Isolated Low Levels of High-density Lipoprotein Cholesterol are Associated with an Increased Risk of Ischemic Cardiovascular Events: The Shizuoka Kokuho Database Study
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.
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BibTeX
@article{tabara2026isolated,
title = {{Isolated Low Levels of High-density Lipoprotein Cholesterol are Associated with an Increased Risk of Ischemic Cardiovascular Events: The Shizuoka Kokuho Database Study}},
author = {Yasuharu Tabara and Sayaka Nagao-Sato and Aya Shoji-Asahina and Yoko Sato},
journal = {Journal of Atherosclerosis and Thrombosis},
year = {2026},
month = jul,
doi = {10.5551/jat.66249},
url = {https://www.jstage.jst.go.jp/article/jat/advpub/0/advpub_66249/_article},
note = {CC BY-NC-SA},
}
RIS
TY - JOUR
TI - Isolated Low Levels of High-density Lipoprotein Cholesterol are Associated with an Increased Risk of Ischemic Cardiovascular Events: The Shizuoka Kokuho Database Study
AU - Yasuharu Tabara
AU - Sayaka Nagao-Sato
AU - Aya Shoji-Asahina
AU - Yoko Sato
PY - 2026
DA - 2026/07/06
JO - Journal of Atherosclerosis and Thrombosis
DO - 10.5551/jat.66249
UR - https://www.jstage.jst.go.jp/article/jat/advpub/0/advpub_66249/_article
AB - 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.
SN - 1880-3873
SN - 1340-3478
ER -