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Modulation of the renin-angiotensin-aldosterone system is a foundation of therapy for cardiovascular and kidney diseases. Excess aldosterone plays an important role in cardiovascular disease, contributing to inflammation, fibrosis, and dysfunction in the heart, kidneys, and vasculature through both genomic and mineralocorticoid receptor (MR)-mediated as well as nongenomic mechanisms. MR antagonists have been a key therapy for attenuating the pathologic effects of aldosterone but are associated with some side effects and may not always adequately attenuate the nongenomic effects of aldosterone. Aldosterone is primarily synthesized by the CYP11B2 aldosterone synthase enzyme, which is very similar in structure to other enzymes involved in steroid biosynthesis including CYP11B1, a key enzyme involved in glucocorticoid production. Lack of specificity for CYP11B2, off-target effects on the hypothalamic-pituitary-adrenal axis, and counterproductive increased levels of bioactive steroid intermediates such as 11-deoxycorticosterone have posed challenges in the development of early aldosterone synthase inhibitors such as osilodrostat. In early-phase clinical trials, newer aldosterone synthase inhibitors demonstrated promise in lowering blood pressure in patients with treatment-resistant and uncontrolled hypertension. It is therefore plausible that these agents offer protection in other disease states including heart failure or chronic kidney disease. Further clinical evaluation will be needed to clarify the role of aldosterone synthase inhibitors, a promising class of agents that represent a potentially major therapeutic advance. [ABSTRACT FROM AUTHOR]

BACKGROUND: Patients with heart failure (HF) with preserved ejection fraction (HFpEF) and obesity experience a high burden of symptoms and functional impairment, and a poor quality of life. In the STEP-HFpEF trial (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity), once-weekly semaglutide 2.4 mg improved symptoms, physical limitations, and exercise function, and reduced inflammation and body weight. This prespecified analysis investigated the effects of semaglutide on the primary and confirmatory secondary end points across the range of the Kansas City Cardiomyopathy Questionnaire (KCCQ) scores at baseline and on all key summary and individual KCCQ domains. METHODS: STEP-HFpEF randomly assigned 529 participants with symptomatic HF, an ejection fraction of ≥45%, and a body mass index of ≥30 kg/m2 to once-weekly semaglutide 2.4 mg or placebo for 52 weeks. Dual primary end points change in KCCQ-Clinical Summary Score (CSS) and body weight. Confirmatory secondary end points included change in 6-minute walk distance, a hierarchical composite end point (death, HF events, and change in KCCQ-CSS and 6-minute walk distance) and change in C-reactive protein. Patients were stratified by KCCQ-CSS tertiles at baseline. Semaglutide effects on the primary, confirmatory secondary, and select exploratory end points (N-terminal pro-brain natriuretic peptide) were examined across these subgroups. Semaglutide effects on additional KCCQ domains (Total Symptom Score [including symptom burden and frequency], Physical Limitations Score, Social Limitations Score, Quality of Life Score, and Overall Summary Score) were also evaluated. RESULTS: Baseline median KCCQ-CSS across tertiles was 37, 59, and 77 points, respectively. Semaglutide consistently improved primary end points across KCCQ tertiles 1 to 3 (estimated treatment differences [95% CI]: for KCCQ-CSS, 10.7 [5.4 to 16.1], 8.1 [2.7 to 13.4], and 4.6 [-0.6 to 9.9] points; for body weight, -11 [-13.2 to -8.8], -9.4 [-11.5 to -7.2], and -11.8 [-14.0 to -9.6], respectively; Pinteraction=0.28 and 0.29, respectively); the same was observed for confirmatory secondary and exploratory end points (Pinteraction>0.1 for all). Semaglutide-treated patients experienced improvements in all key KCCQ domains (estimated treatment differences, 6.7-9.6 points across domains; P≤0.001 for all). Greater proportion of semaglutide-treated versus placebo-treated patients experienced at least 5-, 10-, 15-, and 20-point improvements in all KCCQ domains (odds ratios, 1.6-2.9 across domains; P<0.05 for all). CONCLUSIONS: In patients with HFpEF and obesity, semaglutide produced large improvements in HF-related symptoms, physical limitations, exercise function, inflammation, body weight, and N-terminal pro-brain natriuretic peptide, regardless of baseline health status. The benefits of semaglutide extended to all key KCCQ domains. [ABSTRACT FROM AUTHOR]

Sodium glucose-cotransporter 2 (SGLT2) inhibitors have been reported to reduce cardiovascular events and heart failure in people with and without diabetes. These medications have been shown to counter regenerative cell exhaustion in the context of prevalent diabetes. This study sought to determine if empagliflozin attenuates regenerative cell exhaustion in people without diabetes. Peripheral blood mononuclear cells were collected at the baseline and 6-mo visits from individuals randomized to receive empagliflozin (10 mg/day) or placebo who were participating in the EMPA-HEART 2 CardioLink-7 trial. Precursor cell phenotypes were characterized by flow cytometry for cell-surface markers combined with high aldehyde dehydrogenase activity to identify precursor cell subsets with progenitor (ALDHhi) versus mature effector (ALDHlow) cell attributes. Samples from individuals assigned to empagliflozin (n = 25) and placebo (n = 21) were analyzed. At baseline, overall frequencies of primitive progenitor cells (ALDHhiSSClow), monocyte (ALDHhiSSCmid), and granulocyte (ALDHhiSSChi) precursor cells in both groups were similar. At 6 mo, participants randomized to empagliflozin demonstrated increased ALDHhiSSClowCD133+CD34+ proangiogenic cells (P = 0.048), elevated ALDHhiSSCmidCD163+ regenerative monocyte precursors (P = 0.012), and decreased ALDHhiSSCmidCD86+ CD163- proinflammatory monocyte (P = 0.011) polarization compared with placebo. Empagliflozin promoted the recovery of multiple circulating provascular cell subsets in people without diabetes suggesting that the cardiovascular benefits of SGLT2 inhibitors may be attributed in part to the attenuation of vascular regenerative cell exhaustion that is independent of diabetes status. [ABSTRACT FROM AUTHOR]

The high NLR tertile was associated with a 74% increased risk of expanded MACE and a twofold increased risk of CV death and all-cause death (secondary outcomes) vs. the low NLR tertile (Figure S2A). Antidiabetic drug, cardiovascular disease, GLP-1 analogue, randomized trial, type 2 diabetes Keywords: antidiabetic drug; cardiovascular disease; GLP-1 analogue; randomized trial; type 2 diabetes EN antidiabetic drug cardiovascular disease GLP-1 analogue randomized trial type 2 diabetes 2398 2401 4 07/04/23 20230801 NES 230801 INTRODUCTION Inflammation plays a critical role in the pathobiology of cardiometabolic diseases.[[1]] Neutrophils participate in this inflammatory response by releasing inflammatory mediators that cause vascular wall dysfunction; lymphocytes can augment or mute inflammatory responses, depending on the subtype.[2] Studies suggest that the neutrophil to lymphocyte ratio (NLR) may more accurately predict cardiovascular (CV) events than leukocyte counts,[3] and that NLR can predict CV disease (CVD) risk and all-cause mortality in diverse populations,[2], [4], [5], [6] including people with type 2 diabetes (T2D).[7], [8], [9], [10] The SUSTAIN 6[11] and PIONEER 6[12] trials investigated CV outcomes with subcutaneous and oral semaglutide, respectively, versus placebo in people with T2D at high CV risk. [Extracted from the article]

Cardiovascular safety of oral semaglutide in patients with type 2 diabetes: rationale, design and patient baseline characteristics for the PIONEER 6 trial. Keywords: antidiabetic drug; cardiovascular disease; semaglutide; type 2 diabetes EN antidiabetic drug cardiovascular disease semaglutide type 2 diabetes 2388 2392 5 07/04/23 20230801 NES 230801 BACKGROUND Epidemiological studies have shown that elevated triglycerides (TGs) is associated with higher cardiovascular (CV) risk[[1]] and may help to identify patients at persistent risk of CV events despite treatment with statins and other evidence-based therapies.[[3]] Evidence suggests that some, but not all, pharmacological treatments that appear to reduce TGs might also reduce the occurrence of fatal or non-fatal CV events in individuals at high risk. [Extracted from the article]

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Aim: To investigate the epidemiology and clinical management of patients with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease (eASCVD) or high/very high ASCVD risk, defined by the 2021 European Society of Cardiology Guidelines, in seven countries in the Middle East and Africa (PACT‐MEA; NCT05317845), and to assess physicians' attitudes and the basis for their decision‐making in the management of these patients. Materials and Methods: PACT‐MEA is a cross‐sectional, observational study undertaken in Bahrain, Egypt, Jordan, Kuwait, Qatar, South Africa and the United Arab Emirates based on a medical chart review of approximately 3700 patients with T2D in primary and secondary care settings, and a survey of approximately 400 physicians treating patients with T2D. Results: The primary and secondary objectives are to determine the prevalence of eASCVD and high/very high ASCVD risk in patients with T2D. Current treatment with cardioprotective antidiabetic medication, the proportion of patients meeting the treatment criteria for reimbursement in the study countries where there is an applicable reimbursement guideline, and physician‐reported factors in clinical decision‐making in T2D management, will also be assessed. Conclusions: This large cross‐sectional study will establish the estimated prevalence and management of eASCVD and high/very high ASCVD risk in patients with type 2 diabetes across the Middle East and Africa. [ABSTRACT FROM AUTHOR]

Keywords: Africa; atherosclerosis; cardiovascular diseases; diabetes complications; diabetes mellitus, type 2; Middle East; prevalence EN Africa atherosclerosis cardiovascular diseases diabetes complications diabetes mellitus, type 2 Middle East prevalence 1251 1255 5 04/14/23 20230418 NES 230418 The Middle East and Africa bear a disproportionate burden of diabetes and associated cardiovascular complications,[1],[2] yet high-quality contemporary data on the prevalence of cardiovascular risk in people with type 2 diabetes (T2D) are lacking in these regions.[3],[4] PACT-MEA (An International Chart Review and Survey for the Prevalence and Clinical Management of Atherosclerotic Cardiovascular Diseases in Patients With Type 2 Diabetes Across Countries in the Middle East and Africa; URL: https://www.clinicaltrials.gov; Unique identifier: NCT05317845) is a noninterventional, cross-sectional, observational study conducted at 55 centers in 7 countries. A, Type of atherosclerotic cardiovascular disease (ASCVD) among patients with established ASCVD (eASCVD; left) and type of coronary artery disease (CAD) among patients with eASCVD and CAD (right). Africa, atherosclerosis, cardiovascular diseases, diabetes complications, Middle East, prevalence, diabetes mellitus, type 2. [Extracted from the article]

Adverse events and serious adverse events were comparable for empagliflozin versus placebo in Black patients and White patients (adverse events: Black patients: placebo 88.3%, empagliflozin 85.4%; White patients: placebo 83.6%, empagliflozin 82.9%; serious adverse events: Black patients: placebo 61.5%, empagliflozin 53.1%; White patients: placebo 51.2%, empagliflozin 48.2%); however, the placebo incidence of adverse events was higher in Black patients. Keywords: heart failure; racial groups; therapeutics EN heart failure racial groups therapeutics 101 104 4 12/29/22 20230103 NES 230103 There are disparities in both rates and outcomes of heart failure (HF) between Black patients and White patients, and important questions remain about the generalizability of conventional HF therapies, including angiotensin-converting enzyme inhibitors and -blockers, to Black patients. [Extracted from the article]

Aim: To evaluate the cardiovascular (CV) efficacy of liraglutide and semaglutide in patients with type 2 diabetes (T2D) and peripheral artery disease (PAD). Materials and Methods: LEADER and SUSTAIN 6 trials investigated subcutaneous liraglutide (≤1.8 mg/day) and semaglutide (0.5 or 1.0 mg/week), respectively, versus placebo in patients with T2D and high CV risk (median follow‐up: 3.8 and 2.1 years, respectively). The primary outcome was a composite of CV death, non‐fatal myocardial infarction or non‐fatal stroke (major adverse CV event [MACE]) according to the presence of PAD at baseline. Results: Overall, 1184/9340 (12.7%) patients in LEADER and 460/3297 (14.0%) in SUSTAIN 6 had PAD at baseline. Patients with PAD were at an ~35% increased risk of MACE versus those without (LEADER: hazard ratio [HR] 1.36, 95% confidence interval [CI] 1.17‐1.58; SUSTAIN 6: HR 1.33, 95% CI 0.94‐1.83). The effects of both therapies on MACE were consistently beneficial in patients with PAD (liraglutide: HR 0.77, 95% CI 0.58‐1.01; semaglutide: 0.61, 0.33‐1.13) and without (liraglutide: HR 0.89, 95% CI 0.79‐1.00; semaglutide: HR 0.77, 95% CI 0.58‐1.01; Pinteraction =.34 for liraglutide and.49 for semaglutide). Absolute risk reductions for MACE were higher in patients with PAD (liraglutide: 4.13%‐point, 95% CI −0.15‐8.42; semaglutide: 4.63%‐point, 95% CI −0.58‐9.84) versus without (liraglutide:1.42%‐point, 95% CI −0.03‐2.87; semaglutide: 1.90%‐point, 95% CI 0.00‐3.80). Conclusion: Both liraglutide and semaglutide reduce MACE with consistent CV efficacy regardless of PAD status. [ABSTRACT FROM AUTHOR]

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Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery.Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting.Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63-0.92]; P=0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56-0.87]; P=0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50-0.81]; P=0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%-10.2%) in first events, with a number needed to treat of 16 (95% CI, 10-44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P=0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups.Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01492361. [ABSTRACT FROM AUTHOR]

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibition reduces cardiovascular events in type 2 diabetes (T2DM) and is associated with a reduction in left ventricular (LV) mass index. However, the impact on right ventricular (RV) remodeling is unknown. Accordingly, the objective of this study was to assess the impact of SGLT2 inhibition on RV parameters and function in T2DM and coronary artery disease (CAD). Methods: In EMPA-HEART CardioLink-6, 97 patients with T2DM and CAD were randomly assigned to empagliflozin 10 mg (n = 49) once daily or placebo (n = 48). Cardiac magnetic resonance imaging was performed at baseline and after 6 months. RV mass index (RVMi), RV end-diastolic and end-systolic volume index (RVEDVi, RVESVi) and RV ejection fraction (RVEF) were assessed in blinded fashion. Results: At baseline, mean RVMi (± SD) (11.8 ± 2.4 g/m2), RVEF (53.5 ± 4.8%), RVEDVi (64.3 ± 13.2 mL/m2) and RVESVi (29.9 ± 6.9 mL/m2) were within normal limits and were similar between the empagliflozin and placebo groups. Over 6 months, there were no significant differences in RVMi (− 0.11 g/m2, [95% CI − 0.81 to 0.60], p = 0.76), RVEF (0.54%, [95% CI − 1.4 to 2.4], p = 0.58), RVEDVi (− 1.2 mL/m2, [95% CI − 4.1 to 1.7], p = 0.41) and RVESVi (− 0.81 mL/m2, [95% CI − 2.5 to 0.90], p = 0.35) in the empaglifozin group as compared with the placebo group. In both groups, there was no significant correlation between RVMi and LVMi changes from baseline to 6 months. Conclusions: In this post-hoc analysis, SGLT2 inhibition with empagliflozin had no impact on RVMi and RV volumes in patients with T2DM and CAD. The potentially differential effect of empagliflozin on the LV and RV warrants further investigation. Clinical Trial Registration: URL: https://www.clinicaltrials.gov/ct2/show/NCT02998970?cond=NCT02998970&draw=2&rank=1. Unique identifier: NCT02998970. [ABSTRACT FROM AUTHOR]

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In the REWIND trial, dulaglutide reduced cardiovascular (CV) risk versus placebo in patients with type 2 diabetes in both the "established CV disease" (CVD) and "CV risk factor" subgroups. The SUSTAIN 6 and PIONEER 6 trials of semaglutide used different criteria for established CVD from those used in REWIND. The present post hoc analysis assessed the effect of semaglutide on major adverse CV events (MACE) in a pooled population of SUSTAIN 6 and PIONEER 6 patients, re‐categorized into CV risk subgroups using the REWIND CVD criteria. In the pooled analysis (n = 6480), a lower percentage of patients were in the established CVD subgroup, when using the REWIND CVD criteria, compared with the original trial CVD criteria (66.5% vs. 83.8%, respectively). After re‐categorization, the risk of MACE was significantly lower with semaglutide versus placebo in the established CVD subgroup (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.59, 0.92) and nonsignificantly lower in the CV risk factor subgroup (HR 0.84, 95% CI 0.55, 1.28) (P‐interaction = 0.60). These results suggest that the CV effects of semaglutide may extend to patients with type 2 diabetes across the CV risk continuum. [ABSTRACT FROM AUTHOR]

Aim: To determine the relationship between polyvascular disease and risk of hospitalization for heart failure (HHF) and cardiovascular (CV) death in the EMPA‐REG OUTCOME population, and the relationship of kidney dysfunction co‐existent with polyvascular disease on CV/heart failure (HF) outcomes. Materials and Methods: Patients with type 2 diabetes and atherosclerotic CV (ASCVD) received empagliflozin 10, 25 mg or placebo. Post hoc, subgroups were analyzed by one versus two or more vascular beds, and the estimated glomerular filtration rate ([eGFR] < vs. ≥60 mL/min/1.73 m2) at baseline. The empagliflozin arms were pooled. Time to CV death, HHF, CV death (excluding fatal stroke) or HHF, all‐cause mortality (ACM) and 3‐point major adverse CV events (3P‐MACE) were assessed using multivariable Cox regression models. Results: Baseline characteristics (N = 6959) within subgroups were balanced between treatment groups. In the placebo group, two or more versus one vascular bed increased HHF risk (1.59 [95% confidence interval 1.02, 2.49]), CV death (2.17 [1.52, 3.09]), CV death/HHF (1.79 [1.32, 2.43]), ACM (1.95 [1.44, 2.64]) and 3P‐MACE (1.76 [1.36, 2.27]). Hazard ratios for those with polyvascular disease/kidney dysfunction (vs. 1 vascular bed/eGFR ≥60 mL/min/1.73 m2) were HHF 2.80 (1.46, 5.36), CV death 3.10 (1.87, 5.13), CV death/HHF 2.71 (1.74, 4.23), ACM 2.59 (1.67, 4.02) and 3P‐MACE 2.62 (1.82, 3.77). Empagliflozin reduced the risk of all outcomes across subgroups. Conclusions: Polyvascular disease with/without kidney dysfunction markedly increases the risk of HF/CV events. Empagliflozin consistently reduces risk, regardless of vascular bed and kidney function status. [ABSTRACT FROM AUTHOR]

Multiple studies have attempted to dissect the molecular mechanism underlying seed development in chickpea (Cicer arietinum L.). These studies highlight the need to focus on the role of miRNAs in regulating storage protein accumulation in seeds. Therefore, a total of 8,856,691 short-read sequences were generated from a small RNA library of developing chickpea seeds and were analyzed using miRDeep-P to identify 74 known and 26 novel miRNA sequences. Known miRNAs were classified into 22 miRNA families with miRNA156 family being most abundant. Of the 26 putative novel miRNAs identified, only 22 could be experimentally validated using stem loop end point PCR. Differential expression analyses led to the identification of known as well as novel miRNAs that could regulate various stages of chickpea seed development. In silico target prediction revealed several important target genes and transcription factors like SPL, mediator of RNA Polymerase II transcription subunit 12, aspartic proteinase and NACs, which were further validated by real-time PCR analysis. A comparative expression analysis in chickpea genotypes with contrasting seed protein content revealed one known (Car-miR156h) and two novel miRNA (Car-novmiR7 and Car-novmiR23) candidates to be highly expressed in the LPC (low protein content) chickpea genotypes, targets of which are known to regulate seed storage protein accumulation. Therefore, this study provides a useful resource in the form of miRNA and their targets which can be further utilized to understand and manipulate various regulatory mechanisms involved in seed development with the overall aim of improving yield and nutrition attributes in chickpea. [ABSTRACT FROM AUTHOR]

SGLT2 inhibitors are antihyperglycemic drugs that protect kidneys and the heart of patients with or without type 2 diabetes and preserved or reduced kidney function from failing. The involved protective mechanisms include blood glucose–dependent and –independent mechanisms: SGLT2 inhibitors prevent both hyper- and hypoglycemia, with expectedly little net effect on HbA1C. Metabolic adaptations to induced urinary glucose loss include reduced fat mass and more ketone bodies as additional fuel. SGLT2 inhibitors lower glomerular capillary hypertension and hyperfiltration, thereby reducing the physical stress on the filtration barrier, albuminuria, and the oxygen demand for tubular reabsorption. This improves cortical oxygenation, which, together with lesser tubular gluco-toxicity, may preserve tubular function and glomerular filtration rate in the long term. SGLT2 inhibitors may mimic systemic hypoxia and stimulate erythropoiesis, which improves organ oxygen delivery. SGLT2 inhibitors are proximal tubule and osmotic diuretics that reduce volume retention and blood pressure and preserve heart function, potentially in part by overcoming the resistance to diuretics and atrial-natriuretic-peptide and inhibiting Na-H exchangers and sympathetic tone. [ABSTRACT FROM AUTHOR]

Keywords: dapagliflozin; empagliflozin; heart failure; SGLT2 inhibition EN dapagliflozin empagliflozin heart failure SGLT2 inhibition 2201 2204 4 12/10/20 20201208 NES 201208 Although the sodium-glucose cotransporter-2 (SGLT2) inhibitors were originally developed to manage hyperglycemia in people with type 2 diabetes, they have consistently been found to improve heart failure and kidney outcomes. Background therapy for HFrEF was excellent in both trials, with high rates of goal-directed medical therapy including -blockers, renin-angiotensin-aldosterone system inhibitors, and mineralocorticoid antagonists. Approximately 17% of patients discontinued therapy in EMPEROR-Reduced (versus 11% in DAPA-HF), and vital status was unknown in 21 patients in EMPEROR-Reduced (versus 2 in DAPA-HF). [Extracted from the article]

Aims: To explore cardiometabolic risk profiles, the probability of sustainable control, and the effectiveness of treatment with sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors in black and white adults in the United States with type 2 diabetes. Materials and Methods: Using nationally representative US electronic medical records, 72 690 white and 10 004 black adults diagnosed with type 2 diabetes initiating SGLT2 inhibitors during the period 2013 to 2018, continuing it for ≥6 months, and with follow‐up of ≥12 months, were identified. Glycated haemoglobin (HbA1c), body weight, systolic blood pressure (SBP) and lipid changes at 6 months, and sustainability of control over 18 months post SGLT2 inhibitor initiation were explored, separately in those with and without atherosclerotic cardiovascular disease (ASCVD). Results: The white group was older (58 years) with lower mean HbA1c (8.5%), compared to the black group (age 54 years, HbA1c 9.0%). Body mass index distribution was similar. The proportions of people with uncontrolled SBP, LDL cholesterol, non‐HDL cholesterol and triglyceride levels were 24%, 42%, 51% and 62%, respectively, in white patients, and 31%, 51%, 49% and 32%, respectively, in black patients. At 6‐month follow‐up white and black patients had similar adjusted reductions in HbA1c (1.1%), SBP (8–10 mmHg), LDL cholesterol (0.26 – 0.34 mmol / L) and body weight (1.1–1.4 kg). However, over 18 months' follow‐up, compared to white patients, black patients were significantly less likely to achieve sustainable control in HbA1c (odds ratio [OR] 0.67, 95% confidence interval [CI] 0.63–0.72), body weight (OR 0.81, 95% CI 0.72–0.91), SBP (OR 0.67, 95% CI 0.61–0.74) and LDL cholesterol (OR 0.77, 95% CI 0.67–0.89). Triglyceride control was significantly better among black patients. Black patients had a significantly higher risk factor burden, irrespective of ASCVD status. Conclusions: While the effectiveness of SGLT2 inhibitors was similar among black and white patients, irrespective of ASCVD status, black patients continued to have worse cardiometabolic risk factor burden after SGLT2 inhibitor initiation. [ABSTRACT FROM AUTHOR]

Associations between body mass index (BMI) and the cardiovascular (CV) and kidney efficacy of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) in patients with type 2 diabetes (T2D) are uncertain; therefore, data analysed separately from the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial and the Trial to Evaluate Cardiovascular and Other Long‐term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN 6) were examined. These international, randomized, placebo‐controlled trials investigated liraglutide and semaglutide (both subcutaneous) in patients with T2D and at high risk of CV events. In post hoc analyses, patients were categorized by baseline BMI (<25, ≥25‐<30, ≥30‐<35 and ≥35 kg/m2), and CV and kidney outcomes with GLP‐1 RA versus placebo were analysed. All baseline BMI data from LEADER (n = 9331) and SUSTAIN 6 (n = 3290) were included (91% and 92% of patients with overweight or obesity, respectively). In SUSTAIN 6, nominally significant heterogeneity of semaglutide efficacy by baseline BMI was observed for CV death/myocardial infarction/stroke (major adverse CV events, primary outcome of both; Pinteraction =.02); otherwise, there was no statistical heterogeneity for either GLP‐1 RA versus placebo across BMI categories for key CV and kidney outcomes. The lack of statistical heterogeneity from these cardiorenal outcomes implies that liraglutide and semaglutide may be beneficial for many patients and is probable not to depend on their baseline BMI, but further study is needed. [ABSTRACT FROM AUTHOR]

Approximately 17% of patients discontinued therapy in EMPEROR-Reduced (versus 11% in DAPA-HF), and vital status was unknown in 21 patients in EMPERORReduced (versus 2 in DAPA-HF). Baseline estimated glomerular filtration rate (eGFR) was lower in EMPEROR-Reduced ( 61 mL-min -1 -1.73 m -2) compared with DAPA-HF ( 66 mL-min -1 -1.73 m -2), and proportionally more EMPEROR-Reduced patients had an eGFR that was <=60 mL-min -1 -1.73 m -2. As a reflection of these differences in patient populations, the placebo event rates also differed between the 2 trials. [Extracted from the article]

Genotyping-by-sequencing (GBS) allows rapid identification of markers for use in development of linkage maps, which expedite efficient breeding programs. In the present study, we have utilized GBS approach to identify and genotype single-nucleotide polymorphism (SNP) markers in an inter-specific RIL population of Cicer arietinum L. X C. reticulatum. A total of 141,639 raw SNPs were identified using the TASSEL-GBS pipeline. After stringent filtering, 8208 candidate SNPs were identified of which ~ 37% were localized in the intragenic regions followed by genic regions (~ 30%) and intergenic regions (~ 27%). We then utilized 6920 stringent selected SNPs from present study and 6714 SNPs and microsatellite markers available from previous studies for construction of linkage map. The resulting high-density linkage map comprising of eight linkage groups contained 13,590 markers which spanned 1299.14 cM of map length with an average marker density of 0.095 cM. Further, the derived linkage map was used to improve the available assembly of desi chickpea genome by anchoring 443 previously unplaced scaffolds onto eight linkage groups. The present efforts have refined anchoring of the desi chickpea genome assembly to 55.57% of the ~ 520 Mb of assembled desi genome. To the best of our knowledge, the linkage map generated in the present study represents one of the most dense linkage map developed for the crop till date. It will serve as a valuable resource for fine mapping and positional cloning of important quantitative trait loci (QTLs) associated with agronomical traits and also for anchoring and ordering of future genome sequence assemblies. [ABSTRACT FROM AUTHOR]

The randomized, double-blind, cardiovascular outcomes trials LEADER (NCT01179048) and SUSTAIN 6 (NCT01720446) showed cardiovascular risk reduction in patients with type 2 diabetes treated with liraglutide and semaglutide, respectively, compared with placebo. This post hoc analysis examined the impact of microvascular disease at baseline on cardiovascular outcomes in these trials, and the efficacy of liraglutide (1.8 mg) and once-weekly semaglutide (0.5-1.0 mg) in patients with and without microvascular disease. In total, 9340 patients from LEADER and 3297 patients from SUSTAIN 6 were included in this analysis; of these, 5761 and 2356 had a history of microvascular disease at baseline and 3835 and 1640 had a history of both microvascular and macrovascular disease, respectively. Patients with microvascular disease were shown to have an increased risk of major adverse cardiovascular events compared with patients without microvascular disease (hazard ratio [95% confidence interval] in LEADER: 1.15 [1.03; 1.29], P = .0136; SUSTAIN 6: 1.56 [1.14; 2.17], P = .0064). Liraglutide and semaglutide consistently reduced cardiovascular risk in patients with and without microvascular disease. [ABSTRACT FROM AUTHOR]

Aim: To investigate the association of the Thrombolysis In Myocardial Infarction (TIMI) Risk Score for Heart Failure in Diabetes (TRS‐HFDM) with mortality using data from the EMPA‐REG OUTCOME trial. Materials and Methods: In EMPA‐REG OUTCOME, patients with type 2 diabetes and atherosclerotic cardiovascular (CV) disease (N = 7020) received the sodium‐glucose co‐transporter‐2 inhibitor, empagliflozin, 10 or 25 mg or placebo. Post hoc, patients were stratified into risk categories (low‐intermediate, high, very‐high risk scores) using baseline TRS‐HFDM. Cox regression analyses evaluated the association of TRS‐HFDM categories with all‐cause mortality (ACM), CV death, hospitalization for heart failure (HHF) and CV death (excluding fatal stroke) or HHF, and whether empagliflozin reduced the risk of CV outcomes across these risk categories. Results: In placebo patients, increasing risk category was associated with a higher risk of ACM, CV death, and HHF. Empagliflozin reduced the risk of ACM (low‐intermediate HR 0.68 [95% CI 0.48, 0.97] and very‐high 0.69 [0.52, 0.91]), CV death (0.75 [0.48, 1.18] and 0.56 [0.41, 0.78]), HHF (0.53 [0.28, 1.01] and 0.67 [0.48, 0.96]), and CV death or HHF (0.69 [0.46, 1.03]) and (0.64 [0.49, 0.82]) across all risk categories versus placebo. Higher absolute risk reductions (ARRs) were observed for CV death in the very‐high versus low‐intermediate category (P = 0.01). Conclusions: Applied to EMPA‐REG OUTCOME, higher TRS‐HFDM was associated with increased HHF and mortality risk. Empagliflozin reduced CV outcomes across TRS‐HFDM categories. Higher ARRs were associated with higher risk scores. [ABSTRACT FROM AUTHOR]

In the EMPA‐REG OUTCOME trial, we explored the association between pre‐randomization uric acid level tertile (<309.30 μmol/L; 309.30 to <387.21 μmol/L; ≥387.21 μmol/L) and cardiovascular (CV) death, hospitalization for heart failure (HHF), HHF or CV death, all‐cause mortality, three‐point major adverse CV events (MACE), and incident or worsening nephropathy. Patients with type 2 diabetes and CV disease received empagliflozin or placebo. The median baseline plasma uric acid level was 344.98 μmol/L, and patients' baseline characteristics were mainly balanced across tertiles. Baseline uric acid levels were associated with cardio‐renal outcomes: in the placebo group, for the highest versus lowest tertile, the multivariable hazard ratios for three‐point MACE, HHF or CV death, and incident or worsening nephropathy were 1.22 (95% confidence interval [CI] 0.89–1.67; P = 0.2088), 1.51 (95% CI 1.02–2.23; P = 0.0396) and 1.77 (95% CI 1.33–2.34; P < 0.0001), respectively. When tested as a continuous variable, baseline uric acid was associated with all outcomes in the placebo group. Empagliflozin improved all cardio‐renal outcomes across tertiles, with all interaction P values >0.05. Further investigation of these relationships is required. [ABSTRACT FROM AUTHOR]

Importance: Additional treatments are needed for heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 (SGLT2) inhibitors may be an effective treatment for patients with HFrEF, even those without diabetes.Objective: To evaluate the effects of dapagliflozin in patients with HFrEF with and without diabetes.Design, Setting, and Participants: Exploratory analysis of a phase 3 randomized trial conducted at 410 sites in 20 countries. Patients with New York Heart Association classification II to IV with an ejection fraction less than or equal to 40% and elevated plasma N-terminal pro B-type natriuretic peptide were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019.Interventions: Addition of once-daily 10 mg of dapagliflozin or placebo to recommended therapy.Main Outcomes and Measures: The primary outcome was the composite of an episode of worsening heart failure or cardiovascular death. This outcome was analyzed by baseline diabetes status and, in patients without diabetes, by glycated hemoglobin level less than 5.7% vs greater than or equal to 5.7%.Results: Among 4744 patients randomized (mean age, 66 years; 1109 [23%] women; 2605 [55%] without diabetes), 4742 completed the trial. Among participants without diabetes, the primary outcome occurred in 171 of 1298 (13.2%) in the dapagliflozin group and 231 of 1307 (17.7%) in the placebo group (hazard ratio, 0.73 [95% CI, 0.60-0.88]). In patients with diabetes, the primary outcome occurred in 215 of 1075 (20.0%) in the dapagliflozin group and 271 of 1064 (25.5%) in the placebo group (hazard ratio, 0.75 [95% CI, 0.63-0.90]) (P value for interaction = .80). Among patients without diabetes and a glycated hemoglobin level less than 5.7%, the primary outcome occurred in 53 of 438 patients (12.1%) in the dapagliflozin group and 71 of 419 (16.9%) in the placebo group (hazard ratio, 0.67 [95% CI, 0.47-0.96]). In patients with a glycated hemoglobin of at least 5.7%, the primary outcome occurred in 118 of 860 patients (13.7%) in the dapagliflozin group and 160 of 888 (18.0%) in the placebo group (hazard ratio, 0.74 [95% CI, 0.59-0.94]) (P value for interaction = .72). Volume depletion was reported as an adverse event in 7.3% of patients in the dapagliflozin group and 6.1% in the placebo group among patients without diabetes and in 7.8% of patients in the dapagliflozin group and 7.8% in the placebo group among patients with diabetes. A kidney adverse event was reported in 4.8% of patients in the dapagliflozin group and 6.0% in the placebo group among patients without diabetes and in 8.5% of patients in the dapagliflozin group and 8.7% in the placebo group among patients with diabetes.Conclusions and Relevance: In this exploratory analysis of a randomized trial of patients with HFrEF, dapagliflozin compared with placebo, when added to recommended therapy, significantly reduced the risk of worsening heart failure or cardiovascular death independently of diabetes status.Trial Registration: ClinicalTrials.gov Identifier: NCT03036124. [ABSTRACT FROM AUTHOR]

Background: SGLT2 (sodium-glucose cotransporter 2) inhibitors lower cardiovascular events in type 2 diabetes mellitus but whether they promote direct cardiac effects remains unknown. We sought to determine if empagliflozin causes a decrease in left ventricular (LV) mass in people with type 2 diabetes mellitus and coronary artery disease.Methods: Between November 2016 and April 2018, we recruited 97 individuals ≥40 and ≤80 years old with glycated hemoglobin 6.5% to 10.0%, known coronary artery disease, and estimated glomerular filtration rate ≥60mL/min/1.73m2. The participants were randomized to empagliflozin (10 mg/day, n=49) or placebo (n=48) for 6 months, in addition to standard of care. The primary outcome was the 6-month change in LV mass indexed to body surface area from baseline as measured by cardiac magnetic resonance imaging. Other measures included 6-month changes in LV end-diastolic and -systolic volumes indexed to body surface area, ejection fraction, 24-hour ambulatory blood pressure, hematocrit, and NT-proBNP (N-terminal pro b-type natriuretic peptide).Results: Among the 97 participants (90 men [93%], mean [standard deviation] age 62.8 [9.0] years, type 2 diabetes mellitus duration 11.0 [8.2] years, estimated glomerular filtration rate 88.4 [16.9] mL/min/1.73m2, LV mass indexed to body surface area 60.7 [11.9] g/m2), 90 had evaluable imaging at follow-up. Mean LV mass indexed to body surface area regression over 6 months was 2.6 g/m2 and 0.01 g/m2 for those assigned empagliflozin and placebo, respectively (adjusted difference -3.35 g/m2; 95% CI, -5.9 to -0.81g/m2, P=0.01). In the empagliflozin-allocated group, there was significant lowering of overall ambulatory systolic blood pressure (adjusted difference -6.8mmHg, 95% CI -11.2 to -2.3mmHg, P=0.003), diastolic blood pressure (adjusted difference -3.2mmHg; 95% CI, -5.8 to -0.6mmHg, P=0.02) and elevation of hematocrit (P=0.0003).Conclusions: Among people with type 2 diabetes mellitus and coronary artery disease, SGLT2 inhibition with empagliflozin was associated with significant reduction in LV mass indexed to body surface area after 6 months, which may account in part for the beneficial cardiovascular outcomes observed in the EMPA-REG OUTCOME (BI 10773 [Empagliflozin] Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) trial.Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02998970. [ABSTRACT FROM AUTHOR]

Cardiovascular risk reduction with liraglutide and semaglutide in patients with type 2 diabetes was demonstrated in the LEADER (ClinicalTrials.gov: NCT01179048) and SUSTAIN 6 (ClinicalTrials.gov: NCT01720446) cardiovascular outcome trials. This post hoc analysis assessed the impact of diabetes duration (<5, 5 to <15, 15 to <25 and ≥25 years at baseline) on cardiorenal efficacy of these human glucagon‐like peptide‐1 analogues using a Cox proportional hazards model. Proportions of patients in the LEADER trial across diabetes duration strata were 15% (<5 years, n = 1377), 50% (5 to <15 years, n = 4692), 27% (15 to <25 years, n = 2504) and 8% (≥25 years, n = 748); corresponding proportions in the SUSTAIN‐6 trial were 13% (<5 years, n = 422), 48% (5 to <15 years, n = 1582), 30% (15 to <25 years, n = 977) and 10% (≥25 years, n = 316). Overall, longer diabetes duration was associated with higher age; higher prevalence of females; history of ischaemic stroke, peripheral arterial disease and insulin use; and inferior renal function. There was an increased frequency of major adverse cardiovascular events (MACE), expanded MACE and nephropathy events with increasing diabetes duration. Liraglutide and semaglutide consistently reduced the risk of cardiorenal outcomes across categories of diabetes duration (P‐interaction was not significant for all endpoints analysed). [ABSTRACT FROM AUTHOR]

The article offers information on the U.S. Food and Drug Administration guidance recommended rigorous evaluations of cardiovascular safety for new glucose-lowering therapies. It mentions the cardiovascular outcome trials (CVOTs) have shown benefits with regard to the progression of chronic kidney disease; and also mentions clinicians are reminded that sodium-glucose cotransporter 2 inhibitors (SGLT2) have emerged as powerful cardiovascular therapies.

The authors discuss the serendipitous story of sodium-glucose transporter 2 (SGLT2) inhibitors and heart failure that stems from the Empaglifozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients trial. Highlights include the efficacy of dapagliflozin based on ejection fraction, mechanisms to mediate the cardiorenal benefits of SGLT2 inhibitors, and the use of an SGLT2 inhibitor as part of routine secondary prevention.

Improvement of the quality and quantity of chickpea seed protein can be greatly facilitated by an understanding of the genic organization and the genetic architecture of the genes encoding seed storage proteins (SSPs). The aim of this study was to provide a comprehensive analysis of the chickpea SSP genes, putative co-expressing transcription factors (TFs), and to identify a seed-specific SSP gene promoter. A genome-wide identification of SSP genes in chickpea led to the identification of 21 non-redundant SSP encoding genes located on 6 chromosomes. Phylogenetic analysis grouped SSP genes into 3 subgroups where members within the same clade demonstrated similar motif composition and intron-exon organization. Tandem duplications were identified to be the major contributors to the expansion of the SSP gene family in chickpea. Co-expression analysis revealed 14 TFs having expression profiles similar to the SSP genes that included members of important TF families that are known to regulate seed development. Expression analysis of SSP genes and TFs revealed significantly higher expression in late stages of seed development as well as in high seed protein content (HPC) genotypes. In silico analysis of the promoter regions of the SSP encoding genes revealed several seed-specific cis-regulatory elements such as RY repeats, ACGT motifs, CAANTG, and GCN4. A candidate promoter was analyzed for seed specificity by generating stable transgenics in Arabidopsis. Overall, this study provides a useful resource to explore the regulatory networks involved in SSP synthesis and/or accumulation for utilization in developing nutritionally improved chickpea genotypes. [ABSTRACT FROM AUTHOR]

Background: The glucagon-like peptide-1 analog liraglutide reduced cardiovascular events and mortality in patients with type 2 diabetes mellitus in the LEADER trial (Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes). In a post hoc analysis, we evaluated the efficacy of liraglutide in those with and without a history of myocardial infarction (MI) and/or stroke.Methods: LEADER was a randomized trial of liraglutide (1.8 mg or maximum tolerated dose) versus placebo in 9340 patients with type 2 diabetes mellitus and high cardiovascular risk, with a median follow-up of 3.8 years. The primary outcome was a composite of cardiovascular death, nonfatal MI, or nonfatal stroke (major adverse cardiovascular events). Risk groups in this post hoc analysis were defined by history of MI/stroke, established atherosclerotic cardiovascular disease without MI/stroke, or cardiovascular risk factors alone.Results: Of the 9340 patients, 3692 (39.5%) had a history of MI/stroke, 3083 (33.0%) had established atherosclerotic cardiovascular disease without MI/stroke, and 2565 (27.5%) had risk factors alone. Major adverse cardiovascular events occurred in 18.8% of patients with a history of MI/stroke (incidence rate, 5.0 per 100 patient-years), 11.6% of patients with established atherosclerotic cardiovascular disease without MI/stroke (incidence rate, 3.0 per 100 patient-years), and 9.8% of patients with cardiovascular risk factors alone (incidence rate, 2.6 per 100 patient-years). Liraglutide reduced major adverse cardiovascular events in patients with a history of MI/stroke (322 of 1865 [17.3%] versus 372 of 1827 patients [20.4%]; hazard ratio, 0.85; 95% CI, 0.73-0.99) and in those with established atherosclerotic cardiovascular disease without MI/stroke (158 of 1538 [10.3%] versus 199 of 1545 patients [12.9%]; hazard ratio, 0.76; 95% CI, 0.62-0.94) compared with placebo. In patients with risk factors alone, the hazard ratio for liraglutide versus placebo was 1.08 (95% CI, 0.84-1.38, Pinteraction=0.11). Similar results were seen for secondary outcomes across risk groups.Conclusions: In this post hoc analysis of patients with type 2 diabetes mellitus and high cardiovascular risk, liraglutide reduced cardiovascular outcomes both in patients with a history of MI/stroke and in those with established atherosclerotic cardiovascular disease without MI/stroke. The cardiovascular effect appeared neutral in patients with cardiovascular risk factors alone.Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01179048. [ABSTRACT FROM AUTHOR]

Aortic valve neocuspidization or Ozaki procedure represents an advanced surgical strategy for the management of patients with aortic valvulopathy. It has been shown to have clinical and hemodynamic outcomes that compare favorably with aortic valve replacement as it restores physiological aortic valve function and left ventricular remodeling. There are, however, a new set of issues including structural valve deterioration, leaflet tear/perforation, and need for reoperation. A keen understanding of the technical nuances involved with the Ozaki procedure may help in reducing the incidence of such adverse outcomes. [ABSTRACT FROM AUTHOR]

Although rates of ischemic complications in type 2 diabetes mellitus seem to be declining, some of the most feared and costly complications, namely end-stage kidney disease, heart failure, and lower limb amputations, remain on the rise. The development of chronic kidney disease in type 2 diabetes mellitus marks the beginning of a sharp increase in cardio-renal complications.[2] Indeed, in type 2 diabetes mellitus, chronic kidney disease is one of the strongest determinants of atherosclerotic vascular events and heart failure, with a hazard that parallels the degree/stage of kidney insufficiency. Thus, it is imperative that treatment goals of diabetic kidney disease (DKD) involve both kidney protection and cardiovascular risk reduction, particularly because many patients with DKD will have a cardiovascular event before developing end-stage kidney disease. [Extracted from the article]

Transcatheter aortic valve replacement (TAVR) has become the preferred therapy over surgical aortic valve replacement (SAVR) in intermediate- or greater-risk patients with symptomatic severe aortic stenosis (AS). Fifth, in young patients with AS, the Ross procedure in experienced hands is an excellent alternative to a surgical aortic valve prosthesis, whereas aortic valve repair has become a more mature surgical alternative to SAVR in aortic regurgitation.[4] Finally, TAVR durability remains unknown, and TAVR in a failing transcatheter aortic valve may not be feasible in all patients with current devices.[5] Questions also remain regarding the optimal management of patients with asymptomatic severe AS and moderate AS with heart failure. 2 Popma JJ Deeb GM Yakubov SJ Mumtaz M Gada H O'Hair D Bajwa T Heiser JC Merhi W Kleiman NS Evolut Low Risk Trial Investigators Transcatheter aortic-valve replacement with a self-expanding valve in low-risk patients. [Extracted from the article]

This article reports on the effect of liraglutide on cardiovascular events in patients with type 2 diabetes mellitus and polyvascular disease. The hazard ratios (HR) comparing risk groups were calculated and treatment effect of liraglutide versus placebo within risk groups was estimated. The results showed that patients with polyvascular disease had a higher risk of cardiovascular outcomes than those with single vascular disease.

Coronary artery disease and aortic stenosis often occur concomitantly owing to their shared risk factor profile. While standard management of these patients has been through surgical methods including surgical aortic valve replacement and coronary artery bypass grafting, recent studies have investigated the potential role of complete transcatheter management (i.e., transcatheter aortic valve implantation and percutaneous coronary intervention) for these patients. In this editorial, we discuss the growing body of evidence suggesting long‐term risks of transcatheter interventions despite their short‐term benefits and also look to the future of hybrid approaches for multifaceted structural heart pathologies. [ABSTRACT FROM AUTHOR]

In Great Nicobar island ophiolite is restricted to the eastern coast of the island and occur as small isolated out crops in the terrain of Oligocene sediments. The ophiolitic rocks are represented by pillowed basalt, massive andesite and pyroclastic andesite. These volcanics represent dismembered members of the upper part of the ophiolite. Basalt is porphyritic in nature where phenocrysts of augite and plagioclase laths are set in a fine grained glassy to chloritic matrix. Andesites consists of phenocrysts of augite, altered feldspar and minor quartz which are set in ground mass of epidote-chlorite glass. Trace element and REE pattern suggests more fertile mantle source for andesite than that of basalt. Trace element characteristics indicate that the andesites and basalts were possibly derived from the same melt where andesite represents the more fractionated product. In Andaman Islands dismembered ophiolite with complete ophiolite stratigraphy are found only within the Eocene sediments. But the field disposition suggests that in Great Nicobar emplacement of the ophiolite continued even after the Oligocene sedimentation. The characters of the ophiolitic rocks in Great Nicobar island are similar to that of the Sunda outer arc ridge. [ABSTRACT FROM AUTHOR]

Objectives This meta-analysis compares total arterial revascularization (TAR) versus conventional coronary artery bypass and additionally to two arterial grafts. Methods We searched MEDLINE and EMBASE Databases from 1996-to-2016 for studies comparing TAR versus non-TAR for multi-vessel surgical revascularization. Data were extracted by 2 independent investigators. Meta-analysis used random effects, which incorporates heterogeneity. Results There were 4 smaller shorter follow-up randomized controlled trials (RCTs), plus 15 matched/adjusted and 6 unmatched/unadjusted larger longer follow-up observational studies that met inclusion criteria ( N = 130.305 patients; mean follow-up range: 1–15 years). There were no differences in perioperative stroke, myocardial infarction or mortality. However, TAR was associated with lower long term all-cause mortality in observational studies matched/adjusted for confounders (incident rate ratio 0.85, 95% CI: 0.81–0.89, p < 0.0001; I 2 = 0%) and unmatched/unadjusted (incident rate ratio 0.67, 95% CI: 0.59–0.76, p < 0.0001; I 2 = 67%) for TAR. Decreases in major cardiovascular outcomes and revascularization did not achieve statistical significance. There were greater sternal complications with TAR in the matched/adjusted studies (pooled risk ratio 1.21, 95% CI: 1.03–1.42, p = 0.02; I 2 = 0%). When compared to patients with two arterial grafts, TAR was still associated with reduced long-term all-cause mortality (incident rate ratio 0.85, 95% CI: 0.73–0.99, p = 0.04) with minimal heterogeneity ( I 2 = 5%). Conclusions Data from primarily observational studies suggest that TAR may improve long-term survival compared with conventional coronary bypass by 15–20% even when compared with two arterial grafts. Prospective randomized trials of TAR with long term follow-up are needed. [ABSTRACT FROM AUTHOR]

The article offers information on the randomised trials of glucose-lowering therapies have demonstrated safety with respect to cardiorenal outcomes. Topics include benefits that appear independent of glycaemic control and are mediated through a range of mechanisms including effects on systemic and renal haemodynamics; discussing that the greatest cardiovascular benefit is seen for heart failure, with a relative risk reduction of more than 30 percent observed across the trials.