J Atheroscler Thromb. 2026 Jul 6. doi: 10.5551/jat.66249. Online ahead of print.
ABSTRACT
AIM: Isolated low high-density lipoprotein cholesterol (HDL-C) refers to low HDL-C levels with normal levels of triglycerides and low-density lipoprotein cholesterol. However, its prognostic significance remains controversial. This study aimed to investigate the association between isolated low HDL-C levels and the incidence of stroke and coronary artery disease (CAD).
METHOD: This study included 496,973 Japanese individuals (mean age: 66.4 years) enrolled in municipal health insurance programs. Data on baseline clinical characteristics and cardiovascular outcomes were obtained from annual health checkup and health insurance claims data, respectively. Isolated low HDL-C was defined as HDL-C ＜40 mg/dL with normal levels of triglyceride and low-density lipoprotein cholesterol (LDL-C).
RESULT: The frequency of isolated low HDL-C was 1.3%. Isolated low HDL-C was independently associated with the CAD incidence (hazard ratio [HR] = 1.87, P＜0.001). This association remained significant in age- and sex-separate analyses, as well as in the analysis of participants who were not taking lipid-lowering drugs and had severe comorbidities at baseline. Conversely, isolated low HDL-C levels were not associated with the incidence of ischemic stroke (HR = 1.08, P = 0.266) or hemorrhagic stroke (HR = 1.16, P = 0.223) in all participants. However, it showed a significant association with ischemic stroke in the subgroup analysis of those aged ＜65 years (HR = 2.21, P＜0.001) and men (HR = 1.17, P = 0.035).
CONCLUSION: Isolated low HDL-C was associated with the incidence of CAD and ischemic stroke despite normal plasma levels of triglyceride and low-density lipoprotein cholesterol.
PMID:42402384 | DOI:10.5551/jat.66249