Rationale, Design and Baseline Characteristics of a Randomized Controlled Trial of a Cardiovascular Quality Improvement Strategy in India: The C-QIP Trial.

BACKGROUND: Quality of chronic care for cardiovascular disease (CVD) remains suboptimal worldwide. The Collaborative Quality ImProvement (C-QIP) trial aims to develop and test the feasibility and clinical effect of a multicomponent strategy among patients with prevalent CVD in India. METHODS: The C-QIP is a clinic-based, open randomized trial of a multicomponent intervention versus usual care that was locally developed and adapted for use in Indian settings through rigorous formative research guided by Consolidated Framework for Implementation Research (CFIR). The C-QIP intervention consisted of 5 components: 1) electronic health records and decision support system for clinicians, 2) trained non-physician health workers (NPHW), 3) text-message based lifestyle reminders, 4) patient education materials, 5) quarterly audit and feedback reports. Patients with CVD (ischemic heart disease, ischemic stroke, or heart failure) attending outpatient CVD clinics were recruited from September 2022 to September 2023 and were randomized to the intervention or usual care arm for at least 12 months follow-up. The co-primary outcomes are implementation feasibility, fidelity (i.e., dose delivered and dose received), acceptability, adoption and appropriateness, measured at multiple levels: patient, provider and clinic site-level, The secondary outcomes include prescription of guideline directed medical therapy (GDMT) (provider-level), and adherence to prescribed therapy, change in mean blood pressure (BP) and LDL-cholesterol between the intervention and control groups (patient-level). In addition, a trial-based process and economic evaluations will be performed using standard guidelines. RESULTS: We recruited 410 socio-demographically diverse patients with CVD from four hospitals in India. Mean (SD) age was 57.5 (11.7) years, and 73.0% were males. Self-reported history of hypertension (48.5%) and diabetes (41.5%) was common. At baseline, mean (SD) BP was 127.9 (18.2) /76.2 (11.6) mm Hg, mean (SD) LDLc: 80.3 (37.3) mg/dl and mean (SD) HbA1c: 6.8% (1.6%). At baseline, the GDMT varied from 62.4% for patients with ischemic heart disease, 48.6% for ischemic stroke and 36.1% for heart failure. CONCLUSION: This study will establish the feasibility of delivering contextually relevant, and evidence-based C-QIP strategy and assess whether it is acceptable to the target populations. The study results will inform a larger scale confirmatory trial of a comprehensive CVD care model in low-resource settings. TRIAL REGISTRATION: Clinical Trials Registry India: CTRI/2022/04/041847; Clinicaltrials.gov number: NCT05196659.

Effect of Yoga-Based Cardiac Rehabilitation Program on Endothelial Function, Oxidative Stress, and Inflammatory Markers in Acute Myocardial Infarction: A Randomized Controlled Trial.

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.

Establishing Apolipoprotein-B and non-high-density-lipoprotein-C goals in Indian population: A Cross-sectional study.

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 non-HDL-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.

Role of miR-128-3p and miR-195-5p as biomarkers of coronary artery disease in Indians: a pilot study.

Coronary artery disease (CAD) imposes a significant economic burden in developing countries like India. Timely diagnosis and treatment should be prioritized to mitigate the disease. Current diagnostic tools being invasive and less specific raise the need to develop less invasive and more reliable molecular biomarkers. MicroRNAs (miRNAs) are an emerging class of molecules that can serve as a potential source of non-invasive biomarkers for CAD. The objective of this study was to determine the potential of circulatory miRNAs as diagnostic biomarkers in CAD. In this study, we have reported two microRNAs, miR-128-3p and miR-195-5p in the serum of CAD patients in Indian Population. A total of 124 subjects were recruited which included 89 angiographically proven CAD patients and 35 control subjects. Our results show a significant decrease in the levels of miR-128-3p in CAD patients while there were no significant changes in the levels of miR-195-5p. Further bioinformatics analysis revealed the potential role of miR-128-3p in cholesterol homeostasis. Altered homeostasis due to cholesterol accumulation in macrophages is the driving force behind formation of foam cells which in turn accelerates the progression of CAD. Here, we have shown that miR-128-3p increases cholesterol levels in macrophages by decreasing cholesterol efflux in-vitro.

Inflammation-induced sialin mediates nitrate efflux in dysfunctional endothelium affecting NO bioavailability.

AIM: The mechanism of NO bioavailability in endothelial dysfunction, the trigger for atherogenesis is still unclear as exogenous nitrate therapy fails to alleviate endothelial dysfunction. Recently, sialin, a nitrate transporter, has been linked to affect tissue nitrate/nitrite levels. Hence, we investigated the role of sialin in NO bioavailability in endothelial dysfunction. METHODS: Serum-starved HUVECs were stimulated with either TNFα or AT-2 for 24 h either alone or in the presence of autophagy inducer or autophagy inhibitor alone. Nitric oxide, nitrite, and nitrate levels were measured in cell supernatant and cell lysate. Quantitative real-time PCR, Annexin V-PI, and monocyte adhesion assays were performed. Immunofluorescence staining for sialin, vWF, and LC3 was performed. STRING database was used to create protein interacting partners for sialin. RESULTS: Sialin is strongly expressed in activated EC in vitro and atherosclerotic plaque as well as tumor neo-vessel ECs. Sialin mediates nitrate ion efflux and is negatively regulated by autophagy via mTOR pathway. Blocking sialin enhances NO bioavailability, autophagy, cell survival, and eNOS expression while decreasing monocyte adhesion. PPI shows LGALS8 to directly interact with sialin and regulate autophagy, cell-cell adhesion, and apoptosis. CONCLUSION: Sialin is a potential novel therapeutic target for treating endothelial dysfunction in atherosclerosis and cancer.

Knowledge and Skills in Cardiopulmonary Resuscitation and Effect of Simulation Training on it among Healthcare Workers in a Tertiary Care Center in India.

Aim and background: High-quality cardiopulmonary resuscitation (CPR) is associated with improved patient outcomes, but healthcare workers (HCWs) may be frequently undertrained. This study aimed to assess baseline knowledge and skills among HCWs about basic and advanced life support and the effect of simulation-based training on it. Methods: It was a single-center prospective quasi-interventional study among resident doctors and nurses at a Tertiary Center in New Delhi, India. A questionnaire-based assessment was done to assess baseline knowledge. The participants then underwent simulation-based training followed by questionnaire-based knowledge assessment and skill assessment. A repeat questionnaire-based assessment was done 6 months post-training to assess knowledge retention. Results: A total of 82 HCWs (54 doctors and 28 nurses) were enrolled. The participants scored 22.28 ± 6.06 out of 35 (63.65%) in the pre-training knowledge assessment, with low scores in post-cardiac arrest care, advanced life support, and defibrillation. After the training, there was a significant rise in scores to 28.32 ± 4.08 out of 35 (80.9%) (p < 0.01). The retention of knowledge at 6 months was 68.87% (p < 0.01). The participants scored 92.61 ± 4.75% marks in skill assessment with lower scores in chest compressions and team leadership roles. There was a positive correlation (r = 0.35) between knowledge and skills scores (p < 0.01). Conclusion: There is a progressive decrease in baseline knowledge of HCWs with the further steps in the adult chain of survival. The simulation training program had a positive impact on the knowledge of HCWs. The training programs should focus on defibrillation, advanced life support, post-cardiac arrest care, and leadership roles. How to cite this article: Agarwal A, Baitha U, Ranjan P, Swarnkar NK, Singh GP, Baidya DK, et al. Knowledge and Skills in Cardiopulmonary Resuscitation and Effect of Simulation Training on it among Healthcare Workers in a Tertiary Care Center in India. Indian J Crit Care Med 2024;28(4):336-342.

Effect of Yoga on Endothelial Function: A Systematic Review and Meta-Analysis.

Introduction: Endothelial dysfunction is the initial step in the pathogenesis of atherosclerosis; and it plays a central role in the development of cardiovascular diseases and many types of human diseases (diabetes, kidney failure, cancer, and viral infections). Strategies that are effective in protecting vascular endothelial function and retard or reversing endothelial dysfunction in the early stage appear to be potential in the prevention of vascular, cardiac, and many human diseases. Several studies have been carried out on the effects of yoga on endothelial function, but the results of these studies have not been synthesized. This study aimed at conducting a systematic review and meta-analysis to determine the effectiveness of yoga on endothelial function. Methods: A systematic review and meta-analysis of studies that assessed the effect of yoga practice on vascular endothelial function was done as per the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The PubMed, Scopus, Google Scholar, and Cochrane controlled register of trials (CENTRAL) were searched from inception to August 2022. The search strategy was constructed around yoga-based techniques and endothelial function. All the yoga-based interventional studies on endothelial function or dysfunction were included in this review. A narrative synthesis and descriptive analysis were done due to the diverse methodology of selected studies. We carried out a formal meta-analysis of controlled trials that assessed the effect of yoga on flow-mediated dilatation (FMD), a measure of endothelial function. Results: A total of 18 studies were included for review involving 1043 participants. Yoga training showed improved endothelial function in 12 studies, whereas 6 studies did not find any statistically robust effect. Meta-analysis (n = 395 participants, 6-studies, 7 comparisons) showed an increase in brachial FMD by yoga practice (mean difference = -1.23%; 95% confidence interval -2.23 to -0.23; p = 0.02). The heterogeneity between the studies was 43% (Tau2 = 0.70, χ2 = 10.49). The risk of bias was low to moderate in these studies. No adverse effects were reported. Conclusions: Yoga practice improved endothelial function. Yoga could be a safe and potential integrative medicine to improve endothelial function. However, as the statistical heterogeneity, that is, variation in the FMD among the studies was moderate, large clinical trials are necessary for its clinical recommendations.

A comprehensive proteomic profiling of urinary exosomes and the identification of early non-invasive biomarker in patients with coronary artery disease.

Urinary small extracellular vesicles or exosomes (uEVs) source could be an emerging trove of biomarkers in coronary artery disease (CAD). It is a chronic inflammatory disease having a long asymptomatic phase of fatty-fibrous development in arteries leading to angina, myocardial infarction, and death. Our study was aimed at identifying differential protein expression profiling of uEVs in CAD. We collected urine samples of CAD patients (n = 41) age 18-65 years and gender matched healthy controls (n = 41). We isolated uEVs using differential ultracentrifugation. Further, uEV samples were characterized by western blotting exosome markers (Flotillin, TSG, CD63, and CD9), nano tracking analysis, and transmission and scanning electron microscopy. A total of 508 proteins were identified by iTRAQ-based mass spectrometry. We observed protein expression levels of AZGP1, SEMG1/2, ORM1, IGL, SERPINA5, HSPG2, prosaposin, gelsolin, and CD59 were upregulated, and UMOD, KNG1, AMBP, prothrombin, and TF were downregulated. Protein-protein interactions, gene ontology and pathway analysis were performed to functionally annotate identified uEVs proteins. A novel uEVs differential protein signature is shown. On validating UMOD protein by ELISA in two clinically different CAD, stable-CAD patients had lower levels than healthy controls whereas recent myocardial infarction patients had lowest. Our findings suggest UMOD importance as early diagnostic biomarker. SIGNIFICANCE: Coronary artery disease is a chronic inflammatory disease caused by gradual deposition of cholesterol and fat along with other proteins to develop plaque inside arteries. This further leads to blockage of artery, heart attack and death. There are no identifiable early biomarkers to diagnose this. For the first time, we have identified the differentially expressed proteins isolated from non-invasive uEV of CAD patients compared to healthy controls by using MS Orbitrap and iTRAQ labelling of peptides. We have identified decreased levels of UMOD protein in CAD. These findings have been confirmed by ELISA. Furthermore, the levels of UMOD were observed as more highly decreased in recent myocardial infarction CAD patients, indicating the importance of this protein as an early diagnostic biomarker. Conclusively, our study represents a non-invasive urinary EVs trove of differentially expressed proteins in CAD. This will form a groundwork for understanding the pathophysiology of CAD and will help in future translational research utilizing uEVs.

Bladder indentation sign: A stitch in time can save mine.

A 70-year-old woman with diabetes presented with recurrent episodes of rest angina the previous month. She had undergone coronary angiography, which was suggestive of triple vessel disease.

High density lipoprotein heterogeneity & function among Indians with coronary artery disease.

Background & objectives: Impaired high density lipoprotein (HDL) functionality has been shown to be associated with cardiovascular disease risk. The study was aimed to identify the alterations in HDL function [antioxidative activity (AOA)] and subfraction distribution between acute coronary syndrome (ACS) and stable coronary artery disease (SCAD) individuals and analysing the accuracy of HDL parameters to discriminate between the groups. Methods: HDL subfraction distribution analysis was performed in 200 coronary artery disease patients (ACS and SCAD) and 60 control individuals using dextran sulphate, heparin and manganese chloride precipitation method. In terms of HDL function, AOA was evaluated by dihydrorhodamine-based fluorescent cell-free assay and paraoxonase (PON1) enzyme paraoxonase and arylesterase activity. Results: We found that higher AOA [odds ratio (95% confidence interval {CI})]: 0.09 (0.02-0.44), P<0.01 for SCAD; 0.008 (0.001-0.07), P<0.001 for ACS and higher PON1 activity [0.22 (0.8-0.59), P<0.01 for SCAD; 0.16 (0.06-0.4), P<0.001 for ACS] were associated with a lower odds of developing coronary artery disease (CAD). AOA of apoB-depleted serum was significantly correlated with HDL2-C/HDL3-C (HDL-cholesterol) ratio in controls (r=-0.31, P=0.01) and ACS (r=-0.18, P=0.04). It was observed that AOA and HDL subfraction distribution together could discriminate between the two groups of CAD with an accuracy of 72.8 per cent (P=0.004). Interpretation & conclusions: Impaired AOA and altered subfraction distribution of HDL may be responsible for its diminished anti-athero protective activity and can discriminate between the two groups of CAD individuals.

Hypertension Diagnosis, Treatment, and Control in India.

Importance: Hypertension is a major cause of morbidity and mortality worldwide. Previous efforts to characterize gaps in the hypertension care continuum-including diagnosis, treatment, and control-in India did not assess district-level variation. Local data are critical for planning, implementation, and monitoring efforts to curb the burden of hypertension. Objective: To examine the hypertension care continuum in India among individuals aged 18 to 98 years. Design, Setting, and Participants: The nationally representative Fifth National Family Health Survey study was conducted in 2 phases from June 17, 2019, to March 21, 2020, and from November 21, 2020, to April 30, 2021, among 1 895 297 individuals in 28 states, 8 union territories, and 707 districts of India. Exposures: District and state of residence, urban classification, age (18-39, 40-64, and ≥65 years), sex, and household wealth quintile. Main Outcomes and Measures: Hypertension was defined as a self-reported diagnosis or a newly measured blood pressure of 140/90 mm Hg or more. The proportion of individuals diagnosed (self-reported), the proportion of individuals treated among those diagnosed (self-reported medication use), and the proportion of individuals with blood pressure control among those treated (blood pressure <140/90 mm Hg [aged 18-79 years] or <150/90 mm Hg [aged ≥80 years]) were calculated based on national guidelines. Age-standardized estimates of treatment and control were also provided among the total with hypertension. To assess differences in the care continuum between or within states (ie, between districts), the variance was partitioned using generalized linear mixed models. Results: Of the 1 691 036 adult respondents (52.6% women; mean [SD] age, 41.6 [16.5] years), 28.1% (95% CI, 27.9%-28.3%) had hypertension, of whom 36.9% (95% CI, 36.4%-37.3%) received a diagnosis. Among those who received a diagnosis, 44.7% (95% CI, 44.1%-45.3%) reported taking medication (corresponding to 17.7% [95% CI, 17.5%-17.9%] of the total with hypertension). Among those treated, 52.5% (95% CI, 51.7%-53.4%) had blood pressure control (corresponding to 8.5% [95% CI, 8.3%-8.6%] of the total with hypertension). There were substantial variations across districts in blood pressure diagnosis (range, 6.3%-77.5%), treatment (range, 8.7%-97.1%), and control (range, 2.7%-76.6%). Large proportions of the variation in hypertension diagnosis (94.7%), treatment (93.6%), and control (97.3%) were within states, not just between states. Conclusions and Relevance: In this cross-sectional survey study of Indian adults, more than 1 in 4 people had hypertension, and of these, only 1 in 3 received a diagnosis, less than 1 in 5 were treated, and only 1 in 12 had blood pressure control. National mean values hide considerable state-level and district-level variation in the care continuum, suggesting the need for targeted, decentralized solutions to improve the hypertension care continuum in India.

Different Biofluids, Small Extracellular Vesicles or Exosomes: Structural Analysis in Atherosclerotic Cardiovascular Disease Using Electron Microscopy Techniques.

Small extracellular vesicles (sEVs) or exosomes are secretory vesicles largely involved in cell-cell communications and found to play a role in development as well as diseases including atherosclerosis. They hold a huge potential for translational research by devising better clinical diagnostics, biomarker discovery, drug delivery, and therapeutic strategies. Variations terms of morphology and distribution are crucial to biological function integrity. Moreover, it is dependent on susceptibility to influential factors of the environment like cell stress, inflammation, and secretion by different cells in subsequent biofluids. We have observed the morphological variations in sEVs or exosomes freshly isolated from patients with atherosclerotic cardiovascular disease (AsCVD), in blood plasma, saliva, and urine biofluids compared to healthy controls. High-resolution images were obtained by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) for the characterization of sEVs morphology. Western blotting and immuno-TEM gold labeling confirmed the presence of exosome markers. For the first time, we report size and shape variations, which suggest the existence of different functions of sEVs in the disease state. Morphological variations in sEVs were observed significantly in noninvasive AsCVD saliva and urine samples, important to understand the cell behavior and physiological state. These variations will be useful to investigate their possible role in the disease process.

Prevalence and determinants of delays in care among premature deaths due to acute cardiac conditions and stroke in residents of a district in India.

Background: Lack of timely care is a predictor of poor outcomes in acute cardiovascular emergencies including stroke. We assessed the presence of delay in seeking appropriate care among those who died due to cardiac/stroke emergencies in a community in northern India and identified the reasons and determinants of this delay. Methods: We conducted a social audit among all civil-registered premature (30-69 years) deaths due to acute cardiac event or stroke in the district. The three-delays model was used to qualitatively classify the delays in care-seeking-deciding to seek care, reaching the appropriate health facility (AHF) and initiating definitive treatment. Based on the estimated time from symptom onset to reaching AHF, we classified patients as early (reached within one hour) or delayed arrivers. We used mixed-effect logistic regression with postal code as a random effect to identify determinants of delayed arrival. Findings: Only 10.8% of the deceased reached an AHF within one hour. We noted level-1 delay in 38.4% (60% due to non-recognition of seriousness); level-2 delay in 20% (40% due to going to an inappropriate facility) and level-3 delay in 10.8% (57% due to lack of affordability). Patients with a monthly family income of >270US$ (aOR 0.44; 95% CI 0.21-0.93) were less and those staying farther from AHF (aOR 1.12; 95% CI 1.01-1.25 for each Km) were more likely to have delayed arrival in AHF. Interpretation: A small proportion of patients with cardiac and stroke emergencies reach health facility early with delays at multiple levels. Addressing the reasons for delay could prevent these deaths. Funding: : Indian Council of Medical Research, New Delhi, India.

Echocardiography protocol and cardiometabolic phenotyping in Indian birth cohorts-the IndEcho study.

Background: Asian Indians are at higher risk of cardiometabolic disease compared to other ethnic groups, and the age of onset is typically younger. Cardiac structure and function are poorly characterized in this ethnic group. In this study, we describe image-acquisition methods and the reproducibility of measurements and detailed echocardiography characteristics in two large Indian population-based cohorts (the New Delhi and Vellore Birth Cohorts) from India. Methods: The IndEcho study captured transthoracic echocardiographic measurements of cardiac structure and function from 2,322 men and women aged 43-50 years. M-mode measurements in the parasternal long axis (PLAX) and 2-dimensional (2D) short axis recordings at the mitral valve, mid-papillary and apical level were recorded. Apical 2D recordings of two- three- and four-chamber (2C, 3C and 4C) views and Doppler images (colour, pulsed and continuous) were recorded in cine-loop format. Left ventricular (LV) mass, LV hypertrophy, and indices of LV systolic and diastolic function were derived. Results: Echocardiographic measurements showed good/excellent technical reproducibility. Hetero-geneity across sites, sex and rural/urban differences in cardiac structure and function were observed. Overall, this cohort of South Asian Indians had smaller LV mass and normal systolic and diastolic function when compared with published data on other Asian Indians and the West, (LV mass indexed for body surface area: Delhi men: 68 g/m2, women 63.9; Vellore men: 65.8, women 61.6) but were within ethnic-specific reference ranges. The higher prevalence of obesity, diabetes and hypertension is reflected by the higher proportion of LV remodelling and lesser hypertrophy. Conclusions: Our study adds to scarce population-based echocardiographic data for mid-life Asian Indians. Compared to published literature on other ethnic groups, the Asian Indian heart is characterised by smaller cardiac dimensions and normal range systolic and diastolic function on a background of a high prevalence of hypertension, diabetes and cardiac disease at a relatively young age. This data will form the basis for further analyses of lifecourse, metabolic and body composition predictors of cardiac structure and function, and echocardiographic predictors of future mortality. ISRCTN registration number: 13432279.

The burgeoning cardiovascular disease epidemic in Indians - perspectives on contextual factors and potential solutions.

Cardiovascular diseases (CVD) are the leading cause of death and disability in India. The CVD epidemic in Indians is characterized by a higher relative risk burden, an earlier age of onset, higher case fatality and higher premature deaths. For decades, researchers have been trying to understand the reason for this increased burden and propensity of CVD among Indians. It can partly be explained by population-level changes and the remaining by increased inherent biological risk. While increased biological risk can be attributed to phenotypic changes caused by early life influences, six major transitions can be considered largely responsible for the population-level changes in India-epidemiological, demographic, nutritional, environmental, social-cultural and economic. Although conventional risk factors explain substantial population attributable risk, the thresholds at which these risk factors operate are different among Indians compared with other populations. Therefore, alternate explanations for these ecological differences have been sought and multiple hypotheses have been proposed over the years. Prenatal factors that include maternal and paternal influences on the offspring, and postnatal factors, ranging from birth through childhood, adolescence and young adulthood, as well as inter-generational influences have been explored using the life course approach to chronic disease. In addition to this, recent research has illustrated the importance of the role of inherent biological differences in lipid metabolism, glucose metabolism, inflammatory states, genetic predispositions and epigenetic influences for the increased risk. A multifaceted and holistic approach to CVD prevention that takes into consideration population-level as well as biological risk factors would be needed to control the burgeoning CVD epidemic among Indians.

Global Variations in Heart Failure Etiology, Management, and Outcomes.

Importance: Most epidemiological studies of heart failure (HF) have been conducted in high-income countries with limited comparable data from middle- or low-income countries. Objective: To examine differences in HF etiology, treatment, and outcomes between groups of countries at different levels of economic development. Design, Setting, and Participants: Multinational HF registry of 23 341 participants in 40 high-income, upper-middle-income, lower-middle-income, and low-income countries, followed up for a median period of 2.0 years. Main Outcomes and Measures: HF cause, HF medication use, hospitalization, and death. Results: Mean (SD) age of participants was 63.1 (14.9) years, and 9119 (39.1%) were female. The most common cause of HF was ischemic heart disease (38.1%) followed by hypertension (20.2%). The proportion of participants with HF with reduced ejection fraction taking the combination of a ß-blocker, renin-angiotensin system inhibitor, and mineralocorticoid receptor antagonist was highest in upper-middle-income (61.9%) and high-income countries (51.1%), and it was lowest in low-income (45.7%) and lower-middle-income countries (39.5%) (P < .001). The age- and sex- standardized mortality rate per 100 person-years was lowest in high-income countries (7.8 [95% CI, 7.5-8.2]), 9.3 (95% CI, 8.8-9.9) in upper-middle-income countries, 15.7 (95% CI, 15.0-16.4) in lower-middle-income countries, and it was highest in low-income countries (19.1 [95% CI, 17.6-20.7]). Hospitalization rates were more frequent than death rates in high-income countries (ratio = 3.8) and in upper-middle-income countries (ratio = 2.4), similar in lower-middle-income countries (ratio = 1.1), and less frequent in low-income countries (ratio = 0.6). The 30-day case-fatality rate after first hospital admission was lowest in high-income countries (6.7%), followed by upper-middle-income countries (9.7%), then lower-middle-income countries (21.1%), and highest in low-income countries (31.6%). The proportional risk of death within 30 days of a first hospital admission was 3- to 5-fold higher in lower-middle-income countries and low-income countries compared with high-income countries after adjusting for patient characteristics and use of long-term HF therapies. Conclusions and Relevance: This study of HF patients from 40 different countries and derived from 4 different economic levels demonstrated differences in HF etiologies, management, and outcomes. These data may be useful in planning approaches to improve HF prevention and treatment globally.

Prevalence and predictors of lower extremity atherosclerotic disease amongst high-risk patients using ankle brachial index.

INTRODUCTION: The prevalence of lower extremity artery disease (LEAD) continues to increase worldwide. This is expected to translate into logarithmic rise in lower-limb amputations especially in the developing world. Majority of patients suffering from LEAD remain asymptomatic until late and are vulnerable to limb-threatening complications unless actively screened and treated. METHODS: This was a prospective, single-center, observational study to determine the prevalence and predictors of LEAD. Patients with known atherosclerotic vascular disease (but not known LEAD) or those at risk were enrolled. All underwent ankle brachial index (ABI) measurement as per the standard protocol. A threshold of ABI ≤0.90 was taken to diagnose LEAD. RESULTS: A total of 1000 patients were enrolled. The mean age of the group was 61.4 ± 10.0 years and the prevalence of LEAD was 10.2%. Amongst those who had LEAD, the majority of patients (69.6%) had no symptoms. The prevalence of LEAD in diabetic population in our study was 13.2% and it was 30.9% in coronary artery disease patients . Factors independently linked to LEAD on regression analysis included advanced age, presence of diabetes, smoking history, lower serum HDL and a lower ejection fraction. CONCLUSIONS: The vast majority of patients suffering from LEAD are asymptomatic. Early diagnoses and institution of appropriate medical and physical therapy can prevent excess morbidity and mortality due to LEAD. Factors independently linked to LEAD are advanced age, presence of diabetes, smoking history, lower serum HDL and a lower ejection fraction. The presence of either of these should signal undertaking of appropriate steps to unmask underlying LEAD.

Lung water estimation on cardiac magnetic resonance imaging for predicting adverse cardiovascular outcomes in patients with heart failure.

OBJECTIVES: Pulmonary congestion is a central feature of heart failure (HF) seen in acute decompensated state as well as in chronic stable disease. The present study sought to determine whether simplified cardiac magnetic resonance imaging (CMR)-derived lung water density (LWD) measurement has prognostic relevance in predicting adverse cardiovascular outcomes in patients with HF and left ventricular ejection fraction (LVEF)<50%. METHODS: Eighty consecutive patients referred for CMR with HF and LVEF<50% along with 22 healthy age- and sex-matched controls were prospectively recruited. LWD was the lung-to-liver signal intensity ratio multiplied by 70% (estimated hepatic water density). The primary endpoint was composite of all-cause mortality or HF-related hospitalization within 6 months from CMR. RESULTS: The mean LWD was significantly higher in HF patients compared to healthy controls (19.78 ± 6.1 vs 13.6 ± 2.3; p < 0.001). The mean LWD was significantly different among patients with NYHA class I/II and NYHA class III/IV (17.88 ± 4.8 vs 21.77 ± 1.08; p = 0.004). At 6 months, the primary endpoint was reached in 12 (15%) patients. Patients with "wet lungs" (LWD > 18.1%) had higher incidence of adverse cardiovascular outcomes compared to patients with "dry lungs". LWD was an independent predictor of adverse cardiovascular outcomes in multivariable analysis. At the optimal cut-off of LWD > 23.38%, the sensitivity and specificity were 91.67 and 91.18%, respectively, to predict adverse cardiovascular outcomes. CONCLUSION: LWD on CMR is independently associated with increased risk of mortality and HF-related hospitalization in HF patients with LVEF<50%. ADVANCES IN KNOWLEDGE: Non-invasive quantitative estimation of LWD on CMR can improve risk stratification and guide management in HF patients.

A cluster randomized controlled trial of an electronic decision-support system to enhance antenatal care services in pregnancy at primary healthcare level in Telangana, India: trial protocol.

BACKGROUND: India contributes 15% of the total global maternal mortality burden. An increasing proportion of these deaths are due to Pregnancy Induced Hypertension (PIH), Gestational Diabetes Mellitus (GDM), and anaemia. This study aims to evaluate the effectiveness of a tablet-based electronic decision-support system (EDSS) to enhance routine antenatal care (ANC) and improve the screening and management of PIH, GDM, and anaemia in pregnancy in primary healthcare facilities of Telangana, India. The EDSS will work at two levels of primary health facilities and is customized for three cadres of healthcare providers - Auxiliary Nurse Midwifes (ANMs), staff nurses, and physicians (Medical Officers). METHODS: This will be a cluster randomized controlled trial involving 66 clusters with a total of 1320 women in both the intervention and control arms. Each cluster will include three health facilities-one Primary Health Centre (PHC) and two linked sub-centers (SC). In the facilities under the intervention arm, ANMs, staff nurses, and Medical Officers will use the EDSS while providing ANC for all pregnant women. Facilities in the control arm will continue to provide ANC services using the existing standard of care in Telangana. The primary outcome is ANC quality, measured as provision of a composite of four selected ANC components (measurement of blood pressure, blood glucose, hemoglobin levels, and conducting a urinary dipstick test) by the healthcare providers per visit, observed over two visits. Trained field research staff will collect outcome data via an observation checklist. DISCUSSION: To our knowledge, this is the first trial in India to evaluate an EDSS, targeted to enhance the quality of ANC and improve the screening and management of PIH, GDM, and anaemia, for multiple levels of health facilities and several cadres of healthcare providers. If effective, insights from the trial on the feasibility and cost of implementing the EDSS can inform potential national scale-up. Lessons learned from this trial will also inform recommendations for designing and upscaling similar mHealth interventions in other low and middle-income countries. CLINICALTRIALS: gov, NCT03700034, registered 9 Oct 2018, https://www. CLINICALTRIALS: gov/ct2/show/NCT03700034 CTRI, CTRI/2019/01/016857, registered on 3 Mar 2019, http://www.ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=28627&EncHid=&modid=&compid=%27,%2728627det%27.