Sleep Disorder Phenotypes and the Risk of Incident Heart Failure: A meta-analysis with Mendelian randomization validation.

OBJECTIVES

To quantify how specific sleep-disorder phenotypes are related to incident heart failure (HF) using a meta-analysis of cohort data and to probe causal relevance via 2-sample Mendelian randomization (MR).

METHODS

Fourteen cohorts comprised of participants without HF at baseline were pooled (49,501 exposed; 337,317 controls). A random effects meta-analysis produced pooled hazard ratios (HRs) with 95% confidence intervals (CIs). A bidirectional two-sample MR was used to evaluate the causal effects of sleep phenotypes on HF.

RESULTS

Overall, sleep disorders were linked to a higher incidence of HF (pooled HR 1.46; 95% CI 1.30-1.63; p<0.001). In terms of phenotype, obstructive sleep apnea (OSA) was significantly associated (pooled HR 1.39; 95% CI 1.18-1.64; p < 0.001), whereas insomnia was not independently associated with HF (pooled HR 1.11; 95% CI 0.75-1.62; p = 0.609). The MR analyses supported a causal effect of OSA on HF (inverse-variance weighted odds ratio 1.12; 95% CI 1.03-1.23; p = 0.007) and revealed no causal evidence for insomnia.

CONCLUSIONS

Sleep disorders are associated with increased HF risk, which varies by phenotype. Convergent observational and genetic evidence implicates OSA in increased HF risk, whereas insomnia shows no independent or causal association. These findings prioritize OSA screening and targeted prevention in HF risk mitigation.