{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T19:57:40Z","timestamp":1789934260000,"version":"4.0.1"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T00:00:00Z","timestamp":1661385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>It is unclear whether more severe non\u2013alcoholic fatty liver disease (NAFLD) combined with prehypertension or hypertension is associated with a higher risk of cardiovascular events (CVEs). To evaluate the relationship between the severity of NAFLD and CVEs among patients with prehypertension or hypertension.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this prospective community\u2013based Kailuan cohort, participants without cardiovascular disease and alcohol abuse, or other liver diseases were enrolled. NAFLD was diagnosed by abdominal ultrasonography. Prehypertension was defined as systolic blood pressure (BP) of 120\u2013139 mmHg or diastolic BP of 80\u201389 mmHg. Participants with NAFLD were divided into mild, moderate, and severe subgroups. Follow\u2013up for CVEs including myocardial infarction, hemorrhagic stroke, and ischemic stroke. The Cox proportional hazards model was used to estimate hazard ratios and 95% CIs of CVEs according to the severity of NAFLD and hypertensive statutes. The C-statistic was used to evaluate the efficiency of models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 71926 participants (mean [SD] age, 51.83 [12.72] years, 53794 [74.79%] men, and 18132 [25.21%] women) were enrolled in this study, 6,045 CVEs occurred during a median of 13.02 (0.65) years of follow\u2013up. Compared with participants without NAFLD, the hazard ratios of CVEs for patients with mild, moderate, and severe NAFLD were 1.143 (95% CI 1.071\u20131.221, <jats:italic>P<\/jats:italic> &amp;lt; 0.001), 1.218 (95% CI 1.071\u20131.221, <jats:italic>P<\/jats:italic> &amp;lt; 0.001), and 1.367 (95% CI 1.172\u20131.595, <jats:italic>P<\/jats:italic> &amp;lt; 0.001), respectively. Moreover, participants with prehypertension plus moderate\/severe NAFLD and those with hypertension plus moderate\/severe NAFLD had 1.558\u2013fold (95% CI 1.293\u20131.877, <jats:italic>P<\/jats:italic> &amp;lt; 0.001) and 2.357\u2013fold (95% CI 2.063\u20132.691, <jats:italic>P<\/jats:italic> &amp;lt; 0.001) higher risks of CVEs, respectively, compared with those with normal BP and no NAFLD. Adding a combination of NAFLD and BP status to the crude Cox model increased the C\u2013statistic by 0.0130 (0.0115\u20130.0158, <jats:italic>P<\/jats:italic> &amp;lt; 0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings indicated that the increased cardiovascular risk with elevated BP is largely driven by the coexistence of moderate\/severe NAFLD, suggesting that the severity of NAFLD may help further stratify patients with prehypertension and hypertension.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2022.942647","type":"journal-article","created":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T11:55:48Z","timestamp":1661428548000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Severity of Nonalcoholic Fatty Liver Disease is Associated With Cardiovascular Outcomes in Patients With Prehypertension or Hypertension: A Community\u2013Based Cohort Study"],"prefix":"10.3389","volume":"13","author":[{"given":"Qi\u2013Rui","family":"Song","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo\u2013Lin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian-Hui","family":"Ling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian-Nan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui-Xue","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo-Hua","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shou\u2013Ling","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mu-Lei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1801585","DOI":"10.1002\/advs.201801585","article-title":"Insights Into the Epidemiology, Pathogenesis, and Therapeutics of Nonalcoholic Fatty Liver Diseases","volume":"6","author":"Yu","year":"2019","journal-title":"Adv Sci (Weinh)"},{"key":"B2","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global Epidemiology of Nonalcoholic Fatty Liver Disease-Meta-Analytic Assessment of Prevalence, Incidence, and Outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29367","article-title":"The Diagnosis and Management of Nonalcoholic Fatty Liver Disease: Practice Guidance From the American Association for the Study of Liver Diseases","volume":"67","author":"Chalasani","year":"2018","journal-title":"Hepatol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27368","article-title":"Fibrosis Stage is the Strongest Predictor for Disease-Specific Mortality in NAFLD After Up to 33 Years of Follow-Up","volume":"61","author":"Ekstedt","year":"2015","journal-title":"Hepatol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.09.021","article-title":"Hypertension, Diabetes, Atherosclerosis and NASH: Cause or Consequence","volume":"68","author":"Lonardo","year":"2018","journal-title":"J Hepatol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"182","DOI":"10.11909\/j.issn.1671-5411.2019.03.014","article-title":"2018 Chinese Guidelines for Prevention and Treatment of Hypertension-A Report of the Revision Committee of Chinese Guidelines for Prevention and Treatment of Hypertension","volume":"16","year":"2019","journal-title":"J Geriatr Cardiol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1038\/nrcardio.2015.17","article-title":"Prehypertension\u2013prevalence, Health Risks, and Management Strategies","volume":"12","author":"Egan","year":"2015","journal-title":"Nat Rev Cardiol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e32833a8b9f","article-title":"Prehypertension and the Risk for Cardiovascular Disease in the Japanese General Population: The Jichi Medical School Cohort Study","volume":"28","author":"Ishikawa","year":"2010","journal-title":"J Hypertens"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.656850","article-title":"Prehypertension and Cardiovascular Disease Risk in the Women's Health Initiative","volume":"115","author":"Hsia","year":"2007","journal-title":"Circulation"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/ajh.2011.78","article-title":"Combined Effect of High-Normal Blood Pressure and Low HDL Cholesterol on Mortality in an Elderly Korean Population: The South-West Seoul (SWS) Study","volume":"24","author":"Kim","year":"2011","journal-title":"Am J Hypertens"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e328359a9f7","article-title":"Long-Term Risk of BP Values Above Normal for Cardiovascular Mortality: A 24-Year Observation of Japanese Aged 30 to 92 Years","volume":"30","author":"Takashima","year":"2012","journal-title":"J Hypertens"},{"key":"B12","doi-asserted-by":"publisher","first-page":"323","DOI":"10.21037\/atm.2020.02.144","article-title":"Prehypertension and Risk for All-Cause and Cardiovascular Mortality by Diabetes Status: Results From the National Health and Nutrition Examination Surveys","volume":"8","author":"Huang","year":"2020","journal-title":"Ann Transl Med"},{"key":"B13","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/j.ahj.2013.10.023","article-title":"Association of All-Cause and Cardiovascular Mortality With Prehypertension: A Meta-Analysis","volume":"167","author":"Huang","year":"2014","journal-title":"Am Heart J"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1177\/1010539513483830","article-title":"The Clinical Investigation of Disparity of Nonalcoholic Fatty Liver Disease in a Chinese Occupational Population in Taipei, Taiwan: Experience at a Teaching Hospital","volume":"27","author":"Wang","year":"2015","journal-title":"Asia Pac J Public Health"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0b013e32834b8d52","article-title":"Nonalcoholic Fatty Liver Disease is Associated With Blood Pressure in Hypertensive and Nonhypertensive Individuals From the General Population With Normal Levels of Alanine Aminotransferase","volume":"23","author":"L\u00f3pez-Su\u00e1rez","year":"2011","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000001245","article-title":"Association Between MRI-Derived Hepatic Fat Fraction and Blood Pressure in Participants Without History of Cardiovascular Disease","volume":"35","author":"Lorbeer","year":"2017","journal-title":"J Hypertens"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000004293","article-title":"Association of Blood Pressure Level With Nonalcoholic Fatty Liver Disease in Nonhypertensive Population: Normal is Not the New Normal","volume":"95","author":"Qian","year":"2016","journal-title":"Med (Baltimore)"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.04.038","article-title":"Association of Age of Onset of Hypertension With Cardiovascular Diseases and Mortality","volume":"75","author":"Wang","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/1753-0407.12056","article-title":"Diagnosis and Management of non-Alcoholic Fatty Liver Disease and Related Metabolic Disorders: Consensus Statement From the Study Group of Liver and Metabolism, Chinese Society of Endocrinology","volume":"5","author":"Gao","year":"2013","journal-title":"J Diabetes"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/jhn.12674","article-title":"Prospective Study of Perceived Dietary Salt Intake and the Risk of non-Alcoholic Fatty Liver Disease","volume":"32","author":"Shen","year":"2019","journal-title":"J Hum Nutr Diet"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.120.030433","article-title":"Severity of Nonalcoholic Fatty Liver Disease and Risk of Future Ischemic Stroke Events","volume":"52","author":"Xu","year":"2021","journal-title":"Stroke"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.20.10.1407","article-title":"Stroke\u20131989. Recommendations on Stroke Prevention, Diagnosis, and Therapy. Report of the WHO Task Force on Stroke and Other Cerebrovascular Disorders","volume":"20","year":"1989","journal-title":"Stroke"},{"key":"B23","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1161\/01.CIR.90.1.583","article-title":"Myocardial Infarction and Coronary Deaths in the World Health Organization MONICA Project. Registration Procedures, Event Rates, and Case-Fatality Rates in 38 Populations From 21 Countries in Four Continents","volume":"90","author":"Tunstall-Pedoe","year":"1994","journal-title":"Circulation"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A New Equation to Estimate Glomerular Filtration Rate","volume":"150","author":"Levey","year":"2009","journal-title":"Ann Intern Med"},{"key":"B25","doi-asserted-by":"publisher","first-page":"101215","DOI":"10.1016\/j.diabet.2020.101215","article-title":"NAFLD, and Cardiovascular and Cardiac Diseases: Factors Influencing Risk, Prediction and Treatment","volume":"47","author":"Targher","year":"2021","journal-title":"Diabetes Metab"},{"key":"B26","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1016\/j.jhep.2016.05.013","article-title":"Non-Alcoholic Fatty Liver Disease and Risk of Incident Cardiovascular Disease: A Meta-Analysis","volume":"65","author":"Targher","year":"2016","journal-title":"J Hepatol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-320622","article-title":"NAFLD and Increased Risk of Cardiovascular Disease: Clinical Associations, Pathophysiological Mechanisms and Pharmacological Implications","volume":"69","author":"Targher","year":"2020","journal-title":"Gut"},{"key":"B28","doi-asserted-by":"publisher","first-page":"2138","DOI":"10.1016\/j.cgh.2020.12.022","article-title":"Metabolic Dysfunction-Associated Fatty Liver Disease and Incident Cardiovascular Disease Risk: A Nationwide Cohort Study","volume":"19","author":"Lee","year":"2021","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/hpv156","article-title":"Prehypertension is Associated With Abnormalities of Cardiac Structure and Function in the Atherosclerosis Risk in Communities Study","volume":"29","author":"Santos","year":"2016","journal-title":"Am J Hypertens"},{"key":"B30","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1097\/HJH.0b013e328351d380","article-title":"Impact of Lower Range of Prehypertension on Cardiovascular Events in a General Population: The Hisayama Study","volume":"30","author":"Fukuhara","year":"2012","journal-title":"J Hypertens"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2017-312850","article-title":"Longitudinal Change in Blood Pressure is Associated With Cardiovascular Disease Mortality in a Chinese Cohort","volume":"104","author":"Fan","year":"2018","journal-title":"Heart"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/j.1076-7460.2005.03809.x","article-title":"JNC 7 Category and Risk of Cardiovascular Death in Men: Are There Differences by Age","volume":"14","author":"Bowman","year":"2005","journal-title":"Am J Geriatr Cardiol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000002191","article-title":"Prehypertension and Risk of Cardiovascular Diseases: A Meta-Analysis of 47 Cohort Studies","volume":"37","author":"Han","year":"2019","journal-title":"J Hypertens"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-013-0403-y","article-title":"Association Between Pre-Hypertension and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Prospective Studies","volume":"15","author":"Guo","year":"2013","journal-title":"Curr Hypertens Rep"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.119.13419","article-title":"Nonalcoholic Fatty Liver Disease: An Emerging Driver of Hypertension","volume":"75","author":"Zhao","year":"2020","journal-title":"Hypertension"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.1016\/j.cgh.2009.06.007","article-title":"Independent Predictors of Fibrosis in Patients With Nonalcoholic Fatty Liver Disease","volume":"7","author":"Hossain","year":"2009","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2009.01988.x","article-title":"Association Between Angiotensin II Type 1 Receptor Polymorphisms and the Occurrence of Nonalcoholic Fatty Liver Disease","volume":"29","author":"Yoneda","year":"2009","journal-title":"Liver Int"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0163069","article-title":"Renin-Angiotensin System Inhibitors, Type 2 Diabetes and Fibrosis Progression: An Observational Study in Patients With Nonalcoholic Fatty Liver Disease","volume":"11","author":"Pelusi","year":"2016","journal-title":"PLoS One"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2016.145","article-title":"The Impact of Insulin Resistance on the Kidney and Vasculature","volume":"12","author":"Artunc","year":"2016","journal-title":"Nat Rev Nephrol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000000532","article-title":"Blood Pressure is Associated With the Presence and Severity of Nonalcoholic Fatty Liver Disease Across the Spectrum of Cardiometabolic Risk","volume":"33","author":"Aneni","year":"2015","journal-title":"J Hypertens"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.305200","article-title":"Nonalcoholic Fatty Liver Disease and Vascular Function: Cross-Sectional Analysis in the Framingham Heart Study","volume":"35","author":"Long","year":"2015","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.09.022","article-title":"Bi-Directional Analysis Between Fatty Liver and Cardiovascular Disease Risk Factors","volume":"66","author":"Ma","year":"2017","journal-title":"J Hepatol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.01.009","article-title":"Development of New Fatty Liver, or Resolution of Existing Fatty Liver, Over Five Years of Follow-Up, and Risk of Incident Hypertension","volume":"60","author":"Sung","year":"2014","journal-title":"J Hepatol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000000842","article-title":"Increased Levels of Systolic Blood Pressure Within the Normal Range are Associated With Significantly Elevated Risks of Nonalcoholic Fatty Liver Disease","volume":"94","author":"Wu","year":"2015","journal-title":"Med (Baltimore)"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2014.29.7.973","article-title":"Clinical Significance of non-Alcoholic Fatty Liver Disease as a Risk Factor for Prehypertension","volume":"29","author":"Ryoo","year":"2014","journal-title":"J Korean Med Sci"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.12643","article-title":"Clinical Association Between non-Alcoholic Fatty Liver Disease and the Development of Hypertension","volume":"29","author":"Ryoo","year":"2014","journal-title":"J Gastroenterol Hepatol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2015-008204","article-title":"Identification of Reciprocal Causality Between non-Alcoholic Fatty Liver Disease and Metabolic Syndrome by a Simplified Bayesian Network in a Chinese Population","volume":"5","author":"Zhang","year":"2015","journal-title":"BMJ Open"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.942647\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T11:55:52Z","timestamp":1661428552000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.942647\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,25]]},"references-count":47,"alternative-id":["10.3389\/fendo.2022.942647"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.942647","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,25]]},"article-number":"942647"}}