EPIDEMIOLOGIC CHARACTERIZATION OF THE RELATIONSHIP OF OBESITY WITH SUBCLINICAL MYOCARDIAL INJURY AND HEART FAILURE
Ndumele, Chiadi E
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Obesity is a potent risk factor for heart failure (HF), a cardiovascular condition associated with high morbidity and mortality. However, the relationship between obesity and HF has not been fully characterized. Prior data suggest that obesity may be independently linked to HF. However, there are limited comparisons of the relationship of obesity to various forms of cardiovascular disease (CVD), including HF, coronary heart disease (CHD) and stroke, including the extent to which they are unexplained by traditional mediators of CVD, such as hypertension, dyslipidemia and diabetes. Furthermore, the pathways linking obesity to HF are incompletely understood, with a growing body of laboratory and clinical data suggesting direct toxic effects of obesity on heart muscle. Additionally, the prognostic impact of weight history on HF risk is presently unknown. Therefore, in the following epidemiologic analyses, we compared the associations of obesity with incident HF, CHD and stroke before and after adjusting for traditional CVD mediators (Aim 1); evaluated the cross-sectional association between obesity and a novel biomarker of subclinical myocardial injury, a high sensitivity assay for troponin T (hs-cTnT), and to assess the combined prospective associations of obesity and elevated hs-cTnT with incident HF (Aim 2); assessed the prognostic impact of several weight history metrics on the risk of incident HF (Aim 3); and evaluated the relationship between weight history and myocardial injury, as assessed by hs-cTnT (Aim 4). We demonstrated that: obesity has the strongest association with incident HF among CVD subtypes, and that among CVD subtypes, the association of obesity with HF is uniquely unexplained by traditional risk factors; obesity is independently associated with elevated hs-cTnT and the combination of severe obesity and elevated hs-cTnT is associated with a greater than 9-fold higher risk of incident HF compared to those with normal weight and undetectable hs-cTnT; and that past excess weight and increasing weight over time are significantly associated with incident HF and elevated hs-cTnT, with perhaps the most useful prognostic information provided by cumulative weight. This work has advanced knowledge regarding the epidemiologic association between obesity and HF and potential pathways underlying this relationship.