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.

Patients with stable angina and normal coronary arteries or diffuse non-obstructive CAD have elevated risks of MACE and all-cause mortality compared with a reference population without ischaemic heart disease.

Background-Recent studies have suggested that higher body mass index (BMI) is associated with improved prognosis in chronic heart failure (CHF). The adipocytokine adiponectin is inversely associated with BMI, and in healthy subjects, low adiponectin is a predictor of mortality. In a prospective study, we therefore evaluated the association between plasma adiponectin levels and mortality among patients with CHF. Methods and Results-In 195 CHF patients (age 69.3Ϯ10.2 years, BMI 27.3Ϯ5.2 kg/m 2 , left ventricular ejection fraction 30Ϯ8.9%, meanϮSD), plasma adiponectin and N-terminal pro brain natriuretic peptide (NT-proBNP) were measured at baseline. Adiponectin was positively associated with NT-proBNP (␤ϭ0.47, PϽ0.001), and both biomarkers were negatively associated with BMI (␤ϭϪ0.43, PϽ0.001 for adiponectin and ␤ϭϪ0.38, PϽ0.001 for NT-proBNP, respectively) During a median follow-up of 2.6 years, 46 (23.5%) of the patients died. After adjustment for clinical variables associated with CHF severity (age, systolic blood pressure, left ventricular ejection fraction Ͻ25%, duration of CHF, and creatinine clearance) and for NT-proBNP, the hazard ratio of mortality for values in the 2 upper tertiles relative to the lowest tertile of adiponectin was 3.23 (Pϭ0.032). BMI predicted mortality independently of clinical parameters of CHF severity (hazard ratioϭ0.63, Pϭ0.012), but this association became insignificant after additional adjustment for Pϭ0.13). Conclusions-A high adiponectin level was a predictor of mortality, independent of risk markers of CHF severity, presumably because of its role as a marker for wasting. BMI was also associated with mortality, but a part of this relation may be mediated by adiponectin and NT-proBNP levels.

The embedded cobordism category under study in this paper generalizes the category of conformal surfaces, introduced by G. Segal in [Seg04] in order to formalize the concept of field theories. Our main result identifies the homotopy type of the classifying space of the embedded d-dimensional cobordism category for all d. For d = 2, our results lead to a new proof of the generalized Mumford conjecture, somewhat different in spirit from the original one, presented in [MW02]. Contents 1. Introduction and results 2. The cobordism category and its sheaves 2.1. The cobordism category 2.2. Recollection from [MW02] on sheaves 2.3. A sheaf model for the cobordism category 2.4. Cocycle sheaves 3. The Thom spectra and their sheaves 3.1. The spectrum MT (d) and its infinite loop space 3.2. Using Phillips' submersion theorem 4. Proof of the main theorem 5. Tangential structures 6. Connectedness issues 6.1. Discussion 6.2. Surgery 6.3. Connectivity 6.4. Parametrized surgery 7. Harer type stability and C 2 References