Faculty Bibliography

PURPOSE: Acetylsalicylic acid (ASA) dosing guidelines for ACS treatment are inconsistent and lack supporting data. This analysis evaluated the relationship between ASA maintenance dosing and clinical outcomes in patients with ACS who did not undergo revascularization and are managed medically. METHODS: A meta-analysis was conducted with random-effects modeling to estimate the frequency of clinical outcomes for low (75-149 mg) and high (150-325 mg) doses of ASA, using data from worldwide clinical and observational trials published from Jan 1995 to Feb 2010, available from PubMed, EMBASE and Current Contents. Clinical outcomes measured were: revascularization rate (overall rate, percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG]), cardiovascular (CV) death, all-cause death, myocardial infarction (MI), stroke, and bleeding at 1, 3, 6 and 12 months. RESULTS: Sixty-eight studies including 207,523 patients were accepted and appraised for quality using Oxford Centre for Evidence- Based Medicine scoring. Significant heterogeneity was seen in the results (quantified using the Cochran's Q statistics and the I² measures), due to differences in enrolment procedures, medical management regimens and timing of administration, study designs and some inconsistencies in the definitions of bleeding and MACE. At one month, the incidence of clinical outcomes with high- and low-dose ASA groups were 4.9% and 5.0% for MI; 6.3% and 3.7% for revascularization; 1.4% and 1.3% for stroke; 5.5% and 3.4% for CV death; 5.7% and 4.3% for all cause death; and 4.0% and 1.7% for major bleeding, respectively. Meta regression demonstrated a significant association between aspirin dose and major bleeding (p=0.037). Further data will be presented at the meeting. CONCLUSIONS: This analysis suggests that in patients receiving medical management for ACS, major bleeding occurred more frequently in patients who received higher doses of ASA. ASA dose does not have a statistically significant impact on the other outcomes analyzed

Summary Aim: To determine if an association exists between mean platelet volume (MPV) and acute myocardial infarction (AMI) and other cardiovascular events. Platelet activity is a major culprit in atherothrombotic events. Mean platelet volume, widely available in clinical practice, is a potentially useful biomarker of platelet activity in the setting of cardiovascular disease. Methods and Results: We performed a systematic review and meta-analysis investigating the association between MPV and AMI, all-cause mortality following MI, and restenosis following coronary angioplasty. Results were pooled using random effects modeling. Pooled results from 16 cross-sectional studies involving 2,809 patients investigating the association of MPV and AMI indicated that MPV was significantly higher in those with AMI than those without AMI (mean difference 0.92 fl, 95% confidence interval [CI] 0.67 to 1.16, P < 0.001). In subgroup analyses, significant differences in MPV existed between subjects with AMI versus stable coronary disease (P < 0.001) and versus stable controls (P < 0.001), but not versus unstable angina (P = 0.24). Pooled results from three cohort studies involving 3,184 patients evaluating the risk of death following AMI, demonstrated that an elevated MPV increased the odds of death compared with a normal MPV (11.5% versus 7.1%, odds ratio 1.65, 95% CI 1.12 to 2.52, P = 0.012). Pooled results from five cohort studies involving 430 patients who underwent coronary angioplasty revealed that MPV was significantly higher in patients who developed restenosis compared with those who did not develop restenosis (mean difference 0.98 fl, 95% CI 0.74 to 1.21, P < 0.001). Conclusions: Elevated MPV is associated with AMI, mortality following MI, and restenosis following coronary angioplasty. These data suggest that MPV is a potentially useful prognostic biomarker in patients with cardiovascular disease. Whether the relationship is causal, and whether MPV should influence practice or guide therapy remains unknown

Background The 2007 American Heart Association guidelines for cardiovascular disease prevention in women drew heavily on results from randomized clinical trials; however, representation of women in trials of cardiovascular disease prevention has not been systematically assessed. Methods and Results We abstracted 156 randomized clinical trials cited by the 2007 women's prevention guidelines to determine female representation over time and by clinical indication, prevention type, location of trial conduct, and funding source. Both women and men were represented in 135 of 156 (86.5%) trials; 20 trials enrolled only men; 1 enrolled only women. Among all trials, the proportion of women increased significantly over time, from 9% in 1970 to 41% in 2006. Considering only trials that enrolled both women and men, female enrollment was 18% in 1970 and increased to 34% in 2006. Female representation was higher in international versus United States\Nonly trials (32.7% versus 26.7%) and primary versus secondary prevention trials (42.6% versus 26.6%). Female enrollment was comparable in government/foundation-funded versus industry-funded trials (31.9% versus 31.5%). Representation of women was highest among trials in hypertension (44%), diabetes (40%), and stroke (38%) and lowest for heart failure (29%), coronary artery disease (25%), and hyperlipidemia (28%). By contrast, women accounted for 53% of all individuals with hypertension, 50% with diabetes, 51% with heart failure, 49% with hyperlipidemia, and 46% with coronary artery disease. Sex-specific results were discussed in only 31% of primary trial publications. Conclusions Enrollment of women in randomized clinical trials has increased over time but remains low relative to their overall representation in disease populations. Efforts are needed to reach a level of representation that is adequate to ensure evidence-based sex-specific recommendations

Cardiovascular disease is the number 1 cause of death in the western world and 1 of the leading causes of death worldwide. The lifetime risk of atherosclerotic cardiovascular disease (CVD) for persons at age 50 years, on average, is estimated to be 52% for men and 39% for women, with a wide variation depending on risk factor burden. Assessing patients' cardiovascular risk may be used for the targeting of preventive treatments of individual patients who are asymptomatic but at sufficiently high risk for the development of CVD. Risk stratifying patients for CVD remains challenging, particularly for those with low or intermediate short-term risk. Several algorithms have been described to facilitate the assessment of risk in individual patients. We describe 6 risk algorithms (Framingham Risk Score for coronary heart disease events and for cardiovascular events, Adult Treatment Panel III, SCORE [Systematic Coronary Risk Evaluation] project, Reynolds Risk Score, ASSIGN [Assessing Cardiovascular Risk to Scottish Intercollegiate Guidelines Network/SIGN to Assign Preventative Treatment], and QRISK [QRESEARCH Cardiovascular Risk Algorithm]) for outcomes, population derived/validated, receiver-operating characteristic, variables included, and limitations. Areas of uncertainty include 10-year versus lifetime risk, prediction of CVD or coronary heart disease end points, nonlaboratory-based risk scores, age at which to start, race and sex differences, and whether a risk score should guide therapy. We believe that the best high-risk approach to CVD evaluation and prevention lies in routine testing for cardiovascular risk factors and risk score assessment. We recommend that health care providers discuss the global cardiovascular risk and lifetime cardiovascular risk score assessment with each patient to better explain each patient's future risk. Appropriate intervention, guided by risk assessment, has the potential to bring about a significant reduction in population levels of risk

OBJECTIVES: We sought to determine whether mean platelet volume (MPV) is associated with the prevalence of peripheral artery disease (PAD). BACKGROUND: Platelets play a pivotal role in the pathogenesis of atherosclerosis and PAD. MPV, a measure of platelet size available in every blood count, is increasingly recognized as an important marker of platelet activity. METHODS: We analyzed data from 6354 participants aged 40 years and older from the 1999 to 2004 National Health and Nutrition Examination Survey (NHANES), a nationally representative sample of the US population. PAD was defined as an ankle brachial index </=0.90 in either leg. Odds ratios and 95% confidence intervals were estimated by logistic regression. RESULTS: The prevalence of PAD in the cohort was 5.7%. MPV was significantly associated with PAD prevalence (tertile 1 - 4.4%, tertile 2 - 6.1%, tertile 3 - 7.0%, P for trend=0.003). After adjustment for age, sex, and race, the odds ratio of PAD comparing the highest tertile to the lowest tertile was 1.57 (95% confidence interval 1.15-2.13). After further adjustment for smoking status, hypertension, hypercholesterolemia, diabetes, glomerular filtration rate, body mass index, and platelet count the corresponding odds ratio was 1.58 (95% confidence interval 1.14-2.19). The addition of triglycerides, hemoglobin A1c, and C-reactive protein did not affect the results. The significant association between MPV and PAD was unchanged when MPV was used as a continuous variable. CONCLUSIONS: Mean platelet volume is independently associated with PAD. These findings support the hypothesis that platelet size is an independent predictor of increased risk for PAD

BACKGROUND: The presence of atherosclerosis in extracardiac vascular beds is associated with an increased risk of adverse cardiovascular outcomes among stable patients with coronary artery disease (CAD). However, there is little data regarding the impact of the presence and extent of vascular disease on outcomes in patients with CAD undergoing percutaneous coronary intervention. METHODS AND RESULTS: We analyzed 69,045 consecutive patients from the New York State Coronary Angioplasty Reporting System database who underwent percutaneous coronary intervention between 1998 and 1999. Vascular disease burden was assessed by history of aortoiliac, femoral-popliteal, and carotid disease. Patients were stratified into 3 groups: CAD alone, CAD and 1 additional site, and CAD and 2 or 3 additional sites. A logistic regression model was constructed to determine the relation between vascular disease burden and in-hospital mortality. Any history of vascular disease was present in 5915 (8.6%) of the population, of whom 4840 (82%) had CAD and 1 other disease location and 1075 (18%) had CAD and 2 or 3 other disease locations. There was a significant relationship between the number of disease locations and hospital mortality, ranging from 0.7% in patients with CAD alone to 2.0% and 2.6% for patients with 1 or >or =2 disease locations, respectively (P<0.001). In unadjusted analysis, in-hospital mortality was approximately 3-fold higher (odds ratio, 2.89; 95% CI, 2.31 to 3.60; P<0.001) and 4-fold higher (odds ratio, 3.78; 95% CI, 2.57 to 5.56; P<0.001) for inpatients with CAD and additional vascular disease at 1 site and > or =2 sites, respectively. After multivariable adjustment, each additional vascular bed affected was associated with a 50% increase in in-hospital mortality (odds ratio, 1.50; 95% CI, 1.27 to 1.78; P<0.001). CONCLUSIONS: Among patients with CAD undergoing percutaneous coronary intervention, vascular disease burden is associated with higher rates of adverse events and is an independent predictor of in-hospital mortality