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.

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.

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.

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.

The Relationship of Birth Size and Postnatal Growth with Cellular Senescence in Adults: Data from the New Delhi Birth Cohort.

OBJECTIVE: To assess the effect of birth size and postnatal body mass index (BMI) gain from birth to adulthood on leucocytes cellular senescence in adult life. METHODS: Participants were aged 43.04 (± 0.92) y, and were enrolled from the New Delhi Birth Cohort study, who participated in phase 7 of the study (n = 210). Cellular senescence markers, p16 and p21 gene expression were determined by RT-qPCR in leucocytes and their association with birth size and conditional BMI gain at 2, 11, and 29 y were assessed in univariate and multivariate regression models. RESULTS: Birth weight (regression coefficient; B = -0.087, p = 0.011) and birth BMI (unadjusted B = -0.024, p = 0.026; adjusted B = -0.032, p = 0.022) were inversely associated with p21 gene expression in adult life. The p16 gene expression was not associated with any birth parameters. Conditional BMI gain at 2 y, 11 y, and 29 y was not associated with either p16 or p21 gene expression. The p21 gene expression was inversely associated with circulating insulin (B = -0.065, p = 0.026) and C-peptide levels (unadjusted B = -0.097, p = 0.014; adjusted B = -0.133, p = 0.003). CONCLUSION: Small size at birth is associated with accelerated cellular senescence in adult life. An altered senescent state is likely to be one of the links between LBW and adult chronic diseases.

Meandering Retrosternal Course of Right Coronary Artery: Partially Empty Right Atrioventricular Groove.

We report a case of a 35-year-old man with a dilated ascending aorta and a unique meandering retrosternal course of the right coronary artery (RCA) resulting in a partially empty right atrioventricular groove. The aortic root showed an exaggerated clockwise rotation, resulting in an anteriorly directed RCA ostium and the RCA, instead of entering the right atrioventricular groove, traversed caudally in the subepicardial space over the anterior surface of the right ventricle directly posterior to the sternum.

Health System Performance for Multimorbid Cardiometabolic Disease in India: A Population-Based Cross-Sectional Study.

Background: The prevalence of multimorbidity in low- and middle-income countries (LMICs) is thought to be rising rapidly. Research on the state of healthcare for multimorbidity in LMICs is needed to provide an impetus for integration of care across conditions, a baseline to monitor progress, and information for targeting of interventions to those most in need. Focusing on multimorbid cardiometabolic disease in India, this study thus aimed to determine 1) the proportion of adults with co-morbid diabetes and hypertension who successfully completed each step of the chronic disease care continuum from diagnosis to control for both conditions, and 2) how having additional cardiovascular disease (CVD) risk factors is associated with health system performance along the care continuum for diabetes, hypertension, and co-morbid diabetes and hypertension. Methods: Using a nationally representative household survey carried out in 2015 and 2016 among women aged 15-49 years and men aged 15-54 years, we created a 'cascade of care' for diabetes, hypertension, and co-morbid diabetes and hypertension by determining the proportion of those with the condition who had been diagnosed, were on treatment, and achieved control. We used Poisson regression with a robust error structure to estimate how having additional cardiovascular disease (CVD) risk factors (diabetes, hypertension, current smoking, and obesity) was associated with reaching each cascade step for diabetes, hypertension, and co-morbid diabetes and hypertension. Findings: Seven hundred thirty-four thousand seven hundred ninety-four adults were included in the analysis. Among individuals with co-morbid diabetes and hypertension, 28·8% (95% CI, 26·7%-31·0%), 16·1% (95% CI, 14·4%-17·9%), and 3·7% (95% CI, 2·8%-4·9%) - with these proportions varying between states by a factor of 4·8, 7·9, and 56·8 - were aware, treated, and achieved control of both conditions, respectively. Men, adults with lower household wealth, and those living in rural areas were less likely to reach each cascade step. Having additional CVD risk factors generally did not increase the probability of reaching each cascade step for diabetes, hypertension, and co-morbid diabetes and hypertension, except that having concurrent diabetes increased the probability of successfully transitioning through the hypertension care cascade. Interpretation: While varying widely between states and population groups, health system performance for co-morbid diabetes and hypertension is generally low in India, and there appears to be little integration of care across CVD risk factors. Funding: European Research Council.

Patterns of multimorbidity in India: A nationally representative cross-sectional study of individuals aged 15 to 49 years.

There is a dearth of evidence on the epidemiology of multimorbidity in low- and middle-income countries. This study aimed to determine the prevalence of multimorbidity in India and its variation among states and population groups. We analyzed data from a nationally representative household survey conducted in 2015-2016 among individuals aged 15 to 49 years. Multimorbidity was defined as having two or more conditions out of five common chronic morbidities in India: anemia, asthma, diabetes, hypertension, and obesity. We disaggregated multimorbidity prevalence by condition, state, rural versus urban areas, district-level wealth, and individual-level sociodemographic characteristics. 712,822 individuals were included in the analysis. The prevalence of multimorbidity was 7·2% (95% CI, 7·1% - 7·4%), and was higher in urban (9·7% [95% CI, 9·4% - 10·1%]) than in rural (5·8% [95% CI, 5·7% - 6·0%]) areas. The three most prevalent morbidity combinations were hypertension with obesity (2·9% [95% CI, 2·8% - 3·1%]), hypertension with anemia (2·2% [95% CI, 2·1%- 2·3%]), and obesity with anemia (1·2% [95% CI, 1·1%- 1·2%]). The age-standardized multimorbidity prevalence varied from 3·4% (95% CI: 3·0% - 3·8%) in Chhattisgarh to 16·9% (95% CI: 13·2% - 21·5%) in Puducherry. Being a woman, being married, not currently smoking, greater household wealth, and living in urban areas were all associated with a higher risk of multimorbidity. Multimorbidity is common among young and middle-aged adults in India. This study can inform screening guidelines for chronic conditions and the targeting of relevant policies and interventions to those most in need.

Role of CMR feature-tracking derived left ventricular strain in predicting myocardial iron overload and assessing myocardial contractile dysfunction in patients with thalassemia major.

OBJECTIVE: Myocardial iron overload (MIO) in thalassemia major (TM) may cause subclinical left ventricular (LV) dysfunction which manifests with abnormal strain parameters before a decrease in ejection fraction (EF). Early detection of MIO using cardiovascular magnetic resonance (CMR)-T2* is vital. Our aim was to assess if CMR feature-tracking (FT) strain correlates with T2*, and whether it can identify early contractile dysfunction in patients with MIO but normal EF. METHODS: One hundred and four consecutive TM patients with LVEF > 55% on echocardiography were prospectively enrolled. Those fulfilling the inclusion criteria underwent CMR, with T2* being the gold standard for detecting MIO. Group 1 included patients without significant MIO (T2* > 20 ms) and group 2 with significant MIO (T2* < 20 ms). RESULTS: Eighty-six patients (mean age, 17.32 years, 59 males) underwent CMR. There were 68 (79.1%) patients in group 1 and 18 (20.9%) in group 2. Fourteen patients (16.3%) had mild-moderate MIO, and four (4.6%) had severe MIO. Patients in group 2 had significantly lower global radial strain (GRS). Global longitudinal strain (GLS) and global circumferential strain (GCS) did not correlate with T2*. T1 mapping values were significantly lower in patients with T2* < 10 ms than those with T2* of 10-20 ms; however, FT-strain values were not significantly different between these two groups. CONCLUSION: CMR-derived GRS, but not GLS and GCS, correlated with CMR T2*. GRS is significantly decreased in TM patients with MIO and normal EF when compared with those without. FT-strain may be a useful adjunct to CMR T2* and maybe an early marker of myocardial dysfunction in TM. KEY POINTS: • A global radial strain of < 29.3 derived from cardiac MRI could predict significant myocardial iron overload in patients with thalassemia, with a sensitivity of 76.5% and specificity of 66.7%. • Patients with any myocardial iron overload have significantly lower GRS, compared to those without, suggesting the ability of CMR strain to identify subtle myocardial contractile disturbances. • T1 and T2 mapping values are significantly lower in those with severe myocardial iron than those with mild-moderate iron, suggesting a potential role of T1 and T2 mapping in grading myocardial iron.

Atorvastatin and Aspirin as Adjuvant Therapy in Patients with SARS-CoV-2 Infection: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: To assess the impact of adding statin (atorvastatin) and/or aspirin on clinical deterioration in patients infected with SARS-CoV-2 who require hospitalisation. The safety of these drugs in COVID-19 patients will also be evaluated. TRIAL DESIGN: This is a single-centre, prospective, four-arm parallel design, open-label, randomized control trial. PARTICIPANTS: The study will be conducted at National Cancer Institute (NCI), Jhajjar, Haryana, which is a part of All India Institute of Medical Sciences (AIIMS), New Delhi, and has been converted into a dedicated COVID-19 management centre since the outbreak of the pandemic. All RT-PCR confirmed cases of SARS-CoV-2 infection with age ≥ 40 years and < 75 years requiring hospital admission (patients with WHO clinical improvement ordinal score 3 to 5) will be included in the trial. Written informed consent will be taken for all recruited patients. Patients with a critical illness (WHO clinical improvement ordinal score > 5), documented significant liver disease/dysfunction (aspartate transaminase [AST] / alanine aminotransferase [ALT] > 240), myopathy and rhabdomyolysis (creatine phosphokinase [CPK] > 5x normal), allergy or intolerance to statins or aspirin, prior statin or aspirin use within 30 days, history of active gastrointestinal bleeding in past three months, coagulopathy, thrombocytopenia (platelet count < 100000/ dl), pregnancy, active breastfeeding, or inability to take oral or nasogastric medications will be excluded. Patients refusing to give written consent and taking drugs that are known to have a significant drug interaction with statin or aspirin [including cyclosporine, HIV protease inhibitors, hepatitis C protease inhibitor, telaprevir, fibric acid derivatives (gemfibrozil), niacin, azole antifungals (itraconazole, ketoconazole), clarithromycin and colchicine] will also be excluded from the trial. INTERVENTION AND COMPARATOR: In this study, the benefit and safety of atorvastatin (statin) and/or aspirin as adjuvant therapy will be compared with the control group receiving usual care for management of COVID-19. Atorvastatin will be prescribed as 40 mg oral tablets once daily for ten days or until discharge, whichever is earlier. The dose of aspirin will be 75 mg once daily for ten days or until discharge, whichever is earlier. All other therapies will be administered according to the institute's COVID-19 treatment protocol and the treating physician's clinical judgment. MAIN OUTCOMES: All study participants will be prospectively followed up for ten days or until hospital discharge, whichever is longer for outcomes. The primary outcome will be clinical deterioration characterized by progression to WHO clinical improvement ordinal score ≥ 6 (i.e., endotracheal intubation, non-invasive mechanical ventilation, pressor agents, renal replacement therapy, ECMO requirement, and mortality). The secondary outcomes will be change in serum inflammatory markers (C-reactive protein and Interleukin-6), Troponin I, and creatine phosphokinase (CPK) from time zero to 5th day of study enrolment or 7th day after symptom onset, whichever is later. Other clinical outcomes that will be assessed include progression to Acute Respiratory Distress Syndrome (ARDS), shock, ICU admission, length of ICU admission, length of hospital admission, and in-hospital mortality. Adverse drug effects like myalgia, myopathy, rhabdomyolysis, hepatotoxicity, and bleeding will also be examined in the trial to assess the safety of the interventions. RANDOMISATION: The study will use a four-arm parallel-group design. A computer-generated permuted block randomization with mixed block size will be used to randomize the participants in a 1:1:1:1 ratio to group A (atorvastatin with conventional therapy), group B (aspirin with conventional therapy), group C (aspirin + atorvastatin with conventional therapy), and group D (control; only conventional therapy). BLINDING (MASKING): The study will be an open-label trial. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): As there is no existing study that has evaluated the role of aspirin and atorvastatin in COVID-19 patients, formal sample size calculation has not been done. Patients satisfying the inclusion and exclusion criteria will be recruited during six months of study period. Once the first 200 patients are included in each arm (i.e., total 800 patients), the final sample size calculation will be done on the basis of the interim analysis of the collected data. TRIAL STATUS: The institutional ethical committee has approved the study protocol (Protocol version 3.0 [June 2020]). Participant recruitment starting date: 28th July 2020 Participant recruitment ending date: 27th January 2021 Trial duration: 6 months TRIAL REGISTRATION: The trial has been prospectively registered in Clinical Trial Registry - India (ICMR- NIMS): Reference no. CTRI/2020/07/026791 (registered on 25 July 2020)]. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Yoga-Based Cardiac Rehabilitation After Acute Myocardial Infarction: A Randomized Trial.

BACKGROUND: Given the shortage of cardiac rehabilitation (CR) programs in India and poor uptake worldwide, there is an urgent need to find alternative models of CR that are inexpensive and may offer choice to subgroups with poor uptake (e.g., women and elderly). OBJECTIVES: This study sought to evaluate the effects of yoga-based CR (Yoga-CaRe) on major cardiovascular events and self-rated health in a multicenter randomized controlled trial. METHODS: The trial was conducted in 24 medical centers across India. This study recruited 3,959 patients with acute myocardial infarction with a median and minimum follow-up of 22 and 6 months. Patients were individually randomized to receive either a Yoga-CaRe program (n = 1,970) or enhanced standard care involving educational advice (n = 1,989). The co-primary outcomes were: 1) first occurrence of major adverse cardiovascular events (MACE) (composite of all-cause mortality, myocardial infarction, stroke, or emergency cardiovascular hospitalization); and 2) self-rated health on the European Quality of Life-5 Dimensions-5 Level visual analogue scale at 12 weeks. RESULTS: MACE occurred in 131 (6.7%) patients in the Yoga-CaRe group and 146 (7.4%) patients in the enhanced standard care group (hazard ratio with Yoga-CaRe: 0.90; 95% confidence interval [CI]: 0.71 to 1.15; p = 0.41). Self-rated health was 77 in Yoga-CaRe and 75.7 in the enhanced standard care group (baseline-adjusted mean difference in favor of Yoga-CaRe: 1.5; 95% CI: 0.5 to 2.5; p = 0.002). The Yoga-CaRe group had greater return to pre-infarct activities, but there was no difference in tobacco cessation or medication adherence between the treatment groups (secondary outcomes). CONCLUSIONS: Yoga-CaRe improved self-rated health and return to pre-infarct activities after acute myocardial infarction, but the trial lacked statistical power to show a difference in MACE. Yoga-CaRe may be an option when conventional CR is unavailable or unacceptable to individuals. (A study on effectiveness of YOGA based cardiac rehabilitation programme in India and United Kingdom; CTRI/2012/02/002408).

Risk factors for myocardial infarction in very young South Asians.

PURPOSE OF REVIEW: It is only over the last few decades that the impact of coronary artery disease (CAD) in very young South Asian population has been recognized. There has been a tremendous interest in elucidating the causes behind this phenomenon and these efforts have uncovered several mechanisms that might explain the early onset of CAD in this population. The complete risk profile of very young South Asians being affected by premature CAD still remains unknown. RECENT FINDINGS: The existing data fail to completely explain the burden of premature occurrence of CAD in South Asians especially in very young individuals. Results from some studies identified nine risk factors, including low consumption of fruits and vegetables, smoking, alcohol, diabetes, psychosocial factors, sedentary lifestyle, abdominal obesity, hypertension and dyslipidemia as the cause of myocardial infarction in 90% of the patients in this population. Recent large genome-wide association studies have discovered the association of several novel genetic loci with CAD in South Asians. Nonetheless, continued scientific efforts are required to further our understanding of the causal risk factors of CAD in South Asians to address the rising burden of CVD in this vulnerable population. SUMMARY: In this review, we discuss established and emerging risk factors of CAD in this population.

CABG Improves Outcomes in Patients With Ischemic Cardiomyopathy: 10-Year Follow-Up of the STICH Trial.

OBJECTIVES: The authors investigated the impact of coronary artery bypass grafting (CABG) on first and recurrent hospitalization in this population. BACKGROUND: In the STICH (Surgical Treatment for Ischemic Heart Failure) trial, CABG reduced all-cause death and hospitalization in patients with and ischemic cardiomyopathy and left ventricular ejection fraction <35%. METHODS: A total of 1,212 patients were randomized (610 to CABG + optimal medical therapy [CABG] and 602 to optimal medical therapy alone [MED] alone) and followed for a median of 9.8 years. All-cause and cause-specific hospitalizations were analyzed as time-to-first-event and as recurrent event analysis. RESULTS: Of the 1,212 patients, 757 died (62.4%) and 732 (60.4%) were hospitalized at least once, for a total of 2,549 total all-cause hospitalizations. Most hospitalizations (66.2%) were for cardiovascular causes, of which approximately one-half (907 or 52.9%) were for heart failure. More than 70% of all hospitalizations (1,817 or 71.3%) were recurrent events. The CABG group experienced fewer all-cause hospitalizations in the time-to-first-event (349 CABG vs. 383 MED, adjusted hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.74 to 0.98; p = 0.03) and in recurrent event analyses (1,199 CABG vs. 1,350 MED, HR: 0.78, 95% CI: 0.65 to 0.94; p < 0.001). This was driven by fewer total cardiovascular (CV) hospitalizations (744 vs. 968; p < 0.001, adjusted HR: 0.66, 95% CI: 0.55 to 0.81; p = 0.001), the majority of which were due to HF (395 vs. 512; p < 0.001, adjusted HR: 0.68, 95% CI: 0.52-0.89; p = 0.005). We did not observe a difference in non-CV events. CONCLUSIONS: CABG reduces all-cause, CV, and HF hospitalizations in time-to-first-event and recurrent event analyses. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595).

Burden of medical co-morbidities and benefit from surgical revascularization in patients with ischaemic cardiomyopathy.

AIMS: The landmark STICH trial found that surgical revascularization compared to medical therapy alone improved survival in patients with heart failure (HF) of ischaemic aetiology and an ejection fraction (EF) ≤ 35%. However, the interaction between the burden of medical co-morbidities and the benefit from surgical revascularization has not been previously described in patients with ischaemic cardiomyopathy. METHODS AND RESULTS: The STICH trial (ClinicalTrials.gov Identifier: NCT00023595) enrolled patients ≥ 18 years of age with coronary artery disease amenable to coronary artery bypass grafting (CABG) and an EF ≤ 35%. Eligible participants were randomly assigned 1:1 to receive medical therapy (MED) (n = 602) or MED/CABG (n = 610). A modified Charlson co-morbidity index (CCI) based on the availability of data and study definitions was calculated by summing the weighted points for all co-morbid conditions. Patients were divided into mild/moderate (CCI 1-4) and severe (CCI ≥ 5) co-morbidity. Cox proportional hazards models were used to evaluate the association between CCI and outcomes and the interaction between severity of co-morbidity and treatment effect. The study population included 349 patients (29%) with a mild/moderate CCI score and 863 patients (71%) with a severe CCI score. Patients with a severe CCI score had greater functional limitations based on 6-min walk test and impairments in health-related quality of life as assessed by the Kansas City Cardiomyopathy Questionnaire. A total of 161 patients (Kaplan-Meier rate = 50%) with a mild/moderate CCI score and 579 patients (Kaplan-Meier rate = 69%) with a severe CCI score died over a median follow-up of 9.8 years. After adjusting for baseline confounders, patients with a severe CCI score were at higher risk for all-cause mortality (hazard ratio 1.44, 95% confidence interval 1.19-1.74; P < 0.001). There was no interaction between CCI score and treatment effect on survival (P = 0.756). CONCLUSIONS: More than 70% of patients had a severe burden of medical co-morbidities at baseline, which was independently associated with increased risk of death. There was not a differential benefit of surgical revascularization with respect to survival based on severity of co-morbidity.

Effectiveness of an mHealth-Based Electronic Decision Support System for Integrated Management of Chronic Conditions in Primary Care: The mWellcare Cluster-Randomized Controlled Trial.

BACKGROUND: The burden of noncommunicable diseases and their risk factors has rapidly increased worldwide, including in India. Innovative management strategies with electronic decision support and task sharing have been assessed for hypertension, diabetes mellitus, and depression individually, but an integrated package for multiple chronic condition management in primary care has not been evaluated. METHODS: In a prospective, multicenter, open-label, cluster-randomized controlled trial involving 40 community health centers, using hypertension and diabetes mellitus as entry points, we evaluated the effectiveness of mWellcare, an mHealth system consisting of electronic health record storage and an electronic decision support for the integrated management of 5 chronic conditions (hypertension, diabetes mellitus, current tobacco and alcohol use, and depression) versus enhanced usual care among patients with hypertension and diabetes mellitus in India. At trial end (12-month follow-up), using intention-to-treat analysis, we examined the mean difference between arms in change in systolic blood pressure and glycated hemoglobin as primary outcomes and fasting blood glucose, total cholesterol, predicted 10-year risk of cardiovascular disease, depression score, and proportions reporting tobacco and alcohol use as secondary outcomes. Mixed-effects regression models were used to account for clustering and other confounding variables. RESULTS: Among 3698 enrolled participants across 40 clusters (mean age, 55.1 years; SD, 11 years; 55.2% men), 3324 completed the trial. There was no evidence of difference between the 2 arms for systolic blood pressure (Δ=-0.98; 95% CI, -4.64 to 2.67) and glycated hemoglobin (Δ=0.11; 95% CI, -0.24 to 0.45) even after adjustment of several key variables (adjusted differences for systolic blood pressure: - 0.31 [95% CI, -3.91 to 3.29]; for glycated hemoglobin: 0.08 [95% CI, -0.27 to 0.44]). The mean within-group changes in systolic blood pressure in mWellcare and enhanced usual care were -13.65 mm Hg versus -12.66 mm Hg, respectively, and for glycated hemoglobin were -0.48% and -0.58%, respectively. Similarly, there were no differences in the changes between the 2 groups for tobacco and alcohol use or other secondary outcomes. CONCLUSIONS: We did not find an incremental benefit of mWellcare over enhanced usual care in the management of the chronic conditions studied. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT02480062.

IndEcho study: cohort study investigating birth size, childhood growth and young adult cardiovascular risk factors as predictors of midlife myocardial structure and function in South Asians.

INTRODUCTION: South Asians have high rates of cardiovascular disease (CVD) and its risk factors (hypertension, diabetes, dyslipidaemia and central obesity). Left ventricular (LV) hypertrophy and dysfunction are features of these disorders and important predictors of CVD mortality. Lower birth and infant weight and greater childhood weight gain are associated with increased adult CVD mortality, but there are few data on their relationship to LV function. The IndEcho study will examine associations of birth size, growth during infancy, childhood and adolescence and CVD risk factors in young adulthood with midlife cardiac structure and function in South Asian Indians. METHODS AND ANALYSIS: We propose to study approximately 3000 men and women aged 43-50 years from two birth cohorts established in 1969-1973: the New Delhi Birth Cohort (n=1508) and Vellore Birth Cohort (n=2156). They had serial measurements of weight and height from birth to early adulthood. CVD risk markers (body composition, blood pressure, glucose tolerance and lipids) and lifestyle characteristics (tobacco and alcohol consumption, physical activity, socioeconomic status) were assessed at age ~30 years. Clinical measurements in IndEcho will include anthropometry, blood pressure, biochemistry (glucose, fasting insulin and lipids, urinary albumin/creatinine ratio) and body composition by dual energy X-ray absorptiometry and bioelectrical impedance. Outcomes are LV mass and indices of LV systolic and diastolic function assessed by two-dimensional and Doppler echocardiography, carotid intimal-media thickness and ECG indicators of ischaemia. Regression and conditional growth models, adjusted for potential confounders, will be used to study associations of childhood and young adult exposures with these cardiovascular outcomes. ETHICS AND DISSEMINATION: The study has been approved by the Health Ministry Steering Committee, Government of India and institutional ethics committees of participating centres in India and the University of Southampton, UK. Results will be disseminated through scientific meetings and peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN13432279; Pre-results.

Cost-effectiveness of a fixed dose combination (polypill) in secondary prevention of cardiovascular diseases in India: Within-trial cost-effectiveness analysis of the UMPIRE trial.

BACKGROUND: The Use of Multidrug Pill In Reducing cardiovascular Events (UMPIRE) trial, showed that access to a cardiovascular polypill (aspirin, statin and two blood pressure lowering drugs) significantly improved adherence, lowered systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDLc) in patients with or at high risk of cardiovascular disease (CVD). We aimed to analyze the within-trial cost-effectiveness of the polypill strategy versus usual care in India. METHODS: Relative effectiveness and costs of polypill versus usual care groups in UMPIRE were estimated from the health sector perspective. Only direct medical costs were considered. The effectiveness of the polypill was reported as a percentage increase in adherence and mean reductions in SBP, and LDL-c, over the 15-month trial period. Healthcare resource utilization and costs were collected for each patient during the trial. Polypill price was constructed using a range of scenarios: $0.06-$0.94/day. The cost-effectiveness of the polypill was measured as the additional cost for 10% increase in adherence, and per unit reduction in SBP and LDL-c. RESULTS: Overall, the mean cost per patient was significantly lower with the polypill strategy (-$203 per person, (95% CI: -286, -119, p < 0.01). In scenario analyses that varied polypill price assumptions, incremental cost-effectiveness ratios for a polypill strategy ranged between cost-saving to $75 per 10% increase in adherence for polypill price of $0.94 per day. CONCLUSIONS: The polypill strategy was cost-saving compared to usual care among patients with or at high risk of CVD in India.

Cost-effectiveness of interventions to control cardiovascular diseases and diabetes mellitus in South Asia: a systematic review.

OBJECTIVES: More than 80% of cardiovascular diseases (CVD) and diabetes mellitus (DM) burden now lies in low and middle-income countries. Hence, there is an urgent need to identify and implement the most cost-effective interventions, particularly in the resource-constraint South Asian settings. Thus, we aimed to systematically review the cost-effectiveness of individual-level, group-level and population-level interventions to control CVD and DM in South Asia. METHODS: We searched 14 electronic databases up to August 2016. The search strategy consisted of terms related to 'economic evaluation', 'CVD', 'DM' and 'South Asia'. Per protocol two reviewers assessed the eligibility and methodological quality of studies using standard checklists, and extracted incremental cost-effectiveness ratios of interventions. RESULTS: Of the 2949 identified studies, 42 met full inclusion criteria. Critical appraisal of studies revealed 15 excellent, 18 good and 9 poor quality studies. Most studies were from India (n=37), followed by Bangladesh (n=3), Pakistan (n=2) and Bhutan (n=1). The economic evaluations were based on observational studies (n=9), randomised trials (n=12) and decision models (n=21). Together, these studies evaluated 301 policy or clinical interventions or combination of both. We found a large number of interventions were cost-effective aimed at primordial prevention (tobacco taxation, salt reduction legislation, food labelling and food advertising regulation), and primary and secondary prevention (multidrug therapy for CVD in high-risk group, lifestyle modification and metformin treatment for diabetes prevention, and screening for diabetes complications every 2-5 years). Significant heterogeneity in analytical framework and outcome measures used in these studies restricted meta-analysis and direct ranking of the interventions by their degree of cost-effectiveness. CONCLUSIONS: The cost-effectiveness evidence for CVD and DM interventions in South Asia is growing, but most evidence is from India and limited to decision modelled outcomes. There is an urgent need for formal health technology assessment and policy evaluations in South Asia using local research data. PROSPERO REGISTRATION NUMBER: CRD42013006479.