Abstract-The Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program issued anevidence-based set of guidelines on cholesterol management in 2001. Since the publication of ATP III, 5 major clinical trials of statin therapy with clinical end points have been published. These trials addressed issues that were not examined in previous clinical trials of cholesterol-lowering therapy. The present document reviews the results of these recent trials and assesses their implications for cholesterol management. Therapeutic lifestyle changes (TLC) remain an essential modality in clinical management. The trials confirm the benefit of cholesterol-lowering therapy in high-risk patients and support the ATP III treatment goal of low-density lipoprotein cholesterol (LDL-C) Ͻ100 mg/dL. They support the inclusion of patients with diabetes in the high-risk category and confirm the benefits of LDL-lowering therapy in these patients. They further confirm that older persons benefit from therapeutic lowering of LDL-C. The major recommendations for modifications to footnote the ATP III treatment algorithm are the following. In high-risk persons, the recommended LDL-C goal is Ͻ100 mg/dL, but when risk is very high, an LDL-C goal of Ͻ70 mg/dL is a therapeutic option, ie, a reasonable clinical strategy, on the basis of available clinical trial evidence. This therapeutic option extends also to patients at very high risk who have a baseline LDL-C Ͻ100 mg/dL. Moreover, when a high-risk patient has high triglycerides or low high-density lipoprotein cholesterol (HDL-C), consideration can be given to combining a fibrate or nicotinic acid with an LDL-lowering drug. For moderately high-risk persons (2ϩ risk factors and 10-year risk 10% to 20%), the recommended LDL-C goal is Ͻ130 mg/dL, but an LDL-C goal Ͻ100 mg/dL is a therapeutic option on the basis of recent trial evidence. The latter option extends also to moderately high-risk persons with a baseline LDL-C of 100 to 129 mg/dL. When LDL-lowering drug therapy is employed in high-risk or moderately high-risk persons, it is advised that intensity of therapy be sufficient to achieve at least a 30% to 40% reduction in LDL-C levels. Moreover, any person at high risk or moderately high risk who has lifestyle-related risk factors (eg, obesity, physical inactivity, elevated triglycerides, low HDL-C, or metabolic syndrome) is a candidate for TLC to modify these risk factors regardless of LDL-C level. Finally, for people in lower-risk categories, recent clinical trials do not modify the goals and cutpoints of therapy.

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Objective We investigated whether coronary microvascular dysfunction predicts major adverse outcomes during follow-up among women with signs and symptoms of ischemia. Background Altered coronary reactivity occurs frequently in women evaluated for suspected ischemia and the endothelium-dependent component is linked with adverse outcomes. Possible links between endothelium-independent microvascular coronary reactivity and adverse outcomes remain uncertain. Methods As part of the National Heart, Lung and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE), we investigated relationships between major adverse outcomes and baseline coronary flow reserve (CFR) following intracoronary adenosine in 189 women referred to evaluate suspected ischemia. Results At 5.4 (mean) years, we observed significant associations between CFR and major adverse outcomes (death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure). An exploratory ROC analysis identified CFR <2.32 as the best discriminating threshold for adverse outcomes (event rate 26.7% and ≥2.32 event rate 12.2%; p = 0.01). Lower CFR was associated with increased risk for major adverse outcomes (HR 1.16, 95% CI 1.04 to 1.30; p = 0.009). This held true among the 152 women without obstructive coronary artery disease (CAD) (HR 1.20, 95% CI 1.05 to 1.38; p = 0.008). CFR significantly improved prediction of adverse outcomes over angiographic CAD severity and other risk conditions. Conclusions Among women with suspected ischemia and atherosclerosis risk factors, coronary microvascular reactivity to adenosine significantly improves prediction of major adverse outcomes over angiographic CAD severity and CAD risk factors. These findings suggest coronary microvessels represent novel targets for diagnostic and therapeutic strategies to predict and limit adverse outcomes in women.

Background-Although populations referred for coronary angiography are increasingly diverse, there is limited information on coronary artery disease (CAD) prevalence and in-hospital mortality other than for predominately white male patients. Methods and Results-We examined gender and ethnic differences in CAD prevalence and in-hospital mortality in a prospective cohort of patients referred for angiographic evaluation of stable angina (nϭ375 886) or acute coronary syndromes (ACS; unstable angina or myocardial infarction, nϭ450 329) at 388 US hospitals participating in the American College of Cardiology-National Cardiovascular Data Registry, an angiographic registry. Univariable and multivariable (with covariates that included risk factors, symptoms, and comorbidities) logistic regression models were used to estimate significant CAD, defined as Ն70% stenosis, and in-hospital mortality. Within stable angina and ACS cohorts, 7% of patients were black, 2% were Hispanic, 0.3% were Native American, 1% were Asian, and 90% were white, respectively. In stable angina, the risk-adjusted OR for significant CAD was 0.34 for women compared with men (PϽ0.0001), with black women having the lowest risk-adjusted odds (PϽ0.0001) compared with other females. Among ACS patients, the risk-adjusted OR of significant CAD was 0.47 for women compared with men (PϽ0.0001); similarly, black women had the lowest risk-adjusted odds (PϽ0.0001) compared with other females. Higher in-hospital mortality was reported for white women presenting with stable angina (PϽ0.00001). White women had a 1.34-fold (95% CI 1.21 to 1.48) higher risk-adjusted odds ratio for mortality than white men with stable angina (PϽ0.0001), with higher rates noted for white women who were older or had significant CAD (both PϽ0.0001). Lower utilization of elective coronary revascularization, aspirin, and glycoprotein IIb/IIIa inhibitors (all PϽ0.0001) may have contributed to higher in-hospital mortality for white women. In ACS, higher in-hospital mortality was reported for Hispanic (Pϭ0.015) and white (PϽ0.0001) women; however, neither white (Pϭ0.51) or Hispanic (Pϭ0.13) women had higher in-hospital risk-adjusted mortality. Conclusions-The likelihood for significant CAD at coronary angiography and for in-hospital mortality varied significantly by ethnicity and gender. Future clinical practice guidelines should be tailored to gender subsets of the population, in particular for black women, to improve the efficient use of angiographic laboratories and to target at-risk populations of women and men.

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