High-density lipoprotein cholesterol and clinical outcomes in diabetes mellitus.

Abstract

High-density lipoprotein-cholesterol (HDL-C) has been thought to protect against cardiovascular disease (CVD), whereas a U-shaped association of both low and extremely high HDL-C with a high mortality risk has been increasingly reported in recent years. However, whether this U-shaped association is universal regardless of the individual's clinical background, including lifestyle diseases, remains unclear. We examined whether fasting plasma glucose modifies the U-shaped association between HDL-C level and clinical outcomes. This retrospective observational cohort study analyzed data from the JMDC Claims Database between 2005 and 2021 for 3,282,389 participants without a history of CVD. The median age was 44 years (IQR, 36-51), and 1,878,164 participants (57.2%) were men. The median HDL-C level was 62 (IQR 52-74) mg/dL. The study participants were categorized according to fasting plasma glucose (FPG) levels (<100 mg/dL, 100-125 mg/dL, and ≥126 mg/dL). The primary endpoint was composite CVD outcome, consisting of myocardial infarction, stroke, and all-cause death. During a mean follow-up period of 1,181±932 days, 35,233 composite CVD events were recorded. The association between low HDL-C and CVD risk increased with FPG level, and the relationship of high HDL-C with CV outcome was prominent only in people with diabetes mellitus. A similar relationship was observed in the individual subgroups and in each CV outcome. The U-shaped association between HDL-C and clinical outcomes was amplified with worsening glucose tolerance, suggesting a potential interaction between HDL-C levels and glycemic status on clinical outcomes.