{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T04:37:01Z","timestamp":1777523821796,"version":"3.51.4"},"reference-count":43,"publisher":"Impact Journals, LLC","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging"],"DOI":"10.18632\/aging.205775","type":"journal-article","created":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T14:59:16Z","timestamp":1714143556000},"source":"Crossref","is-referenced-by-count":1,"title":["Causal association of metformin treatment with diverse cardiovascular diseases: a Mendelian randomization analysis"],"prefix":"10.18632","author":[{"given":"Kaiyuan","family":"Li","sequence":"first","affiliation":[{"name":"Graduate School of Dalian Medical University, Dalian Medical University, Dalian, China"},{"name":"Department of Cardiology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital of Nanchang University, Nanchang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Ye","sequence":"additional","affiliation":[{"name":"Graduate School of Dalian Medical University, Dalian Medical University, Dalian, China"},{"name":"Department of Cardiology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Central Hospital Affiliated to Shandong First Medical University, Jinan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Zhu","sequence":"additional","affiliation":[{"name":"Graduate School of Dalian Medical University, Dalian Medical University, Dalian, China"},{"name":"Department of Cardiology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"7892","published-online":{"date-parts":[[2024,4,26]]},"reference":[{"key":"1","doi-asserted-by":"publisher","first-page":"e67","DOI":"10.1161\/CIR.0000000000000558","article-title":"Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association.","volume":"13","author":"Fornage","year":"2018","journal-title":"Circulation"},{"key":"2","doi-asserted-by":"publisher","first-page":"3153","DOI":"10.1016\/j.jacc.2018.11.005","article-title":"Use of Risk Assessment Tools to Guide Decision-Making in the Primary Prevention of Atherosclerotic Cardiovascular Disease: A Special Report From the American Heart Association and American College of Cardiology.","volume":"7","author":"Blumenthal","year":"2019","journal-title":"J Am Coll Cardiol"},{"key":"3","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.2337\/dc06-2558","article-title":"Incidence of coronary heart disease in type 2 diabetic men and women: impact of microvascular complications, treatment, and geographic location.","volume":"3","author":"Ferrannini","year":"2007","journal-title":"Diabetes Care"},{"key":"4","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/s12933-019-0860-y","article-title":"Metformin in patients with and without diabetes: a paradigm shift in cardiovascular disease management.","volume":"1","author":"Fang","year":"2019","journal-title":"Cardiovasc Diabetol"},{"key":"5","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s12933-019-0980-4","article-title":"Sodium-glucose cotransporter 2 inhibitor Dapagliflozin attenuates diabetic cardiomyopathy.","volume":"1","author":"Arad","year":"2020","journal-title":"Cardiovasc Diabetol"},{"key":"6","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1186\/s12916-022-02485-z","article-title":"Dapagliflozin attenuates diabetes-induced diastolic dysfunction and cardiac fibrosis by regulating SGK1 signaling.","volume":"2","author":"Park","year":"2022","journal-title":"BMC Med"},{"key":"7","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1007\/s40256-021-00503-8","article-title":"Dapagliflozin: A Review in Symptomatic Heart Failure with Reduced Ejection Fraction.","volume":"2","author":"Blair","year":"2021","journal-title":"Am J Cardiovasc Drugs"},{"key":"8","doi-asserted-by":"publisher","first-page":"191","DOI":"10.3389\/fendo.2020.00191","article-title":"Metformin and Its Benefits for Various Diseases.","volume":"1","author":"Guo","year":"2020","journal-title":"Front Endocrinol (Lausanne)"},{"key":"9","doi-asserted-by":"publisher","first-page":"1566","DOI":"10.1007\/s00125-017-4318-z","article-title":"Metformin: historical overview.","volume":"6","author":"Bailey","year":"2017","journal-title":"Diabetologia"},{"key":"10","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1007\/s00125-017-4342-z","article-title":"The mechanisms of action of metformin.","volume":"6","author":"Pearson","year":"2017","journal-title":"Diabetologia"},{"key":"11","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1016\/S2213-8587(14)70088-9","article-title":"Intensified insulin-based glycaemic control after myocardial infarction: mortality during 20 year follow-up of the randomised Diabetes Mellitus Insulin Glucose Infusion in Acute Myocardial Infarction (DIGAMI 1) trial.","volume":"2","author":"Norhammar","year":"2014","journal-title":"Lancet Diabetes Endocrinol"},{"key":"12","doi-asserted-by":"publisher","first-page":"1620","DOI":"10.1007\/s00125-017-4337-9","article-title":"Impact of metformin on cardiovascular disease: a meta-analysis of randomised trials among people with type 2 diabetes.","volume":"6","author":"Irving","year":"2017","journal-title":"Diabetologia"},{"key":"13","doi-asserted-by":"publisher","first-page":"2349","DOI":"10.1007\/s00125-020-05243-z","article-title":"Evaluating the impact of AMPK activation, a target of metformin, on risk of cardiovascular diseases and cancer in the UK Biobank: a Mendelian randomisation study.","volume":"6","author":"Au Yeung","year":"2020","journal-title":"Diabetologia"},{"key":"14","doi-asserted-by":"publisher","first-page":"1664","DOI":"10.1007\/s00125-022-05743-0","article-title":"Evaluating the efficacy and mechanism of metformin targets on reducing Alzheimer's disease risk in the general population: a Mendelian randomisation study.","volume":"6","author":"Ning","year":"2022","journal-title":"Diabetologia"},{"key":"15","doi-asserted-by":"publisher","first-page":"3253","DOI":"10.1681\/ASN.2016010098","article-title":"Mendelian Randomization as an Approach to Assess Causality Using Observational Data.","volume":"2","author":"K\u00f6ttgen","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"16","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1186\/s12885-023-11383-3","article-title":"Causal associations between gut microbiota and urological tumors: a two-sample mendelian randomization study.","volume":"2","author":"Hao","year":"2023","journal-title":"BMC Cancer"},{"key":"17","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1093\/ije\/dyr036","article-title":"Avoiding bias from weak instruments in Mendelian randomization studies.","volume":"4","author":"Thompson","year":"2011","journal-title":"Int J Epidemiol"},{"key":"18","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/nature14177","article-title":"Genetic studies of body mass index yield new insights for obesity biology.","volume":"51","author":"Fall","year":"2015","journal-title":"Nature"},{"key":"19","doi-asserted-by":"publisher","first-page":"78","DOI":"10.3803\/EnM.2015.30.1.78","article-title":"Metformin-associated lactic acidosis: predisposing factors and outcome.","volume":"3","author":"Kim","year":"2015","journal-title":"Endocrinol Metab (Seoul)"},{"key":"20","doi-asserted-by":"publisher","first-page":"2461","DOI":"10.3390\/jcm12072461","article-title":"Metformin Treatment Reduces the Incidence of Rheumatoid Arthritis: A Two-Sample Mendelian Randomized Study.","volume":"1","author":"Dang","year":"2023","journal-title":"J Clin Med"},{"key":"21","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1161\/01.HYP.0000221429.94591.72","article-title":"Metformin inhibits cytokine-induced nuclear factor kappaB activation via AMP-activated protein kinase activation in vascular endothelial cells.","volume":"4","author":"Kasai","year":"2006","journal-title":"Hypertension"},{"key":"22","doi-asserted-by":"publisher","first-page":"196","DOI":"10.2174\/1871530315666150316124019","article-title":"Metformin and Inflammation: Its Potential Beyond Glucose-lowering Effect.","volume":"1","author":"Saisho","year":"2015","journal-title":"Endocr Metab Immune Disord Drug Targets"},{"key":"23","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1038\/nm.4345","article-title":"Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug.","volume":"2","author":"Torrents","year":"2017","journal-title":"Nat Med"},{"key":"24","doi-asserted-by":"publisher","first-page":"54","DOI":"10.2337\/dc16-1324","article-title":"Metformin Is Associated With Higher Relative Abundance of Mucin-Degrading Akkermansia muciniphila and Several Short-Chain Fatty Acid-Producing Microbiota in the Gut.","volume":"4","author":"Escobar","year":"2017","journal-title":"Diabetes Care"},{"key":"25","doi-asserted-by":"publisher","first-page":"4886","DOI":"10.1111\/jcmm.17519","article-title":"Protective effects of metformin in various cardiovascular diseases: Clinical evidence and AMPK-dependent mechanisms.","volume":"2","author":"Yang","year":"2022","journal-title":"J Cell Mol Med"},{"key":"26","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1038\/s41574-021-00529-7","article-title":"GDF15: emerging biology and therapeutic applications for obesity and cardiometabolic disease.","volume":"1","author":"Steinberg","year":"2021","journal-title":"Nat Rev Endocrinol"},{"key":"27","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1111\/1753-0407.13334","article-title":"Metformin and growth differentiation factor 15 (GDF15) in type 2 diabetes mellitus: A hidden treasure.","volume":"1","author":"Batiha","year":"2022","journal-title":"J Diabetes"},{"key":"28","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1530\/JOE-13-0381","article-title":"Metformin enhances glucagon-like peptide 1 via cooperation between insulin and Wnt signaling.","volume":"22","author":"Lee","year":"2014","journal-title":"J Endocrinol"},{"key":"29","doi-asserted-by":"publisher","first-page":"155160","DOI":"10.1016\/j.metabol.2022.155160","article-title":"Metformin and the heart: Update on mechanisms of cardiovascular protection with special reference to comorbid type 2 diabetes and heart failure.","volume":"13","author":"Bailey","year":"2022","journal-title":"Metabolism"},{"key":"30","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1111\/j.1365-2796.2004.01420.x","article-title":"Effects of short-term treatment with metformin on markers of endothelial function and inflammatory activity in type 2 diabetes mellitus: a randomized, placebo-controlled trial.","volume":"25","author":"Stehouwer","year":"2005","journal-title":"J Intern Med"},{"key":"31","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/S2213-8587(17)30194-8","article-title":"Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes (REMOVAL): a double-blind, randomised, placebo-controlled trial.","volume":"5","author":"Rossing","year":"2017","journal-title":"Lancet Diabetes Endocrinol"},{"key":"32","doi-asserted-by":"publisher","first-page":"4448","DOI":"10.1210\/jc.2017-00781","article-title":"Effect of Metformin on Vascular Function in Children With Type 1 Diabetes: A 12-Month Randomized Controlled Trial.","volume":"10","author":"Pe\u00f1a","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"key":"33","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1111\/j.1440-1681.2008.04920.x","article-title":"Metformin, arterial function, intima-media thickness and nitroxidation in metabolic syndrome: the mefisto study.","volume":"3","author":"Ceballos","year":"2008","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"34","doi-asserted-by":"publisher","first-page":"e0226303","DOI":"10.1371\/journal.pone.0226303","article-title":"Effects of metformin administration on endocrine-metabolic parameters, visceral adiposity and cardiovascular risk factors in children with obesity and risk markers for metabolic syndrome: A pilot study.","volume":"1","author":"L\u00f3pez-Bermejo","year":"2019","journal-title":"PLoS One"},{"key":"35","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1186\/s12933-020-01100-w","article-title":"Metformin treatment in heart failure with preserved ejection fraction: a systematic review and meta-regression analysis.","volume":"1","author":"Marwick","year":"2020","journal-title":"Cardiovasc Diabetol"},{"key":"36","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1111\/dom.13642","article-title":"Metformin use and cardiovascular events in patients with type 2 diabetes and chronic kidney disease.","volume":"2","author":"McMurray","year":"2019","journal-title":"Diabetes Obes Metab"},{"key":"37","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.2337\/dc12-0719","article-title":"Effects of metformin versus glipizide on cardiovascular outcomes in patients with type 2 diabetes and coronary artery disease.","volume":"3","author":"Li","year":"2013","journal-title":"Diabetes Care"},{"key":"38","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1097\/FJC.0000000000000599","article-title":"Cardioprotective Effects of Metformin.","volume":"7","author":"Owira","year":"2018","journal-title":"J Cardiovasc Pharmacol"},{"key":"39","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1007\/s00395-011-0216-6","article-title":"The potential effects of anti-diabetic medications on myocardial ischemia-reperfusion injury.","volume":"10","author":"Birnbaum","year":"2011","journal-title":"Basic Res Cardiol"},{"key":"40","doi-asserted-by":"publisher","first-page":"327","DOI":"10.2174\/157016110791112359","article-title":"The cardiovascular effects of metformin: further reasons to consider an old drug as a cornerstone in the therapy of type 2 diabetes mellitus.","volume":"8","author":"Trovati","year":"2010","journal-title":"Curr Vasc Pharmacol"},{"key":"41","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1111\/1440-1681.13148","article-title":"Metformin modulates cardiac endothelial dysfunction, oxidative stress and inflammation in irradiated rats: A new perspective of an antidiabetic drug.","volume":"4","author":"Radwan","year":"2019","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"42","doi-asserted-by":"publisher","first-page":"E293","DOI":"10.1152\/ajpendo.00240.2021","article-title":"Metformin prevents endothelial oxidative stress and microvascular insulin resistance during obesity development in male rats.","volume":"32","author":"Liu","year":"2022","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"43","doi-asserted-by":"publisher","first-page":"1681","DOI":"10.3390\/antiox12091681","article-title":"AMPK-Dependent YAP Inhibition Mediates the Protective Effect of Metformin against Obesity-Associated Endothelial Dysfunction and Inflammation.","volume":"1","author":"Wang","year":"2023","journal-title":"Antioxidants (Basel)"}],"container-title":["Aging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.aging-us.com\/lookup\/doi\/10.18632\/aging.205775","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T14:59:19Z","timestamp":1714143559000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.aging-us.com\/lookup\/doi\/10.18632\/aging.205775"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,26]]},"references-count":43,"alternative-id":["205775"],"URL":"https:\/\/doi.org\/10.18632\/aging.205775","relation":{},"ISSN":["1945-4589"],"issn-type":[{"value":"1945-4589","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,26]]}}}