HDL Cholesterol Is Remarkably Cardioprotective Against Coronary Artery Disease in Native Hawaiians and Pacific Islanders

Abstract

Background: High-density lipoprotein cholesterol (HDL-C) is inversely associated with cardiometabolic risk and exhibits nonlinear effects at extreme levels. Cardiometabolic diseases are a leading cause of death and are particularly prevalent among Native Hawaiian and Pacific Islanders (NHPIs). Objectives: This study characterizes HDL-C's association with coronary artery disease (CAD), major adverse cardiovascular events (MACE), and type 2 diabetes (T2D) in NHPIs compared to the general population. Methods: Using electronic health record data from the National Institutes of Health All of Us Research Program, we applied Cox proportional hazards models to compare HDL-C's protective effects on CAD, MACE, and T2D between 261 NHPIs and the remaining cohort (n = 188,802). Models were adjusted for key confounders, and restricted cubic splines were used to assess nonlinear risk dynamics. Results: Tracking individuals across 10,534,661 person-years (mean age 55.7 ± 15.8 years, 38% male), HDL-C was more strongly associated with reduced CAD risk in NHPIs (HR: 0.32; 95% CI: 0.19-0.54) than in the general cohort (HR: 0.57; 95% CI: 0.56-0.58). A marginally stronger association was observed for MACE (NHPI HR: 0.40; 95% CI: 0.23-0.71 vs general HR: = 0.54; 95% CI: 0.53-0.56), while T2D associations were similar. Spline analysis indicated that low HDL-C increases risk for both CAD and T2D in NHPIs. Conclusions: HDL-C's protective role against cardiometabolic diseases is more pronounced in NHPIs, particularly for CAD. These findings support further investigation into tailored clinical assessments for this population.