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The association of resistin with cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis

      Highlights

      • We examined the association of plasma resistin levels and cardiovascular disease.
      • Events included AF, MI, angina, resuscitated cardiac arrest, stroke, HF and death.
      • Increased resistin was associated with HF, atherosclerotic CVD (all & hard) and CHD.
      • Associations remained significant after adjustment for traditional CV risk factors.
      • The association of resistin and CV events was greatest in the Hispanic population.

      Abstract

      Objective: To describe the relationship between circulating resistin levels and cardiovascular diseases (CVD) and all-cause death in a multi-ethnic cohort. Methods and results: We studied 1913 participants from the Multi-Ethnic Study of Atherosclerosis with measurements of plasma resistin levels. Absolute proportions experiencing new-onset atrial fibrillation (AF), atherosclerotic CVD (myocardial infarction, angina, resuscitated cardiac arrest, stroke), heart failure (HF), and all-cause death were calculated for each quartile of resistin. We used adjusted Cox proportional regression modeling resistin as a continuous variable per standard deviation of log-transformed resistin and secondarily as a categorical variable using resistin quartiles. Results were stratified by sex and race/ethnicity. The mean age of the population was 64.5 ± 10 years with half being female and a median resistin concentration of 15.1 ng/mL (11.9–19.1). Mean follow-up time was 7.2 ± 1.8 years. There was a graded increase in the occurrence of all outcomes across increasing quartiles of resistin. Modeled as a continuous variable, after adjustment for anthropomorphic measures, traditional risk factors, markers of inflammation, and other adipokines, significant associations were noted for HF (HR 1.4, CI 1.0–2.0), hard and all CVD (HR 1.3, 1.1–1.7 and 1.3, 1.1–1.6, respectively), and CHD (HR 1.31, 1.0–1.6), but not for AF or death. Significant interaction terms were noted between resistin and race, with Hispanic race/ethnicity showing the strongest relationship between resistin and outcomes. Conclusions: In an ethnically diverse population without known CVD at baseline, there was a strong, independent association between higher resistin levels and incident CVD, CHD and HF.

      Keywords

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      References

        • Murray C.J.L.
        • Lopez A.D.
        Measuring the global burden of disease.
        N. Engl. J. Med. 2013; 369: 448-457https://doi.org/10.1056/NEJMra1201534
        • Go A.S.
        • Mozaffarian D.
        • Roger V.L.
        • et al.
        Heart disease and stroke statistics–2014 update: a report from the American Heart Association.
        Circulation. 2013; 129: e28-e292https://doi.org/10.1161/01.cir.0000441139.02102.80
        • Lavie C.J.
        • Milani R.V.
        • Ventura H.O.
        Obesity and cardiovascular disease: risk factor, paradox, and impact of weight loss.
        J. Am. Coll. Cardiol. 2009; 53: 1925-1932https://doi.org/10.1016/j.jacc.2008.12.068
        • Lee S.E.
        • Kim H.-S.
        Human resistin in cardiovascular disease.
        J. Smooth Muscle Res. 2012; 48: 27-35
        • Schwartz D.
        • Lazar M.
        Human resistin: found in translation from mouse to man.
        Trends Endocrinol. Metab. 2011; 22: 259-265https://doi.org/10.1016/j.tem.2011.03.005.Human
        • Gualillo O.
        • González-Juanatey J.R.
        • Lago F.
        The emerging role of adipokines as mediators of cardiovascular function: physiologic and clinical perspectives.
        Trends Cardiovasc. Med. 2007; 17: 275-283https://doi.org/10.1016/j.tcm.2007.09.005
        • Steppan C.M.
        • Bailey S.T.
        • Bhat S.
        • et al.
        The hormone resistin links obesity to diabetes.
        Nature. 2001; 409: 307-312https://doi.org/10.1038/35053000
        • Steppan C.M.
        • Lazar M.A.
        The current biology of resistin.
        J. Intern. Med. 2004; 255: 439-447https://doi.org/10.1111/j.1365-2796.2004.01306.x
        • Muse E.D.
        • Obici S.
        • Bhanot S.
        • et al.
        Role of resistin in diet-induced hepatic insulin resistance.
        J. Clin. Invest. 2004; 114: 232-239https://doi.org/10.1172/JCI21270
        • Kaser S.
        • Kaser A.
        • Sandhofer A.
        • Ebenbichler C.F.
        • Tilg H.
        • Patsch J.R.
        Resistin messenger-RNA expression is increased by proinflammatory cytokines in vitro.
        Biochem. Biophys. Res. Commun. 2003; 309: 286-290https://doi.org/10.1016/j.bbrc.2003.07.003
        • Reilly M.P.
        • Lehrke M.
        • Wolfe M.L.
        • Rohatgi A.
        • Lazar M.A.
        • Rader D.J.
        Resistin is an inflammatory marker of atherosclerosis in humans.
        Circulation. 2005; 111: 932-939https://doi.org/10.1161/01.CIR.0000155620.10387.43
        • Shetty G.K.
        • Economides P.A.
        • Horton E.S.
        • Mantzoros C.S.
        • Veves A.
        Circulating adiponectin and resistin levels in relation to metabolic factors, inflammatory markers, and vascular reactivity in diabetic patients and subjects at risk for diabetes.
        Diabetes Care. 2004; : 2450-2457https://doi.org/10.2337/diacare.27.10.2450
        • Bokarewa M.
        • Nagaev I.
        • Dahlberg L.
        • Smith U.
        • Tarkowski A.
        Resistin, an adipokine with potent proinflammatory properties.
        J. Immunol. 2005; 174: 5789-5795https://doi.org/10.1042/CS20050078
        • Lehrke M.
        • Reilly M.P.
        • Millington S.C.
        • Iqbal N.
        • Rader D.J.
        • Lazar M.A.
        An inflammatory cascade leading to hyperresistinemia in humans.
        PLoS Med. 2004; 1: e45https://doi.org/10.1371/journal.pmed.0010045
        • Qasim A.N.
        • Metkus T.S.
        • Tadesse M.
        • et al.
        Resistin gene variation is associated with systemic inflammation but not plasma adipokine levels, metabolic syndrome or coronary atherosclerosis in nondiabetic Caucasians.
        Clin. Endocrinol. (Oxf). 2009; 70: 698-705https://doi.org/10.1111/j.1365-2265.2008.03375.x
        • Aquilante C.L.
        • Kosmiski L a
        • Knutsen S.D.
        • Zineh I.
        Relationship between plasma resistin concentrations, inflammatory chemokines, and components of the metabolic syndrome in adults.
        Metabolism. 2008; 57: 494-501https://doi.org/10.1016/j.metabol.2007.11.010
        • Ntaios G.
        • Gatselis N.K.
        • Makaritsis K.
        • Dalekos G.N.
        Adipokines as mediators of endothelial function and atherosclerosis.
        Atherosclerosis. 2013; 227: 216-221https://doi.org/10.1016/j.atherosclerosis.2012.12.029
        • Burnett M.S.
        • Lee C.W.
        • Kinnaird T.D.
        • et al.
        The potential role of resistin in atherogenesis.
        Atherosclerosis. 2005; 182: 241-248https://doi.org/10.1016/j.atherosclerosis.2005.02.014
        • Kim M.
        • Oh J.K.
        • Sakata S.
        • et al.
        Role of resistin in cardiac contractility and hypertrophy.
        J. Mol. Cell. Cardiol. 2008; 45: 270-280https://doi.org/10.1016/j.yjmcc.2008.05.006
        • Melone M.
        • Wilsie L.
        • Palyha O.
        • Strack A.
        • Rashid S.
        Discovery of a new role of human resistin in hepatocyte low-density lipoprotein receptor suppression mediated in part by proprotein convertase subtilisin/kexin type 9.
        J. Am. Coll. Cardiol. 2012; 59: 1697-1705https://doi.org/10.1016/j.jacc.2011.11.064
        • Frankel D.S.
        • Vasan R.S.
        • D'Agostino R.B.
        • et al.
        Resistin, adiponectin, and risk of heart failure the Framingham offspring study.
        J. Am. Coll. Cardiol. 2009; 53: 754-762https://doi.org/10.1016/j.jacc.2008.07.073
        • Lim S.
        • Koo B.K.
        • Cho S.W.
        • et al.
        Association of adiponectin and resistin with cardiovascular events in Korean patients with type 2 diabetes: the Korean atherosclerosis study (KAS): a 42-month prospective study.
        Atherosclerosis. 2008; 196: 398-404https://doi.org/10.1016/j.atherosclerosis.2006.11.017
        • Luc G.
        • Empana J.-P.
        • Morange P.
        • et al.
        Adipocytokines and the risk of coronary heart disease in healthy middle aged men: the PRIME Study.
        Int. J. Obes. (Lond). 2010; 34: 118-126https://doi.org/10.1038/ijo.2009.204
        • Menzaghi C.
        • Bacci S.
        • Salvemini L.
        • et al.
        Serum resistin, cardiovascular disease and all-cause mortality in patients with type 2 diabetes.
        PLoS One. 2013; 8: e64729https://doi.org/10.1371/journal.pone.0064729
        • Yin W.-H.
        • Wei J.
        • Huang W.-P.
        • Chen J.-W.
        • Young M.S.
        • Lin S.-J.
        Prognostic value of circulating adipokine levels and expressions of adipokines in the myocardium of patients with chronic heart failure.
        Circ. J. 2012; 76: 2139-2147https://doi.org/10.1253/circj.CJ-11-1549
        • Bild D.E.
        • Bluemke D.A.
        • Burke G.L.
        • et al.
        Multi-ethnic study of atherosclerosis: objectives and design.
        Am. J. Epidemiol. 2002; 156: 871-881https://doi.org/10.1093/aje/kwf113
        • Rienstra M.
        • Sun J.X.
        • Lubitz S a
        • et al.
        Plasma resistin, adiponectin, and risk of incident atrial fibrillation: the Framingham offspring study.
        Am. Heart J. 2012; 163: 119-124.e1https://doi.org/10.1016/j.ahj.2011.09.029
        • Butler J.
        • Kalogeropoulos A.
        • Georgiopoulou V.
        • et al.
        Serum resistin concentrations and risk of new onset heart failure in older persons: the health, aging, and body composition (Health ABC) study.
        Arterioscler. Thromb. Vasc. Biol. 2009; 29: 1144-1149https://doi.org/10.1161/ATVBAHA.109.186783
        • Schulze P.C.
        • Biolo A.
        • Gopal D.
        • et al.
        Dynamics in insulin resistance and plasma levels of adipokines in patients with acute decompensated and chronic stable heart failure.
        J. Card. Fail. 2011; 17: 1004-1011https://doi.org/10.1016/j.cardfail.2011.08.010
        • Zhang M.H.
        • Na B.
        • Schiller N.B.
        • Whooley M.A.
        Association of resistin with heart failure and mortality in patients with stable coronary heart disease: data from the heart and soul study.
        J. Card. Fail. 2011; 17: 24-30https://doi.org/10.1016/j.cardfail.2010.08.007
        • Bobbert P.
        • Jenke A.
        • Bobbert T.
        • et al.
        High leptin and resistin expression in chronic heart failure: adverse outcome in patients with dilated and inflammatory cardiomyopathy.
        Eur. J. Heart Fail. 2012; 14: 1265-1275https://doi.org/10.1093/eurjhf/hfs111
        • Khan R.S.
        • Kato T.S.
        • Chokshi A.
        • et al.
        Adipose tissue inflammation and adiponectin resistance in patients with advanced heart failure: correction after ventricular assist device implantation.
        Circ. Heart Fail. 2012; 5: 340-348https://doi.org/10.1161/CIRCHEARTFAILURE.111.964031
        • Allison M.A.
        • Bluemke D.A.
        • McClelland R.
        • et al.
        Relation of leptin to left ventricular hypertrophy (from the Multi-Ethnic Study of Atherosclerosis).
        Am. J. Cardiol. 2013; 112: 726-730https://doi.org/10.1016/j.amjcard.2013.04.053
        • McManus D.D.
        • Lyass A.
        • Ingelsson E.
        • et al.
        Relations of circulating resistin and adiponectin and cardiac structure and function: the Framingham offspring study.
        Obes. (Silver Spring). 2012; 20: 1882-1886https://doi.org/10.1038/oby.2011.32
        • Filková M.
        • Haluzík M.
        • Gay S.
        • Senolt L.
        The role of resistin as a regulator of inflammation: implications for various human pathologies.
        Clin. Immunol. 2009; 133: 157-170https://doi.org/10.1016/j.clim.2009.07.013
        • Özcan K.S.
        • Güngör B.
        • Altay S.
        • et al.
        Increased level of resistin predicts development of atrial fibrillation.
        J. Cardiol. 2014; 63: 308-312https://doi.org/10.1016/j.jjcc.2013.10.008
        • Rubio-Guerra A.F.
        • Cabrera-Miranda L.J.
        • Vargas-Robles H.
        • Maceda-Serrano A.
        • Lozano-Nuevo J.J.
        • Escalante-Acosta B.A.
        Correlation between levels of circulating adipokines and adiponectin/resistin index with carotid intima-media thickness in hypertensive type 2 diabetic patients.
        Cardiology. 2013; 125: 150-153https://doi.org/10.1159/000348651
        • Choi H.Y.
        • Kim S.
        • Yang S.J.
        • et al.
        Association of adiponectin, resistin, and vascular inflammation: analysis with 18F-fluorodeoxyglucose positron emission tomography.
        Arterioscler. Thromb. Vasc. Biol. 2011; 31: 944-949https://doi.org/10.1161/ATVBAHA.110.220673