Relation of Leptin to Left Ventricular Hypertrophy (from the Multi-Ethnic Study of Atherosclerosis)

      Increasing adiposity increases the risk for left ventricular (LV) hypertrophy. Adipokines are hormone-like substances from adipose tissue that influence several metabolic pathways relevant to LV hypertrophy. Data were obtained from participants enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA) who underwent magnetic resonance imaging of the heart and who also had fasting venous blood assayed for 4 distinct adipokines (adiponectin, leptin, tumor necrosis factor-α, and resistin). One-thousand four hundred sixty four MESA participants had complete data. The mean age was 61.5 years, the mean body mass index was 27.6 kg/m2, and 49% were women. With adjustment for age, gender, race, height, and weight, multivariate linear regression modeling revealed that a 1-SD increment in leptin was significantly associated with smaller LV mass (ß: −4.66% predicted, p <0.01), LV volume (−5.87% predicted, p <0.01), stroke volume (−3.23 ml, p <0.01), and cardiac output (−120 ml/min, p = 0.01) as well as a lower odds ratio for the presence of LV hypertrophy (odds ratio 0.65, p <0.01), but a higher ejection fraction (0.44%, p = 0.05). Additional adjustment for the traditional cardiovascular disease risk factors, insulin resistance, physical activity, education, income, inflammatory biomarkers, other selected adipokines, and pericardial fat did not materially change the magnitude or significance of the associations. The associations between the other adipokines and LV structure and function were inconsistent and largely nonsignificant. In conclusion, the results indicate that higher levels of leptin are associated with more favorable values of several measures of LV structure and function.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Turkbey E.B.
        • McClelland R.L.
        • Kronmal R.A.
        • Burke G.L.
        • Bild D.E.
        • Tracy R.P.
        • Arai A.E.
        • Lima J.A.
        • Bluemke D.A.
        The impact of obesity on the left ventricle: the Multi-Ethnic Study of Atherosclerosis (MESA).
        JACC Cardiovasc Imaging. 2010; 3: 266-274
        • de Simone G.
        • Devereux R.B.
        • Roman M.J.
        • Alderman M.H.
        • Laragh J.H.
        Relation of obesity and gender to left ventricular hypertrophy in normotensive and hypertensive adults.
        Hypertension. 1994; 23: 600-606
        • McGavock J.M.
        • Victor R.G.
        • Unger R.H.
        • Szczepaniak L.S.
        Adiposity of the heart, revisited.
        Ann Intern Med. 2006; 144: 517-524
        • Montani J.P.
        • Carroll J.F.
        • Dwyer T.M.
        • Antic V.
        • Yang Z.
        • Dulloo A.G.
        Ectopic fat storage in heart, blood vessels and kidneys in the pathogenesis of cardiovascular diseases.
        Int J Obes Relat Metab Disord. 2004; 28: S58-S65
        • Fantuzzi G.
        Adipose tissue, adipokines, and inflammation.
        J Allergy Clin Immunol. 2005; 115: 911-919
        • Moran O.
        • Phillip M.
        Leptin: obesity, diabetes and other peripheral effects—a review.
        Pediatr Diabetes. 2003; 4: 101-109
        • 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
        • Natori S.
        • Lai S.
        • Finn J.P.
        • Gomes A.S.
        • Hundley W.G.
        • Jerosch-Herold M.
        • Pearson G.
        • Sinha S.
        • Arai A.
        • Lima J.A.C.
        • Bluemke D.A.
        Cardiovascular function in Multi-Ethnic Study of Atherosclerosis: normal values by age, sex, and ethnicity.
        Am J Roentgenol. 2006; 186: S357-S365
        • Bluemke D.A.
        • Kronmal R.A.
        • Lima J.A.
        • Liu K.
        • Olson J.
        • Burke G.L.
        • Folsom A.R.
        The relationship of left ventricular mass and geometry to incident cardiovascular events: the MESA (Multi-Ethnic Study of Atherosclerosis) study.
        J Am Coll Cardiol. 2008; 52: 2148-2155
        • Heckbert S.R.
        • Post W.
        • Pearson G.D.N.
        • Arnett D.K.
        • Gomes A.S.
        • Jerosch-Herold M.
        • Hundley W.G.
        • Lima J.A.
        • Bluemke D.A.
        Traditional cardiovascular risk factors in relation to left ventricular mass, volume, and systolic function by cardiac magnetic resonance imaging: the Multiethnic Study of Atherosclerosis.
        J Am Coll Cardiol. 2006; 48: 2285-2292
        • Ding J.
        • Hsu F.C.
        • Harris T.B.
        • Liu Y.
        • Kritchevsky S.B.
        • Szklo M.
        • Ouyang P.
        • Espeland M.A.
        • Lohman K.K.
        • Criqui M.H.
        • Allison M.
        • Bluemke D.A.
        • Carr J.J.
        The association of pericardial fat with incident coronary heart disease: the Multi-Ethnic Study of Atherosclerosis (MESA).
        Am J Clin Nutr. 2009; 90: 499-504
        • Brumback L.C.
        • Kronmal R.
        • Heckbert S.R.
        • Ni H.
        • Hundley W.G.
        • Lima J.A.
        • Bluemke D.A.
        Body size adjustments for left ventricular mass by cardiovascular magnetic resonance and their impact on left ventricular hypertrophy classification.
        Int J Cardiovasc Imaging. 2010; 26: 459-468
        • Belgardt B.F.
        • Bruning J.C.
        CNS leptin and insulin action in the control of energy homeostasis.
        Ann N Y Acad Sci. 2010; 1212: 97-113
        • Steinberg G.R.
        • Parolin M.L.
        • Heigenhauser G.J.
        • Dyck D.J.
        Leptin increases FA oxidation in lean but not obese human skeletal muscle: evidence of peripheral leptin resistance.
        Am J Physiol Endocrinol Metab. 2002; 283: E187-E192
        • Barouch L.A.
        • Berkowitz D.E.
        • Harrison R.W.
        • O'Donnell C.P.
        • Hare J.M.
        Disruption of leptin signaling contributes to cardiac hypertrophy independently of body weight in mice.
        Circulation. 2003; 108: 754-759
        • Lee Y.
        • Naseem R.H.
        • Duplomb L.
        • Park B.H.
        • Garry D.J.
        • Richardson J.A.
        • Schaffer J.E.
        • Unger R.H.
        Hyperleptinemia prevents lipotoxic cardiomyopathy in acyl CoA synthase transgenic mice.
        Proc Natl Acad Sci U S A. 2004; 101: 13624-13629
        • Trivedi P.
        • Yang R.
        • Barouch L.A.
        Decreased p110alpha catalytic activity accompanies increased myocyte apoptosis and cardiac hypertrophy in leptin deficient ob/ob mice.
        Cell Cycle. 2008; 7: 560-565
        • Perego L.
        • Pizzocri P.
        • Corradi D.
        • Maisano F.
        • Paganelli M.
        • Fiorina P.
        • Barbieri M.
        • Morabito A.
        • Paolisso G.
        • Folli F.
        • Pontiroli A.E.
        Circulating leptin correlates with left ventricular mass in morbid (grade III) obesity before and after weight loss induced by bariatric surgery: a potential role for leptin in mediating human left ventricular hypertrophy.
        J Clin Endocrinol Metab. 2005; 90: 4087-4093
        • Heymsfield S.B.
        • Greenberg A.S.
        • Fujioka K.
        • Dixon R.M.
        • Kushner R.
        • Hunt T.
        • Lubina J.A.
        • Patane J.
        • Self B.
        • Hunt P.
        • McCamish M.
        Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial.
        JAMA. 1999; 282: 1568-1575
        • Meier U.
        • Gressner A.M.
        Endocrine regulation of energy metabolism: review of pathobiochemical and clinical chemical aspects of leptin, ghrelin, adiponectin, and resistin.
        Clin Chem. 2004; 50: 1511-1525
        • Rahmouni K.
        • Haynes W.G.
        • Morgan D.A.
        • Mark A.L.
        Selective resistance to central neural administration of leptin in agouti obese mice.
        Hypertension. 2002; 39: 486-490
        • Paolisso G.
        • Tagliamonte M.R.
        • Galderisi M.
        • Zito G.A.
        • Petrocelli A.
        • Carella C.
        • de Divitiis O.
        • Varricchio M.
        Plasma leptin level is associated with myocardial wall thickness in hypertensive insulin-resistant men.
        Hypertension. 1999; 34: 1047-1052
        • Yang R.
        • Barouch L.A.
        Leptin signaling and obesity: cardiovascular consequences.
        Circ Res. 2007; 101: 545-559
        • Pladevall M.
        • Williams K.
        • Guyer H.
        • Sadurni J.
        • Falces C.
        • Ribes A.
        • Pare C.
        • Brotons C.
        • Gabriel R.
        • Serrano-Rios M.
        • Haffner S.
        The association between leptin and left ventricular hypertrophy: a population-based cross-sectional study.
        J Hypertens. 2003; 21: 1467-1473
        • Di Blasio A.
        • Di Donato F.
        • De Stefano A.
        • Gallina S.
        • Granieri M.
        • Napolitano G.
        • Petrella V.
        • Riccardi I.
        • Santarelli F.
        • Valentini P.
        • Ripari P.
        Left ventricle relative wall thickness and plasma leptin levels: baseline relationships and effects of 4 months of walking training in healthy overweight postmenopausal women.
        Menopause. 2011; 18: 77-84
        • Lieb W.
        • Sullivan L.M.
        • Aragam J.
        • Harris T.B.
        • Roubenoff R.
        • Benjamin E.J.
        • Vasan R.S.
        Relation of serum leptin with cardiac mass and left atrial dimension in individuals >70 years of age.
        Am J Cardiol. 2009; 104: 602-605