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Non-High-Density Lipoprotein Cholesterol and Risk of Stroke Subtypes and Coronary Heart Disease: The Japan Public
Isao Saito1, Kazumasa Yamagishi2, Yoshihiro Kokubo3
1Department of Public Health and Epidemiology, Faculty of Medicine, Oita University.
Insights
Lower non-HDL cholesterol is linked to reduced large-artery stroke but increased intracerebral hemorrhage risk in Japanese men. This contrasts with established links to coronary heart disease.
Area of Science:
- Cardiovascular epidemiology
- Biomarkers and disease risk
Background:
- Non-high-density lipoprotein cholesterol (non-HDL-C) is a known risk factor for coronary heart disease (CHD).
- The association between non-HDL-C and specific stroke subtypes remains underexplored.
Purpose of the Study:
- To investigate the relationship between non-HDL-C levels and the risk of different stroke subtypes.
- To determine sex-specific associations of non-HDL-C with stroke and CHD.
Main Methods:
- A prospective study of 30,554 Japanese adults (40-69 years) without prior cardiovascular disease.
- Cox proportional hazard models were used to estimate sex-specific hazard ratios for stroke subtypes and CHD across non-HDL-C quintiles, adjusting for risk factors.
Main Results:
- A U-shaped association between non-HDL-C and overall stroke risk was observed in men.
- In men, lower non-HDL-C was inversely associated with intracerebral hemorrhage (ICH), especially lobar ICH, but positively associated with large-artery occlusive infarction.
- Non-HDL-C showed a positive association with CHD in both sexes.
Conclusions:
- In Japanese men, very low non-HDL-C levels are associated with an increased risk of intracerebral hemorrhage.
- Conversely, higher non-HDL-C levels in men are linked to a greater risk of large-artery occlusive infarction.
- These findings highlight differential associations of non-HDL-C with stroke subtypes, distinct from its established role in CHD.
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.
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