Coronary artery disease in post-menopausal women: are there appropriate means of assessment?

The recognition of sex differences in cardiovascular disease, particularly the manifestations of coronary artery disease (CAD) in post-menopausal women, has introduced new challenges in not only understanding disease mechanisms but also identifying appropriate clinical means of assessing the efficacy of management strategies. For example, the majority of treatment algorithms for CAD are derived from the study of males, focus on epicardial stenoses, and inadequately account for the small intramyocardial vessel disease in women. However, newer investigational modalities, including stress perfusion cardiac magnetic resonance imaging and positron emission tomography are providing enhanced diagnostic accuracy and prognostication for women with microvascular disease. Moreover, these investigations may soon be complemented by simpler screening tools such as retinal vasculature imaging, as well as novel biomarkers (e.g. heat shock protein 27). Hence, it is vital that robust, sex-specific cardiovascular imaging modalities and biomarkers continue to be developed and are incorporated into practice guidelines that are used to manage women with CAD, as well as gauge the efficacy of any new treatment modalities. This review provides an overview of some of the sex differences in CAD and highlights emerging advances in the investigation of CAD in post-menopausal women.

Chronic over-expression of heat shock protein 27 attenuates atherogenesis and enhances plaque remodeling: a combined histological and mechanical assessment of aortic lesions.

AIMS: Expression of Heat Shock Protein-27 (HSP27) is reduced in human coronary atherosclerosis. Over-expression of HSP27 is protective against the early formation of lesions in atherosclerosis-prone apoE(-/-) mice (apoE(-/-)HSP27(o/e)) - however, only in females. We now seek to determine if chronic HSP27 over-expression is protective in a model of advanced atherosclerosis in both male and female apoE(-/-) mice. METHODS AND RESULTS: After 12 weeks on a high fat diet, serum HSP27 levels rose more than 16-fold in male and female apoE(-/-)HSP27(o/e) mice, although females had higher levels than males. Relative to apoE(-/-) mice, female apoE(-/-)HSP27(o/e) mice showed reductions in aortic lesion area of 35% for en face and 30% for cross-sectional sinus tissue sections - with the same parameters reduced by 21% and 24% in male cohorts; respectively. Aortic plaques from apoE(-/-)HSP27(o/e) mice showed almost 50% reductions in the area occupied by cholesterol clefts and free cholesterol, with fewer macrophages and reduced apoptosis but greater intimal smooth muscle cell and collagen content. The analysis of the aortic mechanical properties showed increased vessel stiffness in apoE(-/-)HSP27(o/e) mice (41% in female, 34% in male) compare to apoE(-/-) counterparts. CONCLUSIONS: Chronic over-expression of HSP27 is atheroprotective in both sexes and coincides with reductions in lesion cholesterol accumulation as well as favorable plaque remodeling. These data provide new clues as to how HSP27 may improve not only the composition of atherosclerotic lesions but potentially their stability and resilience to plaque rupture.

Bivalirudin for primary percutaneous coronary interventions: outcome assessment in the Ottawa STEMI registry.

BACKGROUND: Data from randomized trials has demonstrated the superiority of bivalirudin to glycoprotein IIb/IIIa inhibitors plus heparin in patients undergoing primary percutaneous coronary intervention. Real-world performance of bivalirudin in primary percutaneous coronary intervention and the benefit of bivalirudin over heparin remain unknown in an era of routine dual antiplatelet therapy. METHODS AND RESULTS: From July 2004 to December 2010, 2317 consecutive patients were indexed in the University of Ottawa Heart Institute ST-segment-elevation myocardial infarction registry. During this period 748 patients received bivalirudin, 699 patients received glycoprotein IIb/IIIa inhibitors, and 676 patients received unfractionated heparin alone. The primary outcome was the rate of noncoronary artery bypass graft related thrombolysis in myocardial infarction major bleeding. Bivalirudin significantly reduced the primary outcome compared with heparin plus glycoprotein IIb/IIIa inhibitors (2.7% versus 7.3%, adjusted OR 2.96, 95% CI: 1.61-5.45, P<0.001) and the composite end point of death, stroke, reinfarction and major bleed (OR 1.66, 95% CI: 1.12-2.45, P=0.01). Compared with heparin alone, a reduction in major bleeds (OR 1.21, 95% CI: 0.60-2.44, P=0.59) or the composite end point (1.05, 95% CI: 0.68-1.63, P=0.83) with bivalirudin could not be demonstrated. Notably, major bleeding was associated with a 5-fold increase in the risk of mortality both in-hospital (3.5% versus 20.6%) and out to 180 days (5.6% versus 25.8%). CONCLUSIONS: Bivalirudin use compared with glycoprotein IIb/IIIa inhibitors plus heparin as an antithrombotic strategy in primary percutaneous coronary intervention results in less major bleeding in contemporary practice. A benefit of bivalirudin over heparin could not be established with this registry and requires additional investigations to either confirm or refute.

Hospitalization costs of primary stenting versus thrombolysis in acute myocardial infarction: cost analysis of the Canadian STAT Study.

BACKGROUND: We previously showed that primary stenting was more effective than accelerated tPA in reducing the 6-month composite of death, reinfarction, stroke, or repeat revascularization for ischemia. This study looks at the hospitalization costs of primary stenting compared with accelerated tPA. METHODS AND RESULTS: Initial and 6-month hospitalization costs were computed for all patients randomly assigned to primary stenting (n=62) or accelerated tPA (n=61) in the Stenting versus Thrombolysis in Acute myocardial infarction Trial (STAT). Costs and resource usage were collected in detail for each patient. Physician fees were obtained directly from billings to the Ontario Health Insurance Plan. The length of initial hospitalization was 6.7+/-11.3 days in the stent group and 8.7+/-6.7 days in the tPA group (P<0.001). Total hospitalization days at 6 months were 8.3+/-13 days in the stent group and 12.1+/-14.0 days in the tPA group (P=0.001). Hospitalization costs were less in the stent group for the initial hospitalization, 6354 dollars +/-6382 versus 7893 dollars +/-4429 (P=0.001), and at 6 months, 7100 dollars +/-7111 versus 9559 dollars +/-6933 (P=0.001). CONCLUSIONS: In centers in which facilities and experienced interventionists are available, primary stenting is less costly and more effective than thrombolysis.