Systematic fine-mapping of association with BMI and type 2 diabetes at the FTO locus by integrating results from multiple ethnic groups.

BACKGROUND/OBJECTIVE: The 16q12.2 locus in the first intron of FTO has been robustly associated with body mass index (BMI) and type 2 diabetes in genome-wide association studies (GWAS). To improve the resolution of fine-scale mapping at FTO, we performed a systematic approach consisting of two parts. METHODS: The first part is to partition the associated variants into linkage disequilibrium (LD) clusters, followed by conditional and haplotype analyses. The second part is to filter the list of potential causal variants through trans-ethnic comparison. RESULTS: We first examined the LD relationship between FTO SNPs showing significant association with type 2 diabetes in Japanese GWAS and between those previously reported in European GWAS. We could partition all the assayed or imputed SNPs showing significant association in the target FTO region into 7 LD clusters. Assaying 9 selected SNPs in 4 Asian-descent populations--Japanese, Vietnamese, Sri Lankan and Chinese (n≤26,109 for BMI association and n≤24,079 for type 2 diabetes association), we identified a responsible haplotype tagged by a cluster of SNPs and successfully narrowed the list of potential causal variants to 25 SNPs, which are the smallest in number among the studies conducted to date for FTO. CONCLUSIONS: Our data support that the power to resolve the causal variants from those in strong LD increases consistently when three distant populations--Europeans, Asians and Africans--are included in the follow-up study. It has to be noted that this fine-mapping approach has the advantage of applicability to the existing GWAS data set in combination with direct genotyping of selected variants.

Time trends in blood pressure, body mass index and smoking in the Vietnamese population: a meta-analysis from multiple cross-sectional surveys.

INTRODUCTION: Data for trends in cardiovascular disease (CVD) risk factors are needed to set priorities and evaluate intervention programmes in the community. We estimated time trends in blood pressure (BP), anthropometric variables and smoking in the Vietnamese population and highlighted the differences between men and women or between rural and urban areas. METHODS: A dataset of 23,563 adults aged 25-74 from 5 cross-sectional surveys undertaken within Vietnam from 2001 to 2009 by the Vietnam National Heart Institute was used to estimate mean BP, weight, waist circumference (WC), body mass index (BMI), the prevalence of hypertension, adiposity or smoking, which were standardised to the national age structure of 2009. Multilevel mixed linear models were used to estimate annual changes in the variables of interest, adjusted by age, sex, residential area, with random variations for age and surveyed provinces. FINDINGS: Among the adult population, the age-standardised mean systolic and diastolic BP increased by 0.8 and 0.3 mmHg in women, 1.1 and 0.4 mmHg in men, while the mean BMI increased by 0.1 kgm(-2) in women, 0.2 kgm(-2) in men per year. Consequently, the prevalence of hypertension and adiposity increased by 0.9 and 0.3% in women, 1.1 and 0.9% in men with similar time trends in both rural and urban areas, while smoking prevalence only increased in women by 0.3% per year. A U-shaped association was found between age-adjusted BP and BMI in both sexes and in both areas. CONCLUSIONS: From 2001 to 2009, mean BP, weight and WC significantly increased in the Vietnamese population, leading to an increased prevalence of hypertension and adiposity, suggesting the need for the development of multi-sectoral cost-effective population-based interventions to improve CVD management and prevention. The U-shaped relationship between BP and BMI highlighted the hypertension burden in the underweight population, which is usually neglected in CVD interventions.

Effectiveness of community-based comprehensive healthy lifestyle promotion on cardiovascular disease risk factors in a rural Vietnamese population: a quasi-experimental study.

BACKGROUND: Health promotion is a key component for primary prevention of cardiovascular disease (CVD). This study evaluated the impact of healthy lifestyle promotion campaigns on CVD risk factors (CVDRF) in the general population in the context of a community-based programme on hypertension management. METHODS: A quasi-experimental intervention study was carried out in two rural communes of Vietnam from 2006 to 2009. In the intervention commune, a hypertensive-targeted management programme integrated with a community-targeted health promotion was initiated, while no new programme, apart from conventional healthcare services, was provided in the reference commune. Health promotion campaigns focused on smoking cessation, reducing alcohol consumption, encouraging physical activity and reducing salty diets. Repeated cross-sectional surveys in local adult population aged 25 years and over were undertaken to assess changes in blood pressure (BP) and behavioural CVDRFs (smoking, alcohol consumption, physical inactivity and salty diet) in both communes before and after the 3-year intervention. RESULTS: Overall 4,650 adults above 25 years old were surveyed, in four randomly independent samples covering both communes at baseline and after the 3-year intervention. Although physical inactivity and obesity increased over time in the intervention commune, there was a significant reduction in systolic and diastolic BP (3.3 and 4.7 mmHg in women versus 3.0 and 4.6 mmHg in men respectively) in the general population at the intervention commune. Health promotion reduced levels of salty diets but had insignificant impact on the prevalence of daily smoking or heavy alcohol consumption. CONCLUSION: Community-targeted healthy lifestyle promotion can significantly improve some CVDRFs in the general population in a rural area over a relatively short time span. Limited effects on a context-bound CVDRF like smoking suggested that higher intensity of intervention, a supportive environment or a gender approach are required to maximize the effectiveness and maintain the sustainability of the health intervention.

Cardiovascular disease risk factor patterns and their implications for intervention strategies in Vietnam.

Background. Data on cardiovascular disease risk factors (CVDRFs) in Vietnam are limited. This study explores the prevalence of each CVDRF and how they cluster to evaluate CVDRF burdens and potential prevention strategies. Methods. A cross-sectional survey in 2009 (2,130 adults) was done to collect data on behavioural CVDRF, anthropometry and blood pressure, lipidaemia profiles, and oral glucose tolerance tests. Four metabolic CVDRFs (hypertension, dyslipidaemia, diabetes, and obesity) and five behavioural CVDRFs (smoking, excessive alcohol intake, unhealthy diet, physical inactivity, and stress) were analysed to identify their prevalence, cluster patterns, and social predictors. Framingham scores were applied to estimate the global 10-year CVD risks and potential benefits of CVD prevention strategies. Results. The age-standardised prevalence of having at least 2/4 metabolic, 2/5 behavioural, or 4/9 major CVDRF was 28%, 27%, 13% in women and 32%, 62%, 34% in men. Within-individual clustering of metabolic factors was more common among older women and in urban areas. High overall CVD risk (≥20% over 10 years) identified 20% of men and 5% of women-especially at higher ages-who had coexisting CVDRF. Conclusion. Multiple CVDRFs were common in Vietnamese adults with different clustering patterns across sex/age groups. Tackling any single risk factor would not be efficient.

Implementing a hypertension management programme in a rural area: local approaches and experiences from Ba-Vi district, Vietnam.

BACKGROUND: Costly efforts have been invested to control and prevent cardiovascular diseases (CVD) and their risk factors but the ideal solutions for low resource settings remain unclear. This paper aims at summarising our approaches to implementing a programme on hypertension management in a rural commune of Vietnam. METHODS: In a rural commune, a programme has been implemented since 2006 to manage hypertensive people at the commune health station and to deliver health education on CVD risk factors to the entire community. An initial cross-sectional survey was used to screen for hypertensives who might enter the management programme. During 17 months of implementation, other people with hypertension were also followed up and treated. Data were collected from all individual medical records, including demographic factors, behavioural CVD risk factors, blood pressure levels, and number of check-ups. These data were analysed to identify factors relating to adherence to the management programme. RESULTS: Both top-down and bottom-up approaches were applied to implement a hypertension management programme. The programme was able to run independently at the commune health station after 17 months. During the implementation phase, 497 people were followed up with an overall regular follow-up of 65.6% and a dropout of 14.3%. Severity of hypertension and effectiveness of treatment were the main factors influencing the decision of people to adhere to the management programme, while being female, having several behavioural CVD risk factors or a history of chronic disease were the predictors for deviating from the programme. CONCLUSION: Our model showed the feasibility, applicability and future potential of a community-based model of comprehensive hypertension care in a low resource context using both top-down and bottom-up approaches to engage all involved partners. This success also highlighted the important roles of both local authorities and a cardiac care network, led by an outstanding cardiac referral centre.