Hsiu-Ching Hsu

Chin-Shan Community Cardiovascular Cohort in Taiwan–baseline data and five-year follow-up morbidity and mortality

A cohort consisting of 3602 residents (82.8% of the target population) aged 35 years and older was established in 1990 in the Chin-Shan Community, a suburb 20 miles outside of metropolitan Taipei, Taiwan. The long-term objective was to investigate the prospective impact on cardiovascular health in a society undergoing transition from a developing to a developed nation. This article presents the study design, selected baseline risk factors of cardiovascular diseases (CVD), and CVD events at the 5-year follow-up evaluation with an emphasis on sociodemographic differences. The multivariate logistic regression analyses revealed that white-collar individuals were more likely than blue-collar workers to have dyslipidemia including high-density lipoprotein cholesterol (HDL-C) levels <35 mg/dl [odds ratio (OR) = 1.7, 95% confidence interval (CI) = 1.2-2.4] and low-density lipoprotein cholesterol (LDL-C) levels >/=160 mg/dl (OR = 1.3, 95% CI = 1.0-1.7). However, they were at slightly lower risk for stroke and CVD/sudden death, and at moderately higher risk for coronary artery disease and diabetes, although both these trends were not significant. Men were more likely than women to have HDL-C levels <35 mg/dl (OR = 1.8, 95% CI = 1.4-2.2), but they were less likely to have LDL-C levels >/=160 mg/dl (OR = 0.7, 95% CI = 0.6-0.8). The risk of CVD/sudden death was higher for men than for women during the follow-up period (OR = 1.9, 95% CI = 1.3-2.9). This could be due to risk factors such as a much higher prevalence of tobacco (61.9% vs. 4.5%) and alcohol (43.7% vs. 6.4%) use in men. In conclusion, individuals of higher socioeconomic status have a higher prevalence of dyslipidemia but slightly lower 5-year incidence of CVD events.

Apolipoprotein B and non-high density lipoprotein cholesterol and the risk of coronary heart disease in Chinese

The aim of our study was to compare apolipoprotein B (apoB), non-high density lipoprotein cholesterol (nonHDL-C), low density lipoprotein cholesterol (LDL-C), and other lipid markers as predictors of coronary heart disease (CHD) in Chinese. Overall, 122 individuals developed CHD during a median 13.6 years of follow-up in 3,568 adult participants from a community-based cohort. The multivariate relative risk of CHD in the highest quintile compared with the lowest quintile was 2.74 [95% confidence interval (CI), 1.45–5.19] for apoB, 1.98 (95% CI, 1.00–3.92) for nonHDL-C, and 1.86 (95% CI, 1.00–3.49) for LDL-C (all tests for trend, P < 0.05). ApoB also had the highest receiver operator characteristic curve area (0.63; 95% CI, 0.58–0.68) in predicting CHD. When apoB and nonHDL-C were mutually adjusted, only apoB was predictive; the relative risk was 2.80 (95% CI, 1.31–5.96; P = 0.001) compared with 1.09 (95% CI, 0.49–2.40; P = 0.75) for nonHDL-C. Compared with the lowest risk, participants with the highest apoB and total cholesterol/HDL-C had a 3-fold increased risk of developing CHD (relative risk = 3.21; 95% CI, 1.45–7.14). These data provide strong evidence that apoB concentration was a better predictor of CHD than other lipid markers in Chinese.

Red Blood Cell Distribution Width and Risk of Cardiovascular Events and Mortality in a Community Cohort in Taiwan

The authors investigated whether red blood cell distribution width (RDW) was associated with the development of cardiovascular disease (CVD) events and mortality in a community cohort in Taiwan. The influence of anemia on the association was also assessed. RDW levels were measured in 3,226 participants aged 35 years or older who reported no CVD or cancer at baseline in 1990. During a median follow-up period of 15.9 years (1990-2007), 358 participants experienced stroke and/or coronary heart disease, and 810 participants died. The multivariate-adjusted hazard ratio for subjects in the highest RDW quartile as compared with the lowest quartile was 1.46 for both all-cause mortality (95% confidence interval: 1.17, 1.81) and non-CVD mortality (95% confidence interval: 1.13, 1.88) (P for trend < 0.01 for both) but was not significant for CVD morbidity and mortality. Further analyses showed that in comparison with participants with low RDW and no anemia, persons with high RDW but no anemia had elevated risks of all-cause mortality and non-CVD mortality. The authors conclude that elevated RDW values are associated with increased risk of mortality but not the development of CVD in the general population. RDW may precede anemia in predicting the risk of non-CVD death.

Influence of CETP gene variation on plasma lipid levels and coronary heart disease: a survey in Taiwan

Cholesteryl ester transfer protein (CETP) transfers cholesteryl ester from high-density lipoprotein (HDL) to very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and chylomicron in exchange for triglycerides. Two CETP genetic variation and four polymorphisms are investigated by polymerase chain reaction (PCR) and restriction enzyme digestion in a population of Taiwan. The results show that a very rare variation frequency is found for CETP intron 14 splice site G-->A change. The population shows a predominant 405Ile allele (61%), 442Asp (97.7%), intron 1Taq1B(+) G allele (52%), intron 8 Msp1(-) A allele (89%) and intron 9 EcoN1(-) T allele (59.2%) in the control group. Patients with coronary heart disease (CHD) have more CETP EcoN1(+/+) GG genotype (25.3%) than the controls (13.6%) (P=0.049). The intron 1 Taq1B(-) A allele is associated with a high HDL cholesterol and apoA1 level, the EcoN1(+) G allele with a low apoA1 level and the 442Gly with both high total cholesterol and LDL cholesterol levels. Paradoxically, the 442Gly is also present with a higher frequency (5.2%) in HDL cholesterol > or =65 mg/dl group than that in the general population (2.3%) (P=0.04).

Carotid Artery Intima-Media Thickness, Carotid Plaque and Coronary Heart Disease and Stroke in Chinese

Background Our aim was to prospectively investigate the association between carotid artery intima-media thickness (IMT) as well as carotid plaque and incidence of coronary heart disease (CHD) and stroke in Chinese, among whom data are limited. Methods and Findings We conducted a community-based cohort study composed of 2190 participants free of cardiovascular disease at baseline in one community. During a median 10.5-year follow up, we documented 68 new cases of coronary heart disease and 94 cases of stroke. The multivariate relative risks (RRs) associated with a change of 1 standard deviation of maximal common carotid IMT were 1.38 (95% confidence interval [CI], 1.12–1.70) for CHD and 1.47 (95% CI, 1.28–1.69) for stroke. The corresponding RRs with internal carotid IMT were 1.47 (95% CI, 1.21–1.79) for CHD and 1.52 (95% CI, 1.31–1.76) for stroke. Carotid plaque measured by the degree of diameter stenosis was also significantly associated with increased risk of CHD (p for trend<0.0001) and stroke (p for trend<0.0001). However, these associations were largely attenuated when adjusting for IMT measurements. Conclusions This prospective study indicates a significant association between carotid IMT and incidence of CHD and stroke in Chinese adults. These measurements may be useful for cardiovascular risk assessment and stratification in Chinese.

Urinary sodium and potassium excretion and risk of hypertension in Chinese: report from a community-based cohort study in Taiwan.

Background Dietary sodium intake is associated with blood pressure and hypertension risk. However, most of the studies have been conducted in whites and it is not clear whether the effects exist in Asian populations. Objective The purpose of the present study was to investigate the role of 24-h urinary sodium excretion and hypertension risk among ethnic Chinese. Design A prospective cohort design on community. Setting and participants One thousand five hundred and twenty middle-aged and elderly participants who were free from hypertension at baseline and had available urine electrolyte data. Main outcome measures Hypertension incidence. Results During a median 7.93 years of follow-up (interquartile range = 4.07–9.04 years), we documented 669 cases of incident hypertension. The multivariate risk was 1.26 (95% confidence interval = 1.01–1.57; P = 0.043) for individuals in the highest quartile of urinary sodium excretion as compared with those in the second quartile. A significant J-shape relationship between urinary sodium excretion and the risk of hypertension was observed, with the test for linear relation being rejected (P = 0.046). Participants who were in the highest quartile of urinary sodium excretion and higher baseline blood pressure had a 2.43-fold increased risk of hypertension (95% confidence interval = 1.72–3.22) compared with those in the lowest quartiles of urinary sodium and lower blood pressure. Conclusion Urinary sodium excretion was associated with the risk of hypertension among ethnic Chinese. Urinary sodium excretion, as a marker of dietary sodium intake, can be useful for a comprehensive evaluation of hypertension risk in Asian populations.

A Prediction Model for the Risk of Incident Chronic Kidney Disease

BACKGROUND Chronic kidney disease is a health burden for the general population. We designed a cohort study to construct prediction models for chronic kidney disease in the Chinese population. METHODS A total of 5168 participants were followed up during a median of 2.2 (interquartile range, 1.5-2.9) years, and 190 individuals (3.7%) developed chronic kidney disease, defined by a glomerular filtration rate of less than 60 mL/min/1.73 m(2). RESULTS We developed a point system to estimate chronic kidney disease risk at 4 years using the following variables: age (8 points), body mass index (2 points), diastolic blood pressure (2 points), and history of type 2 diabetes (1 point) and stroke (4 points) for the clinical model, with the addition of uric acid (2 points), postprandial glucose (1 point), hemoglobin A1c (1 point), and proteinuria 100 mg/dL or greater (6 points) for the biochemical model. Similar discrimination measures were found between the clinical model (area under the receiver operating characteristic curve, 0.768; 95% confidence interval (CI), 0.738-0.798) and the biochemical model (area under the receiver operating characteristic curve, 0.765; 95% CI, 0.734-0.796). The area under the receiver operating characteristic curve of the clinical model was 0.667 (95% CI, 0.631-0.703) for the external validation data from community-based cohort participants. The optimal cutoff value for the clinical model was set as 7, with a sensitivity of 0.76 and a specificity of 0.66. CONCLUSION We constructed a clinical point-based model to predict the 4-year incidence of chronic kidney disease. This prediction tool may help to target Chinese subjects at risk of developing chronic kidney disease.

The effect of hypercholesterolemia on the sodium inward currents in cardiac myocyte

To determine whether chronic hypercholesterolemia affects sodium inward currents in cardiac myocytes, whole-cell clamp recordings were made in single cardiac myocytes isolated from normo- and hypercholesterolemic rabbits. Modification of the serum cholesterol was accomplished by feeding ten 3-month-old male New Zealand white rabbits with control diet (group I) and ten with 0.5% cholesterol-enriched diet (group II), for 3 months. The serum cholesterol levels of group II were much higher than those of group I (2042 +/- 231 v 82 +/- 9 mg/dl, P < 0.001). The cholesterol-ester and free cholesterol component of cardiac sarcolemma of group II were also significantly higher than those of group I (26.6 +/- 12.4 v 10.8 +/- 4.5 nmole/dl, P < 0.001, and 50.9 +/- 14.8 v 27.5 +/- 6.2 nmole/dl, P < 0.001, respectively). The cell capacitance of hyperlipidemic myocytes seemed larger than that of normolipidemic ones (157.4 +/- 6.4 pF v 103.6 +/- 3.0 pF, P < 0.05). However, the sodium current density on hypercholesterolemic ventricular sarcolemma was significantly lower than that of normolipidemic sarcolemma. This effect was associated with a leftward shift in the inactivation potential and a slowing of the time course of recovery. In conclusion, hypercholesterolemia has important effects on the sodium inward currents in ventricular myocytes, which may be due to a decrease in current density and an alteration in channel functional state.

Constructing the Prediction Model for the Risk of Stroke in a Chinese Population Report From a Cohort Study in Taiwan

Background and Purpose— Prediction rules for the risk of stroke have been proposed. However, most studies were conducted with whites or for secondary prevention, and it is not clear whether these models apply to the Chinese population. The purpose of this study was to construct a simple points-based clinical model for predicting incident stroke among Chinese adults in Taiwan. Methods— We estimated the 10-year risk of stroke in a cohort study of middle-aged and elderly participants who were free from stroke at baseline. Multivariate Cox model-derived coefficients were used to construct the simple points-based clinical and biochemical model and the prediction measures using the area under the receive operating characteristic curve, net reclassification improvement, and integrated discrimination improvement statistics were applied. Results— Of the 3513 participants without stroke at baseline, 240 incident cases of stroke were documented for a median 15.9-year follow-up. Age (8 points), gender (1 point), systolic blood pressure (3 points), diastolic blood pressure (2 points), family history of stroke (1 point), atrial fibrillation (3 points), and diabetes (1 point) were found to significantly predict stroke events. The estimated area under the receive operating characteristic curve for this clinical points-based model was 0.772 (95% CI, 0.744 to 0.799). The discrimination ability of this clinical model was similar to the coefficients-based models and better than available stroke models. Conclusions— We have constructed a model for predicting 15-year incidence of stroke in Chinese adults and this model may be useful in identifying individuals at high risk of stroke.

Comparative assessment of the HAS-BLED score with other published bleeding risk scoring schemes, for intracranial haemorrhage risk in a non-atrial fibrillation population: The Chin-Shan Community Cohort Study

BACKGROUND The HAS-BLED score is a validated bleeding risk model for predicting major bleeding events in anticoagulated individuals with atrial fibrillation (AF). It remains uncertain whether the HAS-BLED score could identify non-AF individuals at risk of developing intracranial haemorrhage (ICH), which is the most intractable and devastating major bleeding complication. METHODS We assessed the predictive value of a modified HAS-BLED and other bleeding risk scoring models to predict the risk for ICH in the Chin-Shan Community Cohort, which followed 1899 women and 1703 men, aged >35 years, for a median of 15.9 years. ICH events (including haemorrhagic strokes) were ascertained according to questionnaires and the national register database. RESULTS Of 3524 individuals without baseline AF, 54 ICH events occurred during follow-up. The risk for ICH was raised with increasing HAS-BLED scores, and was significantly associated with uncontrolled hypertension and older age (Odds Ratios [95% confidence interval (CI)], 4.2[2.3-7.6] and 1.9[1.1-3.4], respectively). Among the five bleeding risk scoring schemes tested, HAS-BLED had highest general discrimination performance (c-statistic [95% CI], 0.72 [0.67-0.78]), and better ability to discriminate between those who were at risk for ICH and who were not (NRI, net reclassification improvement, all p<0.05, compared to other four scoring schemes). CONCLUSION The HAS-BLED score had the highest general discrimination performance and best ability to discriminate risk for ICH. This score may be of clinical use in predicting the risk for occurrence of ICH among non-AF individuals.