The Association Between Blood Pressure and Gallstones and the Age of First Cholecystectomy in U.S. Adults: Results from a Cross-Sectional Study

The Association Between Blood Pressure and Gallstones and the Age of First Cholecystectomy in U.S. Adults: Results from a Cross-Sectional Study | 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 The Association Between Blood Pressure and Gallstones and the Age of First Cholecystectomy in U.S. Adults: Results from a Cross-Sectional Study Yue Zhang, Ruifeng Duan, Xin Chen, lijuan Wei This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5261602/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 07 Feb, 2025 Read the published version in BMC Gastroenterology → Version 1 posted 13 You are reading this latest preprint version Abstract Background To assess the association between hypertension( HTN ) and the prevalence of gallstones and the age at first cholecystectomy in U.S. adults. Methods Data were extracted from the National Health and Nutrition Examination Survey (NHANES) database from 2017 to 2020. Weighted logistic regression analysis, weighted linear regression, weighted subgroup analysis, generalized additive models, smooth fitting curves, and two-piece linear regression models were utilized to evaluate the relationship between HTN, gallstone prevalence, and the age of first cholecystectomy. Results A total of 7,532 participants above 20 years were included in the study. Among them, 817 individuals self-reported a history of cholecystectomy, and 781 individuals self-reported a history of gallstones. After adjusting for age, gender, race, education level, smoking status, marital status,, diabetes, and hypercholesterolemia, HTN was significantly associated with gallstones in individuals aged 48 years and older (OR = 1.39, 95% CI: 1.03, 1.88). Systolic blood pressure was positively related to the age of first cholecystectomy (β = 0.19, 95% CI: 0.12, 0.26), and a nonlinear relationship was observed with a threshold effect at 170 mmHg. Conclusion An association was identified between blood pressure and the prevalence of gallstones in individuals aged 42 years and older. Systolic blood pressure was positively associated with the age of the first cholecystectomy. Although causality cannot be established, these findings may aid in identifying early risk groups for gallstone disease and first cholecystectomy, improving risk stratification, and reducing screening costs. Gallstones Cholecystectomy Hypertension Figures Figure 1 Figure 2 Figure 3 INTRODUCTION The gallbladder is responsible for concentrating and storing bile, and when changes in bile concentration and composition occur, solid formations of bile, known as gallstones, can develop [1] . According to 2016 statistics, approximately 20% of adults worldwide experience gallstones, with gallstones serving as a significant risk factor for gallbladder cancer [2][3] . Gallstones are generally classified into three types: cholesterol stones, pigment stones, and mixed stones. In recent years, the increasing consumption of high-fat diets has contributed to increased cholesterol gallstone cases [4] . The primary clinical manifestation of gallstones is biliary colic, and approximately 1%-2% of patients are at risk of developing severe, potentially life-threatening complications [5][6] . Currently, cholecystectomy remains the primary treatment for gallstones. Studies indicate that the incidence of gallstone spillage following cholecystectomy is as high as 40%, with recurrence rates ranging from 0.08–0.3%, with a potential risk of renal cancer post-cholecystectomy [7][8] . In the United States, approximately 800,000 cholecystectomy procedures are conducted annually, with associated costs nearing $ 6 billion [9] . Therefore, identifying risk factors for cholecystectomy is essential for early detection and intervention in high-risk populations. Hypertension (HTN) is a major public health issue and affects over one billion adults worldwide [10] . In the United States, approximately 33% of adults (80 million individuals) are affected by HTN, with direct and indirect costs estimated to reach $ 49 billion in 2012 [11] . Among these individuals, about half have uncontrolled blood pressure, particularly among gallstone patients, for whom HTN has been reported to have a positive association with gallstone risk [12] . Studies have shown that risk factors for gallstone development include ethnicity, gender, pregnancy, and age over 40, with these factors increasing the risk of gallstones by a factor of 4 to 10 [13][14] . In a study of 2,527 patients, Xu et al. found a positive association between HTN and gallstone disease in a Chinese population [15] . Song et al. [16 ] further confirmed this association; however, their study was limited by a small sample size and failed to explore the relationship between HTN and cholecystectomy. As such, while substantial research has investigated the relationship between HTN and gallstones, relatively little research has explored the association between HTN and cholecystectomy. To address this gap, data from the National Health and Nutrition Examination Survey (NHANES) were used to evaluate the association between HTN, gallstone disease, and cholecystectomy in U.S. adults. MATERIALS AND METHODS Study Design and Participants: The baseline clinical data used in this study were obtained from the 2017–2020 NHANES in the United States. Data were included from participants who provided clear information on whether they had gallstones, as well as the age at which they underwent their first cholecystectomy. A total of 15,560 individuals completed the survey. The exclusion criteria are outlined Ultimately, 7,409 participants were included in this study, including 802 participants who self-reported the age of their first cholecystectomy (Figure 1.) . Data Collection and Definitions: NHANES is a national survey of non-institutionalized U.S. civilians, conducted by the National Center for Health Statistics (NCHS) using a cross-sectional, multistage, stratified, probability sampling design conducted in two-year cycles [17] . The survey encompasses various domains, including face-to-face interviews (demographic, socioeconomic, dietary, and health-related questions) conducted at home, as well as medical assessments and anthropometric and laboratory tests collected at mobile examination centers (MECs) [18][19] . Data collection included laboratory measurements of triglyceride, cholesterol, and fasting blood glucose levels. Blood pressure-oscillometric and body measurements were collected as part of the examination process. Questionnaires were used to assess gallstone presence and to collect data on age, blood pressure, and cholesterol levels at the time of the first gallstone surgery. Exposure factors and outcomes: Blood pressure was treated as an exposure factor according to the American Heart Association Blood Pressure Guidelines 2017 [20] , where HTN is defined as systolic blood pressure (SBP) ≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg, self-reported HTN, or use of antihypertensive medication. Outcome variables included the prevalence of gallstones, the incidence of gallbladder surgery, and the age at first gallstone surgery. In this study, covariates were screened according to the following criteria: (1) demographic data; (2) variables affecting blood pressure, gallstones, and gallbladder surgery reported in previous studies; (3) a change of more than 10% in the base model after the introduction of the covariate, as recommended by the STROBE statement [21] ; and (4) other variables derived from clinical experience. Therefore, the covariates included were sex (male/female), age (years), race (Mexican American/Non-Hispanic White/Non-Hispanic Black/Other), education level (≤ high school/>high school), poverty-to-income ratio (PIR), marital status (married or living with partner/single), hypercholesterolemia (< 6.2mmol/≥6.2mmol), smoking status, diabetes mellitus, and obesity. According to the World Health Organisation criteria, general obesity is classified as normal weight (body mass index( BMI ) ≤ 18.5 kg/m²), overweight (BMI ≥ 25 kg/m², BMI < 30 kg/m²), and obese (BMI ≥ 30 kg/m²) [22] . Possible confounders were summarized in multivariate correction models. All NHANES protocols were carried out in compliance with the U.S. Department of Health and Human Services (HHS) Policy for the Protection of Human Research Subjects and were reviewed and approved annually by the NCHS Research Ethics Review Board. All participants provided informed consent. All data in this study were freely released by NHANES, with no need for additional permissions or ethical reviews. Statistical Methods: Complex weighting of the NHANES data was conducted using R software. According to the recommendations on the official NHANES website, data were merged based on the unique Survey Participant Identification Number( SEQN) of each participant. Continuous variables were expressed as weighted medians (quartiles), and categorical variables were expressed as weighted survey percentages and 95% confidence intervals. The relationship between HTN and gallstone prevalence across three different models was evaluated through multivariate logistic regression models according to the established guidelines [23][24] . Model 1 was not adjusted for covariates, Model 2 was adjusted for gender, age, race, marital status, and education level, and Model 3 was adjusted for all variables. Multiple linear regression models were employed to assess the relationship between systolic blood pressure and time to first gallbladder surgery. Smoothed curve fitting and generalized additive model (GAM) regression were used to further evaluate the relationship between blood pressure, gallstone prevalence, and age at first gallstone surgery. When a non-linear relationship was identified, inflection point values were determined using threshold effects analysis. Subgroup analyses were conducted using weighted multivariate logistic regression. Results from different strata were considered reliable if the interaction p-value was not significant; otherwise, interactions between specific groups may exist. A p-value < 0.05 was considered statistically significant. All statistical analyses were conducted in R (version 4.2.2, http://www.R-project.org ). RESULTS Participant characteristics: The baseline demographic characteristics of the included subjects are presented in weighted Table 1 . Subjects were stratified based on their history of gallbladder surgery. The cohort included 3715 males (48.36%) and 3817 females (51.63%), with a median age of 48 years (interquartile range: 33 to 62 years). HTN was diagnosed in 2907 patients (32.83%), and gallstones were present in 781 patients (10.78%) (Table 1.) . Table 1 Baseline characteristics of participants, weighted. Dependent: Surgery Total (n = 7532) No (N = 6715) Yes (N = 817) OR (univariable) Age, M (Q₁, Q₃) 48.00 (33.00, 62.00) 46.00 (32.00, 60.00) 60.00(47.00, 70.00) 1.04 (1.03 ~ 1.05, p < .001) Gender Woman 3817 (51.63%) 3214 (47.9%) 603 (73.8%) Man 3715 (48.36%) 3501 (52.1%) 214 (26.2%) 1.03(0.77 ~ 1.38, p < .001) Race Mexican American 833 (7.90%) 738 (11%) 95 (11.6%) Non-Hispanic White 2671 (63.88%) 2266 (33.7%) 405 (49.6%) 1.48(1.13 ~ 1.95, p = 0.007) Non-Hispanic Black 2022 (11.21%) 1874 (27.9%) 148 (18.1%) 0.69(0.48 ~ 0.99, p = 0.043) Other 2006 (17.02%) 1837 (27.4%) 169 (20.7%) 0.93 (0.67 ~ 1.29, p = 0.652) Education No 1312 (9.95%) 1173 (17.5%) 139 (17%) Yes 6220 (90.05%) 5542 (82.5%) 678 (83%) 1.03 (0.85 ~ 1.25, p = 0.854) Marital No 3160 (37.145) 2822 (42%) 338 (41.4%) Yes 4372 (62.86%) 3893 (58%) 479 (58.6%) 1.08 (0.82 ~ 1.41, p = .0.58) PIR No 5344 (78.54%) 4744 (70.6%) 600 (73.4%) Yes 2188 (21.46%) 1971 (29.4%) 217 (26.6%) 0.80 (0.60 ~ 1.06, p = 0.122) HTN No 4625 (67.17%) 4291 (63.9%) 334 (40.9%) Yes 2907 (32.83%) 2424 (36.1%) 483 (59.1%) 2.65 (2.04 ~ 3.44, p < .001) SBP,M (Q₁, Q₃) 123.00(113,135) 123.00(113.00,134.00) 125.00(115.00,138.00) 1.01(1.00 ~ 1.02, p = .0.001) DBP,M (Q₁, Q₃) 76.00(69,83) 75.000(68.00,83.00) 76.00(70.00,84.00) 1.00 (0.99 ~ 1.01, p = 0.50) Gallstone No 6751 (89.22%) 6521 (97.1%) 230 (28.2%) Yes 781 (10.78%) 194 (2.9%) 587 (71.8%) 108.41(77.64 ~ 151.37, p < .001) Obesity No 4289 (57.39%) 3978 (59.2%) 311 (38.1%) Yes 3243 (42.61%) 2737 (40.8%) 506 (61.9%) 2.12 (1.69 ~ 2.65, p < .001) High cholesterol No 4508 (60.43%) 4130 (61.5%) 378 (46.3%) Yes 3024 (39.57%) 2585 (38.5%) 439 (53.7%) 1.85 (1.52 ~ 2.24,p < .001) Smoke No 6143 (83.04%) 5456 (81.3%) 687 (84.1%) Yes 1389 (16.96%) 1259 (18.7%) 130 (15.9%) 0.85(0.64 ~ 1.12, p = 0.251) Diabetes No 5985 (84.52) 5452 (81.2%) 533 (65.2%) Yes 1547 (15.48) 1263 (18.8%) 284 (34.8%) 2.60 (1.95 ~ 3.47, p < .001) Table 1 :Data of continuous variables are shown as survey-weighted mean (95% CI), P-value was calculated by survey-weighted linear regression. Data of categorical variables are shown as survey-weighted percentages (95% CI), P-value was calculated by survey-weighted Chi-square test. SBP, Systolic Blood Pressure.DBP, Diastolic Blood Pressure Logistic regression results between HTN and gallbladder stones: Table 2 presents the results of logistic regression analysis stratified by median age. When blood pressure was treated as a categorical variable, HTN was significantly associated with a higher risk of gallstone disease in individuals over the age of 48 (OR = 1.39; 95% CI: 1.03, 1.88; P = 0.033). This suggests that individuals with HTN in this age group had a 39% higher likelihood of undergoing cholecystectomy compared to those with normal blood pressure. However, in individuals aged ≤ 48 years, no significant association was observed between HTN and gallstone disease risk (OR = 1.21; 95% CI: 0.68, 2.17; P = 0.480) (Table 2) . Table 2 Logistic regression analysis between HTN with Gallstone prevalence. Variables Model1 Model2 Model3 OR (95%CI) P OR (95%CI) P OR (95%CI) P Age ≤ 48 HTN 2 1.00 (Reference) 1.00 (Reference) 1.00 (Reference) 1 2.23 (1.74 ~ 2.86) 48 HTN 2 1.00 (Reference) 1.00 (Reference) 1.00 (Reference) 1 1.69 (1.27 ~ 2.25) < .001 1.64 (1.23 ~ 2.20) 0.002 1.39(1.03 ~ 1.88) 0.033 Table 2 . Logistic regression analysis between HTN with Gallstone prevalence.OR: Odds Ratio, CI: Confidence Interval Model1: Crude Model2: Adjust: Age, Gender, Education, Marital, PIR, Race Model3: Adjust: Age, Gender, Education, Marital, PIR, Race, High cholesterol, Obesity, Smoke, Diabetes Association Between Increased Systolic Blood Pressure and Later Age of First Cholecystectomy, and Dose-Response and Threshold Effect Analysis: The relationship between systolic blood pressure (SBP) and the age of first cholecystectomy was analyzed through a weighted multivariate linear regression model. In the fully adjusted Model 3, a significant association was observed between systolic blood pressure and age at first cholecystectomy (β = 0.19, 95% CI: 0.12, 0.26) (Table 3) . Following covariate adjustments, each unit increase in systolic blood pressure was found to increase the age of first cholecystectomy by 0.19 years (95% CI: 0.12, 0.26). To further assess the relationship between SBP and age at first cholecystectomy, a generalized additive model and smooth curve fitting analysis were conducted. The analysis revealed a significant nonlinear relationship between SBP and age at first cholecystectomy (P < 0.05) (Figure 2) . Additionally, it was noted that as SBP increased, the age at which U.S. adults underwent their first cholecystectomy increased accordingly. Using threshold effect analysis, a turning point at 170 mmHg was identified (Table 4) . Before this turning point, a significant positive correlation was observed between SBP and age at first cholecystectomy (OR = 0.245; 95% CI: 0.187, 0.302). However, after the turning point, this correlation was no longer significant (OR=-0.179; 95% CI: -0.476, 0.119) Table 3 The weighted linear regression between systolic blood pressure and the age of first cholecystectomy. Variables Model1 Model2 Model3 β (95%CI) P β(95%CI) P β (95%CI) P Systolic blood pressure 0.21 (0.15 ~ 0.28) < .001 0.21 (0.15 ~ 0.28) < .001 0.19 (0.12 ~ 0.26) < .001 Table 3 . Weighted linear regression between systolic blood pressure and age at first gallbladder surgery.OR: Odds Ratio, CI: Confidence Interval Model1: Crude Model2: Adjust: Gender, Education, Marital, PIR, Race Model3: Adjust: Gender, Education, Marital, PIR, High cholesterol, Gallstone, Obesity, Race, Smoke, Diabetes Table 4 Two-stage linear regression and log-likelihood ratio explaining the threshold effect analysis of systolic blood pressure with age at first gallbladder surgery. Systolic blood pressure ULR Test PLR Test LRT Test β(95%CI) β(95%CI) P-value < 170mmHg 0.207(0.157–0.258,p < .001) 0.245(0.187–0.302,p < .001) 0.01 ≥ 170mmHg -0.179(-0.476-0.119,p = 0.240) ULR , univariate linear regression; PLR , piecewise linear regression; LRT , logarithmic likelihood ratio test, statistically significant: p < 0.05. Subgroup analyses: Subgroup analyses were conducted to evaluate the robustness of the association between HTN and gallbladder surgery and to examine the interactions among age, gender, gallstones, race, obesity, and diabetes mellitus status, demonstrating a stable positive association between HTN and gallbladder surgery occurrence, independently of these factors (p > 0.05) (Figure 3) . DISCUSSION Nahum et al. [25] examined the relationship between gallstone disease and cardiovascular disease among 437 patients in Mexico and reported a significant association between HTN and gallstone disease (OR = 2.55; 95% CI: 1.62–4.03; P < 0.01). After adjusting for factors such as BMI, age, and alcohol intake, HTN was identified as an independent risk factor for gallstone disease (OR = 1.26; 95% CI: 1.05–1.50; P = 0.01) [26] . In our study, the prevalence of gallstones was 10.78%. The results indicated that the prevalence of gallstones in the U.S. is lower than that reported in Norway (21.9%) [27] , France (13.9%) [28] , and Germany (19.7%) [29] , yet higher than that reported in Japan (3.2%) [30] . This discrepancy may stem from the American population's preference for fatty diets and an increase in health check-up frequency. Our study revealed an association between HTN and the risk of gallstones. After stratifying by age, it was found that HTN was significantly associated with gallstone disease in individuals older than 48 years (OR = 1.39; 95% CI: 1.03, 1.88; P = 0.033), indicating that hypertensive patients in this age group exhibited a 39% higher incidence of gallstones relative to individuals with normal blood pressure. However, in individuals aged ≤ 48 years, HTN was not associated with gallstone disease risk (OR = 1.21; 95% CI: 0.68, 2.17; P = 0.480). Currently, there remains disagreement regarding the relationship between blood pressure and cholecystectomy. One cross-sectional study suggested no significant association between HTN and cholecystectomy [31] . However, a 2012 case-control study that included 798 subjects reported a significant correlation between HTN and cholecystectomy [12] . To our knowledge, this study is the first to analyze the relationship between blood pressure and the age at first cholecystectomy. It was found that systolic blood pressure was positively correlated with the age at first cholecystectomy (β = 0.21, 95% CI: 0.12, 0.26). For the first time, smooth curve fitting and two-piece linear regression was employed to examine the nonlinear relationship between systolic blood pressure and age at first cholecystectomy, and a turning point was identified using threshold effect analysis. Before this turning point, a significant correlation was observed (OR = 0.245; 95% CI: 0.187, 0.302), while after the turning point, the correlation was no longer significant (OR = -0.179; 95% CI: -0.476, 0.119). Furthermore, a stable positive correlation was observed between HTN and the occurrence of cholecystectomy through subgroup analyses, independently of age, gender, gallstone presence, race, obesity, and diabetes mellitus (P > 0.05). These findings strongly support the significance of blood pressure as a predictive factor for cholecystectomy development. Therefore, when gallstone disease is present in a population, especially among older patients, monitoring blood pressure is critical for preventing surgery and facilitating early interventions. Previous studies have indicated that leptin levels are associated with blood pressure. Hypertensive patients exhibit higher serum leptin levels compared to healthy individuals [32][33][34] , and both diastolic and systolic blood pressure have shown significant positive correlations with leptin levels [32][34] . Leptin induces inflammation of the gallbladder wall by binding to leptin receptors located on the gallbladder wall[35][36]. Additionally, leptin affects fibroblasts, reducing the contractile function of the gallbladder wall, thereby increasing gallbladder volume and causing bile stasis, which ultimately leads to the formation of gallstones [37] . Furthermore, elevated leptin levels can result in hyperinsulinemia, leading the liver to produce cholesterol-saturated bile [38] . Leptin directly influences the composition of bile by increasing hydrophilic bile salts and decreasing hydrophobic bile salts, cycling bile acids, and intestinal cholesterol absorption, which contributes to stone formation [39] . The formation of gallstones can cause symptoms such as biliary colic, and the primary treatment for symptomatic gallstones remains cholecystectomy. The primary strength of this study lies in its large sample size. The NHANES database employs a complex weighted design, providing a more representative sample of the entire U.S. population, and data from NHANES from 2017 to 2020 were utilized. Additionally, NHANES collects data using standardized protocols by trained professionals, including standardized questionnaires, physical examinations, and laboratory tests for each participant. All blood samples are tested in the same laboratory using standardized protocols within the same time frame, significantly reducing potential biases due to methodological differences. Furthermore, subgroup and interaction analyses were conducted to explore the impact of potential confounding factors on the association between HTN and cholecystectomy, enhancing statistical power. However, our study has several limitations. First, being a cross-sectional study, it does not facilitate the determination of causal relationships between HTN and cholecystectomy. Second, all survey data were based on self-reported questionnaires, which may be subject to recall bias. CONCLUSION This study revealed an association between modifiable risk factors, particularly blood pressure, and gallstone disease in individuals aged over 48 years and the age at which they undergo their first cholecystectomy. It highlights the necessity of monitoring and managing blood pressure among middle-aged and younger individuals to help reduce the incidence of cholecystectomy. Although the causal relationship between these factors remains unclear, these findings warrant further investigation. Abbreviations NHANES, National Health and Nutrition Examination Survey NCHS, National Center for Health Statistics MECs, Mobile Examination Centers HTN, Hypertension SBP, Systolic Blood Pressure DBP, Diastolic Blood Pressure PIR, Poverty-to-Income Ratio HHS, Health and Human Services SEQN, Survey Participant Identification Number GAM, Generalized Additive Model ULR , Univariate Linear Regression PLR , Piecewise Linear Regression LRT , Logarithmic Likelihood Ratio BMI, Body Mass Index Declarations Ethics approval and consent to participate: NHANES was approved by the Ethical Review Board of the National Center for Health Statistics (NCHS). Informed consent was obtained from all participants. Consent for publication: Not applicable. Availability of data and materials: The data used in this study are publically available in the NHANES database (www.cdc.gov/nchs/nhanes). Competing interests: The authors declare that they have no competing interests Funding: This research was funded by the Jilin Provincial Department of Science and Technology( grant number 20210203191SF) Authors' contributions: Yue Zhang: Writing – review & editing, Writing – original draft, Conceptualization.Ruifeng Duan： Writing – review & editing. Xin Chen： Writing – review & editing.. lijuan Wei： Writing – review & editing Acknowledgements: The authors express gratitude to all participants and investigators of the NHANES. Authorship contribution statement References Kim SS, Donahue TR. Laparoscopic Cholecystectomy. JAMA. 2018 May 1;319(17):1834. doi: 10.1001/jama.2018.3438. PMID: 29715356. Lammert F, Gurusamy K, Ko CW, Miquel JF, Méndez-Sánchez N, Portincasa P, van Erpecum KJ, van Laarhoven CJ, Wang DQ. Gallstones. Nat Rev Dis Primers. 2016 Apr 28;2:16024. doi: 10.1038/nrdp.2016.24. PMID: 27121416. Friedman GD. Natural history of asymptomatic and symptomatic gallstones. 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Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones DW, MacLaughlin EJ, Muntner P, Ovbiagele B, Smith SC Jr, Spencer CC, Stafford RS, Taler SJ, Thomas RJ, Williams KA Sr, Williamson JD, Wright JT Jr. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018 Jun;71(6):e13-e115. Doi: 10.1161/HYP.0000000000000065. Epub 2017 Nov 13. Erratum in: Hypertension. 2018 Jun;71(6):e140-e144. PMID: 29133356. Vandenbroucke JP, von Elm E, Altman DG, Gøtzsche PC, Mulrow CD, Pocock SJ, Poole C, Schlesselman JJ, Egger M; STROBE Initiative. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. Epidemiology. 2007 Nov;18(6):805-35. doi: 10.1097/EDE.0b013e3181577511. PMID: 18049195. Kushner RF, Ryan DH. Assessment and lifestyle management of patients with obesity: clinical recommendations from systematic reviews. JAMA. 2014 Sep 3;312(9):943-52. doi: 10.1001/jama.2014.10432. Erratum in: JAMA. 2014 Oct 15;312(15):1593. PMID: 25182103. Chen Y, Shen X, Liang H, Li G, Han K, Liang C, Hao Z. Relationship between hepatitis C and kidney stone in US females: Results from the National Health and Nutrition Examination Survey in 2007-2018. Front Public Health. 2022 Aug 5;10:940905. doi: 10.3389/fpubh.2022.940905. PMID: 35991057; PMCID: PMC9389117. Chen Y, Shen X, Li G, Yue S, Liang C, Hao Z. Association between aldehyde exposure and kidney stones in adults. Front Public Health. 2022 Oct 10;10:978338. doi: 10.3389/fpubh.2022.978338. PMID: 36299743; PMCID: PMC9589346. Méndez-Sánchez N, Bahena-Aponte J, Chávez-Tapia NC, Motola-Kuba D, Sánchez-Lara K, Ponciano-Radríguez G, Ramos MH, Uribe M. Strong association between gallstones and cardiovascular disease. Am J Gastroenterol. 2005 Apr;100(4):827-30. doi: 10.1111/j.1572-0241.2005.41214.x. PMID: 15784027. Lee YC, Wu JS, Yang YC, Chang CS, Lu FH, Chang CJ. Moderate to severe, but not mild, nonalcoholic fatty liver disease associated with increased risk of gallstone disease. Scand J Gastroenterol. 2014 Aug;49(8):1001-6. Doi: 10.3109/00365521.2014.920912. Epub 2014 Jul 3. PMID: 24989169. Glambek I, Kvaale G, Arnesjö B, Søreide O. Prevalence of gallstones in a Norwegian population. Scand J Gastroenterol. 1987 Nov;22(9):1089-94. Doi: 10.3109/00365528708991963. PMID: 3321395. Caroli-Bosc FX, Deveau C, Harris A, Delabre B, Peten EP, Hastier P, Sgro E, Caroli-Bosc C, Stoia M, Demarquay JF, Dumas R, Coussement A, Delmont JP. Prevalence of cholelithiasis: results of an epidemiologic investigation in Vidauban, southeast France. General Practitioner's Group of Vidauban. Dig Dis Sci. 1999 Jul;44(7):1322-9. doi: 10.1023/a:1026627129702. PMID: 10489913. Berndt H, Nürnberg D, Pannwitz H. Prävalenz der Cholelithiasis. Ergebnisse einer epidemiologischen Studie mittels Sonographie in der DDR [Prevalence of cholelithiasis. Results of an epidemiologic study using sonography in East Germany]. Z Gastroenterol. 1989 Nov;27(11):662-6. German. PMID: 2694654. Nomura H, Kashiwagi S, Hayashi J, Kajiyama W, Ikematsu H, Noguchi A, Tani S, Goto M. Prevalence of gallstone disease in a general population of Okinawa, Japan. Am J Epidemiol. 1988 Sep;128(3):598-605. Doi: 10.1093/oxfordjournals.aje.a115007. PMID: 3046339. Zhang Y, Sun L, Wang X, Chen Z. The association between hypertension and the risk of gallstone disease: a cross-sectional study. BMC Gastroenterol. 2022 Mar 26;22(1):138. doi: 10.1186/s12876-022-02149-5. PMID: 35346065; PMCID: PMC8961935. Kunz I, Schorr U, Klaus S, Sharma AM. Resting metabolic rate and substrate use in obesity hypertension. Hypertension. 2000 Jul;36(1):26-32. doi: 10.1161/01.hyp.36.1.26. PMID: 10904008. Golan E, Tal B, Dror Y, Korzets Z, Vered Y, Weiss E, Bernheim J. Reduction in resting metabolic rate and the ratio of plasma leptin to urinary nitric oxide: influence on obesity-related hypertension. Isr Med Assoc J. 2002 Jun;4(6):426-30. PMID: 12073415. Canatan H, Bakan I, Akbulut M, Halifeoglu I, Cikim G, Baydas G, Kilic N. Relationship among levels of leptin and zinc, copper, and zinc/copper ratio in plasma of patients with essential hypertension and healthy normotensive subjects. Biol Trace Elem Res. 2004 Aug;100(2):117-23. doi: 10.1385/BTER:100:2:117. PMID: 15326361。 Zeng DB, Lei ZM, Gan XL, Ye MX. Study on correlation of leptin, cholecystokinin, metabolism of lipids, and cholesterol gallstone disease. China J Modern Med. 2008; 18 (3):354–357. Li ZhJ, Peng Y. Research on the relationship between leptin and insulin in diabetes. Acta Med Sin. 2005; 18 (6):900–902. Li PB, Jin H. [Leptin and wound healing]. Sheng Li Ke Xue Jin Zhan. 2005 Jul;36(3):256-9. Chinese. PMID: 16270830. Clark JM, Diehl AM. Hepatic steatosis and type 2 diabetes mellitus. Curr Diab Rep. 2002 Jun;2(3):210-5. doi: 10.1007/s11892-002-0085-3. PMID: 12643175. Hyogo H, Roy S, Paigen B, Cohen DE. Leptin promotes biliary cholesterol elimination during weight loss in ob/ob mice by regulating the enterohepatic circulation of bile salts. J Biol Chem. 2002 Sep 13;277(37):34117-24. doi: 10.1074/jbc.M203912200. Epub 2002 Jul 11. PMID: 12114517. Additional Declarations No competing interests reported. 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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-5261602","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":381183110,"identity":"8b42e39b-9849-4c44-869a-a460df0d2c85","order_by":0,"name":"Yue Zhang","email":"","orcid":"","institution":"The Second Hospital of Jilin University","correspondingAuthor":false,"prefix":"","firstName":"Yue","middleName":"","lastName":"Zhang","suffix":""},{"id":381183111,"identity":"8488b854-1dd5-4639-a4df-7b86efc4b5c3","order_by":1,"name":"Ruifeng Duan","email":"","orcid":"","institution":"The Second Hospital of Jilin University","correspondingAuthor":false,"prefix":"","firstName":"Ruifeng","middleName":"","lastName":"Duan","suffix":""},{"id":381183112,"identity":"c246528f-69fb-4207-bccf-661b08f5c63a","order_by":2,"name":"Xin Chen","email":"","orcid":"","institution":"The Second Hospital of Jilin University","correspondingAuthor":false,"prefix":"","firstName":"Xin","middleName":"","lastName":"Chen","suffix":""},{"id":381183113,"identity":"43f137ee-b558-4764-adf9-13235234cdc5","order_by":3,"name":"lijuan Wei","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1ElEQVRIiWNgGAWjYBACNvb2459/VNjI2R9vPkCcFj6eM2nMDGfSjBnOHEsgToucRIIZM2Pb4cSGGz4GRDqM50Da4wK2w8aMM3g+3njDYCen20BIC3vjceMZPOlyzNK9my3nMCQbmx0gbEuCBI+EtTGbzNlt0jwMBxK3EdQikWAgwWPAnNgjkfOMaC1m0jwJzokzJHLYiNTCcybZcMaBNGMDnmPGlnMMiPCLfHv7wQcf/9nIGbA3P7zxpsJOjqAWFAD0FCnKIVpI1TEKRsEoGAUjAgAAUcxBqfUsL5MAAAAASUVORK5CYII=","orcid":"","institution":"The Second Hospital of Jilin University","correspondingAuthor":true,"prefix":"","firstName":"lijuan","middleName":"","lastName":"Wei","suffix":""}],"badges":[],"createdAt":"2024-10-14 13:53:04","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5261602/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5261602/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12876-025-03641-4","type":"published","date":"2025-02-07T15:58:04+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":70919654,"identity":"4e0d18be-d5ea-439a-a259-3bdcc67c9bb6","added_by":"auto","created_at":"2024-12-09 08:35:06","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":141126,"visible":true,"origin":"","legend":"\u003cp\u003eThe participant's selection flow chart.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-5261602/v1/c7c9eb592e6d99d1be769a15.png"},{"id":70919179,"identity":"e08cb806-75f3-4645-a30a-07e32d70a3be","added_by":"auto","created_at":"2024-12-09 08:27:06","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":78215,"visible":true,"origin":"","legend":"\u003cp\u003eSmoothed curve fitting using GAM to assess the nonlinear relationship between systolic blood pressure and age at first gallstone surgery. The solid red line represents systolic blood pressure and the dashed line represents the 95% CI curve.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-5261602/v1/ad76826252a1f71b92c5492c.png"},{"id":70919178,"identity":"1e874fda-9208-4cda-8d1d-b8c90a8cc597","added_by":"auto","created_at":"2024-12-09 08:27:06","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":133880,"visible":true,"origin":"","legend":"\u003cp\u003eSubgroup analysis and interaction between HTN and gallbladder surgery.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-5261602/v1/4c6263c3a8700537b579aa35.png"},{"id":75930508,"identity":"25ff8f2b-bb62-4821-89d1-7288ed0b66cf","added_by":"auto","created_at":"2025-02-10 16:12:39","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1142531,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5261602/v1/e47415d0-4860-4f0c-941e-f2f2b3985089.pdf"},{"id":70919180,"identity":"4819579a-31ae-4384-bf09-e7b7c432f6d2","added_by":"auto","created_at":"2024-12-09 08:27:07","extension":"csv","order_by":9,"title":"","display":"","copyAsset":false,"role":"supplement","size":659963,"visible":true,"origin":"","legend":"","description":"","filename":"file.csv","url":"https://assets-eu.researchsquare.com/files/rs-5261602/v1/a9727f8cbb48557a6fd4659f.csv"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eThe Association Between Blood Pressure and Gallstones and the Age of First Cholecystectomy in U.S. Adults: Results from a Cross-Sectional Study\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003e The gallbladder is responsible for concentrating and storing bile, and when changes in bile concentration and composition occur, solid formations of bile, known as gallstones, can develop\u003csup\u003e[1]\u003c/sup\u003e. According to 2016 statistics, approximately 20% of adults worldwide experience gallstones, with gallstones serving as a significant risk factor for gallbladder cancer\u003csup\u003e[2][3]\u003c/sup\u003e. Gallstones are generally classified into three types: cholesterol stones, pigment stones, and mixed stones. In recent years, the increasing consumption of high-fat diets has contributed to increased cholesterol gallstone cases\u003csup\u003e[4]\u003c/sup\u003e. The primary clinical manifestation of gallstones is biliary colic, and approximately 1%-2% of patients are at risk of developing severe, potentially life-threatening complications\u003csup\u003e[5][6]\u003c/sup\u003e. Currently, cholecystectomy remains the primary treatment for gallstones. Studies indicate that the incidence of gallstone spillage following cholecystectomy is as high as 40%, with recurrence rates ranging from 0.08\u0026ndash;0.3%, with a potential risk of renal cancer post-cholecystectomy\u003csup\u003e[7][8]\u003c/sup\u003e. In the United States, approximately 800,000 cholecystectomy procedures are conducted annually, with associated costs nearing \u003cspan\u003e$\u003c/span\u003e6 billion\u003csup\u003e[9]\u003c/sup\u003e. Therefore, identifying risk factors for cholecystectomy is essential for early detection and intervention in high-risk populations.\u003c/p\u003e \u003cp\u003eHypertension (HTN) is a major public health issue and affects over one billion adults worldwide\u003csup\u003e[10]\u003c/sup\u003e. In the United States, approximately 33% of adults (80\u0026nbsp;million individuals) are affected by HTN, with direct and indirect costs estimated to reach \u003cspan\u003e$\u003c/span\u003e49\u0026nbsp;billion in 2012\u003csup\u003e[11]\u003c/sup\u003e. Among these individuals, about half have uncontrolled blood pressure, particularly among gallstone patients, for whom HTN has been reported to have a positive association with gallstone risk\u003csup\u003e[12]\u003c/sup\u003e. Studies have shown that risk factors for gallstone development include ethnicity, gender, pregnancy, and age over 40, with these factors increasing the risk of gallstones by a factor of 4 to 10\u003csup\u003e[13][14]\u003c/sup\u003e. In a study of 2,527 patients, Xu et al. found a positive association between HTN and gallstone disease in a Chinese population\u003csup\u003e[15]\u003c/sup\u003e. Song et al.\u003csup\u003e[16\u003c/sup\u003e] further confirmed this association; however, their study was limited by a small sample size and failed to explore the relationship between HTN and cholecystectomy. As such, while substantial research has investigated the relationship between HTN and gallstones, relatively little research has explored the association between HTN and cholecystectomy. To address this gap, data from the National Health and Nutrition Examination Survey (NHANES) were used to evaluate the association between HTN, gallstone disease, and cholecystectomy in U.S. adults.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Participants:\u003c/h2\u003e \u003cp\u003eThe baseline clinical data used in this study were obtained from the 2017\u0026ndash;2020 NHANES in the United States. Data were included from participants who provided clear information on whether they had gallstones, as well as the age at which they underwent their first cholecystectomy. A total of 15,560 individuals completed the survey. The exclusion criteria are outlined Ultimately, 7,409 participants were included in this study, including 802 participants who self-reported the age of their first cholecystectomy\u003csup\u003e(Figure 1.)\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eData Collection and Definitions:\u003c/h3\u003e\n\u003cp\u003eNHANES is a national survey of non-institutionalized U.S. civilians, conducted by the National Center for Health Statistics (NCHS) using a cross-sectional, multistage, stratified, probability sampling design conducted in two-year cycles\u003csup\u003e[17]\u003c/sup\u003e. The survey encompasses various domains, including face-to-face interviews (demographic, socioeconomic, dietary, and health-related questions) conducted at home, as well as medical assessments and anthropometric and laboratory tests collected at mobile examination centers (MECs)\u003csup\u003e[18][19]\u003c/sup\u003e. Data collection included laboratory measurements of triglyceride, cholesterol, and fasting blood glucose levels. Blood pressure-oscillometric and body measurements were collected as part of the examination process. Questionnaires were used to assess gallstone presence and to collect data on age, blood pressure, and cholesterol levels at the time of the first gallstone surgery.\u003c/p\u003e \u003cp\u003eExposure factors and outcomes: Blood pressure was treated as an exposure factor according to the American Heart Association Blood Pressure Guidelines 2017\u003csup\u003e[20]\u003c/sup\u003e, where HTN is defined as systolic blood pressure (SBP)\u0026thinsp;\u0026ge;\u0026thinsp;140 mmHg and/or diastolic blood pressure (DBP)\u0026thinsp;\u0026ge;\u0026thinsp;90 mmHg, self-reported HTN, or use of antihypertensive medication. Outcome variables included the prevalence of gallstones, the incidence of gallbladder surgery, and the age at first gallstone surgery.\u003c/p\u003e \u003cp\u003eIn this study, covariates were screened according to the following criteria: (1) demographic data; (2) variables affecting blood pressure, gallstones, and gallbladder surgery reported in previous studies; (3) a change of more than 10% in the base model after the introduction of the covariate, as recommended by the STROBE statement\u003csup\u003e[21]\u003c/sup\u003e; and (4) other variables derived from clinical experience. Therefore, the covariates included were sex (male/female), age (years), race (Mexican American/Non-Hispanic White/Non-Hispanic Black/Other), education level (\u0026le;\u0026thinsp;high school/\u0026gt;high school), poverty-to-income ratio (PIR), marital status (married or living with partner/single), hypercholesterolemia (\u0026lt;\u0026thinsp;6.2mmol/\u0026ge;6.2mmol), smoking status, diabetes mellitus, and obesity. According to the World Health Organisation criteria, general obesity is classified as normal weight (body mass index( BMI )\u0026thinsp;\u0026le;\u0026thinsp;18.5 kg/m\u0026sup2;), overweight (BMI\u0026thinsp;\u0026ge;\u0026thinsp;25 kg/m\u0026sup2;, BMI\u0026thinsp;\u0026lt;\u0026thinsp;30 kg/m\u0026sup2;), and obese (BMI\u0026thinsp;\u0026ge;\u0026thinsp;30 kg/m\u0026sup2;)\u003csup\u003e[22]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003ePossible confounders were summarized in multivariate correction models. All NHANES protocols were carried out in compliance with the U.S. Department of Health and Human Services (HHS) Policy for the Protection of Human Research Subjects and were reviewed and approved annually by the NCHS Research Ethics Review Board. All participants provided informed consent. All data in this study were freely released by NHANES, with no need for additional permissions or ethical reviews.\u003c/p\u003e\n\u003ch3\u003eStatistical Methods:\u003c/h3\u003e\n\u003cp\u003eComplex weighting of the NHANES data was conducted using R software. According to the recommendations on the official NHANES website, data were merged based on the unique Survey Participant Identification Number( SEQN) of each participant. Continuous variables were expressed as weighted medians (quartiles), and categorical variables were expressed as weighted survey percentages and 95% confidence intervals. The relationship between HTN and gallstone prevalence across three different models was evaluated through multivariate logistic regression models according to the established guidelines\u003csup\u003e[23][24]\u003c/sup\u003e. Model 1 was not adjusted for covariates, Model 2 was adjusted for gender, age, race, marital status, and education level, and Model 3 was adjusted for all variables. Multiple linear regression models were employed to assess the relationship between systolic blood pressure and time to first gallbladder surgery. Smoothed curve fitting and generalized additive model (GAM) regression were used to further evaluate the relationship between blood pressure, gallstone prevalence, and age at first gallstone surgery. When a non-linear relationship was identified, inflection point values were determined using threshold effects analysis. Subgroup analyses were conducted using weighted multivariate logistic regression. Results from different strata were considered reliable if the interaction p-value was not significant; otherwise, interactions between specific groups may exist. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. All statistical analyses were conducted in R (version 4.2.2, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.R-project.org\u003c/span\u003e\u003cspan address=\"http://www.R-project.org\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e).\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec7\"\u003e\n \u003ch2\u003eParticipant characteristics:\u003c/h2\u003e\n \u003cp\u003eThe baseline demographic characteristics of the included subjects are presented in weighted Table\u0026nbsp;\u003cspan\u003e1\u003c/span\u003e. Subjects were stratified based on their history of gallbladder surgery. The cohort included 3715 males (48.36%) and 3817 females (51.63%), with a median age of 48 years (interquartile range: 33 to 62 years). HTN was diagnosed in 2907 patients (32.83%), and gallstones were present in 781 patients (10.78%)\u003csup\u003e(Table 1.)\u003c/sup\u003e.\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 1\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eBaseline characteristics of participants, weighted.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"5\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDependent: Surgery\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal (n\u0026thinsp;=\u0026thinsp;7532)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNo (N\u0026thinsp;=\u0026thinsp;6715)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eYes (N\u0026thinsp;=\u0026thinsp;817)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOR (univariable)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge, M (Q₁, Q₃)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e48.00 (33.00, 62.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46.00 (32.00, 60.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60.00(47.00, 70.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.04 (1.03\u0026thinsp;~\u0026thinsp;1.05, p\u0026thinsp;\u0026lt;\u0026thinsp;.001)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGender\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWoman\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3817 (51.63%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3214 (47.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e603 (73.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3715 (48.36%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3501 (52.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e214 (26.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.03(0.77\u0026thinsp;~\u0026thinsp;1.38, p\u0026thinsp;\u0026lt;\u0026thinsp;.001)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRace\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMexican American\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e833 (7.90%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e738 (11%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e95 (11.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNon-Hispanic White\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2671 (63.88%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2266 (33.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e405 (49.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.48(1.13\u0026thinsp;~\u0026thinsp;1.95, p\u0026thinsp;=\u0026thinsp;0.007)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNon-Hispanic Black\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2022 (11.21%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1874 (27.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e148 (18.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.69(0.48\u0026thinsp;~\u0026thinsp;0.99, p\u0026thinsp;=\u0026thinsp;0.043)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2006 (17.02%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1837 (27.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e169 (20.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.93 (0.67\u0026thinsp;~\u0026thinsp;1.29, p\u0026thinsp;=\u0026thinsp;0.652)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEducation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1312 (9.95%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1173 (17.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e139 (17%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6220 (90.05%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5542 (82.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e678 (83%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.03 (0.85\u0026thinsp;~\u0026thinsp;1.25, p\u0026thinsp;=\u0026thinsp;0.854)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMarital\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3160 (37.145)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2822 (42%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e338 (41.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4372 (62.86%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3893 (58%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e479 (58.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.08 (0.82\u0026thinsp;~\u0026thinsp;1.41, p\u0026thinsp;=\u0026thinsp;.0.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePIR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5344 (78.54%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4744 (70.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e600 (73.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2188 (21.46%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1971 (29.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e217 (26.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.80 (0.60\u0026thinsp;~\u0026thinsp;1.06, p\u0026thinsp;=\u0026thinsp;0.122)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHTN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4625 (67.17%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4291 (63.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e334 (40.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2907 (32.83%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2424 (36.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e483 (59.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.65 (2.04\u0026thinsp;~\u0026thinsp;3.44, p\u0026thinsp;\u0026lt;\u0026thinsp;.001)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSBP,M (Q₁, Q₃)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e123.00(113,135)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e123.00(113.00,134.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e125.00(115.00,138.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.01(1.00\u0026thinsp;~\u0026thinsp;1.02, p\u0026thinsp;=\u0026thinsp;.0.001)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDBP,M (Q₁, Q₃)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e76.00(69,83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75.000(68.00,83.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76.00(70.00,84.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00 (0.99\u0026thinsp;~\u0026thinsp;1.01, p\u0026thinsp;=\u0026thinsp;0.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGallstone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6751 (89.22%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6521 (97.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e230 (28.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e781 (10.78%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e194 (2.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e587 (71.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e108.41(77.64\u0026thinsp;~\u0026thinsp;151.37, p\u0026thinsp;\u0026lt;\u0026thinsp;.001)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eObesity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4289 (57.39%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3978 (59.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e311 (38.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3243 (42.61%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2737 (40.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e506 (61.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.12 (1.69\u0026thinsp;~\u0026thinsp;2.65, p\u0026thinsp;\u0026lt;\u0026thinsp;.001)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh cholesterol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4508 (60.43%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4130 (61.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e378 (46.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3024 (39.57%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2585 (38.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e439 (53.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.85 (1.52\u0026thinsp;~\u0026thinsp;2.24,p\u0026thinsp;\u0026lt;\u0026thinsp;.001)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSmoke\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6143 (83.04%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5456 (81.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e687 (84.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1389 (16.96%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1259 (18.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e130 (15.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.85(0.64\u0026thinsp;~\u0026thinsp;1.12, p\u0026thinsp;=\u0026thinsp;0.251)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiabetes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5985 (84.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5452 (81.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e533 (65.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1547 (15.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1263 (18.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e284 (34.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.60 (1.95\u0026thinsp;~\u0026thinsp;3.47, p\u0026thinsp;\u0026lt;\u0026thinsp;.001)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eTable\u0026nbsp;\u003cspan\u003e1\u003c/span\u003e:Data of continuous variables are shown as survey-weighted mean (95% CI), P-value was calculated by survey-weighted linear regression. Data of categorical variables are shown as survey-weighted percentages (95% CI), P-value was calculated by survey-weighted Chi-square test.\u003c/p\u003e\n \u003cp\u003eSBP, Systolic Blood Pressure.DBP, Diastolic Blood Pressure\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\"\u003e\n \u003ch2\u003eLogistic regression results between HTN and gallbladder stones:\u003c/h2\u003e\n \u003cp\u003eTable\u0026nbsp;\u003cspan\u003e2\u003c/span\u003e presents the results of logistic regression analysis stratified by median age. When blood pressure was treated as a categorical variable, HTN was significantly associated with a higher risk of gallstone disease in individuals over the age of 48 (OR\u0026thinsp;=\u0026thinsp;1.39; 95% CI: 1.03, 1.88; P\u0026thinsp;=\u0026thinsp;0.033). This suggests that individuals with HTN in this age group had a 39% higher likelihood of undergoing cholecystectomy compared to those with normal blood pressure. However, in individuals aged\u0026thinsp;\u0026le;\u0026thinsp;48 years, no significant association was observed between HTN and gallstone disease risk (OR\u0026thinsp;=\u0026thinsp;1.21; 95% CI: 0.68, 2.17; P\u0026thinsp;=\u0026thinsp;0.480) \u003csup\u003e(Table 2)\u003c/sup\u003e.\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 2\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eLogistic regression analysis between HTN with Gallstone prevalence.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"11\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eModel1\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eModel2\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003eModel3\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOR (95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOR (95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eOR (95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge\u0026thinsp;\u0026le;\u0026thinsp;48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHTN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00 (Reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00 (Reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.00 (Reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.23 (1.74\u0026thinsp;~\u0026thinsp;2.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.66 (1.27\u0026thinsp;~\u0026thinsp;2.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.21(0.68\u0026thinsp;~\u0026thinsp;2.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.480\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge\u0026thinsp;\u0026gt;\u0026thinsp;48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHTN\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00 (Reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00 (Reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.00 (Reference)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.69 (1.27\u0026thinsp;~\u0026thinsp;2.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.64 (1.23\u0026thinsp;~\u0026thinsp;2.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e1.39(1.03\u0026thinsp;~\u0026thinsp;1.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.033\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"11\"\u003e\n \u003cp\u003eTable\u0026nbsp;\u003cspan\u003e2\u003c/span\u003e. Logistic regression analysis between HTN with Gallstone prevalence.OR: Odds Ratio, CI: Confidence Interval\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eModel1: Crude\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"8\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"7\"\u003e\n \u003cp\u003eModel2: Adjust: Age, Gender, Education, Marital, PIR, Race\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"4\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"9\"\u003e\n \u003cp\u003eModel3: Adjust: Age, Gender, Education, Marital, PIR, Race, High cholesterol, Obesity, Smoke, Diabetes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003cstrong\u003eAssociation Between Increased Systolic Blood Pressure and Later Age of First Cholecystectomy, and Dose-Response and Threshold Effect Analysis:\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eThe relationship between systolic blood pressure (SBP) and the age of first cholecystectomy was analyzed through a weighted multivariate linear regression model. In the fully adjusted Model 3, a significant association was observed between systolic blood pressure and age at first cholecystectomy (\u0026beta; = 0.19, 95% CI: 0.12, 0.26)\u003csup\u003e\u0026nbsp;(Table 3)\u003c/sup\u003e. Following covariate adjustments, each unit increase in systolic blood pressure was found to increase the age of first cholecystectomy by 0.19 years (95% CI: 0.12, 0.26). To further assess the relationship between SBP and age at first cholecystectomy, a generalized additive model and smooth curve fitting analysis were conducted. The analysis revealed a significant nonlinear relationship between SBP and age at first cholecystectomy (P \u0026lt; 0.05)\u003csup\u003e\u0026nbsp;(Figure 2)\u003c/sup\u003e. Additionally, it was noted that as SBP increased, the age at which U.S. adults underwent their first cholecystectomy increased accordingly. Using threshold effect analysis, a turning point at 170 mmHg was identified\u003csup\u003e\u0026nbsp;(Table 4)\u003c/sup\u003e. Before this turning point, a significant positive correlation was observed between SBP and age at first cholecystectomy (OR = 0.245; 95% CI: 0.187, 0.302). However, after the turning point, this correlation was no longer significant (OR=-0.179; 95% CI: -0.476, 0.119)\u0026nbsp;\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 3\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eThe weighted linear regression between systolic blood pressure and the age of first cholecystectomy.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"10\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eModel1\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eModel2\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003eModel3\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u0026beta; (95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u0026beta;(95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u0026beta; (95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSystolic blood pressure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.21 (0.15\u0026thinsp;~\u0026thinsp;0.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.21 (0.15\u0026thinsp;~\u0026thinsp;0.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.19 (0.12\u0026thinsp;~\u0026thinsp;0.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"9\"\u003e\n \u003cp\u003eTable\u0026nbsp;\u003cspan\u003e3\u003c/span\u003e. Weighted linear regression between systolic blood pressure and age at first gallbladder surgery.OR: Odds Ratio, CI: Confidence Interval\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"1\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eModel1: Crude\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"8\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"7\"\u003e\n \u003cp\u003eModel2: Adjust: Gender, Education, Marital, PIR, Race\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"10\"\u003e\n \u003cp\u003eModel3: Adjust: Gender, Education, Marital, PIR, High cholesterol, Gallstone, Obesity, Race, Smoke, Diabetes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 4\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eTwo-stage linear regression and log-likelihood ratio explaining the threshold effect analysis of systolic blood pressure with age at first gallbladder surgery.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"4\"\u003e\u003c/colgroup\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eSystolic blood pressure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eULR Test\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePLR Test\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLRT Test\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026beta;(95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026beta;(95%CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;170mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e0.207(0.157\u0026ndash;0.258,p\u0026thinsp;\u0026lt;\u0026thinsp;.001)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.245(0.187\u0026ndash;0.302,p\u0026thinsp;\u003cstrong\u003e\u0026lt;\u003c/strong\u003e\u0026thinsp;.001)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;170mmHg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.179(-0.476-0.119,p\u0026thinsp;=\u0026thinsp;0.240)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003cstrong\u003eULR\u003c/strong\u003e, univariate linear regression; \u003cstrong\u003ePLR\u003c/strong\u003e, piecewise linear regression; \u003cstrong\u003eLRT\u003c/strong\u003e, logarithmic likelihood ratio test, statistically significant: p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eSubgroup analyses:\u003c/h3\u003e\n\u003cp\u003eSubgroup analyses were conducted to evaluate the robustness of the association between HTN and gallbladder surgery and to examine the interactions among age, gender, gallstones, race, obesity, and diabetes mellitus status, demonstrating a stable positive association between HTN and gallbladder surgery occurrence, independently of these factors (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) \u003csup\u003e(Figure 3)\u003c/sup\u003e.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eNahum et al. \u003csup\u003e[25]\u003c/sup\u003e examined the relationship between gallstone disease and cardiovascular disease among 437 patients in Mexico and reported a significant association between HTN and gallstone disease (OR\u0026thinsp;=\u0026thinsp;2.55; 95% CI: 1.62\u0026ndash;4.03; P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). After adjusting for factors such as BMI, age, and alcohol intake, HTN was identified as an independent risk factor for gallstone disease (OR\u0026thinsp;=\u0026thinsp;1.26; 95% CI: 1.05\u0026ndash;1.50; P\u0026thinsp;=\u0026thinsp;0.01)\u003csup\u003e[26]\u003c/sup\u003e. In our study, the prevalence of gallstones was 10.78%. The results indicated that the prevalence of gallstones in the U.S. is lower than that reported in Norway (21.9%)\u003csup\u003e[27]\u003c/sup\u003e, France (13.9%)\u003csup\u003e[28]\u003c/sup\u003e, and Germany (19.7%)\u003csup\u003e[29]\u003c/sup\u003e, yet higher than that reported in Japan (3.2%)\u003csup\u003e[30]\u003c/sup\u003e. This discrepancy may stem from the American population's preference for fatty diets and an increase in health check-up frequency. Our study revealed an association between HTN and the risk of gallstones. After stratifying by age, it was found that HTN was significantly associated with gallstone disease in individuals older than 48 years (OR\u0026thinsp;=\u0026thinsp;1.39; 95% CI: 1.03, 1.88; P\u0026thinsp;=\u0026thinsp;0.033), indicating that hypertensive patients in this age group exhibited a 39% higher incidence of gallstones relative to individuals with normal blood pressure. However, in individuals aged\u0026thinsp;\u0026le;\u0026thinsp;48 years, HTN was not associated with gallstone disease risk (OR\u0026thinsp;=\u0026thinsp;1.21; 95% CI: 0.68, 2.17; P\u0026thinsp;=\u0026thinsp;0.480).\u003c/p\u003e \u003cp\u003eCurrently, there remains disagreement regarding the relationship between blood pressure and cholecystectomy. One cross-sectional study suggested no significant association between HTN and cholecystectomy\u003csup\u003e[31]\u003c/sup\u003e. However, a 2012 case-control study that included 798 subjects reported a significant correlation between HTN and cholecystectomy\u003csup\u003e[12]\u003c/sup\u003e. To our knowledge, this study is the first to analyze the relationship between blood pressure and the age at first cholecystectomy. It was found that systolic blood pressure was positively correlated with the age at first cholecystectomy (β\u0026thinsp;=\u0026thinsp;0.21, 95% CI: 0.12, 0.26). For the first time, smooth curve fitting and two-piece linear regression was employed to examine the nonlinear relationship between systolic blood pressure and age at first cholecystectomy, and a turning point was identified using threshold effect analysis. Before this turning point, a significant correlation was observed (OR\u0026thinsp;=\u0026thinsp;0.245; 95% CI: 0.187, 0.302), while after the turning point, the correlation was no longer significant (OR = -0.179; 95% CI: -0.476, 0.119). Furthermore, a stable positive correlation was observed between HTN and the occurrence of cholecystectomy through subgroup analyses, independently of age, gender, gallstone presence, race, obesity, and diabetes mellitus (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). These findings strongly support the significance of blood pressure as a predictive factor for cholecystectomy development. Therefore, when gallstone disease is present in a population, especially among older patients, monitoring blood pressure is critical for preventing surgery and facilitating early interventions.\u003c/p\u003e \u003cp\u003ePrevious studies have indicated that leptin levels are associated with blood pressure. Hypertensive patients exhibit higher serum leptin levels compared to healthy individuals\u003csup\u003e[32][33][34]\u003c/sup\u003e, and both diastolic and systolic blood pressure have shown significant positive correlations with leptin levels\u003csup\u003e[32][34]\u003c/sup\u003e. Leptin induces inflammation of the gallbladder wall by binding to leptin receptors located on the gallbladder wall[35][36]. Additionally, leptin affects fibroblasts, reducing the contractile function of the gallbladder wall, thereby increasing gallbladder volume and causing bile stasis, which ultimately leads to the formation of gallstones\u003csup\u003e[37]\u003c/sup\u003e. Furthermore, elevated leptin levels can result in hyperinsulinemia, leading the liver to produce cholesterol-saturated bile\u003csup\u003e[38]\u003c/sup\u003e. Leptin directly influences the composition of bile by increasing hydrophilic bile salts and decreasing hydrophobic bile salts, cycling bile acids, and intestinal cholesterol absorption, which contributes to stone formation\u003csup\u003e[39]\u003c/sup\u003e. The formation of gallstones can cause symptoms such as biliary colic, and the primary treatment for symptomatic gallstones remains cholecystectomy.\u003c/p\u003e \u003cp\u003eThe primary strength of this study lies in its large sample size. The NHANES database employs a complex weighted design, providing a more representative sample of the entire U.S. population, and data from NHANES from 2017 to 2020 were utilized. Additionally, NHANES collects data using standardized protocols by trained professionals, including standardized questionnaires, physical examinations, and laboratory tests for each participant. All blood samples are tested in the same laboratory using standardized protocols within the same time frame, significantly reducing potential biases due to methodological differences. Furthermore, subgroup and interaction analyses were conducted to explore the impact of potential confounding factors on the association between HTN and cholecystectomy, enhancing statistical power. However, our study has several limitations. First, being a cross-sectional study, it does not facilitate the determination of causal relationships between HTN and cholecystectomy. Second, all survey data were based on self-reported questionnaires, which may be subject to recall bias.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThis study revealed an association between modifiable risk factors, particularly blood pressure, and gallstone disease in individuals aged over 48 years and the age at which they undergo their first cholecystectomy. It highlights the necessity of monitoring and managing blood pressure among middle-aged and younger individuals to help reduce the incidence of cholecystectomy. Although the causal relationship between these factors remains unclear, these findings warrant further investigation.\u003c/p\u003e "},{"header":"Abbreviations","content":"\u003cp\u003eNHANES, National Health and Nutrition Examination Survey\u003c/p\u003e\n\u003cp\u003eNCHS, National Center for Health Statistics\u003c/p\u003e\n\u003cp\u003eMECs, Mobile Examination Centers\u003c/p\u003e\n\u003cp\u003eHTN, Hypertension\u003c/p\u003e\n\u003cp\u003eSBP, Systolic Blood Pressure\u003c/p\u003e\n\u003cp\u003eDBP, Diastolic Blood Pressure\u003c/p\u003e\n\u003cp\u003ePIR, Poverty-to-Income Ratio\u003c/p\u003e\n\u003cp\u003eHHS, Health and Human Services\u003c/p\u003e\n\u003cp\u003eSEQN, Survey Participant Identification Number\u003c/p\u003e\n\u003cp\u003eGAM, Generalized Additive Model\u003c/p\u003e\n\u003cp\u003eULR\u003cstrong\u003e,\u003c/strong\u003e Univariate Linear Regression\u003c/p\u003e\n\u003cp\u003ePLR\u003cstrong\u003e,\u003c/strong\u003e Piecewise Linear Regression\u003c/p\u003e\n\u003cp\u003eLRT\u003cstrong\u003e,\u003c/strong\u003e Logarithmic Likelihood Ratio\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBMI, Body Mass Index\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate:\u003c/p\u003e\n\u003cp\u003eNHANES was approved by the Ethical Review Board of the National Center for Health Statistics (NCHS). Informed consent was obtained from all participants.\u003c/p\u003e\n\u003cp\u003eConsent for publication:\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials:\u003c/p\u003e\n\u003cp\u003eThe data used in this study are publically available in the NHANES database (www.cdc.gov/nchs/nhanes).\u003c/p\u003e\n\u003cp\u003eCompeting interests:\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003eFunding:\u003c/p\u003e\n\u003cp\u003eThis research was funded by the Jilin Provincial Department of Science and Technology( grant number 20210203191SF)\u003c/p\u003e\n\u003cp\u003eAuthors\u0026apos; contributions:\u003c/p\u003e\n\u003cp\u003eYue Zhang:\u0026nbsp;Writing \u0026ndash; review \u0026amp; editing, Writing \u0026ndash; original draft, Conceptualization.Ruifeng Duan：\u0026nbsp;Writing \u0026ndash; review \u0026amp; editing. Xin Chen：\u0026nbsp;Writing \u0026ndash; review \u0026amp; editing.. lijuan Wei：\u0026nbsp;Writing \u0026ndash; review \u0026amp; editing\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAcknowledgements:\u003c/p\u003e\n\u003cp\u003eThe authors express gratitude to all participants and investigators of the NHANES.\u003c/p\u003e\n\u003cp\u003eAuthorship contribution statement\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKim SS, Donahue TR. Laparoscopic Cholecystectomy. JAMA. 2018 May 1;319(17):1834. doi: 10.1001/jama.2018.3438. PMID: 29715356.\u003c/li\u003e\n\u003cli\u003eLammert F, Gurusamy K, Ko CW, Miquel JF, M\u0026eacute;ndez-S\u0026aacute;nchez N, Portincasa P, van Erpecum KJ, van Laarhoven CJ, Wang DQ. Gallstones. Nat Rev Dis Primers. 2016 Apr 28;2:16024. doi: 10.1038/nrdp.2016.24. PMID: 27121416.\u003c/li\u003e\n\u003cli\u003eFriedman GD. Natural history of asymptomatic and symptomatic gallstones. 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PMID: 12114517.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Gallstones, Cholecystectomy, Hypertension","lastPublishedDoi":"10.21203/rs.3.rs-5261602/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5261602/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eTo assess the association between hypertension( HTN ) and the prevalence of gallstones and the age at first cholecystectomy in U.S. adults.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eData were extracted from the National Health and Nutrition Examination Survey (NHANES) database from 2017 to 2020. Weighted logistic regression analysis, weighted linear regression, weighted subgroup analysis, generalized additive models, smooth fitting curves, and two-piece linear regression models were utilized to evaluate the relationship between HTN, gallstone prevalence, and the age of first cholecystectomy.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 7,532 participants above 20 years were included in the study. Among them, 817 individuals self-reported a history of cholecystectomy, and 781 individuals self-reported a history of gallstones. After adjusting for age, gender, race, education level, smoking status, marital status,, diabetes, and hypercholesterolemia, HTN was significantly associated with gallstones in individuals aged 48 years and older (OR\u0026thinsp;=\u0026thinsp;1.39, 95% CI: 1.03, 1.88). Systolic blood pressure was positively related to the age of first cholecystectomy (β\u0026thinsp;=\u0026thinsp;0.19, 95% CI: 0.12, 0.26), and a nonlinear relationship was observed with a threshold effect at 170 mmHg.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eAn association was identified between blood pressure and the prevalence of gallstones in individuals aged 42 years and older. Systolic blood pressure was positively associated with the age of the first cholecystectomy. Although causality cannot be established, these findings may aid in identifying early risk groups for gallstone disease and first cholecystectomy, improving risk stratification, and reducing screening costs.\u003c/p\u003e","manuscriptTitle":"The Association Between Blood Pressure and Gallstones and the Age of First Cholecystectomy in U.S. Adults: Results from a Cross-Sectional Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-09 08:27:01","doi":"10.21203/rs.3.rs-5261602/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-11-22T03:23:58+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-20T03:04:06+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"40175015190139875149839683994025896213","date":"2024-11-20T02:52:13+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-18T09:52:08+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-16T16:22:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"325141591717232582257705375360840395491","date":"2024-11-16T16:11:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"118934305403692512596132362770569999133","date":"2024-11-13T22:43:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"225798428698761819066786905158683071413","date":"2024-11-11T21:00:24+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-11-09T17:52:06+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-10-24T06:45:41+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-10-24T05:56:57+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-10-14T23:15:53+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Gastroenterology","date":"2024-10-14T13:37:27+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-gastroenterology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmge","sideBox":"Learn more about [BMC Gastroenterology](http://bmcgastroenterol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmge/default.aspx","title":"BMC Gastroenterology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0d345544-b18c-4109-b3ef-aa996fac323f","owner":[],"postedDate":"December 9th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-02-10T16:04:46+00:00","versionOfRecord":{"articleIdentity":"rs-5261602","link":"https://doi.org/10.1186/s12876-025-03641-4","journal":{"identity":"bmc-gastroenterology","isVorOnly":false,"title":"BMC Gastroenterology"},"publishedOn":"2025-02-07 15:58:04","publishedOnDateReadable":"February 7th, 2025"},"versionCreatedAt":"2024-12-09 08:27:01","video":"","vorDoi":"10.1186/s12876-025-03641-4","vorDoiUrl":"https://doi.org/10.1186/s12876-025-03641-4","workflowStages":[]},"version":"v1","identity":"rs-5261602","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5261602","identity":"rs-5261602","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}