Background:Despite epidemiological evidence linking fine particulate matter (PM2.5) to cardiometabolic diseases, links between PM2.5 and kidney function or chronic kidney disease (CKD) remain inconclusive. Methods:In a population representative cohort of 12,271 adults (age ≥ 20 years) in 2 Indian cities (Chennai and Delhi), we investigated time-varying associations between annual average ambient PM2.5 and estimated glomerular filtration rates (eGFR) calculated using CKD-Epidemiology Collaboration (EPI) 2009 equations, at 3 time points during 2010 to 2016. Ambient PM2.5 exposures were assessed at residential geocodes using a national high-resolution spatiotemporal model for daily PM2.5 at 1 km × 1 km. City-specific linear mixed effect models were employed, incorporating inverse probability-based weighting to account for loss-to-follow-up. Effect modification by sex, waist-to-hip ratio, hypertension, and diabetes status were assessed using stratified models. Results:Annual average PM2.5 at baseline and 2 follow-ups in Chennai were 33, 37, and 30 μg/m3 whereas those in Delhi were 118, 123, and 130 μg/m3. Median eGFRs at baseline were 112 ml/min per 1.73 m2 (interquartile range [IQR]: 101.9-121.0) in Chennai and 106.4 ml/min per 1.73 m2 (IQR: 94.4-116.6) in Delhi. Over time, a 5 ug/m3 increase in annual average PM2.5 was associated with a significant decline in eGFR in both cities as follows: -0.32 (95% confidence interval [CI]: -0.49 to -0.15) ml/min per 1.73 m2 in Chennai and -0.42 (95% CI: -0.57 to -0.27) ml/min per 1.73 m2 in Delhi. Conclusion:Annual average PM2.5 levels were associated with declines in eGFR. These data from a relatively young South Asian urban cohort underscore the need to further investigate the potential renal and cardiovascular impacts of sustained air pollution exposure.

BACKGROUND:Cardiovascular disease (CVD) is the leading cause of disability-adjusted life years in South Asia, with adverse trends in CVD risk seen in rural residents in recent decades. Assessment of life-course trajectories of CVD risk factors is important to understand CVD aetiology. METHODS:The Andhra Pradesh Children and Parents cohort Study included all children (n = 2601) born during 1987-90 and their mothers (n = 1963) residing in 29 villages of South India. Participants were followed up in 2003-05, 2009-10, 2010-12, and 2021-23. Children (n = 4777 observations, 35% female) were assessed for body mass index (BMI), waist circumference, waist-hip ratio, waist-height ratio, fasting glucose, and central and peripheral skinfolds. For mothers (n = 3830 observations), repeated measures of BMI were available. Linear mixed-effect models with a random slope were used to model trajectories of CVD risk factors. RESULTS:BMI increased with age and the predicted mean BMI reached the World Health Organization's increased risk action point for adult South Asians (≥23 kg/m2) at 28 years for male and 31 years for female children, while, for mothers, it was much later at 43-65 years. In male children compared with females, there was a faster progression to prediabetes, higher abdominal fat deposition, and a higher rate of increase in subscapular skinfolds. CONCLUSION:South Asians living in rural areas showed increasing trajectories of several CVD risk factors, particularly in males. This highlights the need for interventions to mitigate the potential CVD burden.

Background:Current definitions of type 2 diabetes (T2D) and prediabetes do not capture their pathophysiological heterogeneity. We investigated data-driven subtypes of T2D and prediabetes and evaluated their associations with mortality. Methods:We analyzed data from 14,306 South Asian participants from the CArdiometabolic Risk Reduction cohort using unsupervised k-means clustering based on five variables: age, BMI, HbA1c, insulin resistance, and beta-cell dysfunction. For each subtype of T2D or prediabetes, we estimated Cox hazard ratios (HRs) for all-cause and cardiovascular disease (CVD) mortality and excess years of life lost compared to normal glucose tolerance. Results:Among 2,639 participants with T2D, three subtypes emerged: Severe Insulin-Deficient Diabetes (SIDD;23.0%), Mild Insulin-Deficient Diabetes (MIDD;54.5%), and Severe Insulin-Resistant Diabetes (SIRD;22.5%). Among 4,992 participants with prediabetes, two subtypes were identified: Insulin-Deficient Prediabetes (IDPD;66.0%) and Insulin-Resistant Prediabetes (IRPD;34.0%). Over a median follow-up of 10.6 years, 1,076 deaths occurred (405 due to CVD). Compared with normal glucose tolerance, SIDD had the highest all-cause mortality HR (3.34 [95%CI, 2.39 to 4.68]), followed by MIDD (1.39[95%CI, 1.05 to 1.84]) and SIRD (1.67[95%CI, 1.15 to 2.41]). Among prediabetes subtypes, IDPD was associated with increased all-cause (HR: 1.32 [95%CI, 1.03 to 1.68]) and CVD mortality (HR:1.53 [95%CI, 1.00 to 2.34]), whereas IRPD was not. Excess years of life lost were greatest for SIDD (17.7 years), followed by MIDD (12.8 years) and SIRD (12.0 years). Conclusions:Insulin-deficient subtypes made up a high proportion of T2D and prediabetes cases, harboring increased mortality hazards and excess years of life lost relative to normal glucose tolerance.

Background: Neonates with congenital heart disease may require delivery room interventions beyond standard care. Because existing guidelines and educational programs rarely address these needs, we developed and evaluated targeted educational modules. Methods: Teams were randomized to online eLearning modules or directed readings. Individual pre-/post-knowledge scores were compared. Team performance was tested in simulated delivery scenarios including abruption, hypoplastic left heart syndrome, d-transposition of great arteries and congenital complete heart block. Results: 32 teams from 9 centers participated. The module group had improved knowledge scores (mean change 6% vs -0.3% e-Learning group, p = 0.01). Simulation performance was similar between groups except for hypoplastic left heart syndrome, where module groups scored lower, performing less bag-mask ventilation before intubation (82% vs 88%, p < 0.05). Conclusion: eLearning modules were well-accepted and improved knowledge scores. Simulation performance was similar between groups. Ongoing educational development of CCHD DR adaptations and their incorporation within standard NRP is required.

Background Chronic conditions cause notable health and economic burdens. While health insurance enables access to healthcare, its effects on chronic care outcomes remain under-explored. Objective To examine the association between health insurance coverage and cardiometabolic risk factors among people with chronic conditions in India. Methods Data from the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) and Solan studies, including 2,926 adults with chronic conditions were analyzed using propensity score weighting to evaluate the associations between health insurance and cardiometabolic risk factors (HbA1c, low-density lipoprotein cholesterol [LDLc], and blood pressure [BP]) and self-reported health status (measured using European Quality of Life Visual Analogue Scale [EQ-VAS]). Mediation analysis evaluated healthcare visits as a potential mediator. Results Among 2,926 respondents meeting criteria, mean (SD) age was 54.6 years (11.8), and 1630 (55.7%) were women. Health insurance coverage was low (6.5%) and more prevalent among men, higher-income groups, and rural vs urban residents. Insured participants had lower mean diastolic BP (84.8 vs 86.0 mmHg), mean LDLc (113.3 vs 117.2 mg/dl), mean HbA1c (6.9% vs 7.5%), and higher health status (EQ-VAS: 74.6 vs 69.1) than uninsured participants, respectively (p < 0.05). Mediation analysis showed healthcare visits strongly mediated the relationship between insurance and BP and partially mediated effects on LDLc, HbA1c, and self-rated health. Conclusion Health insurance coverage was associated with better cardiometabolic risk profiles and health status, largely mediated by increased healthcare utilization. Expanding insurance coverage to include outpatient chronic care services should be prioritized to improve health outcomes in low- and middle-income countries.

BACKGROUND:The World Health Organization (WHO) recommends reducing dietary salt intake to < 5g/d as a cost-effective strategy to reduce hypertension and associated cardiovascular diseases. However, salt is also used as a vehicle for iodine supplementation for preventing iodine deficiency disorders. Concerns have been expressed that reducing population salt intake will adversely impact iodine levels. OBJECTIVES:The aim of this paper was to estimate the daily salt and iodine consumption levels of the adult population in India and examine the effect of the WHO-recommended salt intake levels on iodine levels. METHODS:A cross-sectional study was conducted in Delhi and Haryana, India, among adults aged ≥20 y, and 24-h urine samples were collected to assess the salt and iodine levels. RESULTS:The mean salt intake was 8.07 g/d (95% confidence interval: 7.03, 9.11), median urinary iodine concentration (UIC) was 167.8 μg/L (102.63-284.5), and the mean urinary iodine excretion (UIE) was 276.1 μg/ 24h (254.5-297.8). Analysis to assess iodine intake adequacy by salt intake levels indicated that the median UIC, as well as UIE, were adequate when salt intake was as per the WHO-recommended level, i.e., ≤5 g/d. CONCLUSION:Even at the WHO-recommended salt intake levels, population iodine intake in this study population was adequate, likely indicating that upward titration in iodine concentration in salt may not be required. Thus, current salt reduction recommendations are unlikely to impact iodine supplementation efforts, indicating compatibility between the 2 interventions, which should be continuously monitored through robust surveillance.

Background Over 250 million children are developing sub-optimally due to their exposure to early life adversities. While previous studies have examined the independent effects of nutritional status, psychosocial adversities, and environmental pollutants on children’s outcomes, little is known about their interaction and cumulative effects. Objectives This study aims to investigate the independent, interaction, and cumulative effects of nutritional, psychosocial, and environmental factors on children’s cognitive development and mental health in urban and rural India. It also seeks to explain pathways leading to inequities in child outcomes at the individual, household, and neighbourhood levels. Methods A mixed-methods prospective cohort study will be conducted on 1600 caregiver-child dyads (child age 3–10 years) in urban and rural India. Nutritional status, psychosocial adversities, environmental pollutants, and child mental health outcomes will be assessed using parent-report questionnaires. Performance-based measures will be used to assess cognitive outcomes. Venous blood and urine samples will be used to measure nutritional and pesticide biomarkers in 500 children. Indoor air pollution will be monitored in 200 households twice, during two seasons. Multilevel regression, weighted quantile sum regression, and Bayesian kernel machine regression will assess the individual and combined effects of exposures on child outcomes. Thematic analysis of in-depth interviews and focus group discussions will explore pathways to middle-and late childhood development inequities. Discussion The data will be used to formulate a Theory of Change (ToC) to explain the biological, psychosocial, and environmental origins of children’s cognitive and mental health outcomes across the first decade of life in diverse Indian settings, which can inform interventions targets for promoting children’s outcomes beyond the first 1000 days, potentially generalizable to similar under-resourced global settings. The COINCIDE research infrastructure will comprise a valuable global health resource, including prospective cohort data, validated study tools, and stored biological and environmental samples for future studies.

The Asian Indian Beta Cell function (ABCs) in Infants Study examined the associations of maternal weight on infant pancreatic beta cell function across 7 months postpartum. Pregnant women aged 18–35 years were recruited in Hyderabad, India. Women were classified by first trimester weight as underweight (UW), BMI < 18.5 kg/m2; normal weight (NW), BMI 18.5–22.9 kg/m2; or overweight (OW), BMI 23.0 through <28.5 kg/m2. At age > 7 months, infants had an oral glucose tolerance test (OGTT, 1.75 g glucose/kg bodyweight) following a 3 h fast. Infant blood samples were assayed for C-peptide and glucose. Infant beta cell function (HOMA2-B; disposition index, DI) and insulin resistance (HOMA2-IR) were compared across maternal weight groups. Mothers (UW n = 63; NW n = 43; OW n = 29) had similar age at delivery and second trimester 50 g glucose challenge test results. Cord HOMA2-B values were 51% greater for IUW (83.5, SD 55.2) and 44% greater for IOW (79.9, SD 60.8) vs. INW (55.4, SD 51.5), forming a U-shaped relationship between maternal weight and HOMA2-B. No qualitative differences in HOMA2-IR were found at birth. However, at 7 months postpartum, HOMA2-IR changed most within IUW (−64% median reduction) and changed the least in IOW (−7% median reduction). At seven months postpartum, DI was higher in IUW vs. the other groups (geometric mean IUW 1.9 SD 2.5; INW 1.3 SD 2.6 or vs. IOW mean 1.2 SD 3.7), reflecting a +49% difference in DI. Evidence from this study illustrates adaptations in the pancreatic functional response of infants associated with the maternal nutritional environment.

Background:Exposure to ambient PM2.5 is known to affect lipid metabolism through systemic inflammation and oxidative stress. Evidence from developing countries, such as India with high levels of ambient PM2.5 and distinct lipid profiles, is sparse. Methods:Longitudinal nonlinear mixed-effects analysis was conducted on >10,000 participants of Centre for cArdiometabolic Risk Reduction in South Asia (CARRS) cohort in Chennai and Delhi, India. We examined associations between 1-month and 1-year average ambient PM2.5 exposure derived from the spatiotemporal model and lipid levels (total cholesterol [TC], triglycerides [TRIG], high-density lipoprotein cholesterol [HDL-C], and low-density lipoprotein cholesterol [LDL-C]) measured longitudinally, adjusting for residential and neighborhood-level confounders. Results:The mean annual exposure in Chennai and Delhi was 40 and 102 μg/m3 respectively. Elevated ambient PM2.5 levels were associated with an increase in LDL-C and TC at levels up to 100 µg/m3 in both cities and beyond 125 µg/m3 in Delhi. TRIG levels in Chennai increased until 40 µg/m3 for both short- and long-term exposures, then stabilized or declined, while in Delhi, there was a consistent rise with increasing annual exposures. HDL-C showed an increase in both cities against monthly average exposure. HDL-C decreased slightly in Chennai with an increase in long-term exposure, whereas it decreased beyond 130 µg/m3 in Delhi. Conclusion:These findings demonstrate diverse associations between a wide range of ambient PM2.5 and lipid levels in an understudied South Asian population. Further research is needed to establish causality and develop targeted interventions to mitigate the impact of air pollution on lipid metabolism and cardiovascular health.

Introduction Air pollution presents a major public health threat to India, affecting more than three quarters of the country's population. In the current project, GEOHealth Health Effects of Selected Environmental Exposomes Across the Life CourSe-India, we aim to study the effect of environmental exposomes-fine particulate matter (PM2.5), nitrogen dioxide (NO2), ozone (O3) and extremes of temperature-on multiple health outcomes using a modified life course approach. The associated training grant aims to build capacity in India to address the unique environmental health problems.Methods and analysis The project aims to (A) Develop exposure assessments in seven cities, namely Delhi, Chennai, Sonipat, Vizag, Pune, Hyderabad and Bikaner, for: (1) A fine-scale spatiotemporal model for multiple pollutants (PM2.5, NO2, O3, temperature); (2) Combined ground monitoring and modelling for major chemical species of ambient PM2.5 at seven cities; and (3) Personal exposure assessment in a subsample from the six cities, except Pune, and (B) Conduct health association studies covering a range of chronic non-communicable diseases and their risk factors leveraging a unique approach using interdigitating cohorts. We have assembled existing pregnancy, child, adolescent, adult and older adult cohorts across India to explore health effects of exposomes using causal analyses. We propose to use Bayesian kernel machine regression to assess the effects of mixtures of all pollutants including species of PM2.5 on health while accounting for potential non-linearities and interactions between exposures. This builds on earlier work that constructed a fine spatiotemporal model for PM2.5 exposure to study health outcomes in two Indian cities.Ethics and dissemination Ethical clearance for conduct of the study was obtained from the Institutional Ethics Committee (IEC) of the Centre for Chronic Disease Control, and all the participating institutes and organisations. National-level permission was provided by the Indian Council of Medical Research. The research findings will be disseminated through peer-reviewed publications, policy briefs, print and social media, and communicating with the participating communities and stakeholders. Training of Indian scientists will build the capacity to undertake research on selected adverse environmental exposures on population health in India.

Aims:The aim of this study was to evaluate the effects of yoga-based cardiac rehabilitation (Yoga-CaRe) on the endothelial system, oxidative stress, and inflammatory markers in patients with acute myocardial infarction (MI). Methods:A sub-study was conducted in two clinical sites of the Yoga-CaRe trial (a multicenter randomized controlled trial). Participants with acute MI were randomized and allocated to either the Yoga-CaRe program (13 sessions with encouragement to home practice) or enhanced standard care (three educational sessions). Endothelial function, oxidative stress, and inflammatory biomarkers were assessed using biomarkers such as asymmetric dimethylarginine (ADMA), endothelial nitric oxide synthase (eNOS), endothelin-1 (ET-1), E-selectin, P-selectin, vascular cell adhesion molecule (VCAM), intercellular cell-adhesion molecule-1, total nitric oxide concentration (NOx), oxidized low-density lipoprotein (Oxd-LDL), superoxide dismutase, total antioxidant capacity (TAOC), tumor necrosis factor-alpha (TNFα), and C-reactive protein (CRP) at baseline and 12 weeks. Laboratory and statistical analysis were done by staff blinded to group allocation. Results:Eighty-two patients (of the 110 patients recruited) completed the study. The mean age was 53.1 ± 10.6 and 51.9 ± 10.7 years in enhanced standard care and Yoga-CaRe group, respectively. At 12 weeks, Yoga-CaRe significantly reduced ADMA, ET-1, and ICMA-1 than the enhanced standard care group. Although E-selectin and VCAM at 12 weeks were reduced in both groups, enhanced standard care had a significantly higher reduction than the Yoga-CaRe group. Among markers of oxidative stress, TAOC increased in the Yoga-CaRe group. We found no difference in eNOS, NOx, P-selectin, TNFα, CRP, and Oxd-LDL between the two groups. Conclusion:Yoga-CaRe improved the endothelial function (through a reduction in ET-1 and modulating adhesion molecules) and enhanced antioxidant capacity.

To study the association of pro-inflammatory markers with incident diabetes in India. We did a nested case–control study within the CARRS (Centre for Ardiometabolic Risk Reduction in South Asia) cohort. Of the 5739 diabetes-free individuals at the baseline, 216 participants with incident diabetes and 432 age-, gender- and city-matched controls at 2-year follow-up were included. We measured high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 ( MCP-1), adiponectin, leptin and fetuin-A in the stored baseline blood samples. We did multivariate conditional logistic regression to estimate association of inflammatory markers (as quartiles) and incident diabetes. Covariates were baseline fasting plasma glucose (FPG) and lipids, body mass index (BMI), family history of diabetes, smoking and alcohol use. Baseline hsCRP and TNF-α were higher, and IL-6 and adiponectin were lower among cases vs. controls. In multivariate conditional logistic regression models, only quartile-3 (odds ratio [OR]: 2.96 [95

Background: Defining lipid goals solely on low-density lipoprotein-cholesterol (LDL-C) levels in Indian population may cause misclassification due to high prevalence of hypertriglyceridemia and small dense LDL-C particles. International guidelines now recommend Apoliporotein-B (Apo-B) and non-high-density lipoprotein-cholesterol (non-HDL-C) levels as alternative targets. In this study, we used a cross-sectional representative population database to determine Apo-B and non-HDL-C cut-offs corresponding to identified LDL-C targets and compared them to international guidelines. Methods: A community-based survey carried out in urban Delhi and adjacent rural Ballabhgarh provided lipid values for 3047 individuals. The Spearman correlation coefficient was used to evaluate the degree of relationship between Apo-B and LDL-C and non-HDL-C. Cut-off values for Apo-B and non-HDL-C were established using receiver operator curve analysis correlating with guideline-recommended LDL-C targets. Results: Spearman's rank correlations between Apo-B and LDL-C (0.82) and non-HDL-C and LDL-C (0.93) were significant (p < 0.05). Proposed corresponding cut-off values for LDL-C of 55, 70,100,130 and 160 mg/dl for Apo-B and non-HDL-C in our population were 75.3, 75.5, 91.3, 107.6, 119.4 mg/dL and 92.5,96.5, 123.5, 154.5, 179.5 mg/dL respectively. However, in those with triglycerides >150 mg/dl the corresponding Apo-B and nonHDL-C values were 85.1, 92.7, 103.5, 117.5 and 135 mg/dL and 124.5, 126.5, 147.5, 167.5 and 190.5 mg/L respectively. Conclusion: Based on this study we provide Apo-B and non-HDL cut-offs corresponding to target LDL-C values in Indian patients with and without high triglycerides. It is noted that in individuals with triglycerides >= 150 mg/dl, the Apo-B levels are much higher than the values recommended by guidelines.

Background: A heavy burden of cardiometabolic conditions on low- and middle-income countries like India that are rapidly undergoing urbanization remains unaddressed. Indians are known to have high levels of triglycerides and low levels of HDL-C along with moderately higher levels of LDL-C. The genome-wide findings from Western populations need to be validated in an Indian context for a better understanding of the underlying etiology of dyslipidemia in India.Objective: We aim to validate 12 genetic variants associated with lipid levels among rural and urban Indian populations and derive unweighted and weighted genetic risk scores (uGRS and wGRS) for lipid levels among the Indian population.Methods: Assuming an additive model of inheritance, linear regression models adjusted for all the possible covariates were run to examine the association between 12 genetic variants and total cholesterol, triglycerides, HDL-C, LDL-C, and VLDL-C among 2,117 rural and urban Indian participants. The combined effect of validated loci was estimated by allelic risk scores, unweighted and weighted by their effect sizes.Results: The wGRS for triglycerides and VLDL-C was derived based on five associated variants (rs174546 at FADS1, rs17482753 at LPL, rs2293889 at TRPS1, rs4148005 at ABCA8, and rs4420638 at APOC1), which was associated with 36.31 mg/dL of elevated triglyceride and VLDL-C levels (β = 0.95, SE = 0.16, p < 0.001). Similarly, every unit of combined risk score (rs2293889 at TRPS1 and rs4147536 at ADH1B) was associated with 40.62 mg/dL of higher total cholesterol (β = 1.01, SE = 0.23, p < 0.001) and 33.97 mg/dL of higher LDL-C (β = 1.03, SE = 0.19, p < 0.001) based on its wGRS (rs2293889 at TRPS1, rs4147536 at ADH1B, rs4420638 at APOC1, and rs660240 at CELSR2). The wGRS derived from five associated variants (rs174546 at FADS1, rs17482753 at LPL, rs4148005 at ABCA8, rs4420638 at APOC1, and rs7832643 at PLEC) was associated with 10.64 mg/dL of lower HDL-C (β = −0.87, SE = 0.14, p < 0.001).Conclusion: We confirm the role of eight genome-wide association study (GWAS) loci related to different lipid levels in the Indian population and demonstrate the combined effect of variants for lipid traits among Indians by deriving the polygenic risk scores. Similar studies among different populations are required to validate the GWAS loci and effect modification of these loci by lifestyle and environmental factors related to urbanization.

Introduction: Associations between markers of impaired kidney function and adverse outcomes among South Asians is understudied and could differ from existing data derived mostly from North American or European cohorts. Methods: We conducted a prospective analysis of 9797 participants from the ongoing cardiometabolic risk reduction study in South Asia, India. We examined the associations between baseline spot urine albumin-to-creatinine (UACR) ratio and creatinine-based estimated glomerular filtration rate (eGFR) estimating equations with all-cause mortality using Cox proportional hazards regression, adjusting for baseline age, sex, diabetes, systolic blood pressure, tobacco, history of cardiovascular disease, and cholesterol. Additionally, we calculated population attributable fraction (PAF) for both markers. Results: Over a median 7-year follow-up, with 66,909 person-years, 791 deaths occurred. At baseline, the weighted prevalence of UACR >= 30 mg/g and eGFR(CKD-EPI 2009) <60 ml/min per 1.73 m(2) was 6.6% and 1.6%, respectively. The risk for mortality was increased with higher UACR (10-30 hazard ratio [HR]: 1.6 [1.2-2.1]), 30-300 HR: 2.4 [1.8-3.1]), and >= 300 (HR: 6.0 [3.8-9.4] relative to UACR <10 mg/g). Risk for mortality was also higher with lower eGFR(CKD-EPI 2009) (44-30; HR: 4.5 [2.5-8.3] and <30 HR: 7.0 [3.7-13.0], relative to 90-104 ml/min per 1.73 m(2)). PAF for mortality because of UACR >= 30 mg/g and eGFR(CKD-EPI 2009) <45 ml/min per 1.73 m(2) were 24.4% and 13.4%, respectively. Conclusion: Single-time point assessment of UACR >= 30 mg/g or eGFR(CKD-EPI 2009) <45 ml/min per 1.73 m(2) portends higher mortality risk among urban South Asians. Because albuminuria is common and associated with accelerated decline in GFR, screening and targeted efforts to reduce albuminuria are warranted.