Temporal Trends Analysis of the Characteristics, Management, and Outcomes of Women With Acute Coronary Syndrome (ACS): ACS Israeli Survey Registry 2000-2016.

Background Cardiovascular disease remains a leading cause of death among women. Despite improvements in the management of patients with acute coronary syndrome (ACS), women with an ACS remain at higher risk. Methods and Results We performed a time-dependent analysis of the management and outcomes of women admitted with ACS who enrolled in the prospective biennial ACS Israeli Surveys between 2000 and 2016. Surveys were divided into 3 time periods (2000-2004, 2006-2010, and 2013-2016). Outcomes included 30-day major adverse cardiac events (death, myocardial infarction, stroke, unstable angina, stent thrombosis, urgent revascularization) and 1-year mortality. Overall, 3518 women were admitted with an ACS. Their mean age (70±12 years) was similar among the time periods. Over the time course of the study, more women were admitted with non-ST-elevation ACS (51.9%, 59.6%, and 66.1%, respectively; P<0.001), and statins and percutaneous coronary intervention were increasingly utilized (66%, 91%, 93%, and 42%, 60%, and 68%, respectively; P<0.001 for each). Among women with ST-segment-elevation myocardial infarction, more primary percutaneous coronary interventions were performed (48.5%, 84.7%, and 95.3%, respectively; P<0.001). The rate of 30-day major adverse cardiac events has significantly decreased over the years (24.6%, 18.6%, and 13.5%, respectively; P<0.001). However, 1-year mortality rates declined only from 2000 to 2004 (16.9%, 12.8%, and 12.3%; P=0.007 for the overall difference), and this change was not significant after propensity matching or multivariate analysis. Conclusions Over more than a decade, 30-day major adverse cardiac events have decreased among women with ACS. Advances in pharmacological treatments and an early invasive approach may have accounted for this improvement. However, the lack of further reduction in 1-year mortality rates among women suggests that more measures should be provided in this high-risk population.

miRNA proxy approach reveals hidden functions of glycosylation.

Glycosylation, the most abundant posttranslational modification, holds an unprecedented capacity for altering biological function. Our ability to harness glycosylation as a means to control biological systems is hampered by our inability to pinpoint the specific glycans and corresponding biosynthetic enzymes underlying a biological process. Herein we identify glycosylation enzymes acting as regulatory elements within a pathway using microRNA (miRNA) as a proxy. Leveraging the target network of the miRNA-200 family (miR-200f), regulators of epithelial-to-mesenchymal transition (EMT), we pinpoint genes encoding multiple promesenchymal glycosylation enzymes (glycogenes). We focus on three enzymes, beta-1,3-glucosyltransferase (B3GLCT), beta-galactoside alpha-2,3-sialyltransferase 5 (ST3GAL5), and (alpha-N-acetyl-neuraminyl-2,3-beta-galactosyl-1,3)-N-acetylgalactosaminide alpha-2,6-sialyltransferase 5 (ST6GALNAC5), encoding glycans that are difficult to analyze by traditional methods. Silencing these glycogenes phenocopied the effect of miR-200f, inducing mesenchymal-to-epithelial transition. In addition, all three are up-regulated in TGF-ß-induced EMT, suggesting tight integration within the EMT-signaling network. Our work indicates that miRNA can act as a relatively simple proxy to decrypt which glycogenes, including those encoding difficult-to-analyze structures (e.g., proteoglycans, glycolipids), are functionally important in a biological pathway, setting the stage for the rapid identification of glycosylation enzymes driving disease states.