Faculty Bibliography

BACKGROUND AND AIMS/OBJECTIVE:Low functional capacity is an independent risk factor for cardiovascular (CV) events. Regular physical activity may reduce CV risk through suppression of inflammation and reduced platelet activity. We aimed to investigate the association of functional capacity quantified by the validated Duke Activity Status Index (DASI) with platelet activity and incident major adverse CV and limb events (MACLE) in individuals with peripheral artery disease (PAD) undergoing lower extremity revascularization (LER). METHODS:Light transmission aggregometry and platelet RNAseq were performed on specimens isolated from men and women prior to LER. Functional capacity was assessed using DASI. Prospective follow-up occurred at 1, 6, 12, and every 6 months following the LER. Subjects were separated into tertiles of DASI scores and incidence rates for MACLE were calculated using log-rank tests. Mediation analysis using linear regression fit with least squares was performed to test whether DASI exerted its effect on MACLE via platelet aggregation. RESULTS:281 patients completed the DASI questionnaire with scores ranging from 0.0 to 50.2 (bottom tertile: 0.0-9.95). Mean age was 74.4 ± 10.9 years and 32.4 % were female. During a median follow-up of 19 months, 163 (58.0 %) participants experienced a MACLE. After correction for demographics and CV risk factors, individuals in the lowest DASI tertile experienced significantly more MACLE than participants in other tertiles. The association between DASI and MACLE was consistent across multiple subgroups stratified by age, sex, body mass index, antiplatelet therapy, and clinical comorbidities. Mediation analyses suggested higher platelet aggregation to epinephrine in the bottom DASI tertile mediated 24.7 % [5.0 %, 103 %] of increased MACLE risk. Platelet mRNA demonstrated upregulation of inflammation pathways in the most sedentary individuals (lowest DASI tertile). CONCLUSIONS:Patients with PAD and low functional capacity have increased platelet activity and high incidence of MACLE. Our data suggest that elevated platelet aggregation mediates one-quarter of the MACLE risk in persons with low functional capacity undergoing LER. Our findings support a potential platelet-mediated mechanism for improved CV outcomes associated with regular physical activity.

Patients with myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF), are at increased risk of atherosclerosis, including peripheral arterial disease (PAD). Critical limb ischemia (CLI) may complicate PAD and is associated with significant mortality and morbidity. Despite the increased risk of thrombosis with MPN, outcomes of CLI in MPN patients are unclear. We conducted an analysis utilizing the 2017-2020 National Readmission Database (NRD) of patients hospitalized for CLI with and without MPN. Patients with MPN were propensity score matched (PSM) with patients without MPN. Primary outcome was composite outcome of major adverse cardiovascular and limb events (MACLE). Logistic regression was utilized to estimate risk of MACLE in patients with MPN vs. without MPN. Inverse-probability treatment weighted (IPTW) analysis was performed to evaluate the effect of revascularization on MACLE in patients with MPN. A total of 102,598 patients were included, 931 (0.9%) had MPN. After PSM, MPN was associated with increased risk of MACLE (47.3% vs. 39.1%; OR 1.40, 95% CI 1.21-1.62). After IPTW, revascularization was associated with decreased risk of MACLE among patients with MPN (45.0% vs. 50.7%; OR 0.80, 95% CI 0.66-0.96). Among patients admitted with CLI, MPN was associated with increased risk of MACLE especially ET and MF phenotypes. Revascularization was associated with decreased risk of MACLE among patients with MPN. Further investigation is needed in order to improve outcomes in patients with MPN and CLI.

OBJECTIVE:To investigate the relationship between platelet indices (count, size and production/immaturity) and hypertensive disorders of pregnancy. STUDY DESIGN/METHODS:This was a secondary analysis of a prospective cohort of pregnant individuals followed from first trimester through delivery at an academic tertiary care institution. Routine platelet indices obtained prospectively during prenatal care and delivery were compared between those who developed a hypertensive disorder of pregnancy and those who did not. We assessed platelet count (by trimester), mean platelet volume, and immature platelet fraction measured as percent (%) and absolute count. Data were analyzed using Fisher's Exact test, chi-square test, and multivariable logistic regression. P < 0.05 was considered statistically significant. RESULTS: = 0.01) compared to those without a hypertensive disorder of pregnancy, after adjusting for age, race/ethnicity, obesity, nulliparity, and chronic hypertension. The prevalence and likelihood of a hypertensive disorder of pregnancy increased with increasing mean platelet volume, as well as with both the percent and absolute immature platelet fraction. There was no difference between groups in platelet count in the first trimester, second trimester, or at delivery. CONCLUSIONS:An increase in platelet size and immaturity was observed in those with a hypertensive disorder of pregnancy. These data support further investigation of platelets in the mechanisms of the development of hypertensive disorders of pregnancy and the use of platelet indices to better identify high risk groups in pregnancy.

Although platelets play a critical pathogenic role in myocardial infarction (MI), few studies have characterized the MI platelet transcriptome in the acute or chronic setting in women. We report that transcripts associated with the actin cytoskeleton, Rho family GTPases, mitochondrial dysfunction, and inflammatory signaling are enriched in platelets from MI patients in the acute setting (n = 40, MI; n = 38, control) and do not significantly change over time. Furthermore, 79 platelet genes chronically elevated or suppressed after MI are associated with future cardiovascular events in an independent high-risk cohort (n = 135). Compared with women with MI with nonobstructive coronary arteries, platelets from women with MI and obstructive coronary artery disease were enriched in neutrophil activation and proinflammatory signaling pathways driven by increased tumor necrosis factor (TNF)-α signaling. Hierarchic clustering of the MI transcriptomic profile identified 3 subgroups with distinctive biological pathways and MI correlates. Our data demonstrate that platelets from MI patients are phenotypically different from MI-naïve patients in the acute and chronic settings and reveal a platelet transcriptomic signature with distinct clinical features.

STUDY OBJECTIVE/OBJECTIVE:To determine whether preoperative LDL-C concentration affects the risk of perioperative major adverse cardiovascular or cerebrovascular events (MACCE) after noncardiac surgery. DESIGN/METHODS:Single center retrospective cohort study. SETTING/METHODS:Hospital (including medical and surgical floor, intensive care unit) and patient disposition location (including the patient's home or any other receiving facility). PATIENTS/METHODS:43,348 non-cardiac surgeries at NYU Langone Health between January 2016 and September 2020. INTERVENTIONS/METHODS:Patients were grouped based on preoperative LDL-C. MEASUREMENTS/METHODS:Complete serum lipid panel obtained within one year prior to the date of noncardiac surgery and rate of perioperative MACCE, defined as a composite of in-hospital non-fatal myocardial infarction, in-hospital acute ischemic stroke, myocardial injury after noncardiac surgery, and death from any cause within 30 days of surgery. MAIN RESULTS/RESULTS:Perioperative MACCE occurred in 1093 patients (2.5 %) overall. After multivariable adjustment, odds of MACCE were significantly lower in patients with higher (≥100 mg/dL) versus lower (<100 mg/dL) LDL-C (adjusted odds ratio [aOR] 0.783, 95 % CI, 0.660-0.926]). CONCLUSIONS:In a large cohort of patients undergoing non-cardiac surgery at a major academic health system in New York City, lower LDL-C concentrations were not associated with a lower incidence of perioperative MACCE. Further investigation into modifiable perioperative cardiovascular risk factors is needed to improve perioperative outcomes.

BACKGROUND/UNASSIGNED:Elevated perceived stress is associated with adverse outcomes following myocardial infarction (MI) and may account for poorer recovery among women vs men. OBJECTIVES/UNASSIGNED:This randomized controlled trial tested effects of a mindfulness-based intervention on stress levels among women with MI. METHODS/UNASSIGNED:Women with elevated stress (Perceived Stress Scale [PSS-4]≥6) at least 2 months after MI were enrolled from 12 hospitals in the United States and Canada and via community advertising. Participants were randomized to a remotely delivered mindfulness intervention (MBCT-Brief) or heart disease education, both 8 weeks long. Follow-up was 6 months. Changes in stress (PSS-10; primary outcome) and secondary outcomes (depressive symptoms, anxiety, quality of life, disease-specific health status, actigraphy-assessed sleep) were compared between groups. RESULTS/UNASSIGNED: = 0.036). CONCLUSIONS/UNASSIGNED:MBCT-Brief was associated with greater 6-month reductions in stress than an active control among adherent participants. More frequent mindfulness practice was associated with greater improvements in psychological outcomes. Strategies to engage women with MI in mindfulness training and support regular home practice may enhance these effects.

PURPOSE OF REVIEW/OBJECTIVE:Cardiovascular disease (CVD) is a leading cause of preventable morbidity and mortality globally, and retinal imaging modalities (old and new) are being explored as noninvasive tools to predict latent atherosclerosis and cardiovascular disease. This review focuses on the emerging promise of fundoscopy, optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA) in CVD prognostication. RECENT FINDINGS/RESULTS:High-quality studies have established the utility of vessel-based parameters and discrete conditions diagnosable via fundoscopy in subclinical atherosclerosis detection or CVD prediction. Recent research shows OCT measurements of different retinal layers and specific imaging findings (such as retinal ischemic perivascular lesions) are widely accessible and objective biomarkers for incipient CVD and ensuing risk. Myriad OCTA metrics appear to reliably inform on current CVD burden and cardiovascular risk. Fundoscopy, OCT, and OCTA all have a growing body of literature supporting their utility as adjuncts in CVD prediction and risk stratification.