Faculty Bibliography

All patients with stable ischemic heart disease (SIHD) should be managed with guideline-directed medical therapy (GDMT), which reduces progression of atherosclerosis and prevents coronary thrombosis. Revascularization is also indicated in patients with SIHD and progressive or refractory symptoms, despite medical management. Whether a strategy of routine revascularization (with percutaneous coronary intervention or coronary artery bypass graft surgery as appropriate) plus GDMT reduces rates of death or myocardial infarction, or improves quality of life compared to an initial approach of GDMT alone in patients with substantial ischemia is uncertain. Opinions run strongly on both sides, and evidence may be used to support either approach. Careful review of the data demonstrates the limitations of our current knowledge, resulting in a state of community equipoise. The ongoing ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) is being performed to determine the optimal approach to managing patients with SIHD, moderate-to-severe ischemia, and symptoms that can be controlled medically. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

BACKGROUND: The relationship between culprit vessel, infarct size, and outcomes in non-ST-segment elevation acute coronary syndromes (NSTE ACS) is unclear. In some reports, the left circumflex artery (LCX) was more often the culprit at angiography than the right coronary artery (RCA) or left anterior descending artery (LAD), and infarcts were larger with LCX culprits. METHODS: We determined culprit vessel frequency and initial patency (TIMI flow grade), median fold elevation of peak troponin above the upper limit of normal, and outcomes (30-day death or myocardial infarction [MI] and 1-year mortality) by culprit vessel in high-risk NSTE ACS patients in the EARLY ACS trial. RESULTS: Of 9406 patients, 2066 (22.0%) had angiographic core laboratory data. We evaluated 1774 patients for whom the culprit artery was not the left main, a bypass graft, or branch vessel. The culprit was the LCX in 560 (31.6%), LAD in 653 (36.8%), and RCA in 561 (31.6%) patients. There were fewer women (24.1%) and more prior MI (25.5%) among patients with a culprit LCX compared with those with a culprit LAD or RCA. Patients with LCX (21.2%) and RCA (27.5%) culprits more often had an occluded artery (TIMI 0/1) than did those with LAD (11.3%). Peak troponin elevation was significantly higher for LCX than RCA or LAD culprits. LCX culprit vessels were not associated with worse 30-day or 1-year outcomes in adjusted models. CONCLUSIONS: Among patients with NSTE ACS, the frequencies of LCX, LAD, and RCA culprits were similar. Although LCX lesions were associated with higher peak troponin levels, there was no difference in short- or intermediate-term outcomes by culprit artery.

Introduction: Clinical practice guidelines have recommended evidence based medicine (EBM) and treatment targets for optimal management of BP, LDL Cholesterol (LDLc) and of HbA1c in diabetic patients with stable coronary heart disease [CHD]. However the importance of achieving these goals is uncertain Hypothesis: In patients with stable CHD achievement of goals for blood pressure, LDLc, and HbA1c in diabetics, and use of EBM are associated with a lower risk of major adverse cardiovascular events [MACE] Methods: In 13,624 patients with stable CHD, who participated in the STabilisation of Atherosclerotic plaque By Initiation of darapLadIb TherapY (STABILITY) trial, BP, LDLc and HbA1c in diabetes were assessed at baseline, and at 3, 6 and 12 month follow-up visits; BP and medication use were additionally assessed at 1 month. EBM; aspirin, beta blockers, ACE / ARB, and statins, were recommended for patients without contraindications. Standard of care (SOC) targets were BP<140/90 mmHg, LDLc <70mg/dl and <100mg/dl, and HbA1c<7% in 4711 diabetics. Achievement of each of these targets was defined as meeting the target on >4 of 5 visits for BP and EBM, and >3 of 4 biochemical measurements. A landmark analysis assessed the association between achievement of EBM and of each SOC target during the first year of the study and MACE, defined as cardiovascular death, MI, or stroke, during a further 2.7 years follow-up, after adjusting for baseline predictors of MACE in a Cox proportional hazards model Results: See Table Conclusions: High rates of evidence based medicine use were achieved. MACE was related to LDLc. After one year the risk of subsequent MACE was reduced for patients who met target LDLc levels and for diabetic patients who achieved target HbA1c

Introduction: Physical activity (PA) reduces the risk of events in patients with stable coronary heart disease (CHD). Biomarkers reflecting myocardial dysfunction, renal function and inflammatory activity are associated with outcomes in stable CHD. It is poorly known to what extent the benefits of PA may be linked to biomarker levels. Hypothesis: The association between PA and outcomes may be mediated by processes indicated by changes in the levels of prognostic biomarkers. Methods: At baseline, 15,486 patients with stable CHD participating in the global STABILITY trial, completed a baseline lifestyle questionnaire including self-reporting on hours spent each week on mild, moderate and vigorous exercise, corresponding to approximately 2, 4 and 8 METS, respectively. Plasma levels of high-sensitivity (hs) C-reactive protein (hs-CRP), hs-troponin T (hs-TnT), N-terminal pro-B type natriuretic peptide (NT-proBNP), cystatin-C, growth differentiation factor-15 (GDF-15) and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity were assessed from plasma samples obtained at baseline. Associations between PA and biomarker levels were evaluated after multivariable adjustments (age, gender, traditional clinical cardiovascular risk factors and standard biomarkers including cholesterol levels) with sedentary patients as reference. Results: Associations between levels of PA and hs-CRP, hs-TnT, NT-proBNP, cystatin C, GDF-15 and activity of Lp-PLA2 are shown in the Table, after adjustments for co-variables. PA was independently and inversely associated with all biomarker levels, except for Lp-PLA2. Conclusions: Increasing PA, was independentlyand inversely associated with levels of most clinically important biomarkers, except for Lp-PLA2. The effects of PA on outcomes may partly be explained by disease processes reflected by changes in biomarker levels

Introduction: Secondary preventive guidelines recommend patients with stable coronary heart disease (CHD) take at least 30 min of moderate or vigorous physical activity (PA) on at least 5 days/week. Hypothesis: Lower levels of PA may be beneficial for cardiovascular (CV) prognosis. Aim: To evaluate associations between self-reported PA, including mild intensity exercise and outcomes in a global cohort of patients with stable CHD. Methods: A lifestyle questionnaire was completed at baseline by 15,486 (97.8%) STABILITY participants. Total PA was estimated from individual subject self-reports of hours spent each week on mild, moderate and vigorous exercise, 2, 4 and 8 METS respectively. Associations between the total amount of PA and MACE (CV mortality, non-fatal myocardial infarction or non-fatal stroke), CV and non-CV mortality were evaluated using Cox proportional hazard models adjusting for age, gender, treatment allocation, markers of disease severity and CV risk factors during a median follow-up of 3.7 yrs. Results: For all subjects, a greater proportion of MET.hours was spent taking mild (50.4%) compared to moderate (39.7%) and vigorous (10.0%) PA. The mean (+/-SD) PA reported for the 'sedentary' (t1, n=5281), 'mildly active' (t2, n=5055) and 'moderately active' (t3, n=5151) tertiles were t1 12.1+/-7.4, t2 39.6+/-7.4 and t3 104.3+/-45.9 MET.hours/week. Compared to 'sedentary' subjects the 'mild' and 'moderate' PA tertiles had a lower risk of MACE HR 0.96 (95% CI 0.85-1.08) and 0.79 (0.70-0.91), p=0.0019, CV death 0.89 (0.75-1.06) and 0.69 (0.57-0.85), p=0.0019, and non-CV death 0.54 (0.41-0.72) and 0.72 (0.55-0.95), p<.0001. See Figure. Conclusions: In patients with stable CHD there is a strong inverse association between self-reported PA and MACE, CV mortality and non-CV mortality. Even modest amounts of mild intensity exercise are associated with lower mortality

BACKGROUND: Women with acute coronary syndromes (ACS) are less likely to undergo invasive revascularization than men, but sex-specific differences in long-term outcomes and platelet reactivity among medically managed ACS patients remain uncertain. We examined sex-specific differences in long-term ischemic and bleeding outcomes and platelet reactivity for medically managed ACS patients randomized to prasugrel versus clopidogrel plus aspirin. METHODS: Data from 9,326 patients enrolled in TRILOGY ACS were analyzed to determine differences in long-term ischemic and bleeding outcomes between women (n = 3,650 [39%]) and men (n = 5,676 [61%]) randomized to prasugrel 10 mg/d (5 mg/d for patients >/=75 years and/or <60 kg) versus clopidogrel 75 mg/d. Sex-specific differences in 30-day platelet reactivity were analyzed in 2,564 (27%) patients participating in a platelet function substudy. RESULTS: Compared with men, women were older, weighed less, were less likely to have prior myocardial infarction or revascularization, and had lower baseline creatinine clearance and hemoglobin level values. Rates of the composite of cardiovascular death/myocardial infarction/stroke (20.2% vs 19.1%; P = .56), all-cause mortality (12.2% vs 11.7%; P = .88), and Global Use of Strategies to Open Occluded Arteries severe/life-threatening/moderate bleeding (3.8% vs 2.8%; P = .74) through 30 months were similar in women versus men. After adjustment, women had significantly lower risk for ischemic outcomes and all-cause mortality. There were no sex-specific, treatment-related differences in 30-day platelet reactivity. CONCLUSIONS: Long-term ischemic and bleeding outcomes in medically managed ACS patients were similar for women versus men, as was treatment-related platelet reactivity. Women had a higher baseline risk profile and, after adjustment, significantly lower risk of the primary composite end point and all-cause death through 30 months.

To develop the next generation of translational investigators, New York University School of Medicine (NYUSOM) and the NYU-NYC Health and Hospitals Corporation Clinical and Translational Science Institute (NYU-HHC CTSI) developed the Master's of Science in Clinical Investigation dual-degree (MD/MSCI) program. This 5-year program dedicates 1 year to coursework and biomedical research, followed by a medical school/research overlap year, to prepare students for academic research careers. This paper details the MD/MSCI program's curriculum and approach to mentorship, describes the research/professional interests of students, and reports student productivity. In the first 4 years of the program (2010-2014) 20 students were matriculated; 7 (35%) were women, and 12 (60%) research projects were in surgical specialties. To date, 14 students have applied to residency, and half pursued surgical residency programs. Our students have produced 68 accepted abstracts, 15 abstracts in submission, 38 accepted papers, and 24 papers in submission. Despite the time-limited nature of this program, additional training in research design and implementation has promoted a high level of productivity. We conclude that dual-degree training in medicine and translational research is feasible for medical students and allows for meaningful participation in valuable projects. Follow-up is warranted to evaluate the academic trajectory of these students. Clin Trans Sci 2015; Volume #: 1-6.