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

Area of Science:

• Cardiology
• Genetics
• Public Health

Background:

• Cardiometabolic diseases (CMDs) like heart disease, diabetes, stroke, and hypertension are major risk factors for heart failure (HF).
• Cardiometabolic multimorbidity (CMM), the simultaneous presence of multiple CMDs, is increasingly prevalent.
• The independent and combined impact of CMM and genetic predisposition on HF risk requires further elucidation.

Purpose of the Study:

• To investigate the additive association between the number of CMDs and incident HF risk.
• To determine if genetic risk for HF modifies the relationship between CMDs and HF development.
• To quantify the risk of HF in individuals with varying degrees of CMM and genetic predisposition.

Main Methods:

• Utilized data from 374,565 UK Biobank participants.
• Assessed the number of CMDs (coronary heart disease, diabetes, stroke, hypertension) and HF polygenic risk scores (low, intermediate, high) as exposures.
• Employed Cox proportional hazards models to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident HF.

Main Results:

• A dose-dependent increase in HF risk was observed with a higher number of CMDs.
• Participants with 1, 2, and ≥3 CMDs had adjusted HRs of 1.66, 2.93, and 5.13, respectively, compared to those with no CMDs (P_trend < 0.001).
• A synergistic interaction was found between high genetic risk and CMDs, with individuals having high genetic risk and ≥3 CMDs exhibiting a 6.4-fold elevated HF risk.

Conclusions:

• The number of CMDs is strongly and dose-dependently associated with an increased risk of incident HF.
• High genetic risk for HF interacts synergistically with CMDs, amplifying HF risk.
• Cardiometabolic multimorbidity is a critical determinant of incident HF, underscoring the need for integrated management strategies.