Heart failure development in obesity: underlying risk factors and mechanistic pathways

Abstract

Aims People with obesity are at risk for developing heart failure (HF), but little is known about the mechanistic pathways that link obesity with cardiac dysfunction. Methods and results We included 2030 participants from the Swedish Obese Subjects study who received conventional obesity treatment. First‐time detection of HF was obtained by cross‐checking the study population with the Swedish National Patient Register and the Swedish Cause of Death Register. We also examined if atrial fibrillation and myocardial infarction as time‐dependent variables could predict incident HF The mean age of the study cohort was 48.7 years, and 28% were men. The mean body mass index at baseline was 40.1 kg/m2 and remained stable during a median follow‐up of 20.1 years. First‐time diagnosis of HF occurred in 266 of patients and was related to male sex, increasing age, greater waist–hip ratio, hypertension, higher cholesterol, diabetes mellitus, and elevated free thyroxine in univariable analysis. Estimated glomerular filtration rate was negatively related to HF risk. In multivariable analysis, atrial fibrillation, which is related to HF with preserved ejection fraction (HFpEF), and myocardial infarction, which is linked to HF with reduced ejection fraction (HFrEF), were strongly associated with incident HF with sub‐hazard ratios 3.75 (95% confidence interval: 2.72–5.18, P < 0.001) and 3.68 (95% confidence interval: 2.55–5.30, P < 0.001), respectively. Conclusions Both atrial fibrillation and myocardial infarction as time‐dependent variables were independently and strongly related to incident HF in people with excess body fat, suggesting two main obesity‐related mechanistic pathways leading to either HFpEF or HFrEF.

Regional Adiposity and Risk of Heart Failure and Mortality: The Jackson Heart Study

“…Our interaction analyses also demonstrated an association between VAT and mortality dependent on BMI at low BMI, yet similar to other studies, these interactions were not present at BMI values in the range of obesity. 9 Furthermore, CVD risk factors, such as diabetes mellitus, hypertension, and hyperlipidemia, likely serve as mediators between the pathophysiologic mechanisms of regional adiposity and incident HF and its subtypes, 15 , 19 which may explain the attenuated, nonsignificant association between VAT and mortality. This may additionally explain the smaller, but still statistically significant, associations between PAT or VAT on incident HF hospitalization and PAT and mortality in the fully adjusted models compared with our primary models.…”

A year in heart failure: an update of recent findings

“…1 CV comorbidities include hypertension, 20 coronary artery disease, 21 atrial fibrillation (AF), 22 ventricular arrhythmias, valvular heart disease, [23][24][25] cerebrovascular disease, and pulmonary hypertension. Non-CV comorbidities include chronic kidney disease 26,27 and electrolyte disorders, 28,29 DM, 30 obesity, [31][32][33][34] cachexia, [35][36][37][38] sarcopenia, [37][38][39][40][41][42] chronic obstructive pulmonary disease, 19,43 iron deficiency 44,45 and anaemia, 46,47 thyroid disorders, 48 cancer, [49][50][51] infection, 52,53 arthritis, 54,55 frailty, 56,57 and depression. The clinical burden of comorbidities differs between patients with HFrEF and those with HFpEF.…”

Mitochondrial Oxidative Stress Induces Cardiac Fibrosis in Obese Rats through Modulation of Transthyretin

“…Obesity has a considerable impact on metabolism, affecting the entire organism [ 1 ] and predisposing to comorbidities such as cancer [ 2 ], hypertension [ 3 ], insulin resistance and diabetes [ 4 ], neurological disorders [ 5 ] and cardiovascular diseases, including heart failure [ 1 ]. At the cardiac level, obesity exponentially increases the risk of heart failure development due to the impact of obesity on the heart [ 6 ]. An excessive body weight generates higher metabolic demands with consequent increases in cardiac output and workload [ 7 ].…”