Performance of atherosclerotic cardiovascular risk prediction models in a rural Northern Chinese population: Results from the Fangshan Cohort Study.

BACKGROUND: Performance of Pooled Cohort Equations (PCEs) for atherosclerotic cardiovascular disease (ASCVD) risks varied across populations. Whether the recently developed Prediction for ASCVD Risk in China (China-PAR) model could accurately predict cardiovascular risks in real practice remains unclear. METHODS: A population-based cohort study in rural Beijing in the "stroke belt" in North China was used to externally validate PCE and China-PAR models for 5-year ASCVD risk prediction. Expected 5-year prediction risk using China-PAR model was compared with PCE (white). The models were assessed for calibration, discrimination, and reclassification. RESULTS: Among 11,169 adults aged 40 to 79 years over a median 6.44 years of follow-up, 1,921 participants developed a first ASCVD event during total 70,951 person-years. China-PAR model fairly predicted ASCVD risk in men but overestimated by 29.4% risk in women (calibration χ2 = 81.4, P < .001). Underestimations were shown by PCE as 76.2% in men and 88.2% in women with poor calibration (both P < .001). However, discrimination was similar in both models: C-statistics in men were 0.685 (95% CI 0.660-0.710) for China-PAR and 0.675 (95% CI 0.649-0.701) for PCE; C-statistics in women were 0.711 (95% CI 0.694-0.728) for China-PAR and 0.714 (95% CI 0.697-0.731) for PCE. Moreover, China-PAR did not substantially improve accuracy of reclassification compared with PCE. CONCLUSIONS: China-PAR outperformed PCE in 5-year ASCVD risk prediction in this rural Northern Chinese population at average population risk level, fairly predicted risk in men, but overestimated risk in women; however, China-PAR did not meaningfully improve the accuracy of discrimination and reclassification at individual risk level.

Establishment of a reference procedure to measure urine-formed elements and evaluation of an automated urine analyzer.

A standardized reference method is needed to accurately and precisely measure urine-formed elements (UFEs; red blood cells [RBCs], white blood cells [WBCs], and squamous epithelial cells [sECs]). We compared the results from a standard method with those from an automated analyzer. Trained technicians used standardized bright-field microscopy of fresh non-centrifuged urine samples, and disposable 1 µl chambers. Fifteen experienced technicians from 5 hospitals (3 per hospital) each performed 6 manual counts of 10 different native urine samples using a manual chamber and standard methods. The sEC counts were at least 50/µL, and the coefficient of variation (CV) was less than 14%; the RBC and WBC counts were at least 200/µL and the CVs were less than 7%. The same samples were also analyzed 6 times using automated analyzers. The means, CVs, and biases were determined. The median CVs for the manual measurements were 6.4% (WBCs), 6.6% (RBCs), and 12.7% (sECs). The CVs of the automated analyzer were 4.7% (WBCs), 5.6% (RBCs), and 9.2% (sECs). Biases between the automated and manual methods were -2.9% to 5.0%(WBCs), -0.8% to 8.8% (RBCs) and -2.8% to 9.4% (sECs). The count mean values and expanded uncertainties of these counts were (224.5 ± 15.0) cells/µL, (234.2 ± 16.2) cells/µL, and (61.5 ± 7.9) cells/µL, respectively. The standardized manual method for measuring UFEs had high precision and accuracy, making it a suitable reference method. Use of this reference method to calibrate an automated analyzer improved the accuracy of automated analysis.

Cohort profile: the Fangshan Cohort Study of cardiovascular epidemiology in Beijing, China.

BACKGROUND: Urbanizing rural areas in China face a rapidly growing cardiovascular disease burden. Epidemiologic studies and effective preventive strategies are urgently needed. METHODS: The Fangshan Cohort Study is a prospective study that began in 2008 and targets local residents aged 40 years or older living in 3 towns in the Fangshan district of Beijing. The baseline examination included a questionnaire on medical history, health knowledge, and behaviors related to cardiovascular disease, as well as physical and blood biochemical examinations. The questionnaire survey will be readministered every 2 years. A system for surveillance of mortality and morbidity of cardiovascular disease is under development. RESULTS: A total of 20 115 adults (6710 men and 13 405 women) were investigated at baseline (participation rate = 84.5%). The data indicate that overweight/obesity is a serious public health issue in Fangshan: average body mass index was 25.4 kg/m(2) among men and 26.5 kg/m(2) among women, and the prevalences of overweight and obesity were 43.6% and 10.3% among men and 47.0% and 17.7% among women. CONCLUSIONS: The Fangshan Cohort Study will provide data on cardiovascular risk factors and disease profile, which will assist in developing appropriate prevention and control strategies for cardiovascular disease in rural Chinese communities.

[Gender-specific differences in relative effects of cardiovascular risk factors among rural population].

OBJECTIVE: To investigate the prevalence and association of cardiovascular disease and its risk factors in Fangshan District, Beijing. METHODS: A total of 7 577 rural residents aged over 40 years were surveyed to estimate the prevalence of cardiovascular disease and its risk factors by questionnaire survey, physical examination and biochemical measures. The prevalence odds ratio (POR) was calculated for the association of stroke / coronary heart disease (CHD) with its risk factors in multiple logistic regression models. RESULTS: Prevalence of CHD, stroke, diabetes, hypertension, dyslipidemia, overweight and obesity was presented as 6.5%, 4.1%, 10.7%, 39.5%, 56.7%, 44.0% and 13.6%, respectively. In the adjusted multiple logistic regression models, hypertension showed stronger association with stroke (POR=2.780, 95%CI: 2.146-3.602), while diabetes had a higher correlation with CHD (POR=2.671, 95%CI: 2.121-3.363). After stratification by gender, significant risk factors for stroke were overweight / obesity (POR=1.652, 95%CI: 1.122-2.433), body mass index (POR=1.048, 95%CI: 1.002- 1.096), systolic blood pressure (POR=1.017, 95%CI: 1.005-1.030) and serum glucose (POR=1.093, 95%CI: 1.048-1.140) in females, whereas dyslipidemia (POR=1.615, 95%CI: 1.124-2.319), total cholesterol (POR=3.932, 95%CI: 1.533-10.086) and high-density lipoprotein cholesterol (POR=0.072, 95%CI: 0.022-0.236) were associated with stroke in males. CONCLUSION: Highly prevalent cardiovascular risk factors aggravated the burden brought by stroke and CHD in the rural population, and the various risk factors for stroke and CHD exhibited heterogeneous contributions among the population with different gender.

[Strong association between the NINJ2 gene polymorphism and the susceptibility of stroke in Chinese Han population in Fangshan district].

OBJECTIVE: To investigate the association between the NINJ2 gene rs11833579 polymorphism and stroke in Han Chinese population. METHODS: This study was a population-based cross-sectional case-control study. Polymerase chain reaction-restriction fragment length polymorphism (RFLP) and sequencing were used for the detection of NINJ2 genotypes in 790 patients with stroke (679 ischemic stroke) which were Han Chinese population from Fangshan First Hospital and 811 controls which were healthy Han Chinese population without family history of stroke in Fangshan district rural area. RESULTS: In rs11833579 locus of the NINJ2 gene, the frequencies of GG genotype and allele G were higher in ischemic stroke patients than that in controls (P<0.001). The frequency of allele G of the NINJ2 gene was higher in cerebral hemorrhage patients than that in controls (P=0.005). Genotype had little effect on the glucose, total cholesterol and triglyceride. CONCLUSION: There is significant association between rs11833579 site polymorphism of the NINJ2 gene and risk for stroke in Han Chinese population from Fangshan district.

[An association study of abdominal obesity and polymorphisms of UCP2 and SREBP1c genes].

OBJECTIVE: To investigate the association of -866A/G polymorphism of uncoupling protein 2 (UCP2) gene, and 54G/C polymorphism of sterol regulatory element binding protein 1c (SREBP1c) gene with abdominal obesity in the population of type 2 diabetes mellitus families. METHODS: Eligible type 2 diabetes mellitus cases from newly diagnosed and previous hospitalized patients were choson, then their family members (siblings and parents) tracked. A set of questionnaires was administered to obtain information on demographic characteristics. Physical measurements were recorded. DNA was extracted from blood samples and genotyped using polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP). Generalized estimating equation (GEE) was used to adjust for within-family correlation in analysis of relationships of factors. RESULTS: In the study population, the frequency of A allele of UCP2-866A/G polymorphism was 0.459, and of G allele 0.541; the frequency of G allele of SREBP1c 54G/C polymorphism was 0.822, and of C allele 0.178. Totally 762 participants were analyzed using GEE regression. It was shown that the odds ratio (OR) of the population with only 54G/C polymorphism of SREBP1c gene being the mutant type (GC/CC) was statistically significant while -866A/G polymorphism of UCP2 gene not being the mutant type (AG/GG) was not. The OR of the population with the opposite genotype status was 1.8 (P=0.042), and that with mutant types of both polymorphisms 3.2(P=0.001). CONCLUSION: In the population of type 2 diabetes mellitus families, only 54G/C polymorphism of SREBP1c gene being the mutant type (GC/CC) might be a moderate risk factor of abdominal obesity. When both the two polymorphisms studied are the mutant type, the risk of abdominal obesity may increase significantly.

The Fangshan/Family-based Ischemic Stroke Study In China (FISSIC) protocol.

BACKGROUND: The exact etiology of ischemic stroke remains unclear, because multiple genetic predispositions and environmental risk factors may be involved, and their interactions dictate the complexity. Family-based studies provide unique features in design, while they are currently underrepresented for studies of ischemic stroke in developing countries. The Fangshan/Family-based Ischemic Stroke Study In China (FISSIC) program aims to conduct a genetic pedigree study of ischemic stroke in rural communities of China. METHODS/DESIGN: The pedigrees of ischemic stroke with clear documentation are recruited by using the proband-initiated contact method, based on the stroke registry in hospital and communities. Blood samples and detailed information of pedigrees are collected through the health care network in the rural area, and prospective follow-up of the pedigrees cohort is scheduled. Complementary strategies of both family-based design and matched case-spousal control design are used, and comprehensive statistical methods will be implemented to ascertain potential complex genetic and environmental factors and their interactions as well. DISCUSSION: This study is complementary to other genetic pedigree studies of ischemic stroke, such as the Siblings With Ischemic Stroke Study (SWISS), which are established in developed countries. We describe the protocol of this family-based genetic epidemiological study that may be used as a new practical guideline and research paradigm in developing countries and facilitate initiatives of stroke study for international collaborations.

[Genetic epidemiological study on discordant sib pairs of ischemic stroke in Beijing Fangshan District].

OBJECTIVE: To investigate the association among serum lipids, blood pressure, -514C/T polymorphism of hepatic lipase gene and subtypes of ischemic stroke in the discordant sib pairs. METHODS: Ischemic stroke cases were enrolled from a hospital-based stroke registry, the proband-initiated contact was used to recruit pedigrees, and participants' information and blood samples were collected through the community-based health care networks in rural areas of China. Statistical analysis was performed by using the Wilcoxon signed rank test to compare quantitative differences between sib pairs and the McNemar test to compare qualitative differences. Generalized estimating equation (GEE) was used to adjust for within-family correlation in analysis of discordant sib pairs. Family based association test (FBAT) was applied to associations between serum lipids, blood pressure and the -514T allele in hepatic lipase gene. RESULTS: Totally 107 discordant sib pairs from 71 ischemic stroke patients pedigrees were analyzed by univariate and multivariate methods. The blood pressure and serum lipids were associated with ischemic stroke (P<0.05) The lipid level was higher in large-artery atherosclerosis ischemic stroke than in the subtype of small-vessel occlusion, while the blood pressure was higher in the latter. The -514T allele in hepatic lipase gene was associated with low density lipoprotein-cholesterol (LDL-C) and diastolic blood pressure in additive model by FBAT analysis (Z=2.366, P<0.05), and it was also associated with diastolic blood pressure in additive model (Z=-2.277, P<0.05) and recessive model (Z=-2.244,P< 0.05), but not associated with ischemic stroke or its subtypes. CONCLUSION: In these discordant sib pairs, the abnormalities of blood pressure and serum lipids may increase risks of ischemic stroke, and different subtypes of ischemic stroke may differ from each other in etiology. The -514T allele in hepatic lipase gene may be associated with LDL-C and diastolic blood pressure.