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1.  Influence of common genetic variation on blood lipid levels, cardiovascular risk, and coronary events in two British prospective cohort studies 
European Heart Journal  2012;34(13):972-981.
Aims
The aim of this study was to quantify the collective effect of common lipid-associated single nucleotide polymorphisms (SNPs) on blood lipid levels, cardiovascular risk, use of lipid-lowering medication, and risk of coronary heart disease (CHD) events.
Methods and results
Analysis was performed in two prospective cohorts: Whitehall II (WHII; N = 5059) and the British Women’s Heart and Health Study (BWHHS; N = 3414). For each participant, scores were calculated based on the cumulative effect of multiple genetic variants influencing total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). Compared with the bottom quintile, individuals in the top quintile of the LDL-C genetic score distribution had higher LDL-C {mean difference of 0.85 [95% confidence interval, (CI) = 0.76–0.94] and 0.63 [95% CI = 0.50–0.76] mmol/l in WHII and BWHHS, respectively}. They also tended to have greater odds of having ‘high-risk’ status (Framingham 10-year cardiovascular disease risk >20%) [WHII: odds ratio (OR) = 1.36 (0.93–1.98), BWHHS: OR = 1.49 (1.14–1.94)]; receiving lipid-lowering treatment [WHII: OR = 2.38 (1.57–3.59), BWHHS: OR = 2.24 (1.52–3.29)]; and CHD events [WHII: OR = 1.43 (1.02–2.00), BWHHS: OR = 1.31 (0.99–1.72)]. Similar associations were observed for the TC score in both studies. The TG score was associated with high-risk status and medication use in both studies. Neither HDL nor TG scores were associated with the risk of coronary events. The genetic scores did not improve discrimination over the Framingham risk score.
Conclusion
At the population level, common SNPs associated with LDL-C and TC contribute to blood lipid variation, cardiovascular risk, use of lipid-lowering medications and coronary events. However, their effects are too small to discriminate future lipid-lowering medication requirements or coronary events.
doi:10.1093/eurheartj/ehs243
PMCID: PMC3612774  PMID: 22977227
Lipid genetic score; Lipid medication; Framingham
2.  Apolipoprotein E genotype, cardiovascular biomarkers and risk of stroke: Systematic review and meta-analysis of 14 015 stroke cases and pooled analysis of primary biomarker data from up to 60 883 individuals 
Background At the APOE gene, encoding apolipoprotein E, genotypes of the ε2/ε3/ε4 alleles associated with higher LDL-cholesterol (LDL-C) levels are also associated with higher coronary risk. However, the association of APOE genotype with other cardiovascular biomarkers and risk of ischaemic stroke is less clear. We evaluated the association of APOE genotype with risk of ischaemic stroke and assessed whether the observed effect was consistent with the effects of APOE genotype on LDL-C or other lipids and biomarkers of cardiovascular risk.
Methods We conducted a systematic review of published and unpublished studies reporting on APOE genotype and ischaemic stroke. We pooled 41 studies (with a total of 9027 cases and 61 730 controls) using a Bayesian meta-analysis to calculate the odds ratios (ORs) for ischaemic stroke with APOE genotype. To better evaluate potential mechanisms for any observed effect, we also conducted a pooled analysis of primary data using 16 studies (up to 60 883 individuals) of European ancestry. We evaluated the association of APOE genotype with lipids, other circulating biomarkers of cardiovascular risk and carotid intima-media thickness (C-IMT).
Results The ORs for association of APOE genotypes with ischaemic stroke were: 1.09 (95% credible intervals (CrI): 0.84–1.43) for ε2/ε2; 0.85 (95% CrI: 0.78–0.92) for ε2/ε3; 1.05 (95% CrI: 0.89–1.24) for ε2/ε4; 1.05 (95% CrI: 0.99–1.12) for ε3/ε4; and 1.12 (95% CrI: 0.94–1.33) for ε4/ε4 using the ε3/ε3 genotype as the reference group. A regression analysis that investigated the effect of LDL-C (using APOE as the instrument) on ischaemic stroke showed a positive dose-response association with an OR of 1.33 (95% CrI: 1.17, 1.52) per 1 mmol/l increase in LDL-C. In the separate pooled analysis, APOE genotype was linearly and positively associated with levels of LDL-C (P-trend: 2 × 10−152), apolipoprotein B (P-trend: 8.7 × 10−06) and C-IMT (P-trend: 0.001), and negatively and linearly associated with apolipoprotein E (P-trend: 6 × 10−26) and HDL-C (P-trend: 1.6 × 10−12). Associations with lipoprotein(a), C-reactive protein and triglycerides were non-linear.
Conclusions In people of European ancestry, APOE genotype showed a positive dose-response association with LDL-C, C-IMT and ischaemic stroke. However, the association of APOE ε2/ε2 genotype with ischaemic stroke requires further investigation. This cross-domain concordance supports a causal role of LDL-C on ischaemic stroke.
doi:10.1093/ije/dyt034
PMCID: PMC3619955  PMID: 23569189
Stroke; lipids; apolipoprotein E; cardiovascular disease; systematic review; meta-analysis; biomarkers
3.  The Association of Early Life Supplemental Nutrition With Lean Body Mass and Grip Strength in Adulthood: Evidence From APCAPS 
American Journal of Epidemiology  2014;179(6):700-709.
In the present study, we examined the associations of early nutrition with adult lean body mass (LBM) and muscle strength in a birth cohort that was established to assess the long-term impact of a nutrition program. Participants (n = 1,446, 32% female) were born near Hyderabad, India, in 29 villages from 1987 to 1990, during which time only intervention villages (n = 15) had a government program that offered balanced protein-calorie supplementation to pregnant women and children. Participants’ LBM and appendicular skeletal muscle mass were measured using dual energy x-ray absorptiometry; grip strength and information on lifestyle indicators, including diet and physical activity level, were also obtained. Ages (mean = 20.3 years) and body mass indexes (weight (kg)/height (m)2; mean = 19.5) of participants in 2 groups were similar. Current dietary energy intake was higher in the intervention group. Unadjusted LBM and grip strength were similar in 2 groups. After adjustment for potential confounders, the intervention group had lower LBM (β = −0.75; P = 0.03), appendicular skeletal muscle mass, and grip strength than did controls, but these differences were small in magnitude (<0.1 standard deviation). Multivariable regression analyses showed that current socioeconomic position, energy intake, and physical activity level had a positive association with adult LBM and muscle strength. This study could not detect a “programming” effect of early nutrition supplementation on adult LBM and muscle strength.
doi:10.1093/aje/kwt332
PMCID: PMC3939852  PMID: 24553777
body composition; cohort study; developmental origins of health and disease; grip strength; lean body mass; muscle mass; nutrition; physical activity
4.  Hypertension among older adults in low- and middle-income countries: prevalence, awareness and control 
Background This study uses data from the World Health Organization’s Study on Global Ageing and Adult Health (SAGE) to examine patterns of hypertension prevalence, awareness, treatment and control for people aged 50 years and over in China, Ghana, India, Mexico, the Russian Federation and South Africa.
Methods The SAGE sample comprises of 35 125 people aged 50 years and older, selected randomly. Hypertension was defined as ≥140 mmHg (systolic blood pressure) or ≥90 mmHg (diastolic blood pressure) or by currently taking antihypertensives. Control of hypertension was defined as blood pressure below 140/90 mmHg on treatment. A person was defined as aware if he/she was hypertensive and self-reported the condition.
Results Prevalence rates in all countries are broadly comparable to those of developed countries (52.9%; range 32.3% in India to 77.9% in South Africa). Hypertension was associated with overweight/obesity and was more common in women, those in the lowest wealth quintile and in heavy alcohol consumers. Awareness was found to be low for all countries, albeit with substantial national variations (48.3%; range 23.3% in Ghana to 72.1% in the Russian Federation). This was also the case for control (10.2%; range 4.1% in Ghana to 14.1% India) and treatment efficacy (26.3%; range 17.4% in the Russian Federation to 55.2% in India). Awareness was associated with increasing age, being female and being overweight or obese. Effective control of hypertension was more likely in older people, women and in the richest quintile. Obesity was associated with poorer control.
Conclusions The high rates of hypertension in low- and middle-income countries are striking. Levels of treatment and control are inadequate despite half those sampled being aware of their condition. Since cardiovascular disease is by far the largest cause of years of life lost in these settings, these findings emphasize the need for new approaches towards control of this major risk factor.
doi:10.1093/ije/dyt215
PMCID: PMC3937973  PMID: 24505082
Hypertension; older people; risk factors; developing countries
5.  Is hypertension the new HIV epidemic? 
doi:10.1093/ije/dyu019
PMCID: PMC3937981  PMID: 24491955
6.  Socio-Demographic Inequalities in the Prevalence, Diagnosis and Management of Hypertension in India: Analysis of Nationally-Representative Survey Data 
PLoS ONE  2014;9(1):e86043.
Background
Hypertension is a major contributing factor to the current epidemic of cardiovascular disease in India. Small studies suggest high, and increasing, prevalence especially in urban areas, with poor detection and management, but national data has been lacking. The aim of the current study was to use nationally-representative survey data to examine socio-demographic inequalities in the prevalence, diagnosis and management of hypertension in Indian adults.
Methods
Using data on self-reported diagnosis and treatment, and blood pressure measurement, collected from 12,198 respondents aged 18+ in the 2007 WHO Study on Global Ageing and Adult Health in India, factors associated with prevalence, diagnosis and treatment of hypertension were investigated.
Results
22% men and 26% women had hypertension; prevalence increased steeply with body mass index (<18.5 kg/m2: 18% men, 21% women; 25-29.9 kg/m2: 35% men, 35% women), was higher in the least poor vs. poorest (men: odds ratio (95%CI) 1.82 (1.20 to 2.76); women: 1.40 (1.08 to 1.81)), urban vs. rural men (1.64 (1.19 to 2.25)), and men recently vs. never using alcohol (1.96 (1.40 to 2.76)). Over half the hypertension in women, and 70% in men, was undetected with particularly poor detection rates in young urban men, and in poorer households. Two-thirds of men and women with detected hypertension were treated. Two-thirds of women treated had their hypertension controlled, irrespective of urban/rural setting or wealth. Adequate blood pressure control was sub-optimal in urban men.
Conclusion
Hypertension is very common in India, even among underweight adults and those of lower socioeconomic position. Improved detection is needed to reduce the burden of disease attributable to hypertension. Levels of treatment and control are relatively good, particularly in women, although urban men require more careful attention.
doi:10.1371/journal.pone.0086043
PMCID: PMC3900470  PMID: 24465859
7.  Averting Obesity and Type 2 Diabetes in India through Sugar-Sweetened Beverage Taxation: An Economic-Epidemiologic Modeling Study 
PLoS Medicine  2014;11(1):e1001582.
In this modeling study, Sanjay Basu and colleagues estimate the potential health effects of a sugar-sweetened beverage taxation among various sub-populations in India over the period 2014 to 2023.
Please see later in the article for the Editors' Summary
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.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Non-communicable diseases (NCDs) and obesity (excessive body mass) are major threats to global health. Each year NCDs kill 36 million people (including 29 million people in low- and middle-income countries), thereby accounting for nearly two-thirds of the world's annual deaths. Cardiovascular diseases, cancers, respiratory diseases, and diabetes (a condition characterized by raised blood sugar levels) are responsible for most NCD-related deaths. Worldwide, diabetes alone affects about 360 million people and causes nearly 5 million deaths annually. And the number of people affected by NCDs is likely to rise over the next few decades. It is estimated, for example, that 101.2 million people in India will have diabetes by 2030, nearly double the current number. In Asia and other low- and middle-income countries overweight as well as obesity represent a risk factor for NCDs and the global prevalence of obesity (the proportion of the world's population that is obese) has nearly doubled since 1980. Worldwide, around 0.5 billion people are now classified as obese and about 1.5 billion more overweight. That is, they have a body mass index (BMI) of 30 kg/m2 or more (25–30 for overweight); BMI is calculated by dividing a person's weight in kilograms by the square of their height in meters. In India individuals with a BMI of 25 or more (overweight/obese) are at very high risk of diabetes.
Why Was This Study Done?
The consumption of sugar-sweetened beverages (SSBs, soft drinks sweetened with cane sugar or other caloric sweeteners) is a major risk factor for overweight/obesity and, independent of total energy consumption and BMI, for type 2 diabetes (the commonest form of diabetes). In high-income countries, SSB taxation has been proposed as a way to lower the risk of obesity and type 2 diabetes, however it is unknown if this approach will work in low- and middle-income countries. Here, in an economic-epidemiologic modeling study, researchers estimate the potential health effects of SSB taxation in India, a middle-income country in which total SSB consumption is rapidly increasing, but where SSB consumption and chronic disease risk vary greatly within the population and where people are likely to turn to other sugar-rich beverages (for example, fresh fruit juices) if SSBs are taxed.
What Did the Researchers Do and Find?
The researchers used survey data relating SSB consumption to price variations to calculate how changes in the price of SSBs affect the demand for SSBs (own-price elasticity) and for other beverages (cross-price elasticity) in India. They combined these elasticities and data on SSB sales trends, BMIs, and diabetes incidence (the frequency of new diabetes cases) into a mathematical microsimulation model to estimate the effect of a 20% tax on SSBs on caloric (energy) consumption, glycemic load (an estimate of how much a food or drink raises blood sugar levels after consumption; low glycemic load diets lower diabetes risk), the prevalence of overweight/obesity, and the incidence of diabetes among Indian subpopulations. According to the model, if SSB sales continue to increase at the current rate, compared to no tax, a 20% SSB tax would reduce overweight/obesity across India by 3.0% and the incidence of type 2 diabetes by 1.6% over the period 2014–2023. In absolute figures, a 20% SSB tax would avert 11.2 million cases of overweight/obesity and 400,000 cases of type 2 diabetes between 2014 and 2023. Notably, if SSB sales increase more steeply as predicted by drinks industry marketing models, the tax would avert 15.8 million cases of overweight/obesity and 600,000 cases of diabetes. Finally, the model predicted that the largest relative effect of an SSB tax would be among young men in rural areas.
What Do These Findings Mean?
The accuracy of these findings is likely to be affected by the assumptions incorporated in the model and by the data fed into it. In particular, the accuracy of the estimates of the health effects of a 20% tax on SSBs is limited by the assumption that future consumer behavior will reflect historic behavior and by potential underreporting of SSB consumption in surveys. Nevertheless, these findings suggest that a sustained high rate of tax on SSBs could mitigate the rising prevalence of obesity and the rising incidence of diabetes in India in both urban and rural populations by affecting both caloric intake and glycemic load. Thus, SSB taxation might be a way to control obesity and diabetes in India and other low- and middle-income countries where, to date, large-scale interventions designed to address these threats to global health have had no sustained effects.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001582.
The World Health Organization provides information about non-communicable diseases, obesity, and diabetes around the world (in several languages)
The US Centers for Disease Control and Prevention provides information on non-communicable diseases around the world and on overweight and obesity and diabetes (including some information in Spanish)
The US National Diabetes Information Clearinghouse provides information about diabetes for patients, health-care professionals, and the general public, including detailed information on weight control (in English and Spanish)
The UK National Health Service Choices website provides information for patients and carers about type 2 diabetes and about obesity; it includes personal stories about diabetes and about obesity
MedlinePlus provides links to further resources and advice about diabetes and diabetes prevention and about obesity (in English and Spanish)
A 2012 Policy brief from the Yale Rudd Center for food policy and obesity provides information about SSB taxes
doi:10.1371/journal.pmed.1001582
PMCID: PMC3883641  PMID: 24409102
8.  Assessing Risk Prediction Models Using Individual Participant Data From Multiple Studies 
Pennells, Lisa | Kaptoge, Stephen | White, Ian R. | Thompson, Simon G. | Wood, Angela M. | Tipping, Robert W. | Folsom, Aaron R. | Couper, David J. | Ballantyne, Christie M. | Coresh, Josef | Goya Wannamethee, S. | Morris, Richard W. | Kiechl, Stefan | Willeit, Johann | Willeit, Peter | Schett, Georg | Ebrahim, Shah | Lawlor, Debbie A. | Yarnell, John W. | Gallacher, John | Cushman, Mary | Psaty, Bruce M. | Tracy, Russ | Tybjærg-Hansen, Anne | Price, Jackie F. | Lee, Amanda J. | McLachlan, Stela | Khaw, Kay-Tee | Wareham, Nicholas J. | Brenner, Hermann | Schöttker, Ben | Müller, Heiko | Jansson, Jan-Håkan | Wennberg, Patrik | Salomaa, Veikko | Harald, Kennet | Jousilahti, Pekka | Vartiainen, Erkki | Woodward, Mark | D'Agostino, Ralph B. | Bladbjerg, Else-Marie | Jørgensen, Torben | Kiyohara, Yutaka | Arima, Hisatomi | Doi, Yasufumi | Ninomiya, Toshiharu | Dekker, Jacqueline M. | Nijpels, Giel | Stehouwer, Coen D. A. | Kauhanen, Jussi | Salonen, Jukka T. | Meade, Tom W. | Cooper, Jackie A. | Cushman, Mary | Folsom, Aaron R. | Psaty, Bruce M. | Shea, Steven | Döring, Angela | Kuller, Lewis H. | Grandits, Greg | Gillum, Richard F. | Mussolino, Michael | Rimm, Eric B. | Hankinson, Sue E. | Manson, JoAnn E. | Pai, Jennifer K. | Kirkland, Susan | Shaffer, Jonathan A. | Shimbo, Daichi | Bakker, Stephan J. L. | Gansevoort, Ron T. | Hillege, Hans L. | Amouyel, Philippe | Arveiler, Dominique | Evans, Alun | Ferrières, Jean | Sattar, Naveed | Westendorp, Rudi G. | Buckley, Brendan M. | Cantin, Bernard | Lamarche, Benoît | Barrett-Connor, Elizabeth | Wingard, Deborah L. | Bettencourt, Richele | Gudnason, Vilmundur | Aspelund, Thor | Sigurdsson, Gunnar | Thorsson, Bolli | Kavousi, Maryam | Witteman, Jacqueline C. | Hofman, Albert | Franco, Oscar H. | Howard, Barbara V. | Zhang, Ying | Best, Lyle | Umans, Jason G. | Onat, Altan | Sundström, Johan | Michael Gaziano, J. | Stampfer, Meir | Ridker, Paul M. | Michael Gaziano, J. | Ridker, Paul M. | Marmot, Michael | Clarke, Robert | Collins, Rory | Fletcher, Astrid | Brunner, Eric | Shipley, Martin | Kivimäki, Mika | Ridker, Paul M. | Buring, Julie | Cook, Nancy | Ford, Ian | Shepherd, James | Cobbe, Stuart M. | Robertson, Michele | Walker, Matthew | Watson, Sarah | Alexander, Myriam | Butterworth, Adam S. | Angelantonio, Emanuele Di | Gao, Pei | Haycock, Philip | Kaptoge, Stephen | Pennells, Lisa | Thompson, Simon G. | Walker, Matthew | Watson, Sarah | White, Ian R. | Wood, Angela M. | Wormser, David | Danesh, John
American Journal of Epidemiology  2013;179(5):621-632.
Individual participant time-to-event data from multiple prospective epidemiologic studies enable detailed investigation into the predictive ability of risk models. Here we address the challenges in appropriately combining such information across studies. Methods are exemplified by analyses of log C-reactive protein and conventional risk factors for coronary heart disease in the Emerging Risk Factors Collaboration, a collation of individual data from multiple prospective studies with an average follow-up duration of 9.8 years (dates varied). We derive risk prediction models using Cox proportional hazards regression analysis stratified by study and obtain estimates of risk discrimination, Harrell's concordance index, and Royston's discrimination measure within each study; we then combine the estimates across studies using a weighted meta-analysis. Various weighting approaches are compared and lead us to recommend using the number of events in each study. We also discuss the calculation of measures of reclassification for multiple studies. We further show that comparison of differences in predictive ability across subgroups should be based only on within-study information and that combining measures of risk discrimination from case-control studies and prospective studies is problematic. The concordance index and discrimination measure gave qualitatively similar results throughout. While the concordance index was very heterogeneous between studies, principally because of differing age ranges, the increments in the concordance index from adding log C-reactive protein to conventional risk factors were more homogeneous.
doi:10.1093/aje/kwt298
PMCID: PMC3927974  PMID: 24366051
C index; coronary heart disease; D measure; individual participant data; inverse variance; meta-analysis; risk prediction; weighting
9.  Childhood milk consumption is associated with better physical performance in old age 
Age and Ageing  2012;41(6):776-784.
Background: studies have shown that milk and dairy consumption in adulthood have beneficial effects on health.
Methods: we examined the impact of childhood and adult diet on physical performance at age 63–86 years. The Boyd Orr cohort (n = 405) is a 65-year prospective study of children who took part in a 1930's survey; the Caerphilly Prospective Study (CaPS; n = 1,195) provides data from mid-life to old age. We hypothesised that higher intakes of childhood and adult milk, calcium, protein, fat and energy would be associated with a better performance.
Results: in fully adjusted models, a standard deviation (SD) increase in natural log-transformed childhood milk intake was associated with 5% faster walking times from the get-up and go test in Boyd Orr (95% CI: 1 to 9) and 25% lower odds of poor balance (OR: 0.75; 0.55 to 1.02). Childhood calcium intake was positively associated with walking times (4% faster per SD; 0 to 8) and a higher protein intake was associated with lower odds of poor balance (OR: 0.71; 0.54 to 0.92). In adulthood, protein intake was positively associated with walking times (2% faster per SD; 1 to 3; Boyd Orr and CaPS pooled data).
Conclusion: this is the first study to show positive associations of childhood milk intake with physical performance in old age.
doi:10.1093/ageing/afs052
PMCID: PMC3476828  PMID: 22542496
diet; physical performance; walking speed; standing balance; older people
10.  The course and outcome of alcohol use disorders in men in Goa: A population- based follow-up study 
Indian Journal of Psychiatry  2013;55(4):376-379.
Background:
Research on the natural history and long-term outcomes of alcohol use disorders (AUD) is important to guide health policy. However, attrition is a major challenge in longitudinal studies and can affect validity of findings.
Materials and Methods:
A 4-year follow-up study was conducted on a randomly selected subgroup of a sample of men in rural and urban communities in Goa to assess attrition, preliminary estimates of AUD outcomes, and chronic disease risk factors.
Results:
Overall attrition rate was 16.7% with a higher attrition in AUD compared to abstainers or casual drinkers. Incidence of AUD at 4 years was 12.8% while the persistence rate of AUD was 53.9%. A trend for poorer health and health behaviors and higher blood pressure was observed in AUD.
Conclusion:
The results of this study suggest a relatively low attrition rate despite the long follow-up period and support the feasibility of conducting a definitive cohort study with the entire sample.
doi:10.4103/0019-5545.120573
PMCID: PMC3890936  PMID: 24459310
Alcohol use disorders; attrition; health outcomes; incidence
11.  Area-Level Deprivation and Overall and Cause-Specific Mortality: 12 Years’ Observation on British Women and Systematic Review of Prospective Studies 
PLoS ONE  2013;8(9):e72656.
Background
Prospective studies have suggested a negative impact of area deprivation on overall mortality, but its effect on cause-specific mortality and the mechanisms that account for this association remain unclear. We investigate the association of area deprivation, using Index of Multiple deprivation (IMD), with overall and cause-specific mortality, contextualising findings within a systematic review.
Methods And Findings
We used data from 4,286 women from the British Women’s Heart Health Study (BWHHS) recruited at 1999-2001 to examine the association of IMD with overall and cause-specific mortality using Cox regression models. One standard deviation (SD) increase in the IMD score had a hazard ratio (HR) of 1.21 (95% CI: 1.13-1.30) for overall mortality after adjustment for age and lifecourse individual deprivation, which was attenuated to 1.15 (95% CI: 1.04-1.26) after further inclusion of mediators (health behaviours, biological factors and use of statins and blood pressure-lowering medications). A more pronounced association was observed for respiratory disease and vascular deaths. The meta-analysis, based on 20 published studies plus the BWHHS (n=21), yielded a summary relative risk (RR) of 1.15 (95% CI: 1.11-1.19) for area deprivation (top [least deprived; reference] vs. bottom tertile) with overall mortality in an age and sex adjusted model, which reduced to 1.06 (95% CI: 1.04-1.08) in a fully adjusted model.
Conclusions
Health behaviours mediate the association between area deprivation and cause-specific mortality. Efforts to modify health behaviours may be more successful if they are combined with measures that tackle area deprivation.
doi:10.1371/journal.pone.0072656
PMCID: PMC3782490  PMID: 24086262
12.  Genetic loci influencing kidney function and chronic kidney disease in man 
Chambers, John C | Zhang, Weihua | Lord, Graham M | van der Harst, Pim | Lawlor, Debbie A | Sehmi, Joban S | Gale, Daniel P | Wass, Mark N | Ahmadi, Kourosh R | Bakker, Stephan JL | Beckmann, Jacqui | Bilo, Henk JG | Bochud, Murielle | Brown, Morris J | Caulfield, Mark J | Connell, John M C | Cook, Terence | Cotlarciuc, Ioana | Smith, George Davey | de Silva, Ranil | Deng, Guohong | Devuyst, Olivier | Dikkeschei, Lambert D. | Dimkovic, Nada | Dockrell, Mark | Dominiczak, Anna | Ebrahim, Shah | Eggermann, Thomas | Farrall, Martin | Ferrucci, Luigi | Floege, Jurgen | Forouhi, Nita G | Gansevoort, Ron T | Han, Xijin | Hedblad, Bo | van der Heide, Jaap J Homan | Hepkema, Bouke G | Hernandez-Fuentes, Maria | Hypponen, Elina | Johnson, Toby | de Jong, Paul E | Kleefstra, Nanne | Lagou, Vasiliki | Lapsley, Marta | Li, Yun | Loos, Ruth J F | Luan, Jian'an | Luttropp, Karin | Maréchal, Céline | Melander, Olle | Munroe, Patricia B | Nordfors, Louise | Parsa, Afshin | Penninx, Brenda W. | Perucha, Esperanza | Pouta, Anneli | Prokopenko, Inga | Roderick, Paul J | Ruokonen, Aimo | Samani, Nilesh | Sanna, Serena | Schalling, Martin | Schlessinger, David | Schlieper, Georg | Seelen, Marc AJ | Shuldiner, Alan R | Sjögren, Marketa | Smit, Johannes H. | Snieder, Harold | Soranzo, Nicole | Spector, Timothy D | Stenvinkel, Peter | Sternberg, Michael JE | Swaminathan, Ramasamyiyer | Tanaka, Toshiko | Ubink-Veltmaat, Lielith J. | Uda, Manuela | Vollenweider, Peter | Wallace, Chris | Waterworth, Dawn | Zerres, Klaus | Waeber, Gerard | Wareham, Nicholas J | Maxwell, Patrick H | McCarthy, Mark I | Jarvelin, Marjo-Riitta | Mooser, Vincent | Abecasis, Goncalo R | Lightstone, Liz | Scott, James | Navis, Gerjan | Elliott, Paul | Kooner., Jaspal S
Nature genetics  2010;42(5):373-375.
Chronic kidney disease (CKD), the result of permanent loss of kidney function, is a major global problem. We identify common genetic variants at chr2p12-p13, chr6q26, chr17q23 and chr19q13 associated with serum creatinine, a marker of kidney function (P=10−10 to 10−15). SNPs rs10206899 (near NAT8, chr2p12-p13) and rs4805834 (near SLC7A9, chr19q13) were also associated with CKD. Our findings provide new insight into metabolic, solute and drug-transport pathways underlying susceptibility to CKD.
doi:10.1038/ng.566
PMCID: PMC3748585  PMID: 20383145
13.  Population Genomics of Cardiometabolic Traits: Design of the University College London-London School of Hygiene and Tropical Medicine-Edinburgh-Bristol (UCLEB) Consortium 
PLoS ONE  2013;8(8):e71345.
Substantial advances have been made in identifying common genetic variants influencing cardiometabolic traits and disease outcomes through genome wide association studies. Nevertheless, gaps in knowledge remain and new questions have arisen regarding the population relevance, mechanisms, and applications for healthcare. Using a new high-resolution custom single nucleotide polymorphism (SNP) array (Metabochip) incorporating dense coverage of genomic regions linked to cardiometabolic disease, the University College-London School-Edinburgh-Bristol (UCLEB) consortium of highly-phenotyped population-based prospective studies, aims to: (1) fine map functionally relevant SNPs; (2) precisely estimate individual absolute and population attributable risks based on individual SNPs and their combination; (3) investigate mechanisms leading to altered risk factor profiles and CVD events; and (4) use Mendelian randomisation to undertake studies of the causal role in CVD of a range of cardiovascular biomarkers to inform public health policy and help develop new preventative therapies.
doi:10.1371/journal.pone.0071345
PMCID: PMC3748096  PMID: 23977022
14.  Association between legume intake and self-reported diabetes among adult men and women in India 
BMC Public Health  2013;13:706.
Background
It is postulated that a diet high in legumes may be beneficial in preventing diabetes. However, little empirical evidence on this association exists in developing countries. We aimed to examine the association between legume intake and self-reported diabetes status in adult men and women in India.
Methods
The analysis is based on a population-based cross sectional study of 99,574 women and 56,742 men aged 20–49 years included in India’s third National Family Health Survey conducted in 2005–06. Association of legume intake, determined by the frequency of consumption of pulses and beans (daily, weekly and occasionally or never), with the reported prevalence of diabetes were estimated using multiple logistic regression after adjusting for frequency of consumption of other food items, BMI status, tobacco smoking, alcohol drinking, watching television, age, education, living standard of the household, residence and geographic regions.
Results
Daily (OR: 0.71; 95% CI: 0.59–0.87; p=0.001) and weekly (OR: 0.66; 95% CI: 0.54–0.80; p<0.001) legumes intake were associated with a significantly reduced prevalence of diabetes among adult Indian women even after controlling for the effects of potentially confounding factors, whereas non-significant inverse associations were observed in men.
Conclusion
Daily or weekly intake of legumes was inversely associated with presence of diabetes in the Indian population. However, this is an observational finding and uncontrolled confounding cannot be excluded as an explanation for the association. More epidemiological research with better measures of legumes intake and clinical measures of diabetes is needed to clarify this relationship.
doi:10.1186/1471-2458-13-706
PMCID: PMC3735389  PMID: 23915141
Legume intake; Diabetes; Men; Women; NFHS-3; India
15.  Socioeconomic Inequalities in Non-Communicable Diseases Prevalence in India: Disparities between Self-Reported Diagnoses and Standardized Measures 
PLoS ONE  2013;8(7):e68219.
Background
Whether non-communicable diseases (NCDs) are diseases of poverty or affluence in low-and-middle income countries has been vigorously debated. Most analyses of NCDs have used self-reported data, which is biased by differential access to healthcare services between groups of different socioeconomic status (SES). We sought to compare self-reported diagnoses versus standardised measures of NCD prevalence across SES groups in India.
Methods
We calculated age-adjusted prevalence rates of common NCDs from the Study on Global Ageing and Adult Health, a nationally representative cross-sectional survey. We compared self-reported diagnoses to standardized measures of disease for five NCDs. We calculated wealth-related and education-related disparities in NCD prevalence by calculating concentration index (C), which ranges from −1 to +1 (concentration of disease among lower and higher SES groups, respectively).
Findings
NCD prevalence was higher (range 5.2 to 19.1%) for standardised measures than self-reported diagnoses (range 3.1 to 9.4%). Several NCDs were particularly concentrated among higher SES groups according to self-reported diagnoses (Csrd) but were concentrated either among lower SES groups or showed no strong socioeconomic gradient using standardized measures (Csm): age-standardised wealth-related C: angina Csrd 0.02 vs. Csm −0.17; asthma and lung diseases Csrd −0.05 vs. Csm −0.04 (age-standardised education-related Csrd 0.04 vs. Csm −0.05); vision problems Csrd 0.07 vs. Csm −0.05; depression Csrd 0.07 vs. Csm −0.13. Indicating similar trends of standardized measures detecting more cases among low SES, concentration of hypertension declined among higher SES (Csrd 0.19 vs. Csm 0.03).
Conclusions
The socio-economic patterning of NCD prevalence differs markedly when assessed by standardized criteria versus self-reported diagnoses. NCDs in India are not necessarily diseases of affluence but also of poverty, indicating likely under-diagnosis and under-reporting of diseases among the poor. Standardized measures should be used, wherever feasible, to estimate the true prevalence of NCDs.
doi:10.1371/journal.pone.0068219
PMCID: PMC3712012  PMID: 23869213
16.  Associations between Active Travel to Work and Overweight, Hypertension, and Diabetes in India: A Cross-Sectional Study 
PLoS Medicine  2013;10(6):e1001459.
Using data from the Indian Migration Study, Christopher Millett and colleagues examine the associations between active travel to work and overweight, hypertension, and diabetes.
Please see later in the article for the Editors' Summary
Background
Increasing active travel (walking, bicycling, and public transport) is promoted as a key strategy to increase physical activity and reduce the growing burden of noncommunicable diseases (NCDs) globally. Little is known about patterns of active travel or associated cardiovascular health benefits in low- and middle-income countries. This study examines mode and duration of travel to work in rural and urban India and associations between active travel and overweight, hypertension, and diabetes.
Methods and Findings
Cross-sectional study of 3,902 participants (1,366 rural, 2,536 urban) in the Indian Migration Study. Associations between mode and duration of active travel and cardiovascular risk factors were assessed using random-effect logistic regression models adjusting for age, sex, caste, standard of living, occupation, factory location, leisure time physical activity, daily fat intake, smoking status, and alcohol use. Rural dwellers were significantly more likely to bicycle (68.3% versus 15.9%; p<0.001) to work than urban dwellers. The prevalence of overweight or obesity was 50.0%, 37.6%, 24.2%, 24.9%; hypertension was 17.7%, 11.8%, 6.5%, 9.8%; and diabetes was 10.8%, 7.4%, 3.8%, 7.3% in participants who travelled to work by private transport, public transport, bicycling, and walking, respectively. In the adjusted analysis, those walking (adjusted risk ratio [ARR] 0.72; 95% CI 0.58–0.88) or bicycling to work (ARR 0.66; 95% CI 0.55–0.77) were significantly less likely to be overweight or obese than those travelling by private transport. Those bicycling to work were significantly less likely to have hypertension (ARR 0.51; 95% CI 0.36–0.71) or diabetes (ARR 0.65; 95% CI 0.44–0.95). There was evidence of a dose-response relationship between duration of bicycling to work and being overweight, having hypertension or diabetes. The main limitation of the study is the cross-sectional design, which limits causal inference for the associations found.
Conclusions
Walking and bicycling to work was associated with reduced cardiovascular risk in the Indian population. Efforts to increase active travel in urban areas and halt declines in rural areas should be integral to strategies to maintain healthy weight and prevent NCDs in India.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Noncommunicable diseases (NCDs) and obesity (excessive body fat) are major threats to global health. Every year, more than 36 million people (including 29 million in LMICs) die from NCDs—nearly two-thirds of the world's annual deaths. Cardiovascular diseases (conditions that affect the heart and the circulation), diabetes, cancer, and respiratory diseases are responsible for most NCD-related deaths. Obesity is a risk factor for all these NCDs and the global prevalence of obesity (the proportion of the world's population that is obese) has nearly doubled since 1980. In 2008, 35% of adults were overweight and 11% were obese. One reason for the growing burden of both obesity and NCDs is increasing physical inactivity. Regular physical activity helps to maintain a healthy body weight and to prevent or delay the onset of NCDs. For an adult, 30 minutes of moderate physical activity—walking briskly or cycling, for example—five times a week is sufficient to promote and maintain health. But the daily lives of people in both developed and developing countries are becoming increasingly sedentary and, nowadays, at least 60% of the world's population does not do even this modest amount of exercise.
Why Was This Study Done?
Strategies to increase physical activity levels often promote active travel (walking, cycling, and using public transport). The positive impact of active travel on physical activity levels and cardiovascular health is well established in high-income countries, but little is known about the patterns of active travel or the health benefits associated with active travel in poorer countries. In this cross-sectional study (an investigation that measures population characteristics at a single time point), the researchers examine the mode and duration of travel to work in rural and urban India and associations between active travel and overweight/obesity, hypertension (high blood pressure, a risk factor for cardiovascular disease), and diabetes. In India, a lower middle-income country, the prevalence of overweight and NCDs is projected to increase rapidly over the next two decades. Moreover, rapid unplanned urbanization and a large increase in registered motor vehicles has resulted in inadequate development of the public transport infrastructure and hazardous conditions for walking and cycling in most Indian towns and cities.
What Did the Researchers Do and Find?
For their study, researchers analyzed physical activity and health data collected from participants in the Indian Migration Study, which examined the association between migration from rural to urban areas and obesity and diabetes risk. People living in rural areas were more likely to cycle to work than people living in towns and cities (68.3% versus 15.9%). Among people who travelled to work by private transport, public transport, walking, and cycling, the prevalence of overweight or obesity was 50.0%, 37.6%, 24.9%, and 24.2%, respectively. Similar patterns were seen for the prevalence of hypertension and diabetes. After adjustment for factors that affect the risk of obesity, hypertension, and diabetes (for example, daily fat intake and leisure time physical activity), people walking or cycling to work were less likely to be overweight or obese than those travelling by public transport, and those cycling to walk were less likely to have hypertension or diabetes. Finally, people with long cycle rides to work had a lower risk of being overweight or having hypertension or diabetes than people with short cycle rides.
What Do These Findings Mean?
These findings suggest that, as in high-income settings, walking and cycling to work are associated with a reduced risk of cardiovascular disease in India. Because this was a cross-sectional study, these findings do not prove that active travel reduces the risk of cardiovascular disease—people who cycle to work may share other unknown characteristics that are actually responsible for their reduced risk of cardiovascular disease. Moreover, this study did not consider non-cardiovascular outcomes associated with active travel that might affect health such as increased exposure to air pollution. Nevertheless, these findings suggest that programs designed to maintain healthy weight and prevent NCDs in India should endeavor to increase active travel in urban areas and to halt declines in rural areas by, for example, increasing investment in public transport and improving the safety and convenience of walking and cycling routes in urban areas.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001459.
This study is further discussed in a PLOS Medicine Perspective by Kavi Bhalla
The US Centers for Disease Control and Prevention provides information on all aspects of healthy living, on chronic diseases and health promotion, on overweight and obesity and on non-communicable diseases around the world; its Physical Activity for Everyone web pages include guidelines, instructional videos and personal success stories (some information in English and Spanish)
The World Health Organization provides information about physical activity and health, about obesity, and about non-communicable diseases (in several languages); its 2010 Global Recommendations on Physical Activity for Health are available in several languages; its Global Noncommunicable Disease Network (NCDnet) aims to help low- and middle- income countries reduce NCD-related illnesses and death through implementation of the 20082013 Action Plan for the Global Strategy for the Prevention and Control of Noncommunicable Diseases (also available in French); Face to face with chronic diseases is a selection of personal stories from around the world about dealing with NCDs
The American Heart Association provides information on many important risk factors for non-communicable diseases and provides tips for becoming more active
Information about the Indian Migration Study is available
doi:10.1371/journal.pmed.1001459
PMCID: PMC3679004  PMID: 23776412
17.  Disability Transitions and Health Expectancies among Adults 45 Years and Older in Malawi: A Cohort-Based Model 
PLoS Medicine  2013;10(5):e1001435.
Collin Payne and colleagues investigated development of disabilities and years expected to live with disabilities in participants 45 years and older participating in the Malawi Longitudinal Survey of Families and Health.
Please see later in the article for the Editors' Summary
Background
Falling fertility and increasing life expectancy contribute to a growing elderly population in sub-Saharan Africa (SSA); by 2060, persons aged 45 y and older are projected to be 25% of SSA's population, up from 10% in 2010. Aging in SSA is associated with unique challenges because of poverty and inadequate social supports. However, despite its importance for understanding the consequences of population aging, the evidence about the prevalence of disabilities and functional limitations due to poor physical health among older adults in SSA continues to be very limited.
Methods and Findings
Participants came from 2006, 2008, and 2010 waves of the Malawi Longitudinal Survey of Families and Health, a study of the rural population in Malawi. We investigate how poor physical health results in functional limitations that limit the day-to-day activities of individuals in domains relevant to this subsistence-agriculture context. These disabilities were parameterized based on questions from the SF-12 questionnaire about limitations in daily living activities. We estimated age-specific patterns of functional limitations and the transitions over time between different disability states using a discrete-time hazard model. The estimated transition rates were then used to calculate the first (to our knowledge) microdata-based health expectancies calculated for SSA. The risks of experiencing functional limitations due to poor physical health are high in this population, and the onset of disabilities happens early in life. Our analyses show that 45-y-old women can expect to spend 58% (95% CI, 55%–64%) of their remaining 28 y of life (95% CI, 25.7–33.5) with functional limitations; 45-y-old men can expect to live 41% (95% CI, 35%–46%) of their remaining 25.4 y (95% CI, 23.3–28.8) with such limitations. Disabilities related to functional limitations are shown to have a substantial negative effect on individuals' labor activities, and are negatively related to subjective well-being.
Conclusions
Individuals in this population experience a lengthy struggle with disabling conditions in adulthood, with high probabilities of remitting and relapsing between states of functional limitation. Given the strong association of disabilities with work efforts and subjective well-being, this research suggests that current national health policies and international donor-funded health programs in SSA inadequately target the physical health of mature and older adults.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The population of the world is getting older. In almost every country, the over-60 age group is growing faster than any other age group. In 2000, globally, there were about 605 million people aged 60 years or more; by 2050, 2 billion people will be in this age group. Much of this increase in the elderly population will be in low-income countries. In sub-Saharan Africa, for example, 10% of the population is currently aged 45 years or more, but by 2060, a quarter of the population will be so-called mature adults. In all countries, population aging is the result of women having fewer children (falling fertility) and people living longer (increasing life expectancy). Thus, population aging is a demographic transition, a change in birth and death rates. In low- and middle-income countries, population aging is occurring in parallel with an “epidemiological transition,” a shift from communicable (infectious) diseases to non-communicable diseases (for example, heart disease) as the primary causes of illness and death.
Why Was This Study Done?
Both the demographic and the epidemiological transition have public health implications for low-income countries. Good health is important for the independence and economic productivity of older people. Productive older people can help younger populations financially and physically, and help compensate for the limitations experienced by younger populations infected with HIV. Also, low-income countries lack social safety nets, so disabled older adults can be a burden on younger populations. Thus, the health of older individuals is important to the well-being of people of all ages. As populations age, low-income countries will need to invest in health care for mature and elderly adults and in disease prevention programs to prevent or delay the onset of non-communicable diseases, which can limit normal daily activities by causing disabilities. Before providing these services, national policy makers need to know the proportion of their population with disabilities, the functional limitations caused by poor physical health, and the health expectancies (the number of years a person can expect to be in good health) of older people in their country. In this cohort modeling study, the researchers estimate health expectancies and transition rates between different levels of disability among mature adults in Malawi, one of the world's poorest countries, using data collected by the Malawi Longitudinal Survey of Families and Health (MLSFH) on economic, social, and health conditions in a rural population. Because Malawi has shorter life expectancies and earlier onset of disability than wealthier countries, the authors considered individuals aged 45 and older as mature adults at risk for disability.
What Did the Researchers Do and Find?
The researchers categorized the participants in the 2006, 2008, and 2010 waves of the MLSFH into three levels of functional limitation (healthy, moderately limited, and severely limited) based on answers to questions in the SF-12 health survey questionnaire that ask about disabilities that limit daily activities that rural Malawians perform. The researchers estimated age–gender patterns of functional limitations and transition rates between different disability states using a discrete-time hazard model, and health expectancies by running a microsimulation to model the aging of synthetic cohorts with various starting ages but the same gender and functional limitation distributions as the study population. These analyses show that the chance of becoming physically disabled rises sharply with age, with 45-year-old women in rural Malawi expected to spend 58% of their estimated remaining 28 years with functional limitations, and 45-year-old men expected to live 41% of their remaining 25.4 years with functional limitations. Also, on average, a 45-year-old woman will spend 2.7 years with moderate functional limitation and 0.6 years with severe functional limitation before she reaches 55; for men the corresponding values are 1.6 and 0.4 years. Around 50% of moderately and 60%–80% of severely limited individuals stated that pain interfered quite a bit or extremely with their normal work during the past four weeks, suggesting that pain treatment may help reduce disability.
What Do These Findings Mean?
These findings suggest that mature adults in rural Malawi will have some degree of disability during much of their remaining lifetime. The risks of experiencing functional limitations are higher and the onset of persistent disabilities happens earlier in Malawi than in more developed contexts—the proportions of remaining life spent with severe limitations at age 45 in Malawi are comparable to those of 80-year-olds in the US. The accuracy of these findings is likely to be affected by assumptions made during modeling and by the quality of the data fed into the models. Nevertheless, these findings suggest that functional limitations, which have a negative effect on the labor activity of individuals, will become more prominent in Malawi (and probably other sub-Saharan countries) as the age composition of populations shifts over the coming years. Older populations in sub-Saharan Africa are not targeted well by health policies and programs at present. Consequently, these findings suggest that policy makers will need to ensure that additional financial resources are provided to improve health-care provision for aging individuals and to lessen the high rates of functional limitation and associated disabilities.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001435.
This study is further discussed in a PLoS Medicine Perspective by Andreas Stuck, et al.
The World Health Organization provides information on many aspects of aging (in several languages); the WHO Study on Global Ageing and Adult Health (SAGE) is compiling longitudinal information on the health and well-being of adult populations and the aging process
The United Nations Population Fund and HelpAge International publication Ageing in the Twenty-First Century is available
HelpAge International is an international nongovernmental organization that helps older people claim their rights, challenge discrimination, and overcome poverty, so that they can lead dignified, secure, and healthy lives
More information on the Malawi Longitudinal Study of Families and Health is available
doi:10.1371/journal.pmed.1001435
PMCID: PMC3646719  PMID: 23667343
18.  Association between Milk and Milk Product Consumption and Anthropometric Measures in Adult Men and Women in India: A Cross-Sectional Study 
PLoS ONE  2013;8(4):e60739.
Background
The nutritional aetiology of obesity remains unclear, especially with regard to the role of dairy products in developing countries.
Objective
To examine whether milk/milk product consumption is associated with obesity and high waist circumference among adult Indians.
Methods
Information on plain milk, tea, curd and buttermilk/lassi consumption assessed using a Food Frequency Questionnaire was obtained from the cross-sectional sib-pair designed Indian Migration Study (3698 men and 2659 women), conducted at four factory locations across north, central and south India. The anthropometric measures included were Body Mass Index (BMI) and Waist Circumference (WC). Mixed-effect logistic regression models were conducted to accommodate sib-pair design and adjust for potential confounders.
Results
After controlling for potential confounders, the risk of being obese (BMI≥25 kg/m2) was lower among women (OR = 0.57;95%CI:0.43−0.76;p≤0.0001) and men (OR = 0.67;95%CI: 0.51−0.87;p = 0.005), and the risk of a high WC (men: >90 cm; women: >80 cm) was lower among men (OR = 0.71;95%CI:0.54−0.93;p = 0.005) and women (OR = 0.79;95%CI:0.59−1.05;p>0.05) who consume ≥1 portions of plain milk daily than those who do not consume any milk. The inverse association between daily plain milk consumption and obesity was also confirmed in sibling-pair analyses. Daily tea consumption of ≥1 portion was associated with obesity (OR = 1.51;95%CI:1.00−2.25;p>0.050) and high WC (OR = 1.65;95%CI:1.08−2.51;p>0.019) among men but not among women but there was no strong evidence of association of curd and buttermilk/lassi consumption with obesity and high waist circumference among both men and women.
Conclusions
The independent, inverse association of daily plain milk consumption with the risk of being obese suggests that high plain milk intake may lower the risk of obesity in adult Indians. However, this is an observational finding and uncontrolled confounding cannot be excluded as an explanation for the association. Therefore, confirmatory studies are needed to clarify this relationship.
doi:10.1371/journal.pone.0060739
PMCID: PMC3620205  PMID: 23593300
19.  Genetic variation at the SLC23A1 locus is associated with circulating levels of L-ascorbic acid (Vitamin C). Evidence from 5 independent studies with over 15000 participants 
Background
L-ascorbic acid is an essential part of the human diet and has been associated with a wide-range of chronic complex diseases including cardiovascular outcomes. To date, there are no confirmed genetic correlates of circulating levels of L-ascorbic acid.
Objectives
We aimed to confirm the existence of association between common variation at the SLC23A1 gene locus and circulating levels of L-ascorbic acid.
Design
We employed a two-stage design which used a discovery cohort (the British Women’s Heart and Health Study) and a series of follow-up cohorts and meta-analysis (totalling 15087 participants) to assess the relationship between variation at SLC23A1 and circulating levels of L-ascorbic acid.
Results
In the discovery cohort, variation at rs33972313 was associated with a reduction in circulating levels of L-ascorbic acid (−4.15μmol/L (95%CI −0.49, −7.81), p=0.03 reduction per minor allele). Pooled analysis of the relationship between rs33972313 and circulating L-ascorbic acid across all studies confirmed this, showing that each additional rare allele was associated with a reduction in circulating levels of L-ascorbic acid of −5.98μmol/L (95%CI −8.23, −3.73), p=2.0×10−7 per minor allele.
Conclusion
Work here has identified a genetic variant (rs33972313) in the SLC23A1 vitamin C active transporter locus that is reliably associated with circulating levels of L-ascorbic acid in the general population. This finding has implications more generally for the epidemiological investigation of relationships between circulating L-ascorbic acid and health outcomes.
doi:10.3945/ajcn.2010.29438
PMCID: PMC3605792  PMID: 20519558
Vitamin C; genotype; L-ascorbic acid
20.  Differences in estimation of creatinine generation between renal function estimating equations in an Indian population: cross-sectional data from the Hyderabad arm of the Indian migration study 
BMC Nephrology  2013;14:30.
Background
Creatinine based formulae for estimating renal function developed in white populations may be less valid in other ethnic groups. We assessed the performance of various estimating formulae in an Indian population.
Methods
917 subjects were recruited from the Hyderabad arm of the Indian Migration Study. Data were collected on comorbidity, serum creatinine and body composition from DXA scans. Renal function was compared using the modified Cockcroft-Gault, MDRD and CKD-EPI formulae. 24-hour creatinine production was derived from each estimate and the agreement with measured muscle mass examined. 24-hour creatinine production estimates were compared to that derived from a formula by Rule incorporating DXA measured muscle mass. Potential systematic biases were examined by age and eGFR. We assessed the association of renal function by each formula with hypertension and self-reported measures of vascular disease.
Results
Mean modified Cockcroft-Gault eCCl was 98.8 ml/min/1.73 m2, MDRD eGFR 91.2 ml/min/1.73 m2 and CKD-EPI eGFR 96.3 ml/min/1.73 m2. MDRD derived 24-hour creatinine production showed the least age-related underestimation compared to the Rule formula. CKD-EPI showed a marked bias at higher eGFRs. All formulae showed similar strength associations with vascular disease and hypertension.
Conclusions
Our analyses support the use of MDRD for estimating renal function in Indian populations. Further work is required to assess the predictive value of formulae for incident disease and complications of CKD.
doi:10.1186/1471-2369-14-30
PMCID: PMC3599554  PMID: 23379609
Creatinine; Ethnicity; Muscle mass; Renal function
21.  Prospective study of IL-18 and risk of MI and stroke in men and women aged 60–79 years: A nested case-control study 
Cytokine  2013;61(2):513-520.
Highlights
► IL-18 is hypothesized to destabilise atherosclerotic plaques, leading to thrombotic events. ► We prospectively studied serum IL-18 and CHD or stroke onset in older men and women. ► IL-18 was positively associated with adverse lipid and inflammatory profile. ► Results did not suggest independent associations between IL-18 and CHD or stroke risk.
Aim
IL-18 is hypothesized to destabilise atherosclerotic plaques, leading to thrombotic events and epidemiologic studies suggest that IL-18 may increase risk of CHD or CVD.
We examined prospective associations between levels of serum IL-18 and new CHD and stroke events in older men and women from a general population.
Methods
A case-control study was nested within a prospective cohort of men and women aged 60–79 years recruited from general practices in 25 British towns in 1998–2000 and followed-up for 7.5 years for fatal and non-fatal MI and stroke. Baseline IL-18 was measured in stored serum samples of incident cases of MI (n = 364) or stroke (n = 300) and two controls per case.
Results
Geometric mean IL-18 levels were higher among the 364 MI cases than the 706 controls; 417.84 pg/mL (IQR 316.25, 537.44) compared to 386.90 pg/mL (IQR 296.54, 482.33), p(difference) = 0.002. IL-18 was positively associated with adverse lipid and inflammatory profiles. Men and women in the top third of baseline IL-18 levels had an age and sex-adjusted odds ratio (OR) for MI of 1.31 (95%CI 0.92, 1.85) compared with those in the lowest third; this attenuated to 1.05 (95%CI 0.72, 1.53) after additional adjustment for established vascular and inflammatory risk factors. Each doubling of IL-18 level was associated with an increased OR for MI 1.34 (95%CI 1.04, 1.72), which was attenuated on adjustment for established vascular and inflammatory risk factors; 1.09 (95%CI 0.83, 1.44).
Geometric mean IL-18 levels did not differ between stroke cases and controls. The OR for stroke associated with the highest compared to the lowest tertile of IL-18 was 1.24 (95%CI 0.84, 1.84). Results for MI and stroke did not differ by presence of pre-existing CVD, gender or age.
Conclusions
Circulating IL-18 levels were strongly associated with a range of established and novel risk factors but were not independently associated with risk of MI or stroke in our study.
doi:10.1016/j.cyto.2012.10.010
PMCID: PMC3561593  PMID: 23207179
Coronary heart disease; Stroke; Interleukin-18; Epidemiology; Cohort
22.  Erectile Dysfunction Severity as a Risk Marker for Cardiovascular Disease Hospitalisation and All-Cause Mortality: A Prospective Cohort Study 
PLoS Medicine  2013;10(1):e1001372.
In a prospective Australian population-based study linking questionnaire data from 2006–2009 with hospitalisation and death data to June 2010 for 95,038 men aged ≥45 years, Banks and colleagues found that more severe erectile dysfunction was associated with higher risk of cardiovascular disease.
Background
Erectile dysfunction is an emerging risk marker for future cardiovascular disease (CVD) events; however, evidence on dose response and specific CVD outcomes is limited. This study investigates the relationship between severity of erectile dysfunction and specific CVD outcomes.
Methods and Findings
We conducted a prospective population-based Australian study (the 45 and Up Study) linking questionnaire data from 2006–2009 with hospitalisation and death data to 30 June and 31 Dec 2010 respectively for 95,038 men aged ≥45 y. Cox proportional hazards models were used to examine the relationship of reported severity of erectile dysfunction to all-cause mortality and first CVD-related hospitalisation since baseline in men with and without previous CVD, adjusting for age, smoking, alcohol consumption, marital status, income, education, physical activity, body mass index, diabetes, and hypertension and/or hypercholesterolaemia treatment. There were 7,855 incident admissions for CVD and 2,304 deaths during follow-up (mean time from recruitment, 2.2 y for CVD admission and 2.8 y for mortality). Risks of CVD and death increased steadily with severity of erectile dysfunction. Among men without previous CVD, those with severe versus no erectile dysfunction had significantly increased risks of ischaemic heart disease (adjusted relative risk [RR] = 1.60, 95% CI 1.31–1.95), heart failure (8.00, 2.64–24.2), peripheral vascular disease (1.92, 1.12–3.29), “other” CVD (1.26, 1.05–1.51), all CVD combined (1.35, 1.19–1.53), and all-cause mortality (1.93, 1.52–2.44). For men with previous CVD, corresponding RRs (95% CI) were 1.70 (1.46–1.98), 4.40 (2.64–7.33), 2.46 (1.63–3.70), 1.40 (1.21–1.63), 1.64 (1.48–1.81), and 2.37 (1.87–3.01), respectively. Among men without previous CVD, RRs of more specific CVDs increased significantly with severe versus no erectile dysfunction, including acute myocardial infarction (1.66, 1.22–2.26), atrioventricular and left bundle branch block (6.62, 1.86–23.56), and (peripheral) atherosclerosis (2.47, 1.18–5.15), with no significant difference in risk for conditions such as primary hypertension (0.61, 0.16–2.35) and intracerebral haemorrhage (0.78, 0.20–2.97).
Conclusions
These findings give support for CVD risk assessment in men with erectile dysfunction who have not already undergone assessment. The utility of erectile dysfunction as a clinical risk prediction tool requires specific testing.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Erectile dysfunction is the medical term used when a man is unable to achieve or sustain an erection of his penis suitable for sexual intercourse. Although a sensitive topic that can cause much embarrassment and distress, erectile dysfunction is very common, with an estimated 40% of men over the age of 40 years experiencing frequent or occasional difficulties. The most common causes of erectile dysfunction are medications, chronic illnesses such as diabetes, and drinking too much alcohol. Stress and mental health problems can also cause or worsen erectile dysfunction. There is also increasing evidence that erectile dysfunction may actually be a symptom of cardiovascular disease—a leading cause of death worldwide—as erectile dysfunction could indicate a problem with blood vessels or poor blood flow commonly associated with cardiovascular disease.
Why Was This Study Done?
Although previous studies have suggested that erectile dysfunction can serve as a marker for cardiovascular disease in men not previously diagnosed with the condition, few studies to date have investigated whether erectile dysfunction could also indicate worsening disease in men already diagnosed with cardiovascular disease. In addition, previous studies have typically been small and have not graded the severity of erectile dysfunction or investigated the specific types of cardiovascular disease associated with erectile dysfunction. In this large study conducted in Australia, the researchers investigated the relationship of the severity of erectile dysfunction with a range of cardiovascular disease outcomes among men with and without a previous diagnosis of cardiovascular disease.
What Did the Researchers Do and Find?
The researchers used information from the established 45 and Up Study, a large cohort study that includes 123,775 men aged 45 and over, selected at random from the general population of New South Wales, a large region of Australia. A total of 95,038 men were included in this analysis. The male participants completed a postal questionnaire that included a question on erectile functioning, which allowed the researchers to define erectile dysfunction as none, mild, moderate, or severe. Using information captured in the New South Wales Admitted Patient Data Collection—a complete record of all public and private hospital admissions, including the reasons for admission and the clinical diagnosis—and the government death register, the researchers were able to determine health outcomes of all study participants. They then used a statistical model to estimate hospital admissions for cardiovascular disease events for different levels of erectile dysfunction.
The researchers found that the rates of severe erectile dysfunction among study participants were 2.2% for men aged 45–54 years, 6.8% for men aged 55–64 years, 20.2% for men aged 65–74 years, 50.0% for men aged 75–84 years, and 75.4% for men aged 85 years and over. During the study period, the researchers recorded 7,855 hospital admissions related to cardiovascular disease and 2,304 deaths. The researchers found that among men without previous cardiovascular disease, those with severe erectile dysfunction were more likely to develop ischemic heart disease (risk 1.60), heart failure (risk 8.00), peripheral vascular disease (risk 1.92), and other causes of cardiovascular disease (risk 1.26) than men without erectile dysfunction. The risks of heart attacks and heart conduction problems were also increased (1.66 and 6.62, respectively). Furthermore, the combined risk of all cardiovascular disease outcomes was 1.35, and the overall risk of death was also higher (risk 1.93) in these men. The researchers found that these increased risks were similar in men with erectile dysfunction who had previously been diagnosed with cardiovascular disease.
What Do These Findings Mean?
These findings suggest that compared to men without erectile dysfunction, there is an increasing risk of ischemic heart disease, peripheral vascular disease, and death from all causes in those with increasing degrees of severity of erectile dysfunction. The authors emphasize that erectile dysfunction is a risk marker for cardiovascular disease, not a risk factor that causes cardiovascular disease. These findings add to previous studies and highlight the need to consider erectile dysfunction in relation to the risk of different types of cardiovascular disease, including heart failure and heart conduction disorders. However, the study's reliance on the answer to a single self-assessed question on erectile functioning limits the findings. Nevertheless, these findings provide useful information for clinicians: men with erectile dysfunction are at higher risk of cardiovascular disease, and the worse the erectile dysfunction, the higher the risk of cardiovascular disease. Men with erectile dysfunction, even at mild or moderate levels, should be screened and treated for cardiovascular disease accordingly.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001372.
Wikipedia defines erectile dysfunction (note that Wikipedia is a free online encyclopedia that anyone can edit)
MedlinePlus also has some useful patient information on erectile dysfunction
The Mayo Clinic has patient-friendly information on the causes of, and treatments for, erectile dysfunction, and also includes information on the link with cardiovascular disease
The National Heart Foundation of Australia provides information for health professionals, patients, and the general public about how to prevent and manage cardiovascular disease, including assessment and management of cardiovascular disease risk
doi:10.1371/journal.pmed.1001372
PMCID: PMC3558249  PMID: 23382654
23.  Tackling Non-Communicable Diseases In Low- and Middle-Income Countries: Is the Evidence from High-Income Countries All We Need? 
PLoS Medicine  2013;10(1):e1001377.
Shah Ebrahim and colleagues argue that more research on non-communicable diseases (NCDs) in both high-income countries and low- and middle-income countries can result in mutual benefits and will help better address the growing burden of NCDs.
doi:10.1371/journal.pmed.1001377
PMCID: PMC3558465  PMID: 23382655
24.  Association Study of 25 Type 2 Diabetes Related Loci with Measures of Obesity in Indian Sib Pairs 
PLoS ONE  2013;8(1):e53944.
Obesity is an established risk factor for type 2 diabetes (T2D) and they are metabolically related through the mechanism of insulin resistance. In order to explore how common genetic variants associated with T2D correlate with body mass index (BMI), we examined the influence of 25 T2D associated loci on obesity risk. We used 5056 individuals (2528 sib-pairs) recruited in Indian Migration Study and conducted within sib-pair analysis for six obesity phenotypes. We found associations of variants in CXCR4 (rs932206) and HHEX (rs5015480) with higher body mass index (BMI) (β = 0.13, p = 0.001) and (β = 0.09, p = 0.002), respectively and weight (β = 0.13, p = 0.001) and (β = 0.09, p = 0.001), respectively. CXCR4 variant was also strongly associated with body fat (β = 0.10, p = 0.0004). In addition, we demonstrated associations of CXCR4 and HHEX with overweight/obesity (OR = 1.6, p = 0.003) and (OR = 1.4, p = 0.002), respectively, in 1333 sib-pairs (2666 individuals). We observed marginal evidence of associations between variants at six loci (TCF7L2, NGN3, FOXA2, LOC646279, FLJ3970 and THADA) and waist hip ratio (WHR), BMI and/or overweight which needs to be validated in larger set of samples. All the above findings were independent of daily energy consumption and physical activity level. The risk score estimates based on eight significant loci (including nominal associations) showed associations with WHR and body fat which were independent of BMI. In summary, we establish the role of T2D associated loci in influencing the measures of obesity in Indian population, suggesting common underlying pathophysiology across populations.
doi:10.1371/journal.pone.0053944
PMCID: PMC3547960  PMID: 23349771
25.  Dysregulation of the hypothalamic pituitary adrenal (HPA) axis and physical performance at older ages: An individual participant meta-analysis 
Psychoneuroendocrinology  2013;38(1):40-49.
Summary
The association between functioning of the hypothalamic pituitary adrenal (HPA) axis and physical performance at older ages remains poorly understood. We carried out meta-analyses to test the hypothesis that dysregulation of the HPA axis, as indexed by patterns of diurnal cortisol release, is associated with worse physical performance. Data from six adult cohorts (ages 50–92 years) were included in a two stage meta-analysis of individual participant data. We analysed each study separately using linear and logistic regression models and then used meta-analytic methods to pool the results. Physical performance outcome measures were walking speed, balance time, chair rise time and grip strength. Exposure measures were morning (serum and salivary) and evening (salivary) cortisol. Total sample sizes in meta-analyses ranged from n = 2146 for associations between morning Cortisol Awakening Response and balance to n = 8448 for associations between morning cortisol and walking speed. A larger diurnal drop was associated with faster walking speed (standardised coefficient per SD increase 0.052, 95% confidence interval (CI) 0.029, 0.076, p < 0.001; age and gender adjusted) and a quicker chair rise time (standardised coefficient per SD increase −0.075, 95% CI −0.116, −0.034, p < 0.001; age and gender adjusted). There was little evidence of associations with balance or grip strength. Greater diurnal decline of the HPA axis is associated with better physical performance in later life. This may reflect a causal effect of the HPA axis on performance or that other ageing-related factors are associated with both reduced HPA reactivity and performance.
doi:10.1016/j.psyneuen.2012.04.016
PMCID: PMC3533133  PMID: 22658392
HPA axis; Physical capability; Healthy ageing

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