Faculty Bibliography

BACKGROUND: Differences in pathophysiology, diagnosis, and treatment of women with cardiovascular disease compared with men has become a major focus during the past decade. Nevertheless, little attention has focused on improving the quality of healthcare in women compared with other areas of cardiovascular medicine. METHODS: To address this deficit, Duke University Medical Center convened a national Duke Clinical Research Institute (DCRI) Think Tank meeting, including basic science and clinical researchers, payers, legislators, clinical experts, government regulators, and members of the pharmaceutical and device industries. This report provides an overview of the discussions and proposed solutions. RESULTS: Discussion concentrated on the development of strategies to improve the quality of health care for women with heart disease. Key components to improve quality care include: (1) enhance the quantity and quality of evidence-based medicine to guide care in women through improvements in trial design, enrollment and retention of women subjects, results analysis and reporting, and better incentives to perform research in women; (2) provide incentives to develop better data in women through mandating changes in the drug and device development and approval processes; (3) incorporate specific recommendations for women into guidelines when data are sufficient; and (4) apply proven sex-based differences in risk stratification, diagnostic testing, and drug usage and dosing in clinical care. Examples of possible strategies are included. CONCLUSION: The above approach represents a necessary, but not sufficient, platform to improve the overall quality of healthcare in women with cardiovascular disease

OBJECTIVE: Sustained ventricular arrhythmias complicate 2% to 20% of acute myocardial infarctions (MIs) and are associated with increased in-hospital mortality. However, it remains unclear whether successful mechanical revascularization improves outcomes in these patients. The objective of this analysis was to identify predictors of sustained ventricular arrhythmias after acute MI and to determine the influence of successful revascularization on in-hospital mortality. METHODS: We conducted a retrospective cohort study of all patients who underwent percutaneous coronary intervention for acute MI in New York State between 1997 and 1999. RESULTS: Of the 9015 patients who underwent percutaneous coronary intervention for acute MI, 472 (5.2%) developed sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) before revascularization. After multivariable adjustment, independent predictors of sustained VT/VF included cardiogenic shock (odds ratio [OR], 4.10; 95% confidence interval [CI], 3.20-5.58; P <.001), heart failure (OR, 2.86; 95% CI, 2.24-3.67: P <.001), chronic kidney disease (OR, 2.58; 95% CI, 1.27-5.23; P=.009), and presentation within 6 hours of symptom onset (OR, 1.46; 95% CI, 1.18-1.81; P=.001). Patients with sustained VT/VF had greater in-hospital mortality (16.3% vs 3.7%, P <.001). Although successful percutaneous coronary intervention was associated with decreased in-hospital mortality in patients with VT/VF (P <.001), patients with sustained VT/VF and successful revascularization experienced increased mortality compared with patients without sustained ventricular arrhythmias (P <.001). CONCLUSION: Among patients undergoing percutaneous coronary intervention for acute MI, sustained VT/VF remains a significant complication associated with a 4-fold increased risk of in-hospital mortality. Early mortality is reduced after successful percutaneous coronary intervention, but remains elevated in this high-risk group

Few studies have investigated the role of elevated lipoprotein-associated phospholipase A2 (Lp-PLA(2)) with stroke risk, and those that have are based on small numbers of strokes. No study has evaluated the effect of hormone therapy use on the association of Lp-PLA(2) and stroke. We assessed the relationship between Lp-PLA(2) and the risk of incident ischemic stroke in 929 stroke patients and 935 control subjects in the Hormones and Biomarkers Predicting Stroke Study, a nested case-control study from the Women's Health Initiative Observational Study. Mean (SD) levels of Lp-PLA(2) were significantly higher among case subjects (309.0 [97.1]) than control subjects (296.3 [87.3]; P<0.01). Odds ratio for ischemic stroke for the highest quartile of Lp-PLA(2), compared with lowest, controlling for multiple covariates, was 1.08 (95% CI: 0.75 to 1.55). However, among 1137 nonusers of hormone therapy at baseline, the corresponding odds ratio was 1.55 (95% CI: 1.05 to 2.28),whereas there was no significant association among 737 hormone users (odds ratio: 0.70; 95% CI: 0.42 to 1.17; P for interaction=0.055). Moreover, among nonhormone users, women with high C-reactive protein and high Lp-PLA2 had more than twice the risk of stroke (odds ratio: 2.26; 95% CI: 1.55 to 3.35) compared with women low levels in both biomarkers. Furthermore, different stroke cases were identified as high risk by Lp-PLA(2) rather than by C-reactive protein. Lp-PLA(2) was associated with incident ischemic stroke independently of C-reactive protein and traditional cardiovascular risk factors among nonusers of hormone therapy with highest risk in those who had both high C-reactive protein and high Lp-PLA(2)

BACKGROUND: Although treatment with immediate aspirin reduces morbidity and mortality in ST-elevation myocardial infarction, the optimal dose is unclear. We therefore compared the acute mortality and bleeding risks associated with the initial use of 162 versus 325 mg aspirin in fibrinolytic-treated ST-elevation myocardial infarction patients. METHODS AND RESULTS: Using combined data from the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO I) and Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO III) trials (n=48 422 ST-elevation myocardial infarction patients), we compared the association between initial aspirin dose of 162 versus 325 mg and 24-hour and 7-day mortality, as well as rates of in-hospital moderate/severe bleeding. Results were adjusted for previously identified mortality and bleeding risk factors. Overall, 24.4% of patients (n=11 828) received an initial aspirin dose of 325 mg, and 75.6% (n=36 594) received 162 mg. The 24-hour mortality rates were 2.9% versus 2.8% (P=0.894) for those receiving an initial aspirin dose of 325 versus 162 mg. Mortality rates at 7 and 30 days were 5.2% versus 4.9% (P=0.118) and 7.1% versus 6.5% (P=0.017) among patients receiving the 325 versus 162 mg aspirin. After adjustment, aspirin dose was not associated with 24-hour (odds ratio [OR], 1.01; 95% CI, 0.82 to 1.25), 7-day (OR, 1.00; 95% CI, 0.87 to 1.17), or 30-day (OR, 0.99; 95% CI, 0.87 to 1.12) mortality rates. No significant difference was noted for myocardial infarction or the composite of death or myocardial infarction between groups. In-hospital moderate/severe bleeding occurred in 9.3% of those treated with 325 mg versus 12.2% among those receiving 162 mg (P<0.001). After adjustment, 325 mg was associated with a significant increase in moderate/severe bleeding (OR, 1.14; 95% CI, 1.05 to 1.24; P=0.003). CONCLUSIONS: These data suggest that an initial dose of 162 mg aspirin may be as effective as and perhaps safer than 325 mg for the acute treatment of ST-elevation myocardial infarction

We examined risk factors associated with failure of arterial catheterization in the medical intensive care unit of a large urban teaching hospital. We analyzed 92 consecutive arterial catheterizations by internal medicine house staff and critical care fellows. Of the 92 attempts, 26.1% were done on femoral arteries, and 73.9% were done on radial arteries. Failure, which occurred in 28% of attempts, was more common in female patients (P < .001). The failure rate was 50.0% for attempts on femoral arteries and 20.6% on radial arteries. Systolic blood pressure was significantly lower in patients where the attempt failed (P = .024). In univariate analyses, hemoglobin values were lower (P = .028) and number of percutaneous punctures were higher (P = .019) in patients where catheterization failed. After multivariate analysis, only gender and systolic blood pressure remained statistically significant. The strongest predictor of failure was female gender. A possible explanation not explored here could be smaller arterial size in female patients

Previous studies have demonstrated a significant interaction between gender and age after medically treated acute myocardial infarction (AMI), when younger women were found to have a higher mortality rate than younger men, but the mortality rate for older men and women was similar. The study objective was to determine whether a gender-age interaction exists for AMI treated exclusively with primary angioplasty. This analysis was a retrospective cohort study of 9,015 consecutive patients who underwent primary angioplasty for AMI in New York State from 1997 to 1999. The primary end point of interest was in-hospital mortality. A logistic regression model was constructed to determine the relation between gender and mortality among patients with AMI treated with angioplasty. Additional analyses were performed to test whether a mortality difference existed according to age. In-hospital mortality rate was twofold higher in women than in men (6.7% vs 3.4%, p <0.001). After adjusting for age, co-morbid conditions, and hemodynamic status by multivariable logistic regression analysis, the odds ratio for in-hospital death for women was no longer significant (odds ratio 1.21, 95% confidence interval 0.69 to 2.10, p = 0.51). Among patients <75 years of age, women had a 37% increased risk of in-hospital mortality (adjusted odds ratio 1.37, 95% confidence interval 1.01 to 1.98, p = 0.04), whereas there was no significant difference in mortality between men and women who were >or=75 years of age. In conclusion, female gender was found to be an independent predictor of in-hospital mortality in patients <75 years of age after primary angioplasty for AMI

In many individuals, the first indicator of atherosclerosis is an acute heart attack, which is often fatal. Despite innovations in medical therapy and interventional cardiology techniques, coronary artery disease continues to be the leading cause of death in the USA. There is great interest in identifying vulnerable plaques and vulnerable patients as a possible means to stem the tide against coronary artery disease. Improvements in diagnostic studies and development of novel imaging tools have opened the possibilities for significant advances in the management of vulnerable plaque. The result of improved risk stratification, by both noninvasive and invasive means, will be a better assessment of the risk/benefit relationships for the novel therapies that are needed to further reduce the morbidity and mortality of the disease. Correct identification of vulnerable plaque would permit the use of more effective systemic treatment and enable clinical trials to study the supplemental benefit from local treatments

OBJECTIVES: We sought to evaluate the impact of GP IIb/IIIa receptor blockers on long-term mortality in patients undergoing PCI for AMI. BACKGROUND: Glycoprotein (GP) IIb/IIIa inhibitors are potent suppressors of platelet aggregation and when used during percutaneous coronary intervention (PCI) for the treatment of acute myocardial infarction (AMI) may improve short-term clinical outcomes, including survival. However, the impact of GP IIb/IIIa treatment during PCI for AMI on long-term survival is unknown. METHODS: Patients undergoing primary or rescue PCI for AMI within 24 hours of symptom onset with or without GP IIb/IIIa inhibitor treatment were identified from a multicenter PCI database. All cause mortality at a mean follow-up of 3 years was the primary end point. RESULTS: Of the 269 patients treated with primary or rescue PCI for AMI, 107 (40%) received a GP IIb/IIIa antagonist. Patients treated with GP inhibitors were more likely to present with or develop heart failure (13% vs. 6.2%, P = 0.052). Left ventricular ejection fraction was reduced in those treated with GP IIb/IIIa antagonists (44% vs. 48%, P = 0.051). The extent of coronary artery disease did not differ between groups. Stent use was 80% in both groups. Procedural success was high and did not differ between groups. In-hospital mortality was low and did not differ between groups. The mortality at a mean follow-up of 3 years was 1.9% among patients treated with a GP IIb/IIIa antagonist and 15% for those who were not treated (log-rank P = 0.0005). Treatment with a GP IIb/IIIa antagonist was independently associated with a significant reduction in the hazard of long-term mortality (Hazard Ratio, 0.159; 95% Confidence Interval, 0.034-0.729; P = 0.018). CONCLUSIONS: Treatment of patients undergoing PCI for AMI with GP IIb/IIIa antagonists appears to be associated with a profound reduction in late mortality