Non-High-Density Lipoprotein Cholesterol and Risk of Stroke Subtypes and Coronary Heart Disease: The Japan Public Health Center-Based Prospective (JPHC) Study

J Atheroscler Thromb. 2020 Apr 1;27(4):363-374. doi: 10.5551/jat.50385. Epub 2019 Sep 19.


Aim: A positive association between non-high-density lipoprotein cholesterol (non-HDL-C) and coronary heart disease (CHD) has been established; however, associations between non-HDL-C and stroke subtypes have not been determined.

Methods: We conducted a prospective study of 30,554 individuals aged 40-69 yrs with no history of cardiovascular disease (CVD) in Japan. Sex-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for the incidence of stroke subtypes and CHD were estimated according to quintiles of non-HDL-C, using Cox proportional hazard models adjusted for other established risk factors.

Results: We identified 1,705 stroke and 296 CHD events over a median 15 yrs of follow-up. The fractional polynomials analysis revealed a U-shaped association between non-HDL-C and stroke risk in men. When analyzed for stroke subtypes, the data revealed an inverse relationship between non-HDL-C and intracerebral hemorrhage (ICH), primarily with lobar ICH, and a positive association between non-HDL-C and large-artery occlusive infarction in men [adjusted HR 0.55 (95% CI, 0.35-0.87) and 2.05 (95% CI, 1.07-3.93) for the highest and lowest quintile of non-HDL-C, respectively]. The lowest risk of ICH in women was observed in the fourth quintile, and the lowest risk of embolic infarction was observed in the third quintile. In contrast, non-HDL-C was positively associated with CHD in both sexes.

Conclusions: In Japanese men, lower non-HDL-C levels were associated with a decreased risk of large-artery occlusive infarction and an increased risk of ICH, particularly lobar ICH.

Keywords: Coronary heart disease; Epidemiology; Intracerebral hemorrhage; Lacunar infarction; Non-HDL-C.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood*
  • Cholesterol, LDL / blood*
  • Coronary Disease / blood
  • Coronary Disease / diagnosis
  • Coronary Disease / epidemiology*
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Japan / epidemiology
  • Lipoproteins / blood*
  • Male
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Public Health
  • Risk Factors
  • Stroke / blood
  • Stroke / diagnosis
  • Stroke / epidemiology*


  • Biomarkers
  • Cholesterol, LDL
  • Lipoproteins