The association of pulmonary function with carotid atherosclerosis in older Chinese: Guangzhou Biobank Cohort Study-CVD Subcohort.

BACKGROUND: Evidence describing the association between pulmonary function and carotid atherosclerosis has been inconclusive and the role of smoking in this association is unclear. We therefore examined this association in the Guangzhou Biobank Cohort Study-CVD Subcohort. METHODS: Common carotid artery (CCA) intima-media thickness (IMT) and carotid plaques were measured by B-mode ultrasonography and lung function by spirometry using a turbine flowmeter. Chronic obstructive pulmonary disease (COPD) was defined as the ratio of forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) of less than 0.70. Predicted FEV1 and FVC were derived using equations for Chinese. RESULTS: Of 1625 participants aged 50 + years, 382 (23.5%) had evidence of carotid plaque. The mean CCA-IMT was higher in those with COPD than those without (0.82 ± 0.29 mm versus 0.76 ± 0.31 mm, P = 0.02). We found no evidence that the association of pulmonary function with CCA-IMT varied by smoking status (P values interaction: 0.23-0.83). After adjustment for a wide range of potential confounders, the increased risks of thickened CCA-IMT (CCA-IMT ≥1.0 mm) in those with COPD became marginally nonsignificant (adjusted odds ratio (OR) 1.45, 95% confidence interval (CI) 0.91-2.29; P = 0.12). Compared to those in the highest tertile, participants in the lowest tertile of FEV1 observed to predicted ratio had increased risk of thickened CCA-IMT (adjusted OR 2.18, 95% CI 1.42-3.34) and carotid plaque (adjusted OR 1.50, 95% CI 1.08-2.09), while participants in the lowest tertile of FVC observed to predicted ratio had increased risk of thickened CCA-IMT (adjusted OR 2.29, 95% CI 1.46-3.58), but the adjusted OR for carotid plaque was marginally nonsignificant (adjusted OR 1.29, 95% CI 0.93-1.80; P = 0.13). CONCLUSION: Independent of smoking status, poor pulmonary function was dose-dependently associated with carotid atherosclerosis in older Chinese. (281 words).

Alcohol consumption and electrocardiographic left ventricular hypertrophy and mediation by elevated blood pressure in older Chinese men: the Guangzhou Biobank Cohort Study.

BACKGROUND: Chinese people have a markedly lower alcohol consumption than people in the West. Whether alcohol consumption at such levels is associated with left ventricular hypertrophy, and the role of blood pressure (BP) in this relationship is unclear. We investigated the association between alcohol consumption and electrocardiographic left ventricular hypertrophy (ECG-LVH) and the mediating role of BP in Chinese men aged ≥50 years. METHODS AND RESULTS: A case-control analysis was conducted on baseline cross-sectional data from the community-based Guangzhou Biobank Cohort Study (2003-2008), using standard 12-lead resting electrocardiograms. By comparing 191 new ECG-LVH cases with 4311 controls, excessive drinking (>210 g/week) showed excess risks for ECG-LVH (odds ratio [OR] = 1.90, 95% confidence interval [CI] = 1.12-3.24), after adjusting for education, income, occupation, physical activity, smoking, body mass index, fasting glucose, triglyceride, total cholesterol, high-density lipoprotein cholesterol, BP, and antihypertensive medication. Mediation analysis showed a significant mediating effect of BP on the association between excessive drinking and ECG-LVH: systolic (31%) and diastolic (16%). After multivariate adjustment, no significant association was found between occasional drinking (210 g/week in Chinese men is an independent risk factor for ECG-LVH. Low power prevented us from examining whether drinking at

A polymorphism in transforming growth factor-ß1 is associated with carotid plaques and increased carotid intima-media thickness in older Chinese men: the Guangzhou Biobank Cohort Study-Cardiovascular Disease Subcohort.

OBJECTIVE: Polymorphisms of the transforming growth factor-ß1 (TGFB1) gene have not been associated with asymptomatic atherosclerosis previously. We investigated the relationship between a single nucleotide polymorphism (SNP) rs4803455 in TGFB1 and atherosclerosis identified by the presence of carotid plaque and increased intima-media thickness (IMT) in an older Chinese population. METHODS: 1996 subjects (992 (49.7%) men aged 50-85 years) from the Guangzhou Biobank Cohort Study-Cardiovascular Subcohort (GBCS-CVD) were genotyped. Carotid plaque and IMT were assessed by B-mode ultrasonography. RESULTS: In male subjects, the C allele of TGFB1 rs4803455 was significantly associated with prevalence of carotid plaque (adjusted OR: 2.49, 95% CI: 1.16-5.36, P = 0.03). The C allele was related to increased number of common carotid artery (CCA) plaques (P=0.03) and larger carotid plaque area (P = 0.02) in men. The homozygous carriers of allele C in male subjects also had a higher risk of having carotid IMT ≥ 1 mm (adjusted OR: 1.75, 95% CI: 1.05-2.93, P = 0.03). These associations were independent of age, smoking, physical activity, body mass index, blood pressure, lipid profile, fasting glucose and high sensitivity C-reactive protein. CONCLUSION: This is the first study to show that the C allele in TGFB1 was associated with increased risk of atherosclerosis in older Chinese men. Further investigations on the linkage between the TGFB1 gene and progression of atherosclerosis in asymptomatic populations are warranted.

Atrial fibrillation and obesity among older Chinese: the Guangzhou Biobank Cohort Study.

BACKGROUND: Atrial fibrillation (AF) is the most common form of arrhythmia, and its prevalence is increasing. Few studies have examined its association with obesity as defined by different criteria, particularly in developing countries. We investigated the association between atrial fibrillation (AF) and obesity indices among older Chinese. METHODS: We conducted a community-based nested case control study using cross-sectional data of 5882 men and 14,548 women aged 50 or above from Phases I and II (September 2003 to May 2006) of the Guangzhou Biobank Cohort Study (GBCS). AF cases were identified by the 12-lead body surface electrocardiogram. RESULTS: 159 AF cases (65 men and 94 women) were identified from 19,964 participants with ECG records. 9249 participants with other abnormal ECG findings were excluded, resulting in a case control comparison on 159 AF cases and 10,369 controls. After multivariate adjustment, BMI (adjusted odds ratio (OR) 1.06 per kg/m(2), 95% confidence interval (CI)=1.01-1.11) and waist circumference (adjusted OR 1.02 per cm (1.00-1.04)) were significant risk factors. The adjusted OR per Z-score [(individual value-mean)/standard deviation] for BMI and waist circumference was 1.21 (1.03-1.41) and 1.18 (1.01-1.38) respectively. CONCLUSIONS: This is the first report showing that both general and central obesity are associated with increased risk of AF in an Eastern population with much lower level of obesity than in the West. As both AF and obesity are increasing in developing countries, the results should have important public health implications.

Association of a genetic variant in the apolipoprotein A5 gene with the metabolic syndrome in Chinese.

OBJECTIVE: Single nucleotide polymorphisms (SNPs) in the apolipoprotein A5 gene (APOA5) are associated with hypertriglyceridaemia in our population. We studied the associations of SNPs in APOA5 with the metabolic syndrome (MetS) in the Hong Kong and Guangzhou Chinese. METHODS: We genotyped five tagging SNPs in 1330 unrelated subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort with follow-up after a median interval of 6·4 years; 1952 subjects from the Guangzhou Biobank Cohort Study-Cardiovascular Disease Subcohort were used to replicate the findings. The MetS was defined according to the consensus criteria proposed jointly by several organizations in 2009. RESULTS: The SNP rs662799 (-1131T>C) was associated with the MetS (odds ratio = 1·47, P = 0·00082) and the number of its components present (regression coefficient = 0·204, P = 4·6 × 10(-5) ) after adjusting for age, sex, smoking, drinking and education in Hong Kong subjects at baseline. Similar association of this SNP was found in Hong Kong subjects at follow-up (P = 0·010 and 0·00021, respectively) and in Guangzhou subjects (P = 0·0041 and 0·017, respectively). The association of rs662799 with the number of the MetS components was significant regardless of age, sex, obesity and alcohol drinking, but almost disappeared after further adjusting for plasma triglycerides. CONCLUSION: Our results showed that the -1131T>C polymorphism in APOA5 was associated with the MetS because of its strong effect on plasma triglycerides. This may partly explain the higher cardiovascular risk in people with this polymorphism.

[Study on the association between gene polymorphism of ENPP1 and left ventricular hypertrophy: a Guangzhou Biobank Cohort Study-CVD].

OBJECTIVE: To examine the association between genetic polymorphism of rs1409181 in ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) and left ventricular hypertrophy (LVH) among older Chinese in Guangzhou. METHODS: 390 subjects aged ≥ 50 years were randomly selected from the Guangzhou Biobank Cohort Study-CVD. Information on personal history, blood pressure, fasting plasma glucose and lipids were collected. Color Doppler ultrasound was used to measure the indicators of LVH, including left ventricular internal diastolic diameter (LVIDD), thickness of the interventricular septum diastolic wall (IVSD) and the posterior wall diastolic diameter (LVPWD). LVIDD was calculated using Devereux ventricular mass (LVM) equation while the Left ventricular mass index (LVMI) equation was used to estimate LVH. The genotype of rs1409181 was determined by Taqman SNP genotyping kits using the ABI 7900HT real time PCR system. RESULTS: In the GG, CG and CC genotype groups, the proportions of LVH were 21.5%, 28.2% and 37.5% respectively. Compared with GG, the adjusted odds ratios (95% confidence interval) for the LVH were 1.39 (0.78 - 2.50) and 2.36 (1.21 - 4.60) for CG genotype and CC genotype of ENPP1 respectively (P for trend = 0.01). CONCLUSION: Polymorphism of ENPP1 gene rs1409181 was associated with LVH in the older Chinese people in Guangzhou.

[Dose-response relationship between smoking status and carotid atherosclerosis].

OBJECTIVE: To examine the dose-response relationship of smoking status with carotid atherosclerosis in 959 relatively healthy Chinese men. METHODS: 959 older Chinese men were selected from Guangzhou Biobank Cohort Study (GBCS) on cardiovascular disease. Personal histories were collected and fasting plasma glucose and lipids, blood pressure, and common carotid artery intima-median thickness (CCA-IMT) were measured. RESULTS: (1) Composition of the cases: 39.1% were non-smokers, 25.7% were former smokers and 35.2% were current smokers. The mean (95% confidence interval) carotid IMT was 0.78 (0.77 - 0.79) mm. 18.4% of the subjects had carotid IMT equal to or thicker than 1.0 mm while 34.1% had carotid plaque. (2) After adjusting for age, sex, physical activity, body mass index, fasting glucose, triglyceride, high-density lipoprotein cholesterol, systolic and diastolic blood pressure, compared to never smokers, current smokers had significantly increased risk for thicker IMT and carotid plaque [odds ratio (OR) = 1.82, 95%CI: 1.30 - 2.55 and OR = 1.95, 95%CI: 1.38 - 2.75, respectively, all P < 0.001]. The risk for thicker IMT and carotid plaque increased with the increasing amount (cigarettes/day) and duration of smoking (years) as well with cigarette pack-years (P for trend all ≤ 0.01). CONCLUSION: An elevated risk with a clear dose-response relationship was found between cigarette smoking and carotid atherosclerosis. Quitting smoking or reducing the amount of smoking may lower the risk of atherosclerosis, preventing and controlling the occurrence of cardiovascular diseases, and reducing the related cardiovascular mortalities.

A single nucleotide polymorphism in APOA5 determines triglyceride levels in Hong Kong and Guangzhou Chinese.

Single nucleotide polymorphisms (SNPs) in the apolipoprotein A5 (APOA5) gene have been associated with hypertriglyceridaemia. We investigated which SNPs in the APOA5 gene were associated with triglyceride levels in two independent Chinese populations. In all, 1375 subjects in the Hong Kong Cardiovascular Risk Factor Prevalence Study were genotyped for five tagging SNPs chosen from HapMap. Replication was sought in 1996 subjects from the Guangzhou Biobank Cohort Study. Among the five SNPs, rs662799 (-1131T>C) was strongly related to log-transformed triglyceride levels among Hong Kong subjects (ß=0.192, P=2.6 × 10(-13)). Plasma triglyceride level was 36.1% higher in CC compared to TT genotype. This association was confirmed in Guangzhou subjects (ß=0.159, P=1.3 × 10(-12)), and was significantly irrespective of sex, age group, obesity, metabolic syndrome, hypertension, diabetes, smoking and alcohol drinking. The odds ratios and 95% confidence interval for plasma triglycerides ≥1.7 mmol/l associated with TC and CC genotypes were, respectively, 1.81 (1.37-2.39) and 2.22 (1.44-3.43) in Hong Kong and 1.27 (1.05-1.54) and 1.97 (1.42-2.73) in Guangzhou. Haplotype analysis suggested the association was due to rs662799 only. The corroborative findings in two independent populations indicate that the APOA5-1131T>C polymorphism is an important and clinically relevant determinant of plasma triglyceride levels in the Chinese population.

[Polymorphisms of vascular diseases-related genes in Guangzhou Biobank Cohort Study].

OBJECTIVE: To study the polymorphisms of cerebrovascular and cardiovascular disease genes using Taqman single nucleotide polymorphism (SNP) genotyping kits. METHODS: A total of 2000 subjects were recruited from the Guangzhou Biobank Cohort Study (GBCS), and 15 SNPs were detected using Taqman SNP genotyping kits and an ABI 7900HT real time PCR system. The data were tested for the Hardy-Weinberg equilibrium, and then compared with the data of the Chinese population from the International HapMap Project (HapMap_HCN). RESULTS: (1) All genotype data of the 15 SNPs were consistent with the Hardy-Weinberg rules. (2) The significant differences were observed among two SNPs, rs4220 and rs5368 and the HapMap_HCN (rs4220 28.2% vs 17.8%; chi(2) = 4.891, P = 0.028; rs5368 22.1% vs 32.2%, chi(2) = 5.137, P = 0.024). Comparing other gene bank data, such as AFD-CHN-PANEL, the Allele Frequency Database (ALFRED) and JBIC-allele, it would be most likely that our observations represent differences between the Northern and Southern populations in China. CONCLUSION: Such Biobank study provided a useful platform for the study of the role of genetic and environmental determinants on cerebrovascular and cardiovascular disease.

Interleukin-6 receptor gene polymorphism modulates interleukin-6 levels and the metabolic syndrome: GBCS-CVD.

Interleukin-6 (IL-6) is a key pleiotropic cytokine that modulates the inflammatory response. Single-nucleotide polymorphisms (SNPs) within associated genes may contribute to the metabolic syndrome (MES). We examined the role of the IL-6 (rs1524107-C/T) and IL-6 receptor (IL-6R, rs8192284-A/C, Asp358Ala) SNPs in modulating IL-6 levels and the syndrome. A total of 1,979 older Chinese subjects aged 50-92 years from Guangzhou Biobank Cohort Study (GBCS) were recruited. SNPs were detected using Taqman SNP genotyping kits. IL-6 was measured using enzyme-linked immunosorbent assay. The genotype frequencies were 4.9, 33.9, and 61.3% for the IL-6 CC, CT, and TT, and 12.0, 44.9, and 43.1% for the IL-6R CC, AC, and AA, respectively. Both SNPs were in Hardy-Weinberg equilibrium. The IL-6 SNP was not associated with IL-6 levels or the MES, but was dose-dependently associated with fibrinogen levels, P = 0.049. IL-6 levels significantly decreased with increasing proportions of the IL-6R A-allele 9.8 ± 4.9, 9.3 ± 4.8, and 8.4 ± 4.3, respectively, P = 0.001. Conversely, the A-allele was associated with elevated triglyceride, P = 0.009, C-reactive protein, P = 0.047, and potentially with fasting glucose levels, P = 0.077. There was an increasing prevalence of the MES in those carrying the IL-6R CC, AC, and AA genotypes at 18.1, 21.5, 25.2%, respectively, P = 0.010. The SNP was a significant independent predictor of the MES after adjusting for general obesity, age, gender and lifestyle, and socioeconomic parameters, P = 0.023. These data, which are in accord with studies from white populations suggest the IL-6R SNP may play a role in the pathogenesis of the MES possibly through modulating IL-6 levels.

The metabolic syndrome is associated with subclinical atherosclerosis independent of insulin resistance: the Guangzhou Biobank Cohort Study-CVD.

OBJECTIVE: We examined whether the association of the metabolic syndrome (MetS) and subclinical atherosclerosis is independent of insulin resistance in a Chinese community sample with no history of type 2 diabetes. METHODS: Five hundred and ninety-six men and 526 women from a substudy of the Guangzhou Biobank Cohort Study (GBCS-CVD) had carotid intimal-medial thickness (IMT) measured by B-mode ultrasonography, and brachial-ankle pulse wave velocity (PWV) and ankle-brachial systolic blood pressure index (ABI) measured simultaneously by a noninvasive automatic waveform analyser. RESULTS: Fourteen percentage had MetS as defined by the International Diabetes Federation. Obesity indices, systolic and diastolic blood pressure and pulse pressure, lipids, fasting and postload glucose and insulin, homeostatic model assessment of insulin resistance, glycosylated haemoglobin A1c, leptin, high-sensitivity C-reactive protein, IMT and PWV increased and high-density lipoprotein-cholesterol, adiponectin and ABI decreased significantly with increasing number of MetS components after adjusting for age and sex (P for trend from 0.004 to <0.001). After adjusting for traditional cardiovascular risk factors and insulin resistance, the odds ratios [OR (95% CI)] of thicker IMT (> or =1.0 mm), higher PWV (> or =14.0 m/s) and low ABI (< or =1.0) for MetS were significantly increased [2.28 (1.19-4.38), 2.17 (1.36-3.46) and 1.72 (1.14-2.59), respectively, all P < 0.01] but were lower than the adjusted OR for those with three or more MetS components. CONCLUSION: MetS was associated with subclinical atherosclerosis independent of insulin resistance. The presence of increasing number of MetS risk factors appeared to be more important than the diagnosis of MetS in predicting subclinical atherosclerosis. Early screening for MetS risk factors might identify those at greater cardiovascular risk.

Impact of impaired fasting glucose and impaired glucose tolerance on arterial stiffness in an older Chinese population: the Guangzhou Biobank Cohort Study-CVD.

The aim of the study was to compare the impact of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) on vascular function among older Chinese people. A random sample of 671 men and 603 women aged 50 to 85 years without known diabetes from the Guangzhou Biobank Study-CVD was examined in a cross-sectional study. Subjects with no previously confirmed or treated diabetes but with both fasting plasma glucose less than 5.6 mmol/L and 2-hour glucose from 7.8 to less than 11.0 mmol/L were classified as having isolated IGT, and those with no previously confirmed and treated diabetes but with both fasting plasma glucose from 5.6 to less than 7.0 mmol/L and 2-hour glucose less than 7.8 mmol/L were classified as having isolated IFG. A total of 11.0% of the men and 8.6% of the women had isolated IFG, and 17.7% of the men and 18.6% of the women had isolated IGT. The brachial-ankle pulse wave velocity and pulse pressure were increased in both the isolated IFG and isolated IGT subjects compared with the normoglycemia group (both Ps < .001). Compared with subjects with isolated IFG, those with isolated IGT appeared to have a higher age- and sex-adjusted brachial-ankle pulse wave velocity (1543 +/- 22 vs 1566 +/- 17, P = .07) and to be more insulin resistant (2-hour postload insulin: 54.2 +/- 2.13 vs 26.8 +/- 2.99 muU/mL, P < .001), had a worse lipid profile (apolipoprotein [apo] B: 1.07 +/- 0.02 vs 0.97 +/- 0.02 g/L, P < .001; apo B/apo A-1 ratio: 0.80 +/- 0.02 vs 0.69 +/- 0.02, P < .001), but had lower glycosylated hemoglobin levels (6.03% +/- 0.06% vs 5.86% +/- 0.04%, P < .001) (values are mean +/- SE). Subjects with isolated IGT had greater arterial stiffness, probably as a result of being more insulin resistant, with a worse lipid profile than those with isolated IFG. The sole use of fasting glucose level to identify prediabetic people would fail to identify a significant proportion of the at-risk population.

[Effect of physical activity strength on the diabetes mellitus prevalence in the elderly under the influence of International Physical Activity Questionnaire].

OBJECTIVE: To examine the impact of International Physical Activity Questionnaire (IPAQ) physical activity intensity on to the prevalence of diabetes mellitus among Chinese elderly. METHODS: A total number of 1996 residents aged 50 or above living in Guangzhou city were recruited from the phase 3 of the Guangzhou Biobank Cohort Study. Information on physical activity and fasting plasma glucose status was derived from standardized interviews and laboratory assays. RESULTS: Among the participants who were classified as physically active (60.0%), moderate active (29.8%) and inactive (10.2%), the prevalence rates of type 2 diabetes mellitus were 9.1%, 12.0% and 14.2%, respectively. After adjustment on age, sex, obesity and other potential confounding factors, data from logistic regression model showed that the odds ratios (95% confidence interval) for diabetes on subjects in physically moderate active and active group were 0.75(0.46-1.26)and 0.60(0.38-0.97) respectively with P for trend as 0.03, when comparing to those physically inactive ones. CONCLUSION: Promotion of physical activity might have had some effects in reducing the risk of diabetes mellitus among the older adults.

[Electrocardiogram change of workers after disengaging occupational noise exposure].

OBJECTIVE: To examine electrocardiogram (ECG) change of workers after leaving occupational noise exposure. METHODS: In the first phase of the Guangzhou Biobank Cohort Study, 10413 Guangzhou residents aged 50 years or more received a face-to face interview including noise exposure history, a full medical check-up and laboratory tests in 2003 - 4. ECG examination was carried out using 12-lead MAC-CS ECG machine made in HP Ltd, Shanghai, China. ECG of every subject was independently diagnosed by two doctors who had obtained ECG diagnosis qualification. RESULTS: (1) Among 10413 subjects, 70% were female, and more than half were aged 60-69 years. The mean age and education level in males were higher than those in females. (2) 2119 subjects (21.0%) were previously exposed to noise and were retired now. (3) The prevalence of ECG abnormality was respectively 82.4% and 79.1% in females and males. Rate of ECG abnormality increased with age in both females and males (P = 0.000), and was lower in females with higher education level (P = 0.000). There was not significant difference in ECG abnormality between workers previously exposed or unexposed to noise in both females and males (P > 0.05). 4 Comparing workers previously exposed to those unexposed to noise in both females and males, after adjusting for age, educational level and smoking status, the rates of arrhythmia, axes deviation, atria and ventricle hypertrophy, ST-T change and coronary artery syndrome were not significantly different (P > 0.05). CONCLUSION: Our study showed that the prevalence of ECG abnormality was not significantly increased in workers previously exposed to noise and had left exposure now compared to those never exposed to noise. Because our study was cross section and occupational history was obtained from a questionnaire but was not confirmed by the companies, further study is needed.

[Clinical manifestation and ultrasonic characteristics of five patients with acute arsenic poisoning].

OBJECTIVE: To study the clinical manifestation and ultrasonic characteristics of liver, kidney and heart of five patients with acute arsenic poisoning. METHODS: The activity of serum myocardial enzymes, function of liver and kidney, and urinary As concentrations were measured. HDI 3000 Enhanced, and Toshiba 38A two dimensional ultrasound was used to examine the ultrasonic echogram of heart, liver, kidney of the patients. RESULTS: (1) The arsenic concentrations in the urine (1.9 approximately 15.6 micromol/L) were higher than the normal value (1.17 micromol/L) in these patients (blood dialytic fluid of one patient with anuria was measured); (2) Four of them had increased WBC, or anemia, and abnormal urine routine to various degree; (3) The activities of serum myocardial enzymes (CK, AST, LDH and HBDH) in 4 patients were at least 2 items increased; (4) Serum bilirubin and urea nitrogen in all patients were increased; (5) The ultrasonic echogram of liver and kidney in these 5 patients showed abnormality to various degree, one of them had slight enlargements in left atrium and ventricle as well as a little pericardial fluid. CONCLUSION: The clinical manifestation and ultrasonic characteristics of liver, kidney, and heart were consistent with the pathologic changes in acute arsenic poisoning. Early blood dialysis may reduce visceral damage.