ArticleHypertension (Dallas, Tex. : 1979)2026
Antihypertensive Treatment and Risk of Metabolic Associated Fatty Liver Disease: A Drug-Target Mendelian Randomization.
Yifan Hu, Karl Smith-Byrne, Zeinab Bidel, Xiong Xiao, Xing Zhao, Abbas Dehghan, Dexter Canoy, Malgorzata Wamil, Nathalie Conrad, Shishir Rao and 11 more
Abstract read
In one paragraphArticle in Hypertension (Dallas, Tex. : 1979), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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2 · The registryThe trial behind it
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4 · The recordCorrections and comments
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5 · Who and what moneyAuthors and funding
21 authors.
Yifan HuSichuan Provincial Center for Mental Health, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China (Y.H.).
Karl Smith-ByrneCancer Epidemiology Unit, Nuffield Department of Population Health (K.S.B.), University of Oxford, United Kingdom.ORCID 0000-0002-1932-7463 Zeinab BidelDeep Medicine, Nuffield Department of Women's and Reproductive Health, Medical Sciences Division (Y.H., Z.B., M. Wamil, N.C., S.R., B.O.P., Q.Y., M. Woodward, K.R., M.N.), University of Oxford, United Kingdom.ORCID 0000-0002-8852-1622 Xiong XiaoDepartment of Epidemiology and Health Statistics, West China School of Public Health, Sichuan University, Chengdu, China (Y.H., X.X., X.Z.).ORCID 0000-0003-4471-7946 Xing ZhaoDepartment of Epidemiology and Health Statistics, West China School of Public Health, Sichuan University, Chengdu, China (Y.H., X.X., X.Z.).ORCID 0000-0001-5713-3603 Abbas DehghanDepartment of Epidemiology and Biostatistics (A.D., D.G.), Imperial College London, United Kingdom.ORCID 0000-0001-6403-016X Malgorzata WamilDeep Medicine, Nuffield Department of Women's and Reproductive Health, Medical Sciences Division (Y.H., Z.B., M. Wamil, N.C., S.R., B.O.P., Q.Y., M. Woodward, K.R., M.N.), University of Oxford, United Kingdom.ORCID 0000-0002-5361-2532 Nathalie ConradDeep Medicine, Nuffield Department of Women's and Reproductive Health, Medical Sciences Division (Y.H., Z.B., M. Wamil, N.C., S.R., B.O.P., Q.Y., M. Woodward, K.R., M.N.), University of Oxford, United Kingdom.ORCID 0000-0001-5027-5481 Shishir RaoDeep Medicine, Nuffield Department of Women's and Reproductive Health, Medical Sciences Division (Y.H., Z.B., M. Wamil, N.C., S.R., B.O.P., Q.Y., M. Woodward, K.R., M.N.), University of Oxford, United Kingdom.ORCID 0000-0001-7331-9416 Ben Omega PetrazziniDeep Medicine, Nuffield Department of Women's and Reproductive Health, Medical Sciences Division (Y.H., Z.B., M. Wamil, N.C., S.R., B.O.P., Q.Y., M. Woodward, K.R., M.N.), University of Oxford, United Kingdom.ORCID 0000-0001-9789-9371 Qianqian YangDeep Medicine, Nuffield Department of Women's and Reproductive Health, Medical Sciences Division (Y.H., Z.B., M. Wamil, N.C., S.R., B.O.P., Q.Y., M. Woodward, K.R., M.N.), University of Oxford, United Kingdom.
Dipender GillDepartment of Epidemiology and Biostatistics (A.D., D.G.), Imperial College London, United Kingdom.ORCID 0000-0001-7312-7078 Venexia M WalkerMedical Research Council Integrative Epidemiology Unit, University of Bristol, United Kingdom (V.M.W., G.D.S.).ORCID 0000-0001-5064-446X Reza MalekzadehLiver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Iran (R.M.).
Mark WoodwardDeep Medicine, Nuffield Department of Women's and Reproductive Health, Medical Sciences Division (Y.H., Z.B., M. Wamil, N.C., S.R., B.O.P., Q.Y., M. Woodward, K.R., M.N.), University of Oxford, United Kingdom.ORCID 0000-0001-9800-5296 George Davey SmithMedical Research Council Integrative Epidemiology Unit, University of Bristol, United Kingdom (V.M.W., G.D.S.).ORCID 0000-0002-1407-8314 Kazem RahimiDeep Medicine, Nuffield Department of Women's and Reproductive Health, Medical Sciences Division (Y.H., Z.B., M. Wamil, N.C., S.R., B.O.P., Q.Y., M. Woodward, K.R., M.N.), University of Oxford, United Kingdom.ORCID 0000-0002-4807-4610 Milad NazarzadehDeep Medicine, Nuffield Department of Women's and Reproductive Health, Medical Sciences Division (Y.H., Z.B., M. Wamil, N.C., S.R., B.O.P., Q.Y., M. Woodward, K.R., M.N.), University of Oxford, United Kingdom.ORCID 0000-0002-0576-8874 Funding
British Heart Foundation FS/IPBSRF/22/27060Wellcome Trust
6 · The paper itselfAbstract
backgroundMetabolic dysfunction-associated fatty liver disease, conventionally known as nonalcoholic fatty liver disease (NAFLD), affects over a quarter of the global population and lacks approved pharmacological treatments. We investigated whether elevated blood pressure (BP) is a modifiable risk factor for NAFLD and whether antihypertensive drugs could be repurposed for prevention.
methodsWe conducted whole-genome Mendelian randomization using genetic data from over 1 million individuals of European ancestry to assess systolic BP as a risk factor for NAFLD. Drug-target Mendelian randomization was used to investigate the class-specific effects of antihypertensive agents, including renin-angiotensin system inhibitors, β-blockers, calcium channel blockers, and diuretics. NAFLD was defined by persistently elevated alanine aminotransferase levels after excluding alternative liver diseases and alcohol use disorders. Genetic estimates were compared with individual-participant meta-analyses of randomized controlled trials (n=358 636) and summary data from 104 antihypertensive drug trials (≈500 000 participants), using coronary heart disease as a positive control.
resultsA genetically proxied 5-mm Hg reduction in systolic BP was associated with an 8% lower risk of NAFLD (odds ratio, 0.92 [95% CI, 0.90-0.94]). Renin-angiotensin system inhibition was associated with a 27% lower risk (odds ratio, 0.73 [95% CI, 0.62-0.85]), whereas other drug classes showed no substantial associations. For coronary heart disease, effects were directionally consistent across classes in genetic and trial analyses.
conclusionsGenetically lower systolic BP is associated with reduced NAFLD risk, with renin-angiotensin system inhibition showing the most favorable association. These findings support BP lowering, particularly renin-angiotensin system inhibition, as a potential preventive strategy warranting dedicated randomized trials.
Indexed as
Antihypertensive AgentsBlood PressureHypertensionNon-alcoholic Fatty Liver DiseaseAngiotensin-Converting Enzyme InhibitorsCalcium Channel BlockersGenome-Wide Association StudyHumansMendelian Randomization AnalysisRenin-Angiotensin SystemRisk FactorsAngiotensin-Converting Enzyme InhibitorsAntihypertensive AgentsCalcium Channel Blockersantihypertensive agentsblood pressurecoronary diseasehypertensionmendelian randomization analysisnon-alcoholic fatty liver diseaserenin-angiotensin system
Identifiers
PMID42755691
PMCPMC7619608
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