E2 ModerateModerate confidencePEM not requiredObservationalPeer-reviewedReviewed
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Obesity and inactivity cluster the strongest risk factor for the development of heart failure in a population-based study.
van Essen, Bart J, Dan, Nathalie Ang En, Tharsana, Ganash N et al. · International journal of cardiology · 2026 · DOI
Quick Summary
This study found that people with a combination of obesity and physical inactivity have the highest risk of developing heart failure compared to other groups with different health problems. Researchers followed nearly 7,000 people for about 10 years and identified six distinct groups based on their health conditions, discovering that the obesity and inactivity group had almost 4 times higher risk of heart failure than the healthiest group.
Why It Matters
ME/CFS patients often experience cardiovascular complications and comorbid conditions including post-exertional malaise limiting physical activity. This study's systematic approach to understanding how comorbidity clusters influence heart failure risk could inform better cardiovascular monitoring and management strategies for ME/CFS populations who frequently present with multiple overlapping health conditions.
Observed Findings
622 participants developed heart failure over the follow-up period (390 with HFrEF, 220 with HFpEF)
The obese/physical inactivity cluster had an adjusted hazard ratio of 3.80 for heart failure compared to the young cluster
The elderly cluster had an adjusted hazard ratio of 2.46 for heart failure
The pulmonary disease cluster had an adjusted hazard ratio of 2.10 for heart failure
The obese/physical inactivity cluster showed relatively higher rates of HFpEF compared to other clusters
Inferred Conclusions
Comorbidities naturally cluster into distinct multimorbidity patterns, each associated with different heart failure risks
Obesity combined with physical inactivity represents the strongest modifiable multimorbidity pattern for heart failure prevention
Addressing multimorbidity as a composite risk factor is important for heart failure prevention strategies
Different comorbidity clusters may preferentially increase risk for specific HF phenotypes (HFrEF vs HFpEF)
Remaining Questions
How do these multimorbidity clusters evolve over time, and does progression between clusters affect heart failure risk?
What This Study Does Not Prove
This observational study cannot establish causation—it only demonstrates association between comorbidity clusters and heart failure risk. The study does not prove that obesity or inactivity directly causes heart failure, nor does it address whether the relationship differs in ME/CFS patients specifically or whether disease-specific factors (like post-exertional malaise) modify these associations.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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What are the specific mechanisms linking the obesity/inactivity cluster to HFpEF development versus HFrEF?
Do these findings apply to ME/CFS populations, and how does post-exertional malaise-induced inactivity compare to voluntary physical inactivity in this context?
Which interventions targeting obesity and inactivity would most effectively reduce heart failure risk in each multimorbidity cluster?