Association of High-Density Lipoprotein Cholesterol Levels With Heart Failure Hospitalization Among Adults Undergoing Coronary Angiography

Objective Emerging evidence suggests that very high levels of high-density lipoprotein cholesterol (HDL-C) 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 patients undergoing coronary angiography. Methods We analyzed 4,972 participants enrolled in the Emory Cardiovascular Biobank who underwent coronary angiography for suspected or established coronary heart disease. HDL-C was categorized as <40, 40–59, 60–79, and ≥80 mg/dL. Associations between HDL-C categories and risk of HF hospitalization were assessed using multivariable Fine–Gray models with all-cause death as a competing event, adjusting for potential confounders. Nonlinear associations were assessed by modeling HDL-C as a continuous variable using restricted cubic splines. Results The mean age was 63 ± 12 years; 29% were non-White, 36% were women, 34% had a history of HF, and 69% had obstructive coronary artery disease (CAD). Spline analyses demonstrated a nonlinear U-shaped association between HDL-C levels and the risk of HF hospitalization. Over a median follow-up of 5.1 years (interquartile range 2.4–6.5), very high HDL-C (≥80 mg/dL) was associated with a higher 5-year cumulative incidence of HF hospitalizations compared with normal (40–59 mg/dL) HDL-C (18.5% vs. 11.9%). In adjusted analyses, both very high and low HDL-C (<40 mg/dL) were independently associated with increased HF hospitalization risk (sHR 1.77, 95% CI 1.15–2.74; and sHR 1.23, 95% CI 1.04–1.46, respectively), while HDL-C 60–79 mg/dL was not (sHR 1.07, 95% CI 0.82–1.40). Conclusion Among patients undergoing coronary angiography, both low and very high HDL-C are independently associated with a higher risk of HF hospitalization, with the strongest association at very high HDL-C.