The additive association of cardiometabolic diseases with incident heart failure: a prospective cohort study.

Objective: Individual cardiometabolic diseases (CMDs) are critical risk factors for heart failure (HF). However, an increasing number of individuals are simultaneously suffering from multiple CMDs, namely cardiometabolic multimorbidity (CMM). The extent to which CMM increases the risk of HF remains unclear. We aimed to explore the additive association of the number of CMDs with the risk of HF and evaluate whether the genetic risk of HF would modify this association.

Methods: We included 374,565 participants from the UK Biobank. The number of CMDs (including coronary heart disease, diabetes, stroke, and hypertension) and the polygenic risk score for HF (low, intermediate, and high) were assessed as exposures. The adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident HF were calculated using the Cox proportional hazards model.

Results: During a median follow-up of 14.22 years, there were 13,154 cases of incident HF. Compared with participants having no CMD, the adjusted HRs for those with 1, 2, and ≥3 CMDs were 1.66 (95% CI: 1.59-1.73), 2.93 (95% CI: 2.77-3.10), and 5.13 (95% CI: 4.73-5.56), respectively (P_trend < 0.001). Synergistic interactions were observed between high genetic risk and CMDs. Participants with high genetic risk and ≥3 CMDs were estimated to have a 6.4-fold elevated risk of HF compared with those with a low genetic risk and no CMD.

Conclusion: The number of CMDs is dose-dependently associated with incident HF. And there is a synergistic interaction between high genetic risk and CMDs. The findings highlight the critical role of CMM in incident HF.