Assessment of causality between modifiable factors and heart failure: A Mendelian randomization analysis

Observational studies have associated lifestyle, dietary, adiposity, biochemical and clinical measures with heart failure. Whether the associations are causal remains unclear. We aimed to determine the causal associations between modifiable risk factors and incidence or mortality of heart failure.

Using single-nucleotide polymorphism (SNP) as genetic instruments, we conducted a two-sample Mendelian randomization (MR) analysis to estimate the causal effects of 27 modifiable risk factors on incident heart failure (2526 cases; 20926 participants) and mortality of heart failure (1798 deaths; 2828 patients).

None of 27 modifiable risk factors were significantly associated with incidence or mortality of heart failure after the Bonferroni correction (p<0.0019). However, there was suggestive evidence for genetically predicted educational attainment (odds ratio [OR] per educational year increase: 0.57, 95% CI 0.33-0.99, p=0.049), circulating mono-unsaturated fatty acid concentrations (OR per 1-SD increase [ORSD] : 1.50, 1.10-2.04, p=0.011), C-reactive protein (CRP) (1.53, 1.04-2.25, p=0.031), high-density lipoprotein (HDL) (0.84, 0.72-0.99, p=0.036), triglycerides (1.24, 1.00-1.52, p=0.045), and systolic blood pressure (SBP) (1.06, 1.01-1.11, p=0.017) with incident heart failure.

Our findings provide supporting evidence for prioritizing certain modifiable risk factors such as education, lipids, and blood pressure for primary prevention of heart failure, suggesting important clues for further mechanism research.