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Causal relationships between modifiable risk factors and heart failure: A comprehensive Mendelian randomization study
Yingying Fu1, You He, Wanjun Wu
1Department of Clinical Laboratory, Liuzhou Traditional Chinese Medical Hospital, Guangxi, P.R. China.
Medicine
|November 5, 2025
Summary
Identifying heart failure risk factors is crucial. Mendelian randomization linked obesity, lifestyle, and socioeconomic status to increased heart failure risk, while higher education showed a protective effect.
Area of Science:
- Cardiovascular Epidemiology
- Genetic Epidemiology
- Public Health
Background:
- Heart failure (HF) poses a significant global health burden.
- Identifying modifiable risk factors for HF is essential for public health strategies.
- Previous research has suggested various factors, but comprehensive causal inference is needed.
Purpose of the Study:
- To evaluate the causal effects of over 200 modifiable risk factors on heart failure using Mendelian randomization (MR).
- To identify key risk factors for heart failure amenable to public health interventions.
- To validate findings across independent genome-wide association study (GWAS) datasets.
Main Methods:
- Employed the Mendelian randomization (MR) method utilizing large-scale GWAS data.
- Used summary statistics from GWAS datasets for heart failure (IEU and FinnGen) for robustness.
- Applied inverse variance weighted (IVW) and other sensitivity analyses to ensure result validity.
Main Results:
- Obesity indicators (BMI, body fat percentage, waist circumference, etc.) were strongly associated with increased heart failure risk.
- Lifestyle factors (smoking, sedentary behavior) and type 2 diabetes significantly elevated heart failure risk.
- Higher education (college/university degree) demonstrated a protective association against heart failure.
Conclusions:
- Obesity, adverse lifestyle choices, socioeconomic status, and metabolic dysregulation are causally linked to heart failure.
- Findings provide robust evidence for targeted interventions in obesity and lifestyle modification for HF prevention.
- The study highlights the importance of considering socioeconomic determinants in heart failure management policies.
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