Faculty Bibliography

Cardiovascular disease is a major cause of morbidity and mortality. Numerous risk scores exist to identify healthy individuals at increased risk of developing cardiovascular disease. Although platelets are a key mediator in the pathogenesis of cardiovascular disease, the role of platelet activity measurements and the incidence of cardiovascular disease are uncertain. Platelet aggregometry-the most well studied method of platelet function testing-is associated with risk factors for cardiovascular disease. However, data supporting platelet aggregation and incident cardiovascular disease is conflicting. Plasma markers of platelet activation are promising candidates. Soluble CD40L and P-selectin are easily measured with a standardized ELISA, and there is some data to suggest an association with cardiovascular disease, but further studies are required. While mean platelet volume is a promising candidate, platelet count and bleeding time are not specific for platelet activity nor are they associated with cardiovascular disease in a healthy population. For this field to progress, we recommend large-scale, prospective studies that measure a battery of these platelet function tests in individuals without cardiovascular disease to better understand the associations, if any, between platelet activity and cardiovascular disease

BACKGROUND: The benefit of aspirin to prevent cardiovascular events in subjects without clinical cardiovascular disease relative to the increased risk of bleeding is uncertain. METHODS: A meta-analysis of randomized trials of aspirin versus placebo/control to assess the effect of aspirin on major cardiovascular events (MCEs) (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death), individual components of the MCE, stroke subtype, all-cause mortality, and major bleeding. Nine trials involving 102,621 patients were included: 52,145 allocated to aspirin and 50,476 to placebo/control. RESULTS: Over a mean follow-up of 6.9 years, aspirin was associated with a reduction in MCE (risk ratio [RR] 0.90, 95% CI 0.85-0.96, P < .001). There was no significant reduction for myocardial infarction, stroke, ischemic stroke, or all-cause mortality. Aspirin was associated with hemorrhagic stroke (RR 1.35, 95% CI 1.01-1.81, P = .04) and major bleeding (RR 1.62, 95% CI 1.31-2.00, P < .001). In meta-regression, the benefits and bleeding risks of aspirin were independent of baseline cardiovascular risk, background therapy, age, sex, and aspirin dose. The number needed to treat to prevent 1 MCE over a mean follow-up of 6.9 years was 253 (95% CI 163-568), which was offset by the number needed to harm to cause 1 major bleed of 261 (95% CI 182-476). CONCLUSIONS: The current totality of evidence provides only modest support for a benefit of aspirin in patients without clinical cardiovascular disease, which is offset by its risk. For every 1,000 subjects treated with aspirin over a 5-year period, aspirin would prevent 2.9 MCE and cause 2.8 major bleeds

BACKGROUND: The association between bleeding severity and cause of mortality in the non-acute setting is unclear. We sought to investigate the association between bleeding and mortality subtype, and assess whether this association differs in patients on dual antiplatelet therapy (DAPT) versus aspirin alone. METHODS: Using multivariable Cox proportional hazards survival regression, we examined the association between moderate or severe bleeding and all-cause, cardiovascular, and cancer mortality in 15,603 patients with cardiovascular disease or multiple risk factors enrolled in the CHARISMA trial. RESULTS: Patients with moderate or severe bleeding had a higher incidence of all-cause, cardiovascular, and cancer mortality (P < .001 for each). After multivariable adjustment, moderate/severe bleeding remained independently associated with not only all-cause mortality (adjusted hazard ratio [HR] 1.66; 95% confidence interval [CI] 1.24-2.21) and cardiovascular mortality (HR 2.05, 95% CI 1.38-3.04) but also cancer mortality (HR 4.76, 95% CI 2.60-8.69). However, there was a significant interaction between bleeding and potency of antiplatelet therapy for all-cause (P = .002), cardiovascular (P = .02), and cancer mortality (P = .03); in subjects on aspirin alone, moderate/severe bleeding was associated with all-cause (HR 5.27, 95% CI 3.56-7.80), cardiovascular (HR 4.33, 95% CI 2.55-7.37), and cancer mortality (HR 9.01, 95% CI 4.41-18.43), but not in subjects on DAPT (all-cause: HR 1.48, 95% CI 0.93-2.34; cardiovascular: HR 1.04, 95% CI 0.58-1.86; and cancer mortality: HR 1.79, 95% CI 0.56-5.74). CONCLUSIONS: In stable patients, moderate or severe bleeding is associated with a significantly increased risk of all-cause, cardiovascular, and cancer mortality. However, this risk appeared different in subjects on single antiplatelet therapy versus DAPT

BACKGROUND: The benefit of carotid endarterectomy (CEA) in female patients has been questioned by various randomized, prospective trials, particularly in asymptomatic cases; several have noted an increase in perioperative stroke among women after CEA. The outcome of carotid angioplasty and stenting (CAS) has not been extensively examined in women. This study examined the outcome of CEA and CAS in women vs men by using a national database. METHODS: Outcomes of CEA and CAS were stratified by sex using discharge data from the Nationwide Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality. The NIS was used to identify patient discharges that occurred during 2004 and 2005. Appropriate International Classification of Diseases, 9th Revision (ICD-9) procedure and diagnosis codes were used to identify CEA and CAS cases. Outcome measures included in-hospital perioperative stroke and death. Comparisons of demographics, procedures, and outcome were performed between men and women. Additional analysis was performed among women alone to attempt to identify whether improved outcome was noted with either procedure. RESULTS: Of 54,658 procedures, 94.2% were CEA and 5.8% were CAS. Women comprised 42.3% of the analyzed cases. Women and men were equally likely to be symptomatic (5.3% vs 5.3%, P = .8). Women were significantly less likely to undergo CAS than men (5.4% vs 6.1%, P < .001). Women and men had equivalent rates of perioperative stroke when undergoing CEA (1.0% vs 1.0%, P = .9) and CAS (2.7% vs 2.0%, P = .2). Symptomatic women had a significantly higher rate of perioperative stroke overall than did symptomatic men (3.8% vs 2.3%, P = .03). Asymptomatic women had a significantly lower perioperative stroke rate after CEA than after CAS (0.9% vs 2.1%, P < .001). Rates of perioperative showed a trend favoring CEA vs CAS among symptomatic women (3.4% vs 6.2%, P = .1). CONCLUSIONS: The concern regarding an increased perioperative stroke rate after CEA among asymptomatic women appears to be unfounded. The perioperative stroke rate among symptomatic women was higher than that of symptomatic men, but still well within the acceptable range for symptomatic patients undergoing a cerebrovascular intervention. Nationally, women underwent CAS significantly less frequently than did men. Outcome among women for perioperative stroke favored CEA over CAS, particularly in asymptomatic patients. CEA may be the preferred treatment in women seeking intervention for cerebrovascular disease, unless compelling reasons exist to perform CAS