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Impact of Race, Ethnicity, and Multimodality Biomarkers on the Incidence of New-Onset Heart Failure With Preserved Ejection Fraction (from the Multi-Ethnic Study of Atherosclerosis)

Published:February 16, 2016DOI:https://doi.org/10.1016/j.amjcard.2016.02.017
      Heart failure with preserved ejection fraction (HFpEF) is a prevalent condition with no established prevention or treatment strategies. Furthermore, the pathophysiology and predisposing risk factors for HFpEF are incompletely understood. Therefore, we sought to characterize the incidence and determinants of HFpEF in the Multi-Ethnic Study of Atherosclerosis (MESA). Our study included 6,781 MESA participants (White, Black, Chinese, and Hispanic men and women age 45 to 84 years, free of baseline cardiovascular disease). The primary end point was time to diagnosis of HFpEF (left ventricular ejection fraction ≥45%). Multivariable adjusted hazard ratios (HRs) with 95% confidence intervals were calculated to identify predictors of HFpEF. Over median follow-up of 11.2 years (10.6 to 11.7), 111 subjects developed HFpEF (cumulative incidence 1.7%). Incidence rates were similar across all races/ethnicities. Age (HR 2.3 [1.7 to 3.0]), hypertension (HR 1.8 [1.1 to 2.9]), diabetes (HR 2.3 [1.5 to 3.7]), body mass index (HR 1.4 [1.1 to 1.7]), left ventricular hypertrophy by electrocardiography (HR 4.3 [1.7 to 11.0]), interim myocardial infarction (HR 4.8 [2.7 to 8.6]), elevated N-terminal of the prohormone brain natriuretic peptide (HR 2.4 [1.5 to 4.0]), detectable troponin T (HR 4.5 [1.9 to 10.9]), and left ventricular mass index by magnetic resonance imaging (MRI; 1.3 [1.0 to 1.6]) were significant predictors of incident HFpEF. Worsening renal function, inflammatory markers, and coronary artery calcium were significant univariate but not multivariate predictors of HFpEF. Gender was neither a univariate nor multivariate predictor of HFpEF. In conclusion, we demonstrate several risk factors and biomarkers associated with incident HFpEF that were consistent across different racial/ethnic groups and may represent potential therapeutic targets for the prevention and treatment of HFpEF.
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      References

        • Lam C.S.
        • Donal E.
        • Kraigher-Krainer E.
        • Vasan R.S.
        Epidemiology and clinical course of heart failure with preserved ejection fraction.
        Eur J Heart Fail. 2011; 13: 18-28
        • Shah A.M.
        • Pfeffer M.A.
        The many faces of heart failure with preserved ejection fraction.
        Nat Rev Cardiol. 2012; 9: 555-556
        • Butler J.
        • Fonarow G.C.
        • Zile M.R.
        • Lam C.S.
        • Roessig L.
        • Schelbert E.B.
        • Shah S.J.
        • Ahmed A.
        • Bonow R.O.
        • Cleland J.G.
        • Cody R.J.
        • Chioncel O.
        • Collins S.P.
        • Dunnmon P.
        • Filippatos G.
        • Lefkowitz M.P.
        • Marti C.N.
        • McMurray J.J.
        • Misselwitz F.
        • Nodari S.
        • O'Connor C.
        • Pfeffer M.A.
        • Pieske B.
        • Pitt B.
        • Rosano G.
        • Sabbah H.N.
        • Senni M.
        • Solomon S.D.
        • Stockbridge N.
        • Teerlink J.R.
        • Georgiopoulou V.V.
        • Gheorghiade M.
        Developing therapies for heart failure with preserved ejection fraction: current state and future directions.
        JACC Heart Fail. 2014; 2: 97-112
        • Patel K.
        • Fonarow G.C.
        • Kitzman D.W.
        • Aban I.B.
        • Love T.E.
        • Allman R.M.
        • Gheorghiade M.
        • Ahmed A.
        Angiotensin receptor blockers and outcomes in real-world older patients with heart failure and preserved ejection fraction: a propensity-matched inception cohort clinical effectiveness study.
        Eur J Heart Fail. 2012; 14: 1179-1188
        • Redfield M.M.
        • Chen H.H.
        • Borlaug B.A.
        • Semigran M.J.
        • Lee K.L.
        • Lewis G.
        • LeWinter M.M.
        • Rouleau J.L.
        • Bull D.A.
        • Mann D.L.
        • Deswal A.
        • Stevenson L.W.
        • Givertz M.M.
        • Ofili E.O.
        • O'Connor C.M.
        • Felker G.M.
        • Goldsmith S.R.
        • Bart B.A.
        • McNulty S.E.
        • Ibarra J.C.
        • Lin G.
        • Oh J.K.
        • Patel M.R.
        • Kim R.J.
        • Tracy R.P.
        • Velazquez E.J.
        • Anstrom K.J.
        • Hernandez A.F.
        • Mascette A.M.
        • Braunwald E.
        • RELAX Trial
        Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial.
        JAMA. 2013; 309: 1268-1277
        • Edelmann F.
        • Wachter R.
        • Schmidt A.G.
        • Kraigher-Krainer E.
        • Colantonio C.
        • Kamke W.
        • Duvinage A.
        • Stahrenberg R.
        • Durstewitz K.
        • Löffler M.
        • Düngen H.D.
        • Tschöpe C.
        • Herrmann-Lingen C.
        • Halle M.
        • Hasenfuss G.
        • Gelbrich G.
        • Pieske B.
        • Aldo-DHF Investigators
        Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: the Aldo-DHF randomized controlled trial.
        JAMA. 2013; 309: 781-791
        • Pitt B.
        • Pfeffer M.A.
        • Assmann S.F.
        • Boineau R.
        • Anand I.S.
        • Claggett B.
        • Clausell N.
        • Desai A.S.
        • Diaz R.
        • Fleg J.L.
        • Gordeev I.
        • Harty B.
        • Heitner J.F.
        • Kenwood C.T.
        • Lewis E.F.
        • O'Meara E.
        • Probstfield J.L.
        • Shaburishvili T.
        • Shah S.J.
        • Solomon S.D.
        • Sweitzer N.K.
        • Yang S.
        • McKinlay S.M.
        • TOPCAT Investigators
        Spironolactone for heart failure with preserved ejection fraction.
        N Engl J Med. 2014; 370: 1383-1392
        • Redfield M.M.
        • Anstrom K.J.
        • Levine J.A.
        • Koepp G.A.
        • Borlaug B.A.
        • Chen H.H.
        • LeWinter M.M.
        • Joseph S.M.
        • Shah S.J.
        • Semigran M.J.
        • Felker G.M.
        • Cole R.T.
        • Reeves G.R.
        • Tedford R.J.
        • Tang W.H.
        • McNulty S.E.
        • Velazquez E.J.
        • Shah M.R.
        • Braunwald E.
        • NHLBI Heart Failure Clinical Research Network
        Isosorbide mononitrate in heart failure with preserved ejection fraction.
        N Engl J Med. 2015; 373: 2314-2324
        • Ho J.E.
        • Lyass A.
        • Lee D.S.
        • Vasan R.S.
        • Kannel W.B.
        • Larson M.G.
        • Levy D.
        Predictors of new-onset heart failure: differences in preserved versus reduced ejection fraction.
        Circ Heart Fail. 2013; 6: 279-286
        • Brouwers F.P.
        • de Boer R.A.
        • van der Harst P.
        • Voors A.A.
        • Gansevoort R.T.
        • Bakker S.J.
        • Hillege H.L.
        • van Veldhuisen D.J.
        • van Gilst W.H.
        Incidence and epidemiology of new onset heart failure with preserved vs. reduced ejection fraction in a community-based cohort: 11-year follow-up of PREVEND.
        Eur Heart J. 2013; 34: 1424-1431
        • Bild D.E.
        • Bluemke D.A.
        • Burke G.L.
        • Detrano R.
        • Diez Roux A.V.
        • Folsom A.R.
        • Greenland P.
        • Jacob Jr., D.R.
        • Kronmal R.
        • Liu K.
        • Nelson J.C.
        • O'Leary D.
        • Saad M.F.
        • Shea S.
        • Szklo M.
        • Tracy R.P.
        Multi-ethnic study of atherosclerosis: objectives and design.
        Am J Epidemiol. 2002; 156: 871-881
        • Levey A.S.
        • Stevens L.A.
        • Schmid C.H.
        • Zhang Y.L.
        • Castro III, A.F.
        • Feldman H.I.
        • Kusek J.W.
        • Eggers P.
        • Van Lente F.
        • Greene T.
        • Coresh J.
        • CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration)
        A new equation to estimate glomerular filtration rate.
        Ann Intern Med. 2009; 150: 604-612
        • Carr J.J.
        • Nelson J.C.
        • Wong N.D.
        • McNitt-Gray M.
        • Arad Y.
        • Jacobs Jr., D.R.
        • Sidney S.
        • Bild D.E.
        • Williams O.D.
        • Detrano R.C.
        Calcified coronary artery plaque measurement with cardiac CT in population-based studies: standardized protocol of Multi-Ethnic Study of Atherosclerosis (MESA) and Coronary Artery Risk Development in Young Adults (CARDIA) study.
        Radiology. 2005; 234: 35-43
        • Agatston A.S.
        • Janowitz W.R.
        • Hildner F.J.
        • Zusmer N.R.
        • Viamonte Jr., M.
        • Detrano R.
        Quantification of coronary artery calcium using ultrafast computed tomography.
        J Am Coll Cardiol. 1990; 15: 827-832
        • Choi E.Y.
        • Bahrami H.
        • Wu C.O.
        • Greenland P.
        • Cushman M.
        • Daniels L.B.
        • Almeida A.L.
        • Yoneyama K.
        • Opdahl A.
        • Jain A.
        • Criqui M.H.
        • Siscovick D.
        • Darwin C.
        • Maisel A.
        • Bluemke D.A.
        • Lima J.A.
        N-terminal pro-B-type natriuretic peptide, left ventricular mass, and incident heart failure: Multi-Ethnic Study of Atherosclerosis.
        Circ Heart Fail. 2012; 5: 727-734
        • Fine J.P.
        • Gray R.J.
        A proportional hazards model for the subdistribution of a competing risk.
        J Am Stat Assoc. 1999; 94: 496-509
        • Seliger S.L.
        • de Lemos J.
        • Neeland I.J.
        • Christenson R.
        • Gottdiener J.
        • Drazner M.H.
        • Berry J.
        • Sorkin J.
        • deFilippi C.
        Older Adults, “malignant” left ventricular hypertrophy, and associated cardiac-specific biomarker phenotypes to identify the differential risk of new-onset reduced versus preserved ejection fraction heart failure: CHS (Cardiovascular Health Study).
        JACC Heart Fail. 2015; 3: 445-455
        • Owan T.E.
        • Hodge D.O.
        • Herges R.M.
        • Jacobsen S.J.
        • Roger V.L.
        • Redfield M.M.
        Trends in prevalence and outcome of heart failure with preserved ejection fraction.
        N Engl J Med. 2006; 355: 251-259
        • Lenzen M.J.
        • Scholte op Reimer W.J.
        • Boersma E.
        • Vantrimpont P.J.
        • Follath F.
        • Swedberg K.
        • Cleland J.
        • Komajda M.
        Differences between patients with a preserved and a depressed left ventricular function: a report from the EuroHeart Failure Survey.
        Eur Heart J. 2004; 25: 1214-1220
        • Gerber Y.
        • Weston S.A.
        • Berardi C.
        • McNallan S.M.
        • Jiang R.
        • Redfield M.M.
        • Roger V.L.
        Contemporary trends in heart failure with reduced and preserved ejection fraction after myocardial infarction: a community study.
        Am J Epidemiol. 2013; 178: 1272-1280
        • Gerber Y.
        • Weston S.A.
        • Enriquez-Sarano M.
        • Berardi C.
        • Chamberlain A.M.
        • Manemann S.M.
        • Jiang R.
        • Dunlay S.M.
        • Roger V.L.
        Mortality associated with heart failure after myocardial infarction: a contemporary community perspective.
        Circ Heart Fail. 2016; 9: e002460
        • Paulus W.J.
        • Tschöpe C.
        A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation.
        J Am Coll Cardiol. 2013; 62: 263-271
        • Van Tassell B.W.
        • Arena R.
        • Biondi-Zoccai G.
        • McNair Canada J.
        • Oddi C.
        • Abouzaki N.A.
        • Jahangiri A.
        • Falcao R.A.
        • Kontos M.C.
        • Shah K.B.
        • Voelkel N.F.
        • Dinarello C.A.
        • Abbate A.
        Effects of interleukin-1 blockade with anakinra on aerobic exercise capacity in patients with heart failure and preserved ejection fraction (from the D-HART pilot study).
        Am J Cardiol. 2014; 113: 321-327
        • McDonald K.
        • Murphy T.
        Predict, protect, prevent: working toward a personalized approach to heart failure prevention.
        JACC Heart Fail. 2015; 3: 456-458
        • Ledwidge M.
        • Gallagher J.
        • Conlon C.
        • Tallon E.
        • O'Connell E.
        • Dawkins I.
        • Watson C.
        • O'Hanlon R.
        • Bermingham M.
        • Patle A.
        • Badabhagni M.R.
        • Murtagh G.
        • Voon V.
        • Tilson L.
        • Barry M.
        • McDonald L.
        • Maurer B.
        • McDonald K.
        Natriuretic peptide-based screening and collaborative care for heart failure: the STOP-HF randomized trial.
        JAMA. 2013; 310: 66-74