Relationship Between Time‐Varying Achieved High‐Density Lipoprotein Cholesterol and Risk of Coronary Events Depends on Haptoglobin Phenotype Within the ACCORD Lipid Study

Background The Hp (haptoglobin)2‐2 phenotype (~40% of people) is associated with dysfunctional high‐density lipoprotein (HDL) that is heavily oxidized in hyperglycemia, which may explain why raising HDL‐cholesterol (HDL‐C) does not reliably prevent coronary artery disease (CAD) in diabetes. Methods and Results In this observational study using longitudinal data from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) lipid trial, time‐varying (achieved) HDL‐C updated at 4, 8, and 12 months, and annually thereafter over a mean of 4.7 years, was analyzed in relation to risk of CAD and secondary outcomes using Cox proportional hazards regression with time‐varying covariables among participants with (n=1781) and without (n=3191) the Hp2‐2 phenotype. HDL‐C did not differ between the phenotypes throughout the study. Having low HDL‐C (