Heart failure is a leading cause of morbidity and mortality and its prevalence continues to rise. Because obesity has been linked with heart failure, the increasing prevalence of obesity may presage further rise in heart failure in the future. Obesity-related factors are estimated to cause 11% of heart failure cases in men and 14% in women. Obesity may result in heart failure by inducing hemodynamic and myocardial changes that lead to cardiac dysfunction, or due to an increased predisposition to other heart failure risk factors. Direct cardiac lipotoxicity has been described where lipid accumulation in the heart results in cardiac dysfunction inexplicable of other heart failure risk factors. In this overview, we discussed various pathophysiological mechanisms that could lead to heart failure in obesity, including the molecular mechanisms underlying cardiac lipotoxicity. We defined the obesity paradox and enumerated various premises for the paradoxical associations observed in the relationship between obesity and heart failure.

Objective To evaluate associations of early menopause (menopause occurring before 45 years of age) and age at menopause with incident heart failure (HF) in post-menopausal women. We also explored associations of early, and age at menopause with left ventricular (LV) measures of structure and function in post-menopausal women. Methods We included 2947 post-menopausal women, aged 45-84 years, without known cardiovascular disease (2000-2002), from the Multi-Ethnic study of Atherosclerosis. Cox-Proportional hazards models were used to examine associations of early, and age at menopause with incident HF. In 2123 post-menopausal women in whom cardiac magnetic resonance imaging was obtained at baseline, we explored associations of early, and age at menopause with LV measures using multivariable linear regression. Results Over a median follow-up of 8.5 years, we observed 71 HF events. There were no significant interactions with ethnicity for incident HF (Pinteraction>0.05). In adjusted analysis, early menopause was associated with increased risk of incident HF [1.66 (1.01-2.73)], while each year increase in age at menopause was associated with decreased risk of incident HF [0.96 (0.94-0.99)]. We observed significant interactions between early menopause and ethnicity for LV mass to volume ratio (LVMVR), Pinteraction=0.02. In Chinese-American women, early menopause was associated with higher LVMVR (+0.11, p=0.0002), while each year increase in age at menopause was associated with lower LVMVR (−0.004, p=0.04) at baseline. Conclusion An older menopausal age is independently associated with decreased risk of incident HF. Concentric LV remodelling, indicated by a higher LVMVR was present in Chinese-American women with early menopause at baseline.

Author Contributions: Drs Beard and Morrison had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Background Dyslipidemia is a known risk factor for coronary disease, but its role in heart failure (HF) development is less well-defined. Methods and Results We included 5688 participants, aged 45 to 84 years, without clinical cardiovascular disease, and not receiving lipid-lowering medications at baseline, from the Multiethnic Study of Atherosclerosis. Cox-proportional hazards models were used to evaluate associations of triglyceride, total cholesterol/high-density lipoprotein–cholesterol (HDL-C) ratio, HDL-C, and non HDL-C with incident HF. We investigated for effect-modification by diabetes mellitus status and sex. During a median follow-up of 8.5 years, there were 152 incident HF cases. There were no interactions by sex. We observed significant interactions between triglyceride and diabetes mellitus (Pinteraction<0.05). We stratified our analyses by diabetes mellitus status. In participants with diabetes, the hazard ratios were 2.03 (0.97–4.27) and 1.68 (1.18–2.38) for high triglyceride and log of triglyceride, respectively, after adjusting for confounders, comorbidities, and diabetes mellitus severity/treatment. The association of high triglyceride with incident HF was attenuated by interim myocardial infarction. The hazard ratios were greatest in participants with diabetes who also had high triglyceride, low HDL-C, or high total cholesterol/HDL-C ratio (3.59 [2.03–6.33], 3.62 [2.06–6.36], and 3.54 [1.87–6.70], respectively). Lipid measures were not associated with incident HF in individuals without diabetes. Conclusions The risk of incident HF is greater in individuals with diabetes mellitus who also have high triglyceride, low HDL-C, or high total cholesterol/HDL-C ratio. The association of high triglyceride with incident HF is partly mediated by myocardial infarction.