LDL Cholesterol and the Development of Stroke Subtypes and Coronary Heart Disease in a General Japanese Population

Abstract

Background and Purpose-Although the relation between serum LDL cholesterol level and coronary heart disease (CHD) is well established, its relation with stroke subtypes is less clear. Methods-A total of 2351 inhabitants age Ն40 years in a Japanese community were followed up for 19 years. Results-During follow-up, 271 subjects developed stroke and 144 developed CHD. Whereas the age-and sex-adjusted incidences of CHD significantly increased with increasing LDL cholesterol levels (P for trend Ͻ0.001), the associations between LDL cholesterol level and the incidences of ischemic or hemorrhagic stroke were not significant. The age-and sex-adjusted incidences of atherothrombotic infarctions (ATIs) and lacunar infarctions (LIs) significantly increased with increasing LDL cholesterol level (P for trendϭ0.03 for ATIs andϭ0.02 for LIs), but no such association was observed for cardioembolic infarction. After multivariate adjustment, the positive associations of LDL cholesterol level with the risks of ATI and CHD remained significant (P for trendϭ0.02 for ATIs andϭ0.03 for CHD), whereas the association with LIs was not significant. The risk of ATI significantly increased in the fourth quartile of LDL cholesterol compared with the first quartile (multivariate-adjusted hazard ratioϭ2.84; 95% CI, 1.17 to 6.93). The multivariate-adjusted risks for developing nonembolic infarction (ATIs and LIs) and CHD were significantly elevated in the groups with elevated LDL cholesterol values with and without the metabolic syndrome. Conclusions-Our findings suggest that an elevated LDL cholesterol level is a significant risk factor for developing ATI as well as CHD, and these associations are independent of the metabolic syndrome. (Stroke. 2009;40:382-388.)

Development and validation of a cardiovascular risk prediction model for Japanese: the Hisayama study

“…Covariates included in Cox's proportional hazards model were age, sex, systolic blood pressure, diabetes, LDL cholesterol, highdensity lipoprotein cholesterol and smoking habits that were traditional risk factors for cardiovascular disease established in the Hisayama study. 16,17,20,21 The performance of the risk prediction model was then tested among subjects allocated to the validation cohort. Ability of the risk prediction model to discriminate persons who experience a cardiovascular disease from those who do not were evaluated using c-statistic, 24 and calibration of the risk prediction model was evaluated using a Hosmer-Lemeshow w 2 -statistic with 8 d.f.…”

“…Another limitation is that LDL cholesterol, as a continuous variable, did not reach statistical significance in the derivation cohort. However, LDL cholesterol is an established risk factor for cardiovascular disease in the Hisayama study 21 and thus we included LDL cholesterol into the risk prediction model. A third limitation is that our findings are based on a one-time measurement of risk factors (for example, systolic blood pressure, plasma glucose levels, LDL cholesterol levels and high-density lipoprotein cholesterol levels), which may not accurately reflect the status of a study participant.…”

“…A total of 2742 residents aged 40 years or older (80.9% of the total population of this age group) consented to participate in the examination. 2,[18][19][20][21] After the exclusion of 106 subjects with a history of cardiovascular disease and two subjects who died during the examination, the remaining 2634 individuals were enrolled in this study.…”

“…A detailed description of the study methods has been published previously. 2,[18][19][20][21] In brief, the health status of any subject who had not undergone a regular examination or who had moved out of town was checked yearly by mail or telephone. We also established a daily monitoring system among the study team and local physicians or members of the town's Health and Welfare Office.…”

Risk-prediction tools for cardiovascular disease based on Japanese cohort studies

“…Many Japanese cohort studies, including the Hisayama study, have clearly shown, a high level of serum LDL cholesterol is a risk factor for CHD, but not for stroke. 12,13 Third, their risk score sheet is based on a cohort study in one rural town. Accordingly, this score sheet may be limited in its generalizability to urban populations, in which the incidence of CHD is much higher than in rural populations.…”