Abstract Body (Do not enter title and authors here):
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.