Small dense low-density lipoproteins cholesterol can predict incident cardiovascular disease in an urban Japanese cohort: the Suita study.

AIM: Several lines of evidence indicate that small dense low-density lipoproteins (sd-LDL) are more atherogenic than large buoyant LDL; however, few prospective studies have addressed the role of sd-LDL in cardiovascular disease (CVD). We therefore examined the association between sd-LDL cholesterol (sd-LDL-C) and CVD in a Japanese cohort. METHODS: An 11.7-year prospective study was performed using a general population aged 30-79 without a history of cardiovascular disease. Direct LDL-C and sd-LDL-C were measured in samples from 2034 participants (968 men and 1066 women). RESULTS: During the follow-up period, there were 116 incident cases of CVD. The multivariable-adjusted hazard ratios (HRs) of sd-LDL-C for CVD were calculated using a proportional hazards regression model after adjusting for age, hypertension, diabetes, use of lipid-lowering drugs, body mass index, and current smoking and alcohol drinking, and found that increasing quartiles of sd-LDL-C were associated with increased risk of CVD. We also determined that age and sex-adjusted HRs per 10 mg/dL of sd-LDL-C and HRs for CVD, stroke, cerebral infarction, and coronary artery disease were 1.21 (95% CI: 1.12-1.31), 1.17 (95% CI: 1.05-1.30), 1.15 (95% CI: 1.00-1.33), and 1.29 (95% CI: 1.14-1.45), respectively. CONCLUSIONS: It was demonstrated that sd-LDL-C was significantly associated with CVD in a Japanese population, providing evidence of sd-LDL-C as an important biomarker to predict CVD.

Phenotypic variability in Caucasian and Japanese patients with matched LQT1 mutations.

BACKGROUND: Ethnic differences may affect the phenotypic expression of genetic disorders. However, data regarding the effect of ethnicity on outcome in patients with genetic cardiac disorders are limited. We compared the clinical course of Caucasian and Japanese long QT type-1 (LQT1) patients who were matched for mutations in the KCNQ1 gene. METHODS: The study population comprised 62 Caucasian and 38 Japanese LQT1 patients from the International LQTS Registry who were identified as having six identical KCNQ1 mutations. The biophysical function of the mutations was categorized into dominant-negative (> 50%) or haploinsufficiency (< or =50%) reduction in cardiac repolarizing IKs potassium channel current. The primary end point of the study was the occurrence of a first cardiac event from birth through age 40 years. RESULTS: Japanese patients had a significantly higher cumulative rate of cardiac events (67%) than Caucasian patients (39%; P = 0.01). The respective frequencies of dominant negative mutations in the two ethnic groups were 63% and 28% (P < 0.001). In multivariate analysis, Japanese patients had an 81% increase in the risk of cardiac events (P = 0.06) as compared with Caucasians. However, when the biophysical function of the mutations was included in the multivariate model, the risk associated with Japanese ethnicity was no longer evident (HR = 1.05; P = 0.89). Harboring a dominant negative mutation was shown to be the most powerful and significant predictor of outcome (HR = 3.78; P < 0.001). CONCLUSIONS: Our data indicate that ethnic differences in the clinical expression of LQTS can be attributed to the differences in frequencies of the specific mutations within the two populations.