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.610687022900763%\"\u003e\n \u003cp\u003eFluvastatin (80mg/d)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.538713195201744%\"\u003e\n \u003cp\u003eDBP; SBP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003e(Continued)\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"892\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.304932735426009%\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.614349775784754%\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy type\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.632286995515695%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSingle/Multi Center\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.174887892376682%\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy period\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.650224215246636%\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal Patients\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e/ Patients in\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eStatins\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.52914798206278%\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean Age, y\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.52017937219731%\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale/ Male of Patients\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.282511210762333%\"\u003e\n \u003cp\u003e\u003cstrong\u003eExperimental Intervention\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.291479820627803%\"\u003e\n \u003cp\u003e\u003cstrong\u003eReported Outcomes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.304932735426009%\"\u003e\n \u003cp\u003eSirenko, et al (2023)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.614349775784754%\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.632286995515695%\"\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.174887892376682%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.650224215246636%\"\u003e\n \u003cp\u003e99/59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.52914798206278%\"\u003e\n \u003cp\u003eAtorvastatin:58.02\u003c/p\u003e\n \u003cp\u003ePC:50.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.52017937219731%\"\u003e\n \u003cp\u003e41/56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.282511210762333%\"\u003e\n \u003cp\u003eAtorvastatin (20-40mg/d)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.291479820627803%\"\u003e\n \u003cp\u003eLDL-C; Office DBP; Office-SBP;\u0026nbsp;Total Cholesterol\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.304932735426009%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.614349775784754%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.632286995515695%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.174887892376682%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.650224215246636%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.52914798206278%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.52017937219731%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.282511210762333%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.291479820627803%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.304932735426009%\"\u003e\n \u003cp\u003eSirenko, et al (2017)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.614349775784754%\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.632286995515695%\"\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.174887892376682%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.650224215246636%\"\u003e\n \u003cp\u003e587/226\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.52914798206278%\"\u003e\n \u003cp\u003eStatins:58.2\u003c/p\u003e\n \u003cp\u003ePC:55.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.52017937219731%\"\u003e\n \u003cp\u003e305/282\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.282511210762333%\"\u003e\n \u003cp\u003eStatins\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.291479820627803%\"\u003e\n \u003cp\u003eDBP; SBP;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.304932735426009%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.614349775784754%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.632286995515695%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.174887892376682%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.650224215246636%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.52914798206278%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.52017937219731%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.282511210762333%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.291479820627803%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.304932735426009%\"\u003e\n \u003cp\u003eSpannella,et al (2020)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.614349775784754%\"\u003e\n \u003cp\u003eRetrospective Cohort Study\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.632286995515695%\"\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.174887892376682%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.650224215246636%\"\u003e\n \u003cp\u003e738/369\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.52914798206278%\"\u003e\n \u003cp\u003eStatin:65.8\u003c/p\u003e\n \u003cp\u003ePC:65.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.52017937219731%\"\u003e\n \u003cp\u003e355/383\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.282511210762333%\"\u003e\n \u003cp\u003eStatins\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.291479820627803%\"\u003e\n \u003cp\u003eOffice DBP; Office-SBP;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.304932735426009%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.614349775784754%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.632286995515695%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.174887892376682%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.650224215246636%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.52914798206278%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.52017937219731%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.282511210762333%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.291479820627803%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"9.304932735426009%\"\u003e\n \u003cp\u003eDanaoğlu,et al (2003)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.614349775784754%\"\u003e\n \u003cp\u003eRCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.632286995515695%\"\u003e\n \u003cp\u003eSC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.174887892376682%\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.650224215246636%\"\u003e\n \u003cp\u003e39/21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.52914798206278%\"\u003e\n \u003cp\u003eSimvastatin:52\u003c/p\u003e\n \u003cp\u003ePC:54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.52017937219731%\"\u003e\n \u003cp\u003e29/10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.282511210762333%\"\u003e\n \u003cp\u003eSimvastatin (20mg/d)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.291479820627803%\"\u003e\n \u003cp\u003eDBP; SBP；HDL-C; TG;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: RCT, Randomized Controlled Trial; MC, Multi-center; SC, Single-center; PC, Placebo or control; NA, Not acquired; SBP, systolic blood pressure; DBP, diastolic blood pressure; TG,triglycerides; HDL-c, high-density lipoprotein cholesterol; LDL-c, low-density lipoprotein cholesterol;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrimary Outcome\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe illustrated the alterations in SBP in hypertensive patients after being subjected to statin treatment in \u003cstrong\u003eFigure2\u003c/strong\u003e. Notably, outcomes revealed that administering statins did not significantly impact the SBP of hypertensive patients (MD,-1.77; 95% CI, -4.82 to 1.27). Subgroup analyses revealed a decrease in SBP in patients who received rosuvastatin (MD,-1.70; 95% CI,-2.75 to -0.65) and pravastatin (MD,-8.00; 95% CI,-10.79 to -5.21) in \u003cstrong\u003eFigure 3\u003c/strong\u003e. Outcome indicates changes in DBP following statin therapy in hypertensive subjects in \u003cstrong\u003eFigure 4.\u003c/strong\u003e The results indicate no significant effect of statin treatment on DBP in hypertensive patients (MD,-2.04; 95% CI,-4.11 to 0.02). However, subgroup analyses suggest that simvastatin (MD,-2.49; 95% CI, -4.91 to -0.07) and pravastatin (MD,-5.00; 95% CI, -6.60 to -3.40) significantly reduced DBP in hypertensive patients in \u003cstrong\u003eFigure5\u003c/strong\u003e. Statin therapy did not have a significant effect on office SBP (MD,-0.09;95%CI,-2.72 to 2.54; \u003cstrong\u003eFigure 6\u003c/strong\u003e) and had only a minor effect on office DBP (MD,-0.14; 95%,-5.05 to 4.77; \u003cstrong\u003eFigure 7\u003c/strong\u003e). No evidence of publication bias was found for SBP (P=0.688) and DBP (P=0.989) based on the results of the funnel plot and Egger test (\u003cstrong\u003eSupplementary Figure. 1-4)\u003c/strong\u003e.\u003cstrong\u003e\u0026nbsp;Supplementary Figures 5-6\u003c/strong\u003e suggest that the SBP and DBP models were not particularly reliable, as shown by sensitivity analyses.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSecondary Outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigures 8 to 13\u0026nbsp;\u003c/strong\u003edemonstrate the evaluation of secondary outcomes. Abbreviations for technical terms were explained upon first use. Common academic sections were included, and author and institution formatting was maintained. The language was formal, objective, and value-neutral. Causal connections were established between statements and the structure had a logical progression. The text was precise, free from grammatical errors, and followed consistent footnote style and formatting features. Biases were avoided, and positions were made clear through hedging. The use of statins resulted in a significant reduction in LDL-C in hypertensive patients (MD, -0.95; 95% CI, -1.32 to -0.65; \u003cstrong\u003eFigure 8\u003c/strong\u003e), while significantly increasing HDL-C (MD, 0.39; 95% CI, 0.15 to 0.64;\u003cstrong\u003e\u0026nbsp;Figure 9\u003c/strong\u003e). According to the subgroup analysis, atorvastatin (mean difference (MD) -1.27; 95% confidence interval (CI) -1.61 to -0.94), rosuvastatin (MD -0.62; 95% CI -0.69 to -0.55), and fluvastatin (MD -0.56; 95% CI -1.05 to -0.07) were associated with a reduction in LDL-C in \u003cstrong\u003eSupplementary Figure 7\u003c/strong\u003e, whilst simvastatin (MD -0.69; 95% CI -1.89 to 0.50) did not demonstrate a significant decrease. In terms of its effect on HDL-C in \u003cstrong\u003eSupplementary Figure 8\u003c/strong\u003e, pravastatin (MD 0.33, 95% CI 0.15 to 0.51) was found to have no effect when compared with rosuvastatin (MD 0.01, 95% CI -0.11 to 0.14), simvastatin (MD 0.05, 95% CI -0.19 to 0.30), and fluvastatin (MD -0.33, 95% CI -0.80 to 0.14). On the other hand, atorvastatin (MD 1.30, 95% CI -1.66 to 4.27) was found to be more effective. Moreover, statins were shown to significantly reduce TG levels in hypertensive patients (MD -0.14, 95% CI -0.23 to -0.05 in\u003cstrong\u003e\u0026nbsp;Figure 10\u003c/strong\u003e). In the subgroup analyses in \u003cstrong\u003eSupplementary Figure 9\u003c/strong\u003e, simvastatin (mean difference [MD], -0.17; 95% confidence interval [CI], -0.24 to -0.11) demonstrated greater efficacy compared to rosuvastatin (MD, -0.01; 95% CI, -0.25 to 0.23), fluvastatin (MD, 0.23; 95% CI, -0.78 to 1.24), and atorvastatin (MD, -0.19; 95% CI, -0.43 to 0.05). Moreover, statins significantly reduced total cholesterol in those hypertensive patients (MD, -1.75; 95% CI, -2.66 to -0.83 in \u003cstrong\u003eFigure 11\u003c/strong\u003e). Based on the subgroup analysis findings, simvastatin (MD,-1.30; 95% CI,-1.51 to -1.09) and atorvastatin (MD,-2.69; 95% CI,-4.68 to -0.70) were more effective than rosuvastatin (MD,0.00; 95% CI,-0.36 to 0.36) in treating hypertensive patients. Additionally, the results indicate that statins significantly reduced the incidence of cardiovascular events (HR, 0.71; 95% CI, 0.45 to 0.98 in \u003cstrong\u003eFigure 12\u003c/strong\u003e) and mortality (HR, 0.47; 95% CI, 0.33 to 0.60 in \u003cstrong\u003eFigure 13\u003c/strong\u003e). Funnel plots and Egger\u0026apos;s test indicate no publication bias for LDL-C (P=0.472), HDL-C (P=0.430), TG (P=0.583), and total cholesterol (P=0.643) (\u003cstrong\u003eSupplementary Figures 11-18\u003c/strong\u003e). \u003cstrong\u003eSupplementary Figures 19-22\u003c/strong\u003e show that the models for LDL-C, HDL-C, TG, and total cholesterol were less plausible in the sensitivity analyses.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis meta-analysis comprehensively comprised 23 studies (109,694patients), revealing the administration of statin use did not diminish SBP, DBP, office-SBP, office-DBP of patients with hypertension compared with control group. Nevertheless, it was disclosed that statin use contributed to a reduction of LDL-C and elevation of HDL-C, respectively. At the same time, statin use decreased the TG and total cholesterol, related with the lower risk of cardiovascular events and mortality.\u0026nbsp;There are controversial outcomes about effect of statin use on lowering blood pressure. Aligning with our results, a study[30]\u0026nbsp;reported that blood pressure lowering was not affected by statin use plus antihypertensive drugs compared with antihypertensive drug alone. However, previous study[31]\u0026nbsp;reported the efficacy of statin use was associated with reduction of SBP and DBP on patients with blood pressure in normotensive or hypertensive. These results of article included a larger scope of patients. Besides, the addition of statin was associated with a significantly greater reduction of SBP compared with amlodipine monotherapy[32]. A meta-analysis conducted by Ying Wang et al.[33]\u0026nbsp;showed that statin group reduced the risk of cardiovascular events compared with non-statin group, similar with our relevant results.\u003c/p\u003e\n\u003cp\u003eWith the efficacy of elevating nitric oxide bioavailability, statin use is also reported\u0026nbsp;improving arterial compliance so that potentially lower blood pressure.[34, 35].\u0026nbsp;The effects of statin about potentially reduction in blood pressure may profit from anti-inflammatory properties on hypercholesterolemic patients[36]. Combination of and statin and drugs affecting renin-angiotensin-aldosterone system (RAAS) exerts a positive effect since stains use influences RAAS system. Statin inhibit the synthesis of Ang II and aldosterone from following ways, including downregulating the expression of receptors for angiotensin II (Ang II), inhibiting relevant signalling, oxidative stress and inflammation.[37]However there remains little documented the clinical mechanism of it. There is discrepancy from experimental trials and clinical outcomes of statin effect on blood pressure, lack of further exploration.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe drug pharmacokinetics and effect of statins use lowering lipid may differ among ethnicities\u0026nbsp;[38, 39]. The researchers reported statin treatment resulted in significant reductions in cardiovascular events. Patients in the highest tertile of SBP benefited most from intervention.[40]\u0026nbsp;Rosuvastatin therapy reduces incidence of major cardiovascular events regardless of baseline LDL-C level[41].The positive effect of statins may trace back to potential effect of the central or peripheral homeostasis of blood pressure, inhibiting target organ damage, since statin use mediate endothelial vasoactive, downregulating oxidant stress, or inflammation Furthermore, there is also no evidence that statin therapy reducing cardiovascular event morbidity and mortality differ from patients with hypertension and normal blood pressure[42].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis meta-analysis has certain strengths. This study comprehensively assesses the efficacy of statin on patients with hypertension by a thorough literature search. Besides, the results are reliable shown on outcomes of sensitivity analysis. We also have several limitations. Firstly, the ages and complication of patients differ from included studies. Secondly, there is discrepancy on endpoint of administration of drugs. Lastly, high heterogeneity occurs in our results.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eStatin use did not modulate SBP and DBP of patients with hypertension, but SBP was decreased in rosuvastatin or pravastatin subgroup and DBP was decreased in simvastatin or pravastatin subgroup. Statin treatment reduced LDL-C, increased HDL-C, reduced TG and total cholesterol, reduced the risk of cardiovascular events and mortality compared to control groups.\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePD and XG provided the idea for the meta-analysis. DX contributed to the data extraction. QM and ZX prepared all pictures. PD and ZC wrote the article. All authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eXiong P et al (2020) Prevalence of high blood pressure under 2017 ACC/AHA guidelines: a systematic review and meta-analysis. J Hum Hypertens 35(3):193\u0026ndash;206\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFuchs FD, Whelton PK (2020) High Blood Pressure and Cardiovascular Disease. 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Pharmacol Res 88:3\u0026ndash;11\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSirenko Y, Rekovets O (2023) \u003cem\u003eThe impact of statins addind to the fixed combination antihypertensive therapy on the arterial stiffness in patients with moderate and severe hypertension\u003c/em\u003e. Int J Cardiol Cardiovasc Risk Prev, 18\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBriasoulis A et al (2013) Antihypertensive Effects of Statins: A Meta-Analysis of Prospective Controlled Studies. J Clin Hypertens 15(5):310\u0026ndash;320\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStrazzullo P et al (2007) Do Statins Reduce Blood Pressure? Hypertension 49(4):792\u0026ndash;798\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang Y et al (2020) Effect of Combined Statin and Antihypertensive Therapy in Patients with Hypertension: A Systematic Review and Meta-Analysis. 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Hypertension 34(6):1281\u0026ndash;1286\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIchihara A et al (2005) Long-term effects of statins on arterial pressure and stiffness of hypertensives. J Hum Hypertens 19(2):103\u0026ndash;109\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKoh KK et al (2015) Vascular and metabolic effects of ezetimibe combined with simvastatin in patients with hypercholesterolemia. Int J Cardiol 199:126\u0026ndash;131\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKoh KK et al (2011) Additive beneficial effects of atorvastatin combined with amlodipine in patients with mild-to-moderate hypertension. Int J Cardiol 146(3):319\u0026ndash;325\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu Z et al (2014) Treatment with telmisartan/rosuvastatin combination has a beneficial synergistic effect on ameliorating Th17/Treg functional imbalance in hypertensive patients with carotid atherosclerosis. 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High Blood Press Cardiovasc Prev 24(1):85\u0026ndash;93\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWilliams B et al (2009) Impact of statin therapy on central aortic pressures and hemodynamics: principal results of the Conduit Artery Function Evaluation-Lipid-Lowering Arm (CAFE-LLA) Study. Circulation 119(1):53\u0026ndash;61\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDanaoğlu Z et al (2003) Effect of statin therapy added to ACE-inhibitors on blood pressure control and endothelial functions in normolipidemic hypertensive patients. Anadolu Kardiyol Derg 3(4):331\u0026ndash;337\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKanaki AI et al (2012) Low-dose atorvastatin reduces ambulatory blood pressure in patients with mild hypertension and hypercholesterolaemia: a double-blind, randomized, placebo-controlled study. J Hum Hypertens 26(10):577\u0026ndash;584\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMesserli FH et al (2006) \u003cem\u003eEfficacy and safety of coadministered amlodipine and atorvastatin in patients with hypertension and dyslipidemia: results of the AVALON trial\u003c/em\u003e. J Clin Hypertens (Greenwich), 8(8): p. 571 \u0026ndash; 81; quiz 582-3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTeixeira AA et al (2011) Effects of fluvastatin on insulin resistance and cardiac morphology in hypertensive patients. J Hum Hypertens 25(8):492\u0026ndash;499\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSirenko Y, Rekovets O (2023) The impact of statins addind to the fixed combination antihypertensive therapy on the arterial stiffness in patients with moderate and severe hypertension. 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Hypertension 37(6):1450\u0026ndash;1457\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStrazzullo P et al (2007) Do statins reduce blood pressure? a meta-analysis of randomized, controlled trials. Hypertension 49(4):792\u0026ndash;798\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDrapala A, Sikora M, Ufnal M (2014) \u003cem\u003eStatins, the renin-angiotensin-aldosterone system and hypertension - a tale of another beneficial effect of statins.\u003c/em\u003e J Renin Angiotensin Aldosterone Syst, 15(3): p.\u0026nbsp;250-8\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNaito R, Miyauchi K, Daida H (2017) Racial Differences in the Cholesterol-Lowering Effect of Statin. J Atheroscler Thromb 24(1):19\u0026ndash;25\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim K, Johnson JA, Derendorf H (2004) Differences in drug pharmacokinetics between East Asians and Caucasians and the role of genetic polymorphisms. J Clin Pharmacol 44(10):1083\u0026ndash;1105\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcNavish DE, German CA, Shapiro MD (2022) Should a Statin be Given to All Hypertensive Patients? Curr Hypertens Rep 24(1):21\u0026ndash;27\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRidker PM et al (2008) Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 359(21):2195\u0026ndash;2207\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMesserli FH et al (2008) Impact of systemic hypertension on the cardiovascular benefits of statin therapy\u0026ndash;a meta-analysis. Am J Cardiol 101(3):319\u0026ndash;325\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-3503243/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3503243/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction\u003c/h2\u003e \u003cp\u003eThis meta-analysis focused on the effects of statin use (either alone or in combination with antihypertensive drugs) on hypertension-related outcome measures, including systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein-cholesterol (LDL-C), low-density lipoprotein- cholesterol (HDL-C), triglyceride (TG), total cholesterol, TG and total cholesterol.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe searched the PubMed, EMBASE, and Cochrane databases before October1 2023.Studies designed as cohort study or randomized controlled trials and investigating the effects of statin use or combined with antihypertensive therapy versus no statin use or antihypertensive therapy alone were included. Authors extracted the data independently; differences were decided to discussion. we use random-effects models to evaluate the merged outcomes. Due to the high heterogeneity of HDL-C group, we performed subgroup analysis according to the type of statin. We use sensitivity analysis, Egger\u0026rsquo;s test and Funnel plots to evaluate the stability and publication bias of our study.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003e23 trials were included in this meta-analysis. The primary outcomes revealed that (1) administering statins did not significantly impact the SBP of hypertensive patients (MD,-1.77; 95% CI, -4.82 to 1.27). Subgroup analyses revealed a decrease in SBP in patients who received rosuvastatin (MD,-1.70; 95% CI,-2.75 to -0.65) and pravastatin (MD,-8.00; 95% CI,-10.79 to -5.21); (2) no significant effect of statin treatment on DBP in hypertensive patients (MD,-2.04; 95% CI,-4.11 to 0.02). However, subgroup analyses suggest that simvastatin (MD,-2.49; 95% CI, -4.91 to -0.07) and pravastatin (MD,-5.00; 95% CI, -6.60 to -3.40) significantly reduced DBP in hypertensive patients. The secondary outcomes revealed that (1) the use of statins resulted in a significant reduction in LDL-C in hypertensive patients (MD, -0.95; 95% CI, -1.32 to -0.65), while significantly increasing HDL-C (MD, 0.39; 95% CI, 0.15 to 0.64); (2) statins were shown to significantly reduce TG levels in hypertensive patients (MD -0.14, 95% CI -0.23 to -0.05); (3) statins significantly reduced total cholesterol in those hypertensive patients (MD, -1.75; 95% CI, -2.66 to -0.83); (4) statins significantly reduced the incidence of cardiovascular events (HR, 0.73; 95% CI, 0.62 to 0.85) and mortality (HR, 0.47; 95% CI, 0.33 to 0.60).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eStatin use did not modulate SBP and DBP of patients with hypertension, but SBP was decreased in rosuvastatin or pravastatin subgroup and DBP was decreased in simvastatin or pravastatin subgroup. Statin treatment reduced LDL-C, increased HDL-C, reduced TG and total cholesterol, reduced the incidence of cardiovascular events and mortality compared to control groups.\u003c/p\u003e","manuscriptTitle":"Effect of Statin use on Patients with Hypertension: A Systematic Review and Meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-11-02 20:39:59","doi":"10.21203/rs.3.rs-3503243/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f7f0f504-a2ef-451f-b30f-482e29775c9e","owner":[],"postedDate":"November 2nd, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-11-11T11:14:12+00:00","versionOfRecord":[],"versionCreatedAt":"2023-11-02 20:39:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3503243","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3503243","identity":"rs-3503243","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}