Faculty Bibliography

Introduction/UNASSIGNED:Platelet dysfunction and cardiovascular risk are well-recognized features of chronic kidney disease (CKD). Platelets drive the development and progression of cardiovascular disease (CVD). The relationships between kidney function, platelet activity, and cardiovascular risk are poorly defined. Methods/UNASSIGNED:) using data from the Platelet Activity and Cardiovascular Events study, a prospective cohort study that enrolled adults with peripheral artery disease (PAD) undergoing lower extremity revascularization. Platelet activity was measured using light transmission aggregometry (LTA) in response to submaximal dose agonist stimulation, and the subjects were followed for incident adverse cardiovascular events for a median of 18 months. Results/UNASSIGNED: < 0.05 for each). Following multivariable adjustment, subjects with CKD had elevated risk for myocardial infarction (MI) (adjusted hazard ratio 2.2, 95% confidence interval [1.02-4.9]) and major adverse cardiovascular events (MACE) (1.9 [1.2-3.3]) compared to those without CKD. Platelet aggregation in response to submaximal dose agonist stimulation mediated 7% to 26% of the excess risk for cardiovascular events associated with CKD. Conclusion/UNASSIGNED:Among subjects with PAD undergoing lower extremity revascularization, CKD is associated with increased platelet activity that mediates, in part, elevated cardiovascular risk.

BACKGROUND:Recommended systolic blood pressure (SBP) targets often do not consider the relationship of low diastolic blood pressure (DBP) levels with cardiovascular disease (CVD) and all-cause mortality risk, which is especially relevant for older people with concurrent comorbidities.We examined the relationship of DBP levels to CVD and all-cause mortality in older women in the Women's Health Initiative Long Life Study (WHI-LLS). METHODS:The study sample included 7,875 women (mean age: 79 years) who underwent a BP measurement at an in-person home visit conducted in 2012-2013. CVD and all-cause mortality were centrally adjudicated. Hazard ratios (HR) were obtained from adjusted Cox proportional hazards models. RESULTS:After 5 years follow-up, all-cause mortality occurred in 18.4% of women. Compared to a DBP of 80 mmHg, the fully adjusted hazards ratio (HR) for mortality was 1.33 (95% CI: 1.04-1.71) for a DBP of 50 mmHg and 1.67 (95% CI: 1.29-2.16) for a DBP of 100 mmHg. The HRs for CVD were 1.14 (95% CI: 0.78-1.67) for a DBP of 50 mmHg and HR 1.50 (95% CI: 1.03-2.17) for a DBP of 100 mmHg. The nadir DBP associated with lowest mortality risk was 72 mmHg overall. CONCLUSIONS:In older women, consideration should be given to the potential adverse effects of low and high DBP. Low DBP may serve as a risk marker. DBP target levels between 68 and 75 mmHg may avoid higher mortality risk.

BACKGROUND:Clinical characteristics of patients with acute myocardial infarction after gastrointestinal bleeding are poorly characterized. We sought to evaluate the incidence, management and outcomes of myocardial infarction following hospitalization for gastrointestinal bleeding. METHODS:Patients admitted with a diagnosis of gastrointestinal bleeding with and without subsequent hospital readmissions for acute myocardial infarction within 90 days were identified in the 2014 United States Nationwide Readmission Database. Patients with myocardial infarction with and without a recent prior gastrointestinal bleed were compared to determine differences in management and in-hospital outcomes. Logistic regression models were used to estimate odds of invasive management and all-cause in-hospital mortality after covariate adjustment. RESULTS:A total of 644,622 patients with gastrointestinal bleeding were identified, of which 7,523 (1.2%) were readmitted for myocardial infarction within 90 days. Compared to myocardial infarction patients without recent gastrointestinal bleeding, patients with myocardial infarction within 90 days after gastrointestinal bleeding were older, more likely to be women, have kidney disease, present with non-ST segment elevation MI, and were less likely to undergo invasive management of AMI (28% vs 63%, P<0.01). Prior gastrointestinal bleeding was associated with higher all-cause in-hospital myocardial infarction mortality (22% vs 9%, P<0.01). CONCLUSION/CONCLUSIONS:In the first 3 months after hospitalization for gastrointestinal bleeding, 1 of every 83 patients was readmitted with acute myocardial infarction. Patients with myocardial infarction after gastrointestinal bleeding were less likely to undergo invasive management and coronary revascularization and had higher mortality than those without recent bleeding.

Coronavirus disease 2019 (COVID-19) predisposes patients to thrombotic and thromboembolic events, owing to excessive inflammation, endothelial cell activation and injury, platelet activation and hypercoagulability. Patients with COVID-19 have a prothrombotic or thrombophilic state, with elevations in the levels of several biomarkers of thrombosis, which are associated with disease severity and prognosis. Although some biomarkers of COVID-19-associated coagulopathy, including high levels of fibrinogen and D-dimer, were recognized early during the pandemic, many new biomarkers of thrombotic risk in COVID-19 have emerged. In this Consensus Statement, we delineate the thrombotic signature of COVID-19 and present the latest biomarkers and platforms to assess the risk of thrombosis in these patients, including markers of platelet activation, platelet aggregation, endothelial cell activation or injury, coagulation and fibrinolysis as well as biomarkers of the newly recognized post-vaccine thrombosis with thrombocytopenia syndrome. We then make consensus recommendations for the clinical use of these biomarkers to inform prognosis, assess disease acuity, and predict thrombotic risk and in-hospital mortality. A thorough understanding of these biomarkers might aid risk stratification and prognostication, guide interventions and provide a platform for future research.

Aspirin's clinical efficacy may be influenced by body weight and mass. Although inadequate platelet inhibition by aspirin is suggested as responsible, evidence for this in non-diabetic patients is sparse. We investigated the influence of body weight and mass on aspirin's inhibition of platelet aggregation in healthy adults without diabetes. Cohort one (NYU, n = 84) had light transmission aggregometry (LTA) of platelet-rich plasma to submaximal adenosine diphosphate (ADP) and arachidonic acid (AA) before and following 1 week of daily 81 mg non-enteric coated aspirin. Subjects in the validation cohort (Duke, n = 66) were randomized to 81 mg or 325 mg non-enteric coated aspirin for 4 weeks, immediately followed by 4 weeks of the other dose, with LTA to submaximal collagen, ADP, and AA before and after each dosage period. Body mass index (BMI) range was 18.0-57.5 kg/m² and 25% were obese. Inhibition of platelet aggregation was similar irrespective of BMI, body weight and aspirin dose. There was no correlation between platelet aggregation before or after aspirin with BMI or body weight. Our data demonstrate that aspirin produces potent inhibition of direct and indirect COX1-mediated platelet aggregation in healthy adults without diabetes regardless of body weight or mass - suggesting that other mechanisms explain lower preventive efficacy of low-dose aspirin with increasing body weight/mass.

Background Peripheral artery disease (PAD) is associated with heightened risk for major adverse cardiovascular and limb events, but data on the burden of risk for total (first and potentially subsequent) events, and the association with polyvascular disease, are limited. This post hoc analysis of the EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) trial evaluated total cardiovascular and limb events among patients with symptomatic PAD, overall and by number of symptomatic vascular territories. Methods and Results In the EUCLID trial, patients with symptomatic PAD (lower extremity revascularization >30 days before randomization or ankle-brachial index ≤0.80) were randomized to treatment with ticagrelor or clopidogrel. Relative effects on total events (cardiovascular death; nonfatal myocardial infarction and ischemic stroke; acute limb ischemia, unstable angina, and transient ischemic attack requiring hospitalization; coronary, carotid, and peripheral revascularization procedures; and amputation for symptomatic PAD) were summarized by hazard ratios (HRs), whereas absolute risks were estimated by incidence rates and mean cumulative functions. Among 13 885 randomized patients, 7600 total cardiovascular and limb events occurred during a median 2.7 years of follow-up, translating to 60.0 and 62.5 events per 100 patients through 3 years for the ticagrelor and clopidogrel groups, respectively (HR, 0.96; 95% CI, 0.89-1.03; P=0.27). Among 1393 patients with disease in 3 vascular territories, event accrual rates through 3 years for the ticagrelor and clopidogrel groups were 87.3 and 97.7 events per 100 patients, respectively. Absolute risk reductions for ticagrelor relative to clopidogrel at 3 years were -0.2, 6.7, and 10.3 events per 100 patients for 1, 2, and 3 affected vascular territories, respectively (P

BACKGROUND:Type 2 myocardial infarction (MI) occurs due to a mismatch in myocardial oxygen supply and demand without unstable coronary artery disease. We sought to identify patterns, predictors and outcomes of invasive management of type 2 MI in the USA. METHODS:Adults aged ≥18 years hospitalized with type 2 MI were identified in a cross-sectional study from the 2018 National Inpatient Sample. Invasive management was defined as invasive coronary angiography or revascularization. Patient, hospital and geographic characteristics associated with invasive management were identified by multivariable logistic regression. Propensity-matched cohorts were generated to evaluate associations between invasive vs. conservative management and mortality. RESULTS:We identified 268 850 admissions with type 2 MI in 2018. Type 2 MI patients had a high burden of comorbidities and were commonly admitted with diagnoses of circulatory (39.7%), infectious (23.1%) or respiratory (10.8%) illness. Only 11.2% of type 2 MI were managed invasively, of which 17.9% underwent coronary revascularization. Odds of invasive management were higher with commercial insurance [adjusted OR (aOR) 1.39; 95% confidence interval (CI), 1.27-1.52] and lower with Medicaid (aOR 0.86; 95% CI, 0.76-0.96) vs. Medicare. Significant heterogeneity in invasive management of type 2 MI was observed by geographic region (range 7.2-13.8%), independent of patient and hospital factors. Invasive management was associated with lower in-hospital mortality than conservative management overall (3.9 vs. 9.1%; P < 0.001) and in propensity-matched analyses (OR, 0.70; 95% CI, 0.59-0.84). CONCLUSION/CONCLUSIONS:Invasive management of type 2 MI varies by insurance status and geography, highlighting uncertainty regarding optimal management and potential disparities in clinical care.

OBJECTIVES/OBJECTIVE:Clopidogrel is effective at decreasing cardiovascular events in patients with peripheral artery disease (PAD); however, its effect on limb outcomes are less known. This study investigated the variability in response to clopidogrel and its relationship with clinical limb outcomes. METHODS: RESULTS: CONCLUSIONS:Among patients undergoing lower extremity revascularization on clopidogrel, higher baseline percent aggregation is associated with increased risk for major adverse limb events.