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.

Effect of Yoga Based Cardiac Rehabilitation on Blood Pressure Variability and Baroreflex Sensitivity: RCT in Patients Post MI.

To assess the effects of 12 weeks Yoga based Cardiac Rehabilitation program on Blood Pressure Variability and Baroreflex Sensitivity in Eighty patients post myocardial infarction. Randomized controlled trial with two parallel groups. A tertiary care institution in India. The Yoga group received 13 hospital-based structured yoga sessions in adjunct to the standard care. Control Group participants received enhanced standard care involving three brief educational sessions on importance of diet and physical activity. Beat to beat arterial pressure variability and baroreflex sensitivity was determined non-invasively. Baseline measurement was done at 3 weeks post Myocardial Infarction. The measurements were repeated at 13th week and at 26th week post MI. There was no significant difference between the groups in time domain indices of SBP variability. At 26th week post MI, after normalization the Low Frequency power increased in the yoga group as compared to the decrease in the standard care group (p = 0.02). Though the High Frequency power increased in both the groups, the magnitude of increase was higher in the standard care group (p = 0.005). However, the total power increased significantly in yoga group with a concurrent decrease in standard care group (p = < 0.001). The SBP All BRS was significantly different between the groups with an increase in the yoga group and a decline in standard care group (p = 0.003) at 13th week. A short-term Yoga based cardiac rehabilitation has additive effects in improving baroreflex sensitivity and dampening blood pressure variability post myocardial infarction in patients under optimal medication.The main trial is registered in Clinical Trials Registry-India (CTRI) (Ref. No: CTRI/2012/02/002408). In addition, CTRI has also been registered for the sub-study. (Ref. No: CTRI/2017/09/009925).

Determinants of high-density lipoprotein (HDL) functions beyond proteome in Asian Indians: exploring the fatty acid profile of HDL phospholipids.

Impaired high-density lipoprotein (HDL) functions are associated with development of coronary artery disease. In this study, we explored the quantitative differences in HDL (i.e. HDL proteome and fatty acid profile of HDL phospholipids) underlying the functional deficits associated with acute coronary syndrome (ACS). The relationship between HDL function and composition was assessed in 65 consecutive ACS patients and 40 healthy controls. Cholesterol efflux capacity (CEC) of HDL and lecithin cholesterol acyl transferase (LCAT) activity were significantly lower in patients with ACS compared to controls. In HDL proteome analysis, HDL isolated from ACS individuals was enriched in apolipoprotein C2 (inhibitor of LCAT), apolipoprotein C4 and serum amyloid A proteins and was deficient in apolipoprotein A-I and A-II. The fatty acid profile of HDL phospholipids analyzed using gas chromatography showed significantly lower percentages of stearic acid (17.4 ± 2.4 vs 15.8 ± 2.8, p = 0.004) and omega-3 fatty acids [eicosapentaenoic acid (1.0 (0.6-1.4) vs 0.7 (0.4-1.0), p = 0.009) and docosahexaenoic acid (1.5 ± 0.7 vs 1.3 ± 0.5, p = 0.03)] in ACS patients compared to controls. Lower percentages of these fatty acids in HDL were associated with higher odds of developing ACS. Our results suggest that distinct phospholipid fatty acid profiles found in HDL from ACS patients could be one of the contributing factors to the deranged HDL functions in these patients apart from the protein content and the inflammatory conditions.

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).

Effect of Yoga-Based Cardiac Rehabilitation on Heart Rate Variability: Randomized Controlled Trial in Patients Post-MI.

Autonomic dysfunction is an independent predictor of cardiovascular and all-cause mortality after myocardial infarction (MI). We tested the effects of a 12-week yoga-based cardiac rehabilitation program on heart rate variability (HRV) in 80 patients post-MI. This randomized controlled trial with two parallel groups was carried out in a tertiary care institution in India. The yoga group received 13 hospital-based structured yoga sessions as an adjunct to standard care. Control group participants received enhanced standard care involving three brief educational sessions with a leaflet on the importance of diet and physical activity. HRV was measured in all participants with lead II electrocardiogram (ECG) signals. One yoga group patient's data were excluded due to ECG abnormalities. Baseline measurement was done 3 weeks post-MI, and postintervention assessment took place at the 13th week. HRV frequency and time domain indices were analyzed. There were no significant between-group differences in the HRV time domain indices. Frequency domain indices showed significant between-group differences in HF power (absolute) (yoga vs. control: 114.42 [-794.80-7,993.78] vs. -38.14 [-4,843.50-1,617.87], p = 0.005) and total power (nu) (yoga vs. control: 44.96 [21.94] vs. -19.55 [15.42], p = 0.01) with higher HF power and total power (nu) in the yoga group. It should be noted that these results cannot be generalized to high risk patients. Respiratory frequency control to check for influence of respiratory rate on RR interval was not evaluated. This short-term yoga-based cardiac rehabilitation program had additive effects in shifting sympathovagal balance toward parasympathetic predominance while increasing overall HRV in optimally medicated post-MI patients.