{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T16:05:15Z","timestamp":1793549115474,"version":"4.5.0"},"reference-count":42,"publisher":"American Medical Association (AMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Cardiol"],"published-print":{"date-parts":[[2024,7,1]]},"abstract":"<jats:sec id=\"ab-hoi240024-1\"><jats:title>Importance<\/jats:title><jats:p>Heart failure (HF) and frailty frequently coexist and may share a common pathobiology, although the underlying mechanisms remain unclear. Understanding these mechanisms may provide guidance for preventing and treating both conditions.<\/jats:p><\/jats:sec><jats:sec id=\"ab-hoi240024-2\"><jats:title>Objective<\/jats:title><jats:p>To identify shared pathways between incident HF and frailty in late life using large-scale proteomics.<\/jats:p><\/jats:sec><jats:sec id=\"ab-hoi240024-3\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>In this cohort study, 4877 aptamers (Somascan v4) were measured among participants in the community-based longitudinal Atherosclerosis Risk In Communities (ARIC) cohort study at visit 3 (V3; 1993-1995; n\u2009=\u200910\u202f638) and at visit 5 (V5; 2011-2013; n\u2009=\u20093908). Analyses were externally replicated among 3189 participants in the Cardiovascular Health Study (CHS). Data analysis was conducted from February 2022 to June 2023.<\/jats:p><\/jats:sec><jats:sec id=\"ab-hoi240024-4\"><jats:title>Exposures<\/jats:title><jats:p>Protein aptamers, measured at study V3 and V5.<\/jats:p><\/jats:sec><jats:sec id=\"ab-hoi240024-5\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>Outcomes assessed included incident HF hospitalization after V3 and after V5, prevalent frailty at V5, and incident frailty between V5 and visit 6 (V6; 2016-2017; n\u2009=\u20094131). Frailty was assessed using the Fried criteria. Analyses were adjusted for age, gender, race, field center, hypertension, diabetes, smoking status, body mass index, estimated glomerular filtration rate, prevalent coronary heart disease, prevalent atrial fibrillation, and history of myocardial infarction. Mendelian randomization (MR) analysis was performed to assess potential causal effects of candidate proteins on HF and frailty.<\/jats:p><\/jats:sec><jats:sec id=\"ab-hoi240024-6\"><jats:title>Results<\/jats:title><jats:p>A total of 4877 protein aptamers were measured among 10\u202f638 participants at V3 (mean [SD] age, 60 [6] years; 4886 [46%] men). Overall, 286 proteins were associated with incident HF after V3 (822 events; <jats:italic>P<\/jats:italic>\u2009&amp;amp;lt;\u20091.0\u2009\u00d7\u200910<jats:sup>\u22125<\/jats:sup>), 83 of which were also associated with incident after V5 (336 events; <jats:italic>P<\/jats:italic>\u2009&amp;amp;lt;\u20091.7\u2009\u00d7\u200910<jats:sup>\u22124<\/jats:sup>). Among HF-free participants at V5 (n\u2009=\u20093908; mean [SD] age, 75 [5] years; 1861 [42%] men), 48 of 83 HF-associated proteins were associated with prevalent frailty (223 cases; <jats:italic>P<\/jats:italic>\u2009&amp;amp;lt;\u20096.0\u2009\u00d7\u200910<jats:sup>\u22124<\/jats:sup>), 18 of which were also associated with incident frailty at V6 (152 cases; <jats:italic>P<\/jats:italic>\u2009&amp;amp;lt;\u20091.0\u2009\u00d7\u200910<jats:sup>\u22123<\/jats:sup>). These proteins enriched fibrosis and inflammation pathways and demonstrated stronger associations with incident HF with preserved ejection fraction (HFpEF) than HF with reduced ejection fraction. All 18 proteins were associated with both prevalent frailty and incident HF in CHS. MR identified potential causal effects of several proteins on frailty and HF.<\/jats:p><\/jats:sec><jats:sec id=\"ab-hoi240024-7\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>In this study, the proteins associated with risk of HF and frailty enrich for pathways related to inflammation and fibrosis as well as risk of HFpEF. Several of these proteins could potentially contribute to the shared pathophysiology of frailty and HF.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamacardio.2024.1178","type":"journal-article","created":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T15:01:17Z","timestamp":1716994877000},"page":"649","source":"Crossref","is-referenced-by-count":25,"title":["High Throughput Plasma Proteomics and Risk of Heart Failure and Frailty in Late Life"],"prefix":"10.1001","volume":"9","author":[{"given":"Diego","family":"Ramonfaur","sequence":"first","affiliation":[{"name":"University of Texas Southwestern Medical Center, Dallas"},{"name":"Brigham and Women\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo F.","family":"Buckley","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Arthur","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimin","family":"Yang","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L.","family":"Claggett","sequence":"additional","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiadi E.","family":"Ndumele","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, Baltimore, Maryland"},{"name":"Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keenan A.","family":"Walker","sequence":"additional","affiliation":[{"name":"Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Austin","sequence":"additional","affiliation":[{"name":"Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle C.","family":"Odden","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Population Health, Stanford University, Stanford, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James S.","family":"Floyd","sequence":"additional","affiliation":[{"name":"Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Sanders-van Wijk","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Zuyderland Medical Center, Heerlen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce","family":"Njoroge","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Stanford University Medical Center, Palo Alto, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge R.","family":"Kizer","sequence":"additional","affiliation":[{"name":"Division of Cardiology, San Francisco Veterans Affairs Health Care System, and Departments of Medicine, Epidemiology and Biostatistics, San Francisco, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalane","family":"Kitzman","sequence":"additional","affiliation":[{"name":"Wake Forest School of Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suma H.","family":"Konety","sequence":"additional","affiliation":[{"name":"University of Minnesota, Minneapolis"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Schrack","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyu","family":"Liu","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. Gwen","family":"Windham","sequence":"additional","affiliation":[{"name":"University of Mississippi Medical Center, Jackson"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Palta","sequence":"additional","affiliation":[{"name":"University of North Carolina School of Medicine, Chapel Hill"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"Coresh","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Population Health, NYU Langone Health, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Yu","sequence":"additional","affiliation":[{"name":"The University of Texas Health Science Center at Houston School of Public Health, Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amil M.","family":"Shah","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"4","key":"hoi240024r1","doi-asserted-by":"publisher","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 Fail"},{"issue":"3","key":"hoi240024r2","doi-asserted-by":"publisher","first-page":"M146","DOI":"10.1093\/gerona\/56.3.M146","article-title":"Frailty in older adults: evidence for a phenotype.","volume":"56","author":"Fried","year":"2001","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"hoi240024r3","doi-asserted-by":"publisher","author":"Kucharska-Newton","journal-title":"J Geron A Biol Sci Med Sci","DOI":"10.1093\/gerona\/glw144"},{"key":"hoi240024r4","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.bone.2016.06.009","article-title":"Frailty as a predictor of fractures among community-dwelling older people: a systematic review and meta-analysis.","volume":"90","author":"Kojima","year":"2016","journal-title":"Bone"},{"key":"hoi240024r5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.exger.2018.10.010","article-title":"A systematic review of the association between sedentary behaviors with frailty.","volume":"114","author":"Kehler","year":"2018","journal-title":"Exp Gerontol"},{"issue":"3","key":"hoi240024r6","doi-asserted-by":"publisher","first-page":"M158","DOI":"10.1093\/gerona\/56.3.M158","article-title":"Associations of subclinical cardiovascular disease with frailty.","volume":"56","author":"Newman","year":"2001","journal-title":"J Gerontol A Biol Sci Med Sci"},{"key":"hoi240024r7","doi-asserted-by":"publisher","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"},{"issue":"5","key":"hoi240024r8","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1056\/NEJMoa020245","article-title":"Obesity and the risk of heart failure.","volume":"347","author":"Kenchaiah","year":"2002","journal-title":"N Engl J Med"},{"issue":"1","key":"hoi240024r9","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1161\/CIRCULATIONAHA.108.807289","article-title":"Body mass index and vigorous physical activity and the risk of heart failure among men.","volume":"119","author":"Kenchaiah","year":"2009","journal-title":"Circulation"},{"issue":"17","key":"hoi240024r10","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.121.021660","article-title":"Coronary artery disease and heart failure with preserved ejection fraction: The ARIC Study.","volume":"11","author":"John","year":"2022","journal-title":"J Am Heart Assoc"},{"issue":"8","key":"hoi240024r11","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1016\/j.amjcard.2016.12.024","article-title":"Frequency of and significance of physical frailty in patients with heart failure.","volume":"119","author":"Denfeld","year":"2017","journal-title":"Am J Cardiol"},{"issue":"12","key":"hoi240024r12","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1111\/eci.2005.35.issue-12","article-title":"Frailty predicts long-term mortality in elderly subjects with chronic heart failure.","volume":"35","author":"Cacciatore","year":"2005","journal-title":"Eur J Clin Invest"},{"issue":"5","key":"hoi240024r13","doi-asserted-by":"publisher","first-page":"1242","DOI":"10.1002\/jcsm.v11.5","article-title":"Muscle wasting as an independent predictor of survival in patients with chronic heart failure.","volume":"11","author":"von Haehling","year":"2020","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"hoi240024r14","doi-asserted-by":"publisher","author":"Nadruz","journal-title":"J Geron A Biol Sci Med Sci","DOI":"10.1093\/gerona\/glw199"},{"issue":"10","key":"hoi240024r15","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1016\/j.amjcard.2015.08.023","article-title":"Echocardiographic indices associated with frailty in adults =65 years.","volume":"116","author":"Gharacholou","year":"2015","journal-title":"Am J Cardiol"},{"key":"hoi240024r16","doi-asserted-by":"publisher","journal-title":"Geroscience","DOI":"10.1007\/s11357-021-00334-0"},{"issue":"10","key":"hoi240024r17","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1038\/s41574-018-0059-4","article-title":"Inflammaging: a new immune-metabolic viewpoint for age-related diseases.","volume":"14","author":"Franceschi","year":"2018","journal-title":"Nat Rev Endocrinol"},{"issue":"5","key":"hoi240024r18","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.118.005897","article-title":"Proteomic bioprofiles and mechanistic pathways of progression to heart failure.","volume":"12","author":"Ferreira","year":"2019","journal-title":"Circ Heart Fail"},{"issue":"1","key":"hoi240024r19","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.hfc.2017.08.010","article-title":"Proteomic biomarkers of heart failure.","volume":"14","author":"Israr","year":"2018","journal-title":"Heart Fail Clin"},{"issue":"16","key":"hoi240024r20","doi-asserted-by":"publisher","first-page":"5635","DOI":"10.3390\/ijms21165635","article-title":"Biomarkers of physical frailty and sarcopenia: coming up to the place?","volume":"21","author":"Picca","year":"2020","journal-title":"Int J Mol Sci"},{"key":"hoi240024r21","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2019.100935","article-title":"Altered immune system in frailty: genetics and diet may influence inflammation.","volume":"54","author":"Pansarasa","year":"2019","journal-title":"Ageing Res Rev"},{"key":"hoi240024r22","doi-asserted-by":"publisher","first-page":"389","DOI":"10.2147\/CIA","article-title":"Current and emerging biomarkers of frailty in the elderly.","volume":"14","author":"Saedi","year":"2019","journal-title":"Clin Interv Aging"},{"issue":"10","key":"hoi240024r23","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1161\/CIRCRESAHA.121.318159","article-title":"From systemic inflammation to myocardial fibrosis: the heart failure with preserved ejection fraction paradigm revisited.","volume":"128","author":"Paulus","year":"2021","journal-title":"Circ Res"},{"issue":"23","key":"hoi240024r24","doi-asserted-by":"publisher","first-page":"2939","DOI":"10.1016\/j.jacc.2021.04.035","article-title":"The ARIC (Atherosclerosis Risk In Communities) Study: JACC Focus Seminar 3\/8.","volume":"77","author":"Wright","year":"2021","journal-title":"J Am Coll Cardiol"},{"issue":"5","key":"hoi240024r25","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1038\/s43587-021-00064-0","article-title":"Large-scale plasma proteomic analysis identifies proteins and pathways associated with dementia risk.","volume":"1","author":"Walker","year":"2021","journal-title":"Nat Aging"},{"issue":"3","key":"hoi240024r26","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1093\/gerona\/61.3.262","article-title":"Phenotype of frailty: characterization in the women\u2019s health and aging studies.","volume":"61","author":"Bandeen-Roche","year":"2006","journal-title":"J Gerontol A Biol Sci Med Sci"},{"issue":"7","key":"hoi240024r27","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1016\/j.amjcard.2007.11.061","article-title":"Heart failure incidence and survival (from the Atherosclerosis Risk in Communities study).","volume":"101","author":"Loehr","year":"2008","journal-title":"Am J Cardiol"},{"issue":"2","key":"hoi240024r28","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1161\/CIRCHEARTFAILURE.111.963199","article-title":"Classification of heart failure in the atherosclerosis risk in communities (ARIC) study: a comparison of diagnostic criteria.","volume":"5","author":"Rosamond","year":"2012","journal-title":"Circ Heart Fail"},{"issue":"15","key":"hoi240024r29","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.122.029458","article-title":"Bidirectional association between frailty and cardiac structure and function: the Atherosclerosis Risk in Communities Study.","volume":"12","author":"Ramonfaur","year":"2023","journal-title":"J Am Heart Assoc"},{"issue":"4","key":"hoi240024r30","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/S0002-9149(00)01393-X","article-title":"Importance of heart failure with preserved systolic function in patients =65 years of age.","volume":"87","author":"Kitzman","year":"2001","journal-title":"Am J Cardiol"},{"issue":"5","key":"hoi240024r31","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1161\/CIRCULATIONAHA.116.024825","article-title":"Contemporary assessment of left ventricular diastolic function in older adults: the Atherosclerosis Risk in Communities Study.","volume":"135","author":"Shah","year":"2017","journal-title":"Circulation"},{"key":"hoi240024r32","doi-asserted-by":"publisher","author":"Kizer","journal-title":"J Gerontol A Biol Sci Med Sci","DOI":"10.1093\/gerona\/glad206"},{"issue":"11","key":"hoi240024r33","doi-asserted-by":"publisher","DOI":"10.1111\/acel.v22.11","article-title":"Late-life plasma proteins associated with prevalent and incident frailty: a proteomic analysis.","volume":"22","author":"Liu","year":"2023","journal-title":"Aging Cell"},{"issue":"1","key":"hoi240024r34","doi-asserted-by":"publisher","first-page":"13151","DOI":"10.1038\/ncomms13151","article-title":"TREM-1 links dyslipidemia to inflammation and lipid deposition in atherosclerosis.","volume":"7","author":"Zysset","year":"2016","journal-title":"Nat Commun"},{"issue":"11","key":"hoi240024r35","doi-asserted-by":"publisher","first-page":"1772","DOI":"10.1161\/CIRCRESAHA.116.305628","article-title":"TREM-1 mediates inflammatory injury and cardiac remodeling following myocardial infarction.","volume":"116","author":"Boufenzer","year":"2015","journal-title":"Circ Res"},{"issue":"9","key":"hoi240024r36","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1007\/s003350010135","article-title":"The WFDC1 gene encoding ps20 localizes to 16q24, a region of LOH in multiple cancers.","volume":"11","author":"Larsen","year":"2000","journal-title":"Mamm Genome"},{"issue":"11","key":"hoi240024r37","doi-asserted-by":"publisher","first-page":"2951","DOI":"10.1016\/j.ajpath.2014.07.013","article-title":"WFDC1 is a key modulator of inflammatory and wound repair responses.","volume":"184","author":"Ressler","year":"2014","journal-title":"Am J Pathol"},{"issue":"1","key":"hoi240024r38","doi-asserted-by":"publisher","first-page":"9562","DOI":"10.1038\/s41598-017-10126-2","article-title":"The cellular and molecular determinants of emphysematous destruction in COPD.","volume":"7","author":"Suzuki","year":"2017","journal-title":"Sci Rep"},{"issue":"5","key":"hoi240024r39","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1291\/hypres.31.941","article-title":"Myocardial gene expression associated with genetic cardiac hypertrophy in the absence of hypertension.","volume":"31","author":"Dwyer","year":"2008","journal-title":"Hypertens Res"},{"issue":"3","key":"hoi240024r40","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.122.026003","article-title":"Growth differentiation factor-15 predicts mortality and heart failure exacerbation but not ventricular arrhythmias in patients with cardiomyopathy.","volume":"12","author":"Binder","year":"2023","journal-title":"J Am Heart Assoc"},{"issue":"12","key":"hoi240024r41","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.120.007198","article-title":"Skeletal muscle function, structure, and metabolism in patients with heart failure with reduced ejection fraction and heart failure with preserved ejection fraction.","volume":"13","author":"Bekfani","year":"2020","journal-title":"Circ Heart Fail"},{"key":"hoi240024r42","doi-asserted-by":"publisher","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"}],"container-title":["JAMA Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamacardiology\/articlepdf\/2819212\/jamacardiology_ramonfaur_2024_oi_240024_1719329869.30289.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T15:05:43Z","timestamp":1720623943000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamacardiology\/fullarticle\/2819212"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,1]]},"references-count":42,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,7,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamacardio.2024.1178","relation":{},"ISSN":["2380-6583"],"issn-type":[{"value":"2380-6583","type":"print"}],"subject":[],"published":{"date-parts":[[2024,7,1]]}}}