Abstract 4362928: Very High HDL Cholesterol Is Associated With Increased Risk of Heart Failure Hospitalization

Background: Emerging evidence suggests that very-high High-density lipoprotein cholesterol (HDL-C) levels are paradoxically associated with adverse clinical outcomes. We investigated the association between very high HDL-C and the risk of heart failure (HF) hospitalization among individuals with coronary artery disease (CAD). Methods: A total of 8,120 participants undergoing angiography after enrolment in the Emory Cardiovascular Biobank (EmCAB) had their HDL-C levels categorized as low, normal, or very-high according to sex-specific thresholds: <40, 40-80, >80 mg/dL in men and <50, 50-100, >100 mg/dL in women, respectively. Multivariable Fine-Gray subdistribution hazard models were performed to assess the relationship between HDL-C category and incident HF hospitalization during long-term follow-up, treating all-cause death as a competing event. Models were adjusted for age, sex, race, BMI, smoking history, alcohol use, and history of MI, HF, atrial fibrillation, diabetes, hypertension, LDL-C, triglycerides and total cholesterol levels, eGFR, and medication use. Subgroup analyses assessed the consistency of associations by sex, and sensitivity analyses were conducted within clinical subgroups. Results: Mean age was 62 (13), 30% non-white, 36% women, and 58% had obstructive CAD (>50% epicardial stenosis). Over a median follow-up of 5.1 years (IQR 2.2–6.3), participants with very-high HDL-C levels, using sex-specific cut-offs, had a higher cumulative incidence of HF hospitalization compared to those with normal HDL-C levels: 24.4% vs. 12.5% in men, and 16.7% vs. 15.1% in women, respectively. In multivariable modeling, very-high HDL-C was significantly associated with increased risk of HF hospitalization (subdistribution hazard ratio [SHR] 1.91, 95% confidence interval 1.05–3.46, p = 0.03), Figure 1. By contrast, low HDL-C was not significantly associated with HF hospitalization (SHR 1.02, 95% CI 0.87–1.19, p = 0.84). Although the interaction by sex was not significant, subgroup analysis demonstrated that very-high HDL-C was associated with increased risk of HF hospitalization only among men, but not women (SHR, 2.58; 95% CI, 1.28-5.22; P 0.01 vs SHR, 0.81; CI, 0.19-3.43; P 0.78), Figure 1. Conclusion: In patients with CAD, very-high HDL-C is associated with a higher risk of HF hospitalization. Further investigations of HDL functionality and subtypes of HF impacted are warranted.