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Updated: Nov 29, 2025
Author Spotlight: Exploring the Relationship Between Lipotoxicity and HFpEF
Published on: March 29, 2024
Heart failure development in obesity: underlying risk factors and mechanistic pathways
Shabbar Jamaly1,2, Lena Carlsson2, Markku Peltonen3
1Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, 41345, Sweden.
Insights
Obesity increases heart failure risk through two main pathways: atrial fibrillation linked to HFpEF and myocardial infarction linked to HFrEF. These conditions independently predict heart failure in individuals with excess body fat.
Area of Science:
- Cardiology
- Metabolic Disorders
- Public Health
Background:
- Obesity is a significant risk factor for developing heart failure (HF).
- The specific mechanistic links between obesity and cardiac dysfunction remain incompletely understood.
- Understanding these pathways is crucial for targeted prevention and treatment strategies.
Purpose of the Study:
- To investigate the mechanistic pathways linking obesity to cardiac dysfunction and incident heart failure.
- To examine the independent predictive value of atrial fibrillation and myocardial infarction for heart failure in an obese population.
Main Methods:
- Utilized data from 2030 participants in the Swedish Obese Subjects study.
- Incident heart failure (HF) was identified through national patient and death registers.
- Atrial fibrillation and myocardial infarction were analyzed as time-dependent predictors of HF over a median follow-up of 20.1 years.
Main Results:
- Incident HF occurred in 266 patients, associated with male sex, age, waist-hip ratio, hypertension, high cholesterol, diabetes, and elevated free thyroxine.
- Estimated glomerular filtration rate showed a negative relationship with HF risk.
- Atrial fibrillation and myocardial infarction were strongly and independently associated with incident HF (SHRs 3.75 and 3.68, respectively).
Conclusions:
- Atrial fibrillation and myocardial infarction are independently associated with incident heart failure in individuals with obesity.
- These findings suggest distinct obesity-related mechanistic pathways leading to HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF).
- Identifying these pathways can inform the development of targeted interventions for obesity-related cardiovascular complications.
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.
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