Pathways Forward in Cardiovascular Disease Prevention One and a Half Years After Publication of the 2013 ACC/AHA Cardiovascular Disease Prevention Guidelines.

The 2013 American College of Cardiology/American Heart Association cardiovascular disease prevention guidelines represent an important step forward in the risk assessment and management of atherosclerotic cardiovascular disease in clinical practice. Differentiated risk prediction equations for women and black individuals were developed, and convenient 10-year and lifetime risk assessment tools were provided, facilitating their implementation. Lifestyle modification was portrayed as the foundation of preventive therapy. In addition, based on high-quality evidence from randomized controlled trials, statins were prioritized as the first lipid-lowering pharmacologic treatment, and a shared decision-making model between the physician and the patient was emphasized as a key feature of personalized care. After publication of the guidelines, however, important limitations were also identified. This resulted in a constructive scientific debate yielding valuable insights into potential opportunities to refine recommendations, fill gaps in guidance, and better harmonize recommendations within and outside the United States. The latter point deserves emphasis because when guidelines are in disagreement, this may result in nonaction on the part of professional caregivers or nonadherence by patients. In this review, we discuss the key scientific literature relevant to the guidelines published in the year and a half after their release. We aim to provide cohesive, evidence-based views that may offer pathways forward in cardiovascular disease prevention toward greater consensus and benefit the practice of clinical medicine.

Estrogen attenuates TGF-ß1-induced EMT in intrauterine adhesion by activating Wnt/ß-catenin signaling pathway

Although estrogen has crucial functions for endometrium growth, the specific dose and underlying molecular mechanism in intrauterine adhesion (IUA) remain unclear. In this study, we aimed to investigate the effects of estrogen on epithelial-mesenchymal transition (EMT) in normal and fibrotic endometrium, and the role of estrogen and Wnt/β-catenin signaling in the formation of endometrial fibrosis. CCK-8 and immunofluorescence assay were performed to access the proliferation of different concentrations of estrogen on normal human endometrial epithelial cells (hEECs). qRT-PCR and western blot assay were utilized to explore the effect of estrogen on EMT in normal and fibrotic endometrium, and main components of Wnt/β-catenin signaling pathway in vitro. Hematoxylin and eosin and Masson staining were used to evaluate the effect of estrogen on endometrial morphology and fibrosis in vivo. Our results indicated that the proliferation of normal hEECs was inhibited by estrogen at a concentration of 30 nM accompanied by upregulation of mesenchymal markers and downregulation of epithelial markers. Interestingly, in the model of transforming growth factor β1 (TGF-β1)-induced endometrial fibrosis, the same concentration of estrogen inhibited the process of EMT, which might be partially mediated by regulation of the Wnt/β-catenin pathway. In addition, relatively high doses of estrogen efficiently increased the number of endometrial glands and reduced the area of fibrosis as determined by the reduction of EMT in IUA animal models. Taken together, our results demonstrated that an appropriate concentration of estrogen may prevent the occurrence and development of IUA by inhibiting the TGF-β1-induced EMT and activating the Wnt/β-catenin pathway.

Landmark lipid-lowering trials in the primary prevention of cardiovascular disease.

Although atherosclerotic cardiovascular disease (CVD) is the most common cause of morbidity and mortality in the world, the long disease latency affords ample opportunity for preventive care. Indeed, lifelong exposure to atherogenic apoliprotein B-containing lipoproteins has consistently been shown to increase the cumulative risk of suffering a CVD event, including myocardial infarction, stroke, and symptomatic peripheral arterial disease. Over the past 25 years, lipid-lowering therapies have been developed that are proven to not only lower cholesterol, but also to decrease adverse CVD events and CVD mortality. This review will highlight several key clinical trials encompassing several classes of lipid-lowering medications that have provided clinicians with an evidence-based framework for managing their patients' cardiovascular risk.