Background: Glucagon-like peptide 1 agonists differ in chemical structure, duration of action and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. Methods: We randomly assigned patients with type 2 diabetes and cardiovascular disease to the addition of once-weekly subcutaneous injection of albiglutide (30 mg to 50 mg) or matching placebo to standard care. We hypothesized that albiglutide would be noninferior to placebo for the primary outcome of first occurrence of cardiovascular death, myocardial infarction, or stroke. If noninferiority was confirmed by an upper limit of the 95% confidence interval for the hazard ratio of less than 1.30, closed-testing for superiority was prespecified. Findings: Overall, 9463 participants were followed for a median of 1.6 years. The primary composite outcome occurred in 338 of 4731 patients (7.1%; 4.6 events per 100 person-years) in the albiglutide group and in 428 of 4732 patients (9.0%; 5.9 events per 100 person-years) in the placebo group (hazard ratio, 0.78; 95% confidence interval [CI ], 0.68 to 0.90), indicating that albiglutide, was superior to placebo (P<0.0001 for noninferiority, P=0.0006 for superiority). The incidence of acute pancreatitis (albiglutide 10 patients and placebo 7 patients), pancreatic cancer (6 and 5), medullary thyroid carcinoma (0 and 0), and other serious adverse events did not differ significantly between the two groups. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. (Funded by GlaxoSmithKline; Harmony Outcomes ClinicalTrials.gov number, NCT02465515.) noninferiority; P = 0.06 for superiority). There seems to be variation in the results of existing trials with GLP-1 receptor agonists, which if correct, might reflect drug structure or duration of action, patients studied, duration of follow-up or other factors.

This study aimed to investigate the adipokine and cytokine profiles of adipocytes from epicardial and subcutaneous adipose tissues in interconnection with the visceral adipose tissue area and the biochemical and clinical characteristics of patients with coronary artery disease. We assessed 84 patients with coronary artery disease (65 men, 19 women) and divided them into two groups based on the presence of visceral obesity. We sampled epicardial and subcutaneous adipose tissues from the patients with visceral obesity. We then cultured the adipocytes and evaluated their adipokine profiles and pro-inflammatory activity. Results show that the mRNA expression of adiponectin in cultures of epicardial adipocytes from patients with and without visceral obesity was lower than that in subcutaneous adipocytes. Moreover, adiponectin mRNA expression in cultures of subcutaneous and epicardial adipocytes from patients with visceral obesity was lower than that in patients without obesity. For leptin, the reverse pattern was observed, with expression higher in cultures of epicardial adipocytes than in subcutaneous adipocytes and higher in epicardial adipocytes from patients with visceral obesity than in those from subjects without visceral obesity. In addition, in epicardial adipocytes, increased expression of proinflammatory cytokine genes (IL6, TNF) was observed compared with that in subcutaneous adipocytes. In contrast, expression of IL10 was higher in cultures of subcutaneous adipocytes than in epicardial adipocytes. The epicardial adipose tissue area was associated with the presence of higher levels of leptin and TNF-α within adipocytes and serum, increased lipid and carbohydrate metabolism. Coronary artery disease, in the context of the status of epicardial adipocytes, can be characterized as “metabolic inflammation,” suggesting the direct involvement of adipocytes in pathogenesis through the development of adipokine imbalances and activation of proinflammatory processes.

Improvement of risk scoring is particularly important for patients with preserved left ventricular ejection fraction (LVEF) who generally lack efficient monitoring of progressing heart failure. Here, we evaluated whether the combination of serum biomarkers and echocardiographic parameters may be useful to predict the remodeling-related outcomes in patients with ST-segment elevation myocardial infarction (STEMI) and preserved LVEF (HFpEF) as compared to those with reduced LVEF (HFrEF). Echocardiographic assessment and measurement of the serum levels of NT-proBNP, sST2, galectin-3, matrix metalloproteinases, and their inhibitors (MMP-1, MMP-2, MMP-3, TIMP-1) was performed at the time of admission (1st day) and on the 10th–12th day upon STEMI onset. We found a reduction in NT-proBNP, sST2, galectin-3, and TIMP-1 in both patient categories from hospital admission to the discharge, as well as numerous correlations between the indicated biomarkers and echocardiographic parameters, testifying to the ongoing ventricular remodeling. In patients with HFpEF, NT-proBNP, sST2, galectin-3, and MMP-3 correlated with the parameters reflecting the diastolic dysfunction, while in patients with HFrEF, these markers were mainly associated with LVEF and left ventricular end-systolic volume/diameter. Therefore, the combination of the mentioned serum biomarkers and echocardiographic parameters might be useful for the prediction of adverse cardiac remodeling in patients with HFpEF.

BackgroundThe aim of this study was to assess significance of serum neutrophil gelatinase-associated lipocalin (sNGAL) and cystatin C (sCC) in prediction of adverse cardiovascular outcome after ST-segment elevation myocardial infarction (STEMI).MethodsWe recruited 357 consecutive patients who were admitted to the hospital within 24 h after onset of STEMI. On the 1st and 12th-14th day after hospital admission, we measured levels of sNGAL and sCC. We also determined presence of renal dysfunction (RD), defined as glomerular filtration rate < 60 mL/min/1.73 m2. After 3 years of follow-up, we performed a logistic regression and assessed the value of RD, sNGAL, and sCC in prediction of combined endpoint, defined as cardiovascular death or any cardiovascular complication.ResultsRD, sCC level ≥ 1.9 mg/L, and sNGAL level ≥ 1.25 ng/mL on the 12th-14th day of hospitalization were associated with a 1.6-fold, 1.9-fold, and 2.9-fold higher risk of adverse cardiovascular outcome, respectively. Area under the ROC curve was the highest for the model based on sNGAL level compared to the models based on sCC level or RD presence.ConclusionsMeasurement of sNGAL level in patients with STEMI on the 12th-14th day after hospital admission may improve prediction of adverse cardiovascular outcome.

IntroductionOn average, 19–23% of patients with acute myocardial infarction (MI) suffer from type 2 diabetes mellitus, which is newly diagnosed in a significant number of patients. Both classic carbohydrate metabolism and lipid metabolism may be promising diagnostic markers for insulin resistance in acute coronary syndrome.Material and methodsTwo hundred patients (130 males and 70 females aged 61.4 ±1.12 years) with ST-segment elevation MI were included in the study. Patients were divided into two groups based on manifestations of diabetes: (1) 171 patients without diabetes within 1 year after MI; and (2) 29 patients with manifestations of diabetes. The control group comprised 33 people without diseases of the cardiovascular system and diabetes and was matched by age and gender with patients.ResultsIn patients with an imbalanced adipokine state during the acute phase of MI, we noted an increased concentration of free fatty acids (p > 0.05) and reduced ghrelin levels (p > 0.05) and activation of the proinflammatory and thrombotic potentials of blood plasma. Patients who developed diabetes 1 year after MI showed hospital stays with more pronounced changes in the study parameters.ConclusionsThe most informative biochemical parameters associated with the development of diabetes at 1 year after MI were adiponectin, retinol protein, ghrelin, tumor necrosis factor α, and plasminogen activator inhibitor.

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We aimed to assess the clinical significance of serum levels of neutrophil gelatinase-associated lipocalin (sNGAL) for predicting in-hospital outcomes in patients with ST-elevated myocardial infarction (STEMI). Patients admitted within 24 hours of developing STEMI clinical symptoms were evaluated for sNGAL on hospitalization days 1 and 12. Recurrent myocardial infarction, early post-infarction angina, acute cerebrovascular accident, and death were assessed as adverse outcomes during hospitalization. The actors associated with adverse outcome were evaluated using univariate and multivariate regression analysis. Among the 260 STEMI patients included, 32% had ≥1 adverse in-hospital outcome, and significantly higher sNGAL on day 12, (but not on day 1) compared to sNGAL in patients with favorable outcome (p = 0.033). Type-2 diabetes mellitus, age > 60 years, reduced glomerular filtration rate during hospitalization, and high sNGAL on day 12 were identified as risk factors for adverse in-hospital outcome, associated with a 14% increase for each 1-year increment in age after 60 years, and a dramatic increase (3.2 times) for high sNGAL on day 12, with sNGAL ≥ 1.046 ng/ml indicating complicated hospitalization course. sNGAL concentration on the 12th day was associated with the existing adverse outcomes, acting as a marker of MI severity.