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Isolated Low Levels of High-density Lipoprotein Cholesterol are Associated with an Increased Risk of Ischemic Cardiovascular Events: The Shizuoka Kokuho Database Study

Year: 2026

Type: article

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.

Source: Journal of Atherosclerosis and Thrombosis

DOI: 10.5551/jat.66249

Authors: Yasuharu Tabara, Sayaka Nagao-Sato, Aya Shoji-Asahina, Yoko Sato

Institutions: Kyoto University, Shizuoka Graduate University of Public Health, Center for Genomic Medicine, Graduate School of Medicine, Kyoto University

Language: English

Topic: Lipoproteins and Cardiovascular Health

Subfield: Cardiology and Cardiovascular Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: diamond

OpenAlex ID: W7167418706

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