{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T22:42:24Z","timestamp":1793227344818,"version":"4.5.0"},"reference-count":52,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","nmcd-journal.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Nutrition, Metabolism and Cardiovascular Diseases"],"published-print":{"date-parts":[[2024,3]]},"DOI":"10.1016\/j.numecd.2023.10.018","type":"journal-article","created":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T04:37:15Z","timestamp":1698122235000},"page":"624-632","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":20,"title":["The bidirectional association between frailty index and cardiovascular disease: A Mendelian randomization study"],"prefix":"10.1016","volume":"34","author":[{"given":"Qingyun","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pinni","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daoxia","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyao","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengbao","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.numecd.2023.10.018_bib1","doi-asserted-by":"crossref","first-page":"559751","DOI":"10.3389\/fpubh.2021.559751","article-title":"Global, regional, and national death, and disability-adjusted life-years (dalys) for cardiovascular disease in 2017 and trends and risk analysis from 1990 to 2017 using the global burden of disease study and implications for prevention","volume":"9","author":"Li","year":"2021","journal-title":"Front Public Health"},{"key":"10.1016\/j.numecd.2023.10.018_bib2","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1016\/S0140-6736(18)32279-7","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the global burden of disease study 2017","volume":"392","year":"2018","journal-title":"Lancet"},{"key":"10.1016\/j.numecd.2023.10.018_bib3","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1016\/S0140-6736(18)32203-7","article-title":"Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the global burden of disease study 2017","volume":"392","year":"2018","journal-title":"Lancet"},{"key":"10.1016\/j.numecd.2023.10.018_bib4","first-page":"433","article-title":"Frailty syndrome: an overview","volume":"9","author":"Chen","year":"2014","journal-title":"Clin Interv Aging"},{"key":"10.1016\/j.numecd.2023.10.018_bib5","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.mad.2019.04.005","article-title":"Age-related deficit accumulation and the diseases of ageing","volume":"180","author":"Rockwood","year":"2019","journal-title":"Mech Ageing Dev"},{"key":"10.1016\/j.numecd.2023.10.018_bib6","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/1471-2318-8-24","article-title":"A standard procedure for creating a frailty index","volume":"8","author":"Searle","year":"2008","journal-title":"BMC Geriatr"},{"key":"10.1016\/j.numecd.2023.10.018_bib7","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/s41569-018-0064-2","article-title":"Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty","volume":"15","author":"Ferrucci","year":"2018","journal-title":"Nat Rev Cardiol"},{"key":"10.1016\/j.numecd.2023.10.018_bib8","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/978-3-030-33330-0_8","article-title":"Oxidative stress, frailty and cardiovascular diseases: current evidence","volume":"1216","author":"Uchmanowicz","year":"2020","journal-title":"Adv Exp Med Biol"},{"key":"10.1016\/j.numecd.2023.10.018_bib9","doi-asserted-by":"crossref","first-page":"111302","DOI":"10.1016\/j.exger.2021.111302","article-title":"Benchside to the bedside of frailty and cardiovascular aging: main shared cellular and molecular mechanisms","volume":"148","author":"Barbalho","year":"2021","journal-title":"Exp Gerontol"},{"key":"10.1016\/j.numecd.2023.10.018_bib10","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.arr.2017.01.003","article-title":"Risk of cardiovascular disease morbidity and mortality in frail and pre-frail older adults: results from a meta-analysis and exploratory meta-regression analysis","volume":"35","author":"Veronese","year":"2017","journal-title":"Ageing Res Rev"},{"key":"10.1016\/j.numecd.2023.10.018_bib11","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1038\/s41440-021-00769-0","article-title":"Blood pressure, frailty status, and all-cause mortality in elderly hypertensives; the nambu cohort study","volume":"45","author":"Inoue","year":"2022","journal-title":"Hypertens Res"},{"key":"10.1016\/j.numecd.2023.10.018_bib12","doi-asserted-by":"crossref","first-page":"111522","DOI":"10.1016\/j.exger.2021.111522","article-title":"Subclinical cardiovascular disease and risk of incident frailty: the british regional heart study","volume":"154","author":"McKechnie","year":"2021","journal-title":"Exp Gerontol"},{"key":"10.1016\/j.numecd.2023.10.018_bib13","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1016\/S0140-6736(04)16261-2","article-title":"When are observational studies as credible as randomised trials?","volume":"363","author":"Vandenbroucke","year":"2004","journal-title":"Lancet"},{"key":"10.1016\/j.numecd.2023.10.018_bib14","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1002\/sim.3034","article-title":"Mendelian randomization: using genes as instruments for making causal inferences in epidemiology","volume":"27","author":"Lawlor","year":"2008","journal-title":"Stat Med"},{"key":"10.1016\/j.numecd.2023.10.018_bib15","doi-asserted-by":"crossref","first-page":"k601","DOI":"10.1136\/bmj.k601","article-title":"Reading mendelian randomisation studies: a guide, glossary, and checklist for clinicians","volume":"362","author":"Davies","year":"2018","journal-title":"BMJ"},{"key":"10.1016\/j.numecd.2023.10.018_bib16","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1001\/jama.2017.17219","article-title":"Mendelian randomization","volume":"318","author":"Emdin","year":"2017","journal-title":"JAMA"},{"key":"10.1016\/j.numecd.2023.10.018_bib17","article-title":"Frailty and cardiometabolic diseases: a bidirectional mendelian randomisation study","volume":"51","author":"Zhu","year":"2022","journal-title":"Age Ageing"},{"key":"10.1016\/j.numecd.2023.10.018_bib18","volume":"20","author":"Atkins","year":"2021"},{"key":"10.1016\/j.numecd.2023.10.018_bib19","volume":"7","author":"Hemani","year":"2018"},{"key":"10.1016\/j.numecd.2023.10.018_bib20","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1038\/ng.3396","article-title":"A comprehensive 1,000 genomes-based genome-wide association meta-analysis of coronary artery disease","volume":"47","author":"Nikpay","year":"2015","journal-title":"Nat Genet"},{"key":"10.1016\/j.numecd.2023.10.018_bib21","first-page":"163","volume":"11","author":"Shah","year":"2020"},{"key":"10.1016\/j.numecd.2023.10.018_bib22","first-page":"1234","volume":"50","author":"Nielsen","year":"2018"},{"key":"10.1016\/j.numecd.2023.10.018_bib23","first-page":"467","volume":"20","author":"Tam","year":"2019"},{"key":"10.1016\/j.numecd.2023.10.018_bib24","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1002\/ana.26464","article-title":"Association between human blood metabolome and the risk of alzheimer's disease","volume":"92","author":"Sun","year":"2022","journal-title":"Ann Neurol"},{"key":"10.1016\/j.numecd.2023.10.018_bib25","article-title":"The mrc ieu opengwas data infrastructure","author":"Ben Elsworth","year":"2020","journal-title":"bioRxiv"},{"key":"10.1016\/j.numecd.2023.10.018_bib26","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1002\/gepi.21758","article-title":"Mendelian randomization analysis with multiple genetic variants using summarized data","volume":"37","author":"Burgess","year":"2013","journal-title":"Genet Epidemiol"},{"key":"10.1016\/j.numecd.2023.10.018_bib27","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1002\/gepi.21965","article-title":"Consistent estimation in mendelian randomization with some invalid instruments using a weighted median estimator","volume":"40","author":"Bowden","year":"2016","journal-title":"Genet Epidemiol"},{"key":"10.1016\/j.numecd.2023.10.018_bib28","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1214\/19-AOS1866","article-title":"Statistical inference in two-sample summary-data mendelian randomization using robust adjusted profile score","volume":"48","author":"Zhao","year":"2020","journal-title":"Ann Stat"},{"key":"10.1016\/j.numecd.2023.10.018_bib29","first-page":"693","volume":"50","author":"Verbanck","year":"2018"},{"key":"10.1016\/j.numecd.2023.10.018_bib30","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s10654-017-0255-x","article-title":"Interpreting findings from mendelian randomization using the mr-egger method","volume":"32","author":"Burgess","year":"2017","journal-title":"Eur J Epidemiol"},{"key":"10.1016\/j.numecd.2023.10.018_bib31","doi-asserted-by":"crossref","first-page":"104279","DOI":"10.1016\/j.archger.2020.104279","article-title":"Frailty syndrome and risk of cardiovascular disease: analysis from the international mobility in aging study","volume":"92","author":"Fernandes","year":"2021","journal-title":"Arch Gerontol Geriatr"},{"key":"10.1016\/j.numecd.2023.10.018_bib32","doi-asserted-by":"crossref","first-page":"111061","DOI":"10.1016\/j.exger.2020.111061","article-title":"Frailty status and cardiovascular disease risk profile in middle-aged and older females","volume":"140","author":"Boreskie","year":"2020","journal-title":"Exp Gerontol"},{"key":"10.1016\/j.numecd.2023.10.018_bib33","first-page":"104598","volume":"vol. 99","author":"Hou","year":"2022"},{"key":"10.1016\/j.numecd.2023.10.018_bib34","doi-asserted-by":"crossref","first-page":"111475","DOI":"10.1016\/j.exger.2021.111475","article-title":"The association between cardiovascular risk factors and major cardiovascular diseases decreases with increasing frailty levels in geriatric outpatients","volume":"153","author":"Aprahamian","year":"2021","journal-title":"Exp Gerontol"},{"key":"10.1016\/j.numecd.2023.10.018_bib35","doi-asserted-by":"crossref","first-page":"111658","DOI":"10.1016\/j.exger.2021.111658","article-title":"Association between frailty and c-terminal agrin fragment with 3-month mortality following st-elevation myocardial infarction","volume":"158","author":"Ramos","year":"2022","journal-title":"Exp Gerontol"},{"key":"10.1016\/j.numecd.2023.10.018_bib36","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/j.ahj.2013.07.032","article-title":"Frailty and risk for heart failure in older adults: the health, aging, and body composition study","volume":"166","author":"Khan","year":"2013","journal-title":"Am Heart J"},{"key":"10.1016\/j.numecd.2023.10.018_bib37","doi-asserted-by":"crossref","first-page":"881946","DOI":"10.3389\/fcvm.2022.881946","article-title":"Association between the frailty and new-onset atrial fibrillation\/flutter among elderly hypertensive patients","volume":"9","author":"Hang","year":"2022","journal-title":"Front Cardiovas Med"},{"key":"10.1016\/j.numecd.2023.10.018_bib38","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1093\/ageing\/afy080","article-title":"Cardiovascular risk factors and frailty in a cross-sectional study of older people: implications for prevention","volume":"47","author":"Wong","year":"2018","journal-title":"Age Ageing"},{"key":"10.1016\/j.numecd.2023.10.018_bib39","first-page":"817","volume":"43","author":"Matsuoka","year":"2020"},{"key":"10.1016\/j.numecd.2023.10.018_bib40","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1097\/HJH.0000000000002650","article-title":"Epidemiological characteristics and related factors of frailty in older Chinese adults with hypertension: a population-based study","volume":"38","author":"Ma","year":"2020","journal-title":"J Hypertens"},{"key":"10.1016\/j.numecd.2023.10.018_bib41","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.2147\/CIA.S315837","article-title":"Silent myocardial infarction and long-term risk of frailty: the atherosclerosis risk in communities study","volume":"16","author":"Li","year":"2021","journal-title":"Clin Interv Aging"},{"key":"10.1016\/j.numecd.2023.10.018_bib42","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.jchf.2018.11.017","article-title":"Identification of frailty in chronic heart failure","volume":"7","author":"Sze","year":"2019","journal-title":"Jacc-Heart Failure"},{"key":"10.1016\/j.numecd.2023.10.018_bib43","doi-asserted-by":"crossref","first-page":"104103","DOI":"10.1016\/j.archger.2020.104103","article-title":"The relationship between atrial fibrillation and frailty in community-dwelling older adults","volume":"90","author":"Yang","year":"2020","journal-title":"Arch Gerontol Geriatr"},{"key":"10.1016\/j.numecd.2023.10.018_bib44","doi-asserted-by":"crossref","first-page":"113238","DOI":"10.1016\/j.biopha.2022.113238","article-title":"Oxidative stress - complex pathological issues concerning the hallmark of cardiovascular and metabolic disorders","volume":"152","author":"Rotariu","year":"2022","journal-title":"Biomed Pharmacother"},{"key":"10.1016\/j.numecd.2023.10.018_bib45","first-page":"1553","article-title":"Hearts on fire: the role of inflammation in the pathogenesis of atherosclerotic cardiovascular disease and how we can tend to the flames","volume":"38","author":"Boczar","year":"2022","journal-title":"Can J Cardiol"},{"key":"10.1016\/j.numecd.2023.10.018_bib46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.arr.2016.08.006","article-title":"Inflammation and frailty in the elderly: a systematic review and meta-analysis","volume":"31","author":"Soysal","year":"2016","journal-title":"Ageing Res Rev"},{"key":"10.1016\/j.numecd.2023.10.018_bib47","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.maturitas.2017.01.006","article-title":"Oxidative stress and frailty: a systematic review and synthesis of the best evidence","volume":"99","author":"Soysal","year":"2017","journal-title":"Maturitas"},{"key":"10.1016\/j.numecd.2023.10.018_bib48","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.archger.2011.05.020","article-title":"Association between inflammatory-related disease burden and frailty: results from the women's health and aging studies (whas) i and ii","volume":"54","author":"Chang","year":"2012","journal-title":"Arch Gerontol Geriatr"},{"key":"10.1016\/j.numecd.2023.10.018_bib49","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.freeradbiomed.2020.01.007","article-title":"Older adults with frailty syndrome present an altered platelet function and an increased level of circulating oxidative stress and mitochondrial dysfunction biomarker gdf-15","volume":"149","author":"Arauna","year":"2020","journal-title":"Free Radic Biol Med"},{"key":"10.1016\/j.numecd.2023.10.018_bib50","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1159\/000381134","article-title":"Frailty, inflammation and immunosenescence","volume":"41","author":"Fulop","year":"2015","journal-title":"Interdiscip Top Gerontol Geriatr"},{"key":"10.1016\/j.numecd.2023.10.018_bib51","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.18632\/oncotarget.2725","article-title":"Age-independent rise of inflammatory scores may contribute to accelerated aging in multi-morbidity","volume":"6","author":"Stepanova","year":"2015","journal-title":"Oncotarget"},{"key":"10.1016\/j.numecd.2023.10.018_bib52","first-page":"34121","volume":"28","author":"Donia","year":"2021"}],"container-title":["Nutrition, Metabolism and Cardiovascular Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0939475323004258?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0939475323004258?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T16:27:54Z","timestamp":1760545674000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0939475323004258"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3]]},"references-count":52,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["S0939475323004258"],"URL":"https:\/\/doi.org\/10.1016\/j.numecd.2023.10.018","relation":{},"ISSN":["0939-4753"],"issn-type":[{"value":"0939-4753","type":"print"}],"subject":[],"published":{"date-parts":[[2024,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The bidirectional association between frailty index and cardiovascular disease: A Mendelian randomization study","name":"articletitle","label":"Article Title"},{"value":"Nutrition, Metabolism and Cardiovascular Diseases","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.numecd.2023.10.018","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}]}}