The fibronectin-splicing variant containing extra domain A (Fn-EDA) is present in negligible amounts in the plasma of healthy humans but markedly elevated in patients with comorbid conditions, including diabetes mellitus and hypercholesterolemia, which are risk factors for stroke. It remains unknown, however, whether Fn-EDA worsens stroke outcomes in such conditions. We determined the role of Fn-EDA in stroke outcome in a model of hypercholesterolemia, the apolipoprotein E-deficient (Apoe(-/-)) mouse.

Little is known about whether enrollment versus nonenrollment in Medicare's prescription drug plan (Part D) is associated with better outcomes after acute myocardial infarction (AMI).

Sex differences were observed with regard to warfarin treatment in patients with atrial fibrillation, with women having a higher risk of stroke compared with men. We aimed to compare sex differences in use, safety, and effectiveness of dabigatran.

The relationship between intake of fruits and vegetables (F/V) during young adulthood and coronary atherosclerosis later in life is unclear.

There is a global commitment to reduce premature cardiovascular diseases (CVDs) 25% by 2025. CVD mortality rates have declined dramatically over the past 2 decades, yet the number of life years lost to premature CVD deaths is increasing in low- and middle-income regions. Ischemic heart disease and stroke remain the leading causes of premature death in the world; however, there is wide regional variation in these patterns. Some regions, led by Central Asia, face particularly high rates of premature death from ischemic heart disease. Sub-Saharan Africa and Asia suffer disproportionately from death from stroke. The purpose of the present report is to (1) describe global trends and regional variation in premature mortality attributable to CVD, (2) review past and current approaches to the measurement of these trends, and (3) describe the limitations of existing models of epidemiological transitions for explaining the observed distribution and trends of CVD mortality. We describe extensive variation both between and within regions even while CVD remains a dominant cause of death. Policies and health interventions will need to be tailored and scaled for a broad range of local conditions to achieve global goals for the improvement of cardiovascular health.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in the regulation of cholesterol homeostasis. By binding to hepatic low-density lipoprotein (LDL) receptors and promoting their lysosomal degradation, PCSK9 reduces LDL uptake, leading to an increase in LDL cholesterol concentrations. Gain-of-function mutations in PCSK9 associated with high LDL cholesterol and premature cardiovascular disease have been causally implicated in the pathophysiology of autosomal-dominant familial hypercholesterolemia. In contrast, the more commonly expressed loss-of-function mutations in PCSK9 are associated with reduced LDL cholesterol and cardiovascular disease risk. The development of therapeutic approaches that inhibit PCSK9 function has therefore attracted considerable attention from clinicians and the pharmaceutical industry for the management of hypercholesterolemia and its associated cardiovascular disease risk. This review summarizes the effects of PCSK9 on hepatic and intestinal lipid metabolism and the more recently explored functions of PCSK9 in extrahepatic tissues. Therapeutic approaches that prevent interaction of PCSK9 with hepatic LDL receptors (monoclonal antibodies, mimetic peptides), inhibit PCSK9 synthesis in the endoplasmic reticulum (antisense oligonucleotides, siRNAs), and interfere with PCSK9 function (small molecules) are also described. Finally, clinical trials testing the safety and efficacy of monoclonal antibodies to PCSK9 are reviewed. These have shown dose-dependent decreases in LDL cholesterol (44%-65%), apolipoprotein B (48%-59%), and lipoprotein(a) (27%-50%) without major adverse effects in various high-risk patient categories, including those with statin intolerance. Initial reports from 2 of these trials have indicated the expected reduction in cardiovascular events. Hence, inhibition of PCSK9 holds considerable promise as a therapeutic option for decreasing cardiovascular disease risk.

The development of effective and safe antiarrhythmic drugs for atrial fibrillation (AF) rhythm control is an unmet clinical need. Multichannel blockers are believed to have advantages over single-channel blockers for AF, but their development has been completely empirical to date. We tested the hypothesis that adding K(+)-channel blockade improves the atrium-selective electrophysiological profile and anti-AF effects of optimized Na(+)-channel blockers.

The mechanism(s) of persistent and long-standing persistent (LSP) atrial fibrillation (AF) is/are poorly understood. We performed high-density, simultaneous, biatrial, epicardial mapping of persistent and LSP AF in patients undergoing open heart surgery (1) to test the hypothesis that persistent and LSP AF are due to ≥ 1 drivers, either focal or reentrant, and (2) to characterize associated atrial activation.