Novel genomic variants related to visceral adiposity index (VAI) and body adiposity index (BAI) in Indian sib-pairs.

BACKGROUND: Obesity is among the leading public health threats globally. Over the last few years, visceral adiposity index (VAI), and body adiposity index (BAI), derived from anthropometric, and biochemical measures, have gained importance as a measure of obesity. However, unlike other common indices like body mass index, and waist circumference, the genetic predisposition of VAI, and BAI under-examined. METHODS: 2265 sib-pairs from Indian Migration Study were used for examining the association of genetic variants from the Cardio-Metabochip array with VAI, and BAI. Mixed linear regression models were run, and all inferences were based on the within-sib component of the Fulker's association models. Gene-environment/lifestyle interaction analyses were also undertaken. RESULTS: rs6659428 at LOC400796 | SEC16B (ß = 0.26, SE = 0.05), and rs7611535 at DRD3 | LOC645180 (ß = 0.18, SE = 0.04) were associated with VAI at suggestive significance value of <8.21 × 10-6. For BAI, rs73300702 at JAZF1-AS1 (ß = 0.27, SE = 0.06), was the top hit at p value < 8.21 × 10-6. Further, rs6659428 showed marginal effect modification with rural/urban location (ß = 0.26, SE = 0.13, p value = 0.047), and rs73300702 with physical activity (ß = -0.29,SE = 0.14, p value = 0.034). CONCLUSION: We report three novel genetic loci for VAI, and BAI in Indians that are important indicators of adiposity. These findings need to be replicated and validated with larger samples from different ethnicities. Further, functional studies for understanding the biological mechanisms of these adiposity indices need to be undertaken to understand the underlying pathophysiology.

A Community-Based Intervention for Managing Hypertension in Rural South Asia.

BACKGROUND: The burden of hypertension is escalating, and control rates are poor in low- and middle-income countries. Cardiovascular mortality is high in rural areas. METHODS: We conducted a cluster-randomized, controlled trial in rural districts in Bangladesh, Pakistan, and Sri Lanka. A total of 30 communities were randomly assigned to either a multicomponent intervention (intervention group) or usual care (control group). The intervention involved home visits by trained government community health workers for blood-pressure monitoring and counseling, training of physicians, and care coordination in the public sector. A total of 2645 adults with hypertension were enrolled. The primary outcome was reduction in systolic blood pressure at 24 months. Follow-up at 24 months was completed for more than 90% of the participants. RESULTS: At baseline, the mean systolic blood pressure was 146.7 mm Hg in the intervention group and 144.7 mm Hg in the control group. At 24 months, the mean systolic blood pressure fell by 9.0 mm Hg in the intervention group and by 3.9 mm Hg in the control group; the mean reduction was 5.2 mm Hg greater with the intervention (95% confidence interval [CI], 3.2 to 7.1; P<0.001). The mean reduction in diastolic blood pressure was 2.8 mm Hg greater in the intervention group than in the control group (95% CI, 1.7 to 3.9). Blood-pressure control (<140/90 mm Hg) was achieved in 53.2% of the participants in the intervention group, as compared with 43.7% of those in the control group (relative risk, 1.22; 95% CI, 1.10 to 1.35). All-cause mortality was 2.9% in the intervention group and 4.3% in the control group. CONCLUSIONS: In rural communities in Bangladesh, Pakistan, and Sri Lanka, a multicomponent intervention that was centered on proactive home visits by trained government community health workers who were linked with existing public health care infrastructure led to a greater reduction in blood pressure than usual care among adults with hypertension. (Funded by the Joint Global Health Trials scheme; COBRA-BPS ClinicalTrials.gov number, NCT02657746.).

Relative contribution of diet and physical activity to increased adiposity among rural to urban migrants in India: A cross-sectional study.

BACKGROUND: In common with many other low- and middle-income countries (LMICs), rural to urban migrants in India are at increased risk of obesity, but it is unclear whether this is due to increased energy intake, reduced energy expenditure, or both. Knowing this and the relative contribution of specific dietary and physical activity behaviours to greater adiposity among urban migrants could inform policies for control of the obesity epidemic in India and other urbanising LMICs. In the Indian Migration Study, we previously found that urban migrants had greater prevalence of obesity and diabetes compared with their nonmigrant rural-dwelling siblings. In this study, we investigated the relative contribution of energy intake and expenditure and specific diet and activity behaviours to greater adiposity among urban migrants in India. METHODS AND FINDINGS: The Indian Migration Study was conducted between 2005 and 2007. Factory workers and their spouses from four cities in north, central, and south of India, together with their rural-dwelling siblings, were surveyed. Self-reported data on diet and physical activity was collected using validated questionnaires, and adiposity was estimated from thickness of skinfolds. The association of differences in dietary intake, physical activity, and adiposity between siblings was examined using multivariable linear regression. Data on 2,464 participants (median age 43 years) comprised of 1,232 sibling pairs (urban migrant and their rural-dwelling sibling) of the same sex (31% female) were analysed. Compared with the rural siblings, urban migrants had 18% greater adiposity, 12% (360 calories/day) more energy intake, and 18% (11 kilojoules/kg/day) less energy expenditure (P < 0.001 for all). Energy intake and expenditure were independently associated with increased adiposity of urban siblings, accounting for 4% and 6.5% of adiposity difference between siblings, respectively. Difference in dietary fat/oil (10 g/day), time spent engaged in moderate or vigorous activity (69 minutes/day), and watching television (30 minutes/day) were associated with difference in adiposity between siblings, but no clear association was observed for intake of fruits and vegetables, sugary foods and sweets, cereals, animal and dairy products, and sedentary time. The limitations of this study include a cross-sectional design, systematic differences in premigration characteristics of migrants and nonmigrants, low response rate, and measurement error in estimating diet and activity from questionnaires. CONCLUSIONS: We found that increased energy intake and reduced energy expenditure contributed equally to greater adiposity among urban migrants in India. Policies aimed at controlling the rising prevalence of obesity in India and potentially other urbanising LMICs need to be multicomponent, target both energy intake and expenditure, and focus particularly on behaviours such as dietary fat/oil intake, time spent on watching television, and time spent engaged in moderate or vigorous intensity physical activity.

Effect of supplemental nutrition in pregnancy on offspring's risk of cardiovascular disease in young adulthood: Long-term follow-up of a cluster trial from India.

BACKGROUND: Undernutrition during intrauterine life and early childhood is hypothesised to increase the risk of cardiovascular disease (Developmental Origins of Health and Disease Hypothesis), but experimental evidence from humans is limited. This hypothesis has major implications for control of the cardiovascular disease epidemic in South Asia (home to a quarter of world's population), where a quarter of newborns have low birth weight. We investigated whether, in an area with prevalent undernutrition, supplemental nutrition offered to pregnant women and their offspring below the age of 6 years was associated with a lower risk of cardiovascular disease in the offspring when they were young adults. METHODS AND FINDINGS: The Hyderabad Nutrition Trial was a community-based nonrandomised controlled intervention trial conducted in 29 villages near Hyderabad, India (1987-1990). Protein-calorie food supplement was offered daily to pregnant and lactating women (2.09 MJ energy and 20-25 g protein) and their offspring (1.25 MJ energy and 8-10 g protein) until the age of six years in the 15 intervention villages, but not in the 14 control villages. A total of 1,826 participants (949 from the intervention villages and 877 from the control villages, representing 70% of the cohort) at a mean age of 21.6 years (62% males) were examined between 2009 and 2012. The mean body mass index (BMI) of the participants was 20 kg/m2 and the mean systolic blood pressure was 115 mm Hg. The age, sex, socioeconomic position, and urbanisation-adjusted effects of intervention (beta coefficients and 95% confidence intervals) on outcomes were as follows: carotid intima-media thickness, 0.01 mm (-0.01 to 0.03), p = 0.36; arterial stiffness (augmentation index), -1.1% (-2.5 to 0.3), p = 0.097; systolic blood pressure, 0.5 mm Hg (-0.6 to 1.6), p = 0.36; BMI, -0.13 kg/m2 (-0.75 to 0.09), p = 0.093; low-density lipoprotein (LDL) cholesterol, 0.06 mmol/L (-0.07 to 0.2), p = 0.37; and fasting insulin (log), -0.06 mU/L (-0.19 to 0.07), p = 0.43. The limitations of this study include nonrandomised allocation of intervention and lack of data on compliance, and potential for selection bias due to incomplete follow-up. CONCLUSIONS: Our results showed that in an area with prevalent undernutrition, protein-calorie food supplements offered to pregnant women and their offspring below the age of 6 years were not associated with lower levels of cardiovascular risk factors among offspring when they were young adults. Our findings, coupled with evidence from other intervention studies to date, suggest that policy makers should attach limited value to cardiovascular health benefits of maternal and child protein-calorie food supplementation programmes.

Mendel's laws, Mendelian randomization and causal inference in observational data: substantive and nomenclatural issues.

We respond to criticisms of Mendelian randomization (MR) by Mukamal, Stampfer and Rimm (MSR). MSR consider that MR is receiving too much attention and should be renamed. We explain how MR links to Mendel's laws, the origin of the name and our lack of concern regarding nomenclature. We address MSR's substantive points regarding MR of alcohol and cardiovascular disease, an issue on which they dispute the MR findings. We demonstrate that their strictures with respect to population stratification, confounding, weak instrument bias, pleiotropy and confounding have been addressed, and summarise how the field has advanced in relation to the issues they raise. We agree with MSR that "the hard problem of conducting high-quality, reproducible epidemiology" should be addressed by epidemiologists. However we see more evidence of confrontation of this issue within MR, as opposed to conventional observational epidemiology, within which the same methods that have demonstrably failed in the past are simply rolled out into new areas, leaving their previous failures unexamined.

Medical training for universal health coverage: a review of Cuba-South Africa collaboration.

Achieving improvements in Universal Health Coverage will require a re-orientation of medical education towards a stronger focus on primary health care. Innovative medical curricula have been implemented in some countries, but in many low- and middle-income countries (LMICs), the emphasis remains focused on hospital and speciality services. Cuba has a long history of supporting LMICs and has made major contributions to African health care and medical training. A scheme for training South African students in Cuba was established 20 years ago and expanded more recently, with around 700 Cuban-trained graduates returning to South Africa each year from 2018 to 2022. The current strategy is to re-orientate and re-train these graduates in South African medical schools for up to 3 years as they are perceived to have inadequate skills. This negative narrative on Cuban-trained doctors in South Africa could be changed dramatically. They have highly appropriate skills in primary care and prevention and could provide much needed services to rural and urban under-served populations whilst gaining an orientation to the health problems of South Africa and strengthening their skills. Bilateral arrangements between South Africa and the United Kingdom are providing mechanisms to support such schemes. The Cuban approach to medical education may have lessons for many countries attempting to meet the challenges of Universal Health Coverage.

Cuban medical training for South African students: a mixed methods study.

BACKGROUND: Achieving universal health care coverage will require greater investment in primary health care, particularly in rural and underserved populations in low and middle-income countries. South Africa has invested in training black students from disadvantaged backgrounds in Cuba and large numbers of these Cuban-trained students are now returning for final year and internship training in South Africa. There is controversy about the scheme, the quality and relevance of training received and the place of Cuban-trained doctors in the health care system. Exploring the experiences of Cuban- and South African-trained students, recent graduates and medical school faculty may help understand and resolve the current controversy. METHODS: Using a mixed methods approach, in-depth interviews and a focus group discussion were held with deans of medical schools, senior faculty, and Cuban-trained and South African-trained students and recent graduates. An online structured questionnaire, adapted from the USA medical student survey, was developed and administered to Cuban- and South African-trained students and recent graduates. RESULTS: South African students trained in Cuba have had beneficial experiences which orientate them towards primary health care and prevention. Their subsequent training in South Africa is intended to fill skill gaps related to TB, HIV and major trauma. However this training is ad hoc and variable in duration and demoralizing for some students. Cuban-trained students have stronger aspirations than those trained in South Africa to work in rural and underserved communities from which many of them are drawn. CONCLUSION: Attempts to assimilate returning Cuban-trained students will require a reframing of the current negative narrative by focusing on positive aspects of their training, orientation towards primary care and public health, and their aspirations to work in rural and under-served urban areas. Cuban-trained doctors could be part of the solution to South Africa's health workforce problems.

Association between empirically derived dietary patterns with blood lipids, fasting blood glucose and blood pressure in adults - the India migration study.

BACKGROUND: Dietary patterns (DPs) in India are heterogenous. To date, data on association of indigenous DPs in India with risk factors of nutrition-related noncommunicable diseases (cardiovascular disease and diabetes), leading causes of premature death and disability, are limited. We aimed to evaluate the associations of empirically-derived DPs with blood lipids, fasting glucose and blood pressure levels in an adult Indian population recruited across four geographical regions of India. METHODS: We used cross-sectional data from the Indian Migration Study (2005-2007). Study participants included urban migrants, their rural siblings and urban residents and their urban siblings from Lucknow, Nagpur, Hyderabad and Bangalore (n = 7067, mean age 40.8 yrs). Information on diet (validated interviewer-administered, 184-item semi-quantitative food frequency questionnaire), tobacco consumption, alcohol intake, physical activity, medical history, as well as anthropometric measurements were collected. Fasting-blood samples were collected for estimation of blood lipids and glucose. Principal component analysis (PCA) was used to identify major DPs based on eigenvalue> 1 and component interpretability. Robust standard error multivariable linear regression models were used to investigate the association of DPs (tertiles) with total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides, fasting-blood glucose (FBG), systolic and diastolic blood pressure (SBP and DBP) levels. RESULTS: Three major DPs were identified: 'cereal-savoury' (cooked grains, rice/rice-based dishes, snacks, condiments, soups, nuts), 'fruit-vegetable-sweets-snacks' (Western cereals, vegetables, fruit, fruit juices, cooked milk products, snacks, sugars, sweets) and 'animal food' (red meat, poultry, fish/seafood, eggs) patterns. High intake of the 'animal food' pattern was positively associated with levels of TC (ß = 0.10 mmol/L; 95% CI: 0.02, 0.17 mmol/L; p-trend = 0.013); LDL-C (ß = 0.07 mmol/L; 95% CI: 0.004, 0.14 mmol/L; p-trend = 0.041); HDL-C (ß = 0.02 mmol/L; 95% CI: 0.004, 0.04 mmol/L; p-trend = 0.016), FBG: (ß = 0.09 mmol/L; 95% CI: 0.01, 0.16 mmol/L; p-trend = 0.021) SBP (ß = 1.2 mm/Hg; 95% CI: 0.1, 2.3 mm/Hg; p-trend = 0.032); DBP: (ß = 0.9 mm/Hg; 95% CI: 0.2, 1.5 mm/Hg; p-trend = 0.013). The 'cereal-savoury' and 'fruit-vegetable-sweets-snacks' patterns showed no association with any parameter except for a positive association with diastolic blood pressure for high intake of 'fruits-vegetables-sweets-snacks' pattern. CONCLUSION: Our results indicate positive associations of the 'animal food' pattern with cardio-metabolic risk factors in India. Further longitudinal assessments of dietary patterns in India are required to validate the findings.

Fixed-dose combination therapy for the prevention of atherosclerotic cardiovascular diseases.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death and disability worldwide, yet ASCVD risk factor control and secondary prevention rates remain low. A fixed-dose combination of blood pressure- and cholesterol-lowering and antiplatelet treatments into a single pill, or polypill, has been proposed as one strategy to reduce the global burden of ASCVD. OBJECTIVES: To determine the effect of fixed-dose combination therapy on all-cause mortality, fatal and non-fatal ASCVD events, and adverse events. We also sought to determine the effect of fixed-dose combination therapy on blood pressure, lipids, adherence, discontinuation rates, health-related quality of life, and costs. SEARCH METHODS: We updated our previous searches in September 2016 of CENTRAL, MEDLINE, Embase, ISI Web of Science, and DARE, HTA, and HEED. We also searched two clinical trials registers in September 2016. We used no language restrictions. SELECTION CRITERIA: We included randomised controlled trials of a fixed-dose combination therapy including at least one blood pressure-lowering and one lipid-lowering component versus usual care, placebo, or an active drug comparator for any treatment duration in adults 18 years old or older, with no restrictions on presence or absence of pre-existing ASCVD. DATA COLLECTION AND ANALYSIS: Three review authors independently selected studies for inclusion and extracted the data for this update. We evaluated risk of bias using the Cochrane 'Risk of bias' assessment tool. We calculated risk ratios (RR) for dichotomous data and mean differences (MD) for continuous data with 95% confidence intervals (CI) using fixed-effect models when heterogeneity was low (I2 < 50%) and random-effects models when heterogeneity was high (I2 ≥ 50%). We used the GRADE approach to evaluate the quality of evidence. MAIN RESULTS: In the initial review, we identified nine randomised controlled trials with a total of 7047 participants and four additional trials (n = 2012 participants; mean age range 62 to 63 years; 30% to 37% women) were included in this update. Eight of the 13 trials evaluated the effects of fixed-dose combination (FDC) therapy in populations without prevalent ASCVD, and the median follow-up ranged from six weeks to 23 months. More recent trials were generally larger with longer follow-up and lower risk of bias. The main risk of bias was related to lack of blinding of participants and personnel, which was inherent to the intervention. Compared with the comparator groups (placebo, usual care, or active drug comparator), the effects of the fixed-dose combination treatment on mortality (FDC = 1.0% versus control = 1.0%, RR 1.10, 95% CI 0.64 to 1.89,  I2 = 0%, 5 studies, N = 5300) and fatal and non-fatal ASCVD events (FDC = 4.7% versus control = 3.7%, RR 1.26, 95% CI 0.95 to 1.66, I2 = 0%, 6 studies, N = 4517) were uncertain (low-quality evidence). The low event rates for these outcomes and indirectness of evidence for comparing fixed-dose combination to usual care versus individual drugs suggest that these results should be viewed with caution. Adverse events were common in both the intervention (32%) and comparator (27%) groups, with participants randomised to fixed-dose combination therapy being 16% (RR 1.16, 95% CI 1.09 to 1.25, 11 studies, 6906 participants, moderate-quality evidence) more likely to report an adverse event . The mean differences in systolic blood pressure between the intervention and control arms was -6.34 mmHg (95% CI -9.03 to -3.64, 13 trials, 7638 participants, moderate-quality evidence). The mean differences (95% CI) in total and LDL cholesterol between the intervention and control arms were -0.61 mmol/L (95% CI -0.88 to -0.35, 11 trials, 6565 participants, low-quality evidence) and -0.70 mmol/L (95% CI -0.98 to -0.41, 12 trials, 7153 participants, moderate-quality evidence), respectively. There was a high degree of statistical heterogeneity in comparisons of blood pressure and lipids (I2 ≥ 80% for all) that could not be explained, so these results should be viewed with caution. Fixed-dose combination therapy improved adherence to a multidrug strategy by 44% (26% to 65%) compared with usual care (4 trials, 3835 participants, moderate-quality evidence). AUTHORS' CONCLUSIONS: The effects of fixed-dose combination therapy on all-cause mortality or ASCVD events are uncertain. A limited number of trials reported these outcomes, and the included trials were primarily designed to observe changes in ASCVD risk factor levels rather than clinical events, which may partially explain the observed differences in risk factors that were not translated into differences in clinical outcomes among the included trials. Fixed-dose combination therapy is associated with modest increases in adverse events compared with placebo, active comparator, or usual care but may be associated with improved adherence to a multidrug regimen. Ongoing, longer-term trials of fixed-dose combination therapy will help demonstrate whether short-term changes in risk factors might be maintained and lead to expected differences in clinical events based on these changes.

Legume consumption and its association with fasting glucose, insulin resistance and type 2 diabetes in the Indian Migration Study.

OBJECTIVE: Legume consumption is associated with lower fasting glucose (FG) and insulin levels in nutrition trials and lower CVD mortality in large-scale epidemiological studies. In India, legumes are widely consumed in various preparations, yet no epidemiological study has evaluated the association of legumes with FG levels, insulin resistance and diabetes risk. The present study aimed to fill this gap. DESIGN: Fasting blood samples, in-person interviews to obtain information on demographic/socio-economic factors, physical activity, alcohol and tobacco use, and anthropometric measurements were collected. Dietary intakes were assessed by an interviewer-administered, validated, semi-quantitative FFQ. SETTING: Lucknow, Nagpur, Hyderabad and Bangalore, India. SUBJECTS: Men and women (n 6367) aged 15-76 years - urban residents, urban migrants and their rural siblings. RESULTS: In multivariate random-effects models adjusted for age, BMI, total energy intake, macronutrients, physical activity and rural/migration status, daily legume consumption was not associated with FG (P-for-trend=0·78), insulin resistance (homeostasis model assessment score; P-for-trend=0·73) or the prevalence of type 2 diabetes mellitus (P-for-trend=0·41). Stratified analyses by vegetarian diet and migration status did not change the findings. Inverse associations between legumes and FG emerged for participants with lower BMI and higher carbohydrate, protein, fat and sugar intakes. CONCLUSIONS: Although legumes are essential in traditional Indian diets, as well as in prudent and Mediterranean diets in the West, we did not find an association between legumes and markers of glycaemic control, insulin resistance or diabetes, except for subgroups based on BMI and macronutrient intake. The ubiquitous presence and complexity of legume preparations in Indian diets may contribute to these findings.

Food Price Spikes Are Associated with Increased Malnutrition among Children in Andhra Pradesh, India.

BACKGROUND: Global food prices have risen sharply since 2007. The impact of food price spikes on the risk of malnutrition in children is not well understood. OBJECTIVE: We investigated the associations between food price spikes and childhood malnutrition in Andhra Pradesh, one of India's largest states, with >85 million people. Because wasting (thinness) indicates in most cases a recent and severe process of weight loss that is often associated with acute food shortage, we tested the hypothesis that the escalating prices of rice, legumes, eggs, and other staples of Indian diets significantly increased the risk of wasting (weight-for-height z scores) in children. METHODS: We studied periods before (2006) and directly after (2009) India's food price spikes with the use of the Young Lives longitudinal cohort of 1918 children in Andhra Pradesh linked to food price data from the National Sample Survey Office. Two-stage least squares instrumental variable models assessed the relation of food price changes to food consumption and wasting prevalence (weight-for-height z scores). RESULTS: Before the 2007 food price spike, wasting prevalence fell from 19.4% in 2002 to 18.8% in 2006. Coinciding with India's escalating food prices, wasting increased significantly to 28.0% in 2009. These increases were concentrated among low- (χ(2): 21.6, P < 0.001) and middle- (χ(2): 25.9, P < 0.001) income groups, but not among high-income groups (χ(2): 3.08, P = 0.079). Each 10.0 rupee ($0.170) increase in the price of rice/kg was associated with a drop in child-level rice consumption of 73.0 g/d (ß: -7.30; 95% CI: -10.5, -3.90). Correspondingly, lower rice consumption was significantly associated with lower weight-for-height z scores (i.e., wasting) by 0.005 (95% CI: 0.001, 0.008), as seen with most other food categories. CONCLUSION: Rising food prices were associated with an increased risk of malnutrition among children in India. Policies to help ensure the affordability of food in the context of economic growth are likely critical for promoting children's nutrition.

Incident disability in older adults: prediction models based on two British prospective cohort studies.

OBJECTIVE: To develop and validate a prediction model for incident locomotor disability after 7 years in older adults. SETTING: Prospective British cohort studies: British Women's Heart and Health Study (BWHHS) for development and the English Longitudinal Study of Ageing (ELSA) for validation. SUBJECTS: Community-dwelling older adults. METHODS: Multivariable logistic regression models after selection of predictors with backward elimination. Model performance was assessed using metrics of discrimination and calibration. Models were internally and externally validated. RESULTS: Locomotor disability was reported in BWHHS by 861 of 1,786 (48%) women after 7 years. Age, a history of arthritis and low physical activity levels were the most important predictors of locomotor disability. Models using routine measures as predictors had satisfactory calibration and discrimination (c-index 0.73). Addition of 31 blood markers did not increase the predictive performance. External validation in ELSA showed reduced discrimination (c-index 0.65) and an underestimation of disability risks. A web-based calculator for locomotor disability is available (http://www.sealedenvelope.com/trials/bwhhsmodel/). CONCLUSIONS: We developed and externally validated a prediction model for incident locomotor disability in older adults based on routine measures available to general practitioners, patients and public health workers, and showed an adequate discrimination. Addition of blood markers from major biological pathways did not improve the performance of the model. Further replication in additional data sets may lead to further enhancement of the current model.

Multiple risk factor interventions for primary prevention of cardiovascular disease in low- and middle-income countries.

BACKGROUND: In many low- and middle-income countries (LMICs) morbidity and mortality associated with cardiovascular diseases (CVDs) have grown exponentially over recent years. It is estimated that about 80% of CVD deaths occur in LMICs. People in LMICs are more exposed to cardiovascular risk factors such as tobacco, and often do not have access to effective and equitable healthcare services (including early detection services). Evidence from high-income countries indicates that multiple risk factor intervention programmes do not result in reductions in CVD events. Given the increasing incidence of CVDs and lower CVD health awareness in LMICs it is possible that such programmes may have beneficial effects. OBJECTIVES: To determine the effectiveness of multiple risk factor interventions (with or without pharmacological treatment) aimed at modifying major cardiovascular risk factors for the primary prevention of CVD in LMICs. SEARCH METHODS: We searched (from inception to 27 June 2014) the Cochrane Library (CENTRAL, HTA, DARE, EED), MEDLINE, EMBASE, Global Health and three other databases on 27 June 2014. We also searched two clinical trial registers and conducted reference checking to identify additional studies. We applied no language limits. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of health promotion interventions to achieve behaviour change (i.e. smoking cessation, dietary advice, increasing activity levels) with or without pharmacological treatments, which aim to alter more than one cardiovascular risk factor (i.e. diet, reduce blood pressure, smoking, total blood cholesterol or increase physical activity) of at least six months duration of follow-up conducted in LMICs. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility and risk of bias, and extracted data. We combined dichotomous data using risk ratios (RRs) and continuous data using mean differences (MDs), and presented all results with a 95% confidence interval (CI). The primary outcome was combined fatal and non-fatal cardiovascular disease events. MAIN RESULTS: Thirteen trials met the inclusion criteria and are included in the review. All studies had at least one domain with unclear risk of bias. Some studies were at high risk of bias for random sequence generation (two trials), allocation concealment (two trials), blinding of outcome assessors (one trial) and incomplete outcome data (one trial). Duration and content of multiple risk factor interventions varied across the trials. Two trials recruited healthy participants and the other 11 trials recruited people with varying risks of CVD, such as participants with known hypertension and type 2 diabetes. Only one study reported CVD outcomes and multiple risk factor interventions did not reduce the incidence of cardiovascular events (RR 0.57, 95% CI 0.11 to 3.07, 232 participants, low-quality evidence); the result is imprecise (a wide confidence interval and small sample size) and makes it difficult to draw a reliable conclusion. None of the included trials reported all-cause mortality. The pooled effect indicated a reduction in systolic blood pressure (MD -6.72 mmHg, 95% CI -9.82 to -3.61, I² = 91%, 4868 participants, low-quality evidence), diastolic blood pressure (MD -4.40 mmHg, 95% CI -6.47 to -2.34, I² = 92%, 4701 participants, low-quality evidence), body mass index (MD -0.76 kg/m², 95% CI -1.29 to -0.22, I² = 80%, 2984 participants, low-quality evidence) and waist circumference (MD -3.31, 95% CI -4.77 to -1.86, I² = 55%, 393 participants, moderate-quality evidence) in favour of multiple risk factor interventions, but there was substantial heterogeneity. There was insufficient evidence to determine the effect of these interventions on consumption of fruit or vegetables, smoking cessation, glycated haemoglobin, fasting blood sugar, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol and total cholesterol. None of the included trials reported on adverse events. AUTHORS' CONCLUSIONS: Due to the limited evidence currently available, we can draw no conclusions as to the effectiveness of multiple risk factor interventions on combined CVD events and mortality. There is some evidence that multiple risk factor interventions may lower blood pressure levels, body mass index and waist circumference in populations in LMIC settings at high risk of hypertension and diabetes. There was considerable heterogeneity between the trials, the trials were small, and at some risk of bias. Larger studies with longer follow-up periods are required to confirm whether multiple risk factor interventions lead to reduced CVD events and mortality in LMIC settings.

Dietary patterns in India and their association with obesity and central obesity.

OBJECTIVE: Obesity is a growing problem in India, the dietary determinants of which have been studied using an 'individual food/nutrient' approach. Examining dietary patterns may provide more coherent findings, but few studies in developing countries have adopted this approach. The present study aimed to identify dietary patterns in an Indian population and assess their relationship with anthropometric risk factors. DESIGN: FFQ data from the cross-sectional sib-pair Indian Migration Study (IMS; n 7067) were used to identify dietary patterns using principal component analysis. Mixed-effects logistic regression was used to examine associations with obesity and central obesity. SETTING: The IMS was conducted at four factory locations across India: Lucknow, Nagpur, Hyderabad and Bangalore. SUBJECTS: The participants were rural-to-urban migrant and urban non-migrant factory workers, their rural and urban resident siblings, and their co-resident spouses. RESULTS: Three dietary patterns were identified: 'cereals-savoury foods' (cooked grains, rice/rice-based dishes, snacks, condiments, soups, nuts), 'fruit-veg-sweets-snacks' (Western cereals, vegetables, fruit, fruit juices, cooked milk products, snacks, sugars, sweets) and 'animal-food' (red meat, poultry, fish/seafood, eggs). In adjusted analysis, positive graded associations were found between the 'animal-food' pattern and both anthropometric risk factors. Moderate intake of the 'cereals-savoury foods' pattern was associated with reduced odds of obesity and central obesity. CONCLUSIONS: Distinct dietary patterns were identified in a large Indian sample, which were different from those identified in previous literature. A clear 'plant food-based/animal food-based pattern' dichotomy emerged, with the latter being associated with higher odds of anthropometric risk factors. Longitudinal studies are needed to further clarify this relationship in India.

What do Indian children drink when they do not receive water? Statistical analysis of water and alternative beverage consumption from the 2005-2006 Indian National Family Health Survey.

BACKGROUND: Over 1.2 billion people lack access to clean water. However, little is known about what children drink when there is no clean water. We investigated the prevalence of receiving no water and what Indian children drink instead. METHODS: We analysed children's beverage consumption using representative data from India's National Family and Health Survey (NFHS-3, 2005-2006). Consumption was based on mothers' reports (n = 22,668) for children aged 6-59 months (n = 30,656). RESULTS: About 10 % of Indian children had no water in the last 24 h, corresponding to 12,700,000 children nationally, (95 % CI: 12,260,000 to 13,200,000). Among children who received no water, 23 % received breast or fresh milk and 24 % consumed formula, "other liquid", juice, or two or more beverages. Children over 2 were more likely to consume non-milk beverages, including tea, coffee, and juice than those under 2 years. Those in the lowest two wealth quintiles were 16 % less likely to have received water (OR = 0.84; 95 % CI: 0.74 to 0.96). Compared to those living in households with bottled, piped, or tanker water, children were significantly less likely to receive water in households using well water (OR = 0.75; 95 % CI: 0.64 to 0.89) or river, spring, or rain water (OR =0.70; 95 % CI: 0.53 to 0.92) in the last 24 h. CONCLUSIONS: About 13 million Indian children aged 6-59 months received no water in the last 24 h. Further research is needed to assess the risks potentially arising from insufficient water, caffeinated beverages, and high sugar drinks at early stages of life.

Intra-household evaluations of alcohol abuse in men with depression and suicide in women: A cross-sectional community-based study in Chennai, India.

BACKGROUND: Harmful effects of alcohol abuse are well documented for drinkers, and adverse effects are also reported for the physical and emotional well-being of family members, with evidence often originating from either drinkers or their families in clinic-based settings. This study evaluates intra-household associations between alcohol abuse in men, and depression and suicidal attempts in women, in community-based settings of Chennai, India. METHODS: This community-based cross-sectional study of chronic disease risk factors and outcomes was conducted in n = 259 households and n = 1053 adults (aged 15 years and above) in rural and urban Chennai. The Alcohol Use Disorder Identification Test (AUDIT) score was used to classify alcohol consumption into 'low-risk', 'harmful', 'hazardous' and 'alcohol dependence' drinking and the Patient Health Questionnaire (PHQ-9) score to classify depression as 'mild', 'moderate', 'moderate-severe' and 'severe'. Multivariate logistic regression models estimated the association of depression in women with men's drinking patterns in the same household. RESULTS: A significant 2.5-fold increase in any depression (PHQ-9 ≥ 5) was observed in men who were 'alcohol-dependent' compared to non-drinkers (OR = 2.53; 95% CI: 1.26, 5.09). However, there was no association between men's drinking behavior and depression in women of the same household, although suicidal attempts approached a significant dose-response relationship with increasing hazard-level of men's drinking (p = 0.08). CONCLUSION: No significant intra-household association was observed between men's alcohol consumption and women's depression, though an increasing (non-significant) trend was associated with suicidal attempts. Complex relationships between suicidal attempts and depression in women and male abusive drinking require further exploration, with an emphasis on intra-household mechanisms and pathways.

Associations between active travel and adiposity in rural India and Bangladesh: a cross-sectional study.

BACKGROUND: Data on use and health benefits of active travel in rural low- and middle- income country settings are sparse. We aimed to examine correlates of active travel, and its association with adiposity, in rural India and Bangladesh. METHODS: Cross sectional study of 2,122 adults (≥18 years) sampled in 2011-13 from two rural sites in India (Goa and Chennai) and one in Bangladesh (Matlab). Logistic regression was used to examine whether ≥150 min/week of active travel was associated with socio-demographic indices, smoking, oil/butter consumption, and additional physical activity. Adjusting for these same factors, associations between active travel and BMI, waist circumference and waist-to-hip ratio were examined using linear and logistic regression. RESULTS: Forty-six percent of the sample achieved recommended levels of physical activity (≥150 min/week) through active travel alone (range: 33.1 % in Matlab to 54.8 % in Goa). This was more frequent among smokers (adjusted odds ratio 1.36, 95 % confidence interval 1.07-1.72; p = 0.011) and those that spent ≥150 min/week in work-based physical activity (OR 1.71, 1.35-2.16; p < 0.001), but less frequent among females than males (OR 0.25, 0.20-0.31; p < 0.001). In fully adjusted analyses, ≥150 min/week of active travel was associated with lower BMI (adjusted coefficient -0.39 kg/m(2), -0.77 to -0.02; p = 0.037) and a lower likelihood of high waist circumference (OR 0.77, 0.63-0.96; p = 0.018) and high waist-to-hip ratio (OR 0.72, 0.58-0.89; p = 0.002). CONCLUSIONS: Use of active travel for ≥150 min/week was associated with being male, smoking, and higher levels of work-based physical activity. It was associated with lower BMI, and lower risk of a high waist circumference or high waist-to-hip ratio. Promotion of active travel is an important component of strategies to address the growing prevalence of overweight in rural low- and middle- income country settings.

Associations between diet, physical activity and body fat distribution: a cross sectional study in an Indian population.

BACKGROUND: Obesity is a growing health problem in India and worldwide, due to changes in lifestyle. This study aimed to explore the independent associations between dietary and physical activity exposure variables and total body fat and distribution in an Indian setting. METHODS: Individuals who had participated in the Indian Migration Study (IMS) or the Andhra Pradesh Children And Parents' Study (APCAPS), were invited to participate in the Hyderabad DXA Study. Total and abdominal body fat of study participants was measured using DXA scans. Diet and physical activity (PA) levels were measured using questionnaires. RESULTS: Data on 2208 participants was available for analysis; mean age was 49 yrs in IMS, 21 yrs in APCAPS. Total energy intake was positively associated with total body fat in the APCAPS sample: a 100 kcal higher energy intake was associated with 45 g higher body fat (95% CI 22, 68). In the IMS sample no association was found with total energy intake, but there was a positive association with percent protein intake (1% higher proportion of energy from protein associated with 509 g (95% CI 138,880) higher total body fat). Broadly the same pattern of associations was found with proportion of fat in the abdominal region as the outcome. PA was inversely associated with total body fat in both populations (in APCAPS, one MET-hour higher activity was associated with 46 g (95% CI 12, 81) less body fat; in the IMS it was associated with 145 g less body fat (95% CI 73, 218)). An inverse association was observed between PA and percentage abdominal fat in the IMS but no association was seen in the APCAPS population. CONCLUSIONS: In this Indian population, there was an inverse association between PA and body fat. Associations between body fat and dietary variables differed between the younger APCAPS population and older IMS population. Further longitudinal research is needed to elucidate causality and directions of these associations across the life course.

Averting obesity and type 2 diabetes in India through sugar-sweetened beverage taxation: an economic-epidemiologic modeling study.

BACKGROUND: Taxing sugar-sweetened beverages (SSBs) has been proposed in high-income countries to reduce obesity and type 2 diabetes. We sought to estimate the potential health effects of such a fiscal strategy in the middle-income country of India, where there is heterogeneity in SSB consumption, patterns of substitution between SSBs and other beverages after tax increases, and vast differences in chronic disease risk within the population. METHODS AND FINDINGS: Using consumption and price variations data from a nationally representative survey of 100,855 Indian households, we first calculated how changes in SSB price alter per capita consumption of SSBs and substitution with other beverages. We then incorporated SSB sales trends, body mass index (BMI), and diabetes incidence data stratified by age, sex, income, and urban/rural residence into a validated microsimulation of caloric consumption, glycemic load, overweight/obesity prevalence, and type 2 diabetes incidence among Indian subpopulations facing a 20% SSB excise tax. The 20% SSB tax was anticipated to reduce overweight and obesity prevalence by 3.0% (95% CI 1.6%-5.9%) and type 2 diabetes incidence by 1.6% (95% CI 1.2%-1.9%) among various Indian subpopulations over the period 2014-2023, if SSB consumption continued to increase linearly in accordance with secular trends. However, acceleration in SSB consumption trends consistent with industry marketing models would be expected to increase the impact efficacy of taxation, averting 4.2% of prevalent overweight/obesity (95% CI 2.5-10.0%) and 2.5% (95% CI 1.0-2.8%) of incident type 2 diabetes from 2014-2023. Given current consumption and BMI distributions, our results suggest the largest relative effect would be expected among young rural men, refuting our a priori hypothesis that urban populations would be isolated beneficiaries of SSB taxation. Key limitations of this estimation approach include the assumption that consumer expenditure behavior from prior years, captured in price elasticities, will reflect future behavior among consumers, and potential underreporting of consumption in dietary recall data used to inform our calculations. CONCLUSION: Sustained SSB taxation at a high tax rate could mitigate rising obesity and type 2 diabetes in India among both urban and rural subpopulations.