Faculty Bibliography
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547
Interleukin-6 and the Risk of Adverse Outcomes in Patients After an Acute Coronary Syndrome: Observations From the SOLID-TIMI 52 (Stabilization of Plaque Using Darapladib-Thrombolysis in Myocardial Infarction 52) Trial
BACKGROUND: Interleukin-6 (IL-6) is an inflammatory cytokine implicated in plaque instability in acute coronary syndrome (ACS). We aimed to evaluate the prognostic implications of IL-6 post-ACS. METHODS AND RESULTS: IL-6 concentration was assessed at baseline in 4939 subjects in SOLID-TIMI 52 (Stabilization of Plaque Using Darapladib-Thrombolysis in Myocardial Infarction 52), a randomized trial of darapladib in patients
PMCID:5721825
PMID: 29066436
ISSN: 2047-9980
CID: 2756652
Inflammatory Biomarkers Interleukin-6 and C-Reactive Protein and Outcomes in Stable Coronary Heart Disease: Experiences From the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) Trial
BACKGROUND: Evaluation of cardiovascular prognosis in patients with stable coronary heart disease is based on clinical characteristics and biomarkers indicating dysglycemia, dyslipidemia, renal dysfunction, and possibly cardiac dysfunction. Inflammation plays a key role in atherosclerosis, but the association between inflammatory biomarkers and clinical outcomes is less studied in this population. METHODS AND RESULTS: Overall, 15 828 patients with coronary heart disease in the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial were randomized to treatment with darapladib or placebo and observed for a median of 3.7 years. In 14 611 patients, levels of interleukin-6 (IL-6) and high-sensitivity C-reactive protein were measured in plasma samples: median levels were 2.1 (interquartile range, 1.4-3.2) ng/L and 1.3 (interquartile range, 0.6-3.1) mg/L, respectively. Associations between continuous levels or quartile groups and adjudicated outcomes were evaluated by spline graphs and Cox regression adjusted for clinical factors and cardiovascular biomarkers. IL-6 was associated with increased risk of major adverse cardiovascular events (quartile 4 versus quartile 1 hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.30-1.97; P<0.0001); cardiovascular death (HR, 2.15; 95% CI, 1.53-3.04; P<0.0001); myocardial infarction (HR, 1.53; 95% CI, 1.14-2.04; P<0.05); all-cause mortality (HR, 2.11; 95% CI, 1.62-2.76; P<0.0001); and risk of hospitalization for heart failure (HR, 2.28; 95% CI, 1.34-3.89; P<0.001). Cancer death was doubled in the highest IL-6 quartile group (HR, 2.34; 95% CI, 1.20-4.53; P<0.05). High-sensitivity C-reactive protein was associated with both cardiovascular and non-cardiovascular events in the unadjusted model, but these did not remain after multivariable adjustments. CONCLUSIONS: IL-6, an upstream inflammatory marker, was independently associated with the risk of major adverse cardiovascular events, cardiovascular and all-cause mortality, myocardial infarction, heart failure, and cancer mortality in patients with stable coronary heart disease. IL-6 might reflect a pathophysiological process involved in the development of these events. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00799903.
PMCID:5721818
PMID: 29066452
ISSN: 2047-9980
CID: 2756642
Journal of the American College of Cardiology. 2017:70(14):1689-1700.DOI: 10.1016/j.jacc.2017.08.017
Physical Activity and Mortality in Patients With Stable Coronary Heart Disease
BACKGROUND: Recommendations for physical activity in patients with stable coronary heart disease (CHD) are based on modest evidence. OBJECTIVES: The authors analyzed the association between self-reported exercise and mortality in patients with stable CHD. METHODS: A total of 15,486 patients from 39 countries with stable CHD who participated in the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) study completed questions at baseline on hours spent each week taking mild, moderate, and vigorous exercise. Associations between the volume of habitual exercise in metabolic equivalents of task hours/week and adverse outcomes during a median follow-up of 3.7 years were evaluated. RESULTS: A graded decrease in mortality occurred with increased habitual exercise that was steeper at lower compared with higher exercise levels. Doubling exercise volume was associated with lower all-cause mortality (unadjusted hazard ratio [HR]: 0.82; 95% confidence interval [CI]: 0.79 to 0.85; adjusting for covariates, HR: 0.90; 95% CI: 0.87 to 0.93). These associations were similar for cardiovascular mortality (unadjusted HR: 0.83; 95% CI: 0.80 to 0.87; adjusted HR: 0.92; 95% CI: 0.88 to 0.96), but myocardial infarction and stroke were not associated with exercise volume after adjusting for covariates. The association between decrease in mortality and greater physical activity was stronger in the subgroup of patients at higher risk estimated by the ABC-CHD (Age, Biomarkers, Clinical-Coronary Heart Disease) risk score (p for interaction = 0.0007). CONCLUSIONS: In patients with stable CHD, more physical activity was associated with lower mortality. The largest benefits occurred between sedentary patient groups and between those with the highest mortality risk.
PMID: 28958324
ISSN: 1558-3597
CID: 2717512
Sex Differences in Clinical Characteristics, Psychosocial Factors, and Outcomes Among Patients With Stable Coronary Heart Disease: Insights from the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) Trial
BACKGROUND: Greater understanding of differences between men and women with coronary heart disease is needed. METHODS AND RESULTS: In this post hoc analysis of the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial, we described psychosocial factors, treatments, and outcomes of men versus women with stable coronary heart disease and explored the association of sex with psychosocial characteristics and cardiovascular risk. Cox proportional hazards models were used to assess the relationship between sex and outcomes. Interactions among sex, psychosocial factors, and the composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke were tested. Of 15 828 patients, 2967 (19%) were women. Among women, 21.2% felt often or always stressed at home (versus 9.8% of men), and 19.2% felt often or always sad or depressed (versus 10.1% of men; all P<0.0001). The median duration of follow-up was 3.7 years (25th-75th percentiles: 3.5-3.8 years). Use of evidence-based medications for coronary heart disease at baseline and 24 months was similar between sexes, as were event rates for all outcomes analyzed. In the multivariable model including psychosocial measures, female sex was associated with lower cardiovascular risk. There was a statistically significant interaction (P=0.03) such that the lower risk in women varied by depressive symptom frequency, whereby women who were more depressed had a risk similar to men. CONCLUSIONS: Female sex was independently associated with better long-term clinical outcomes, although this was modified by frequency of depressive symptoms. This suggests that emotional state may be an important target for improving outcomes in patients with coronary heart disease, specifically in women. CLINICAL TRIAL REGISTRATION: STABILITY ClinicalTrials.gov number (NCT00799903).
PMCID:5634306
PMID: 28912210
ISSN: 2047-9980
CID: 2701352
Hospital Practice of Direct-Home Discharge and 30-Day Readmission After Transcatheter Aortic Valve Replacement in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (STS/ACC TVT) Registry
BACKGROUND: Nearly 17% of patients are readmitted within 30 days of discharge after transcatheter aortic valve replacement. Selected patients are discharged to skilled nursing facilities, yet the association between a hospital's practice to discharge home versus to skilled nursing facilities, and readmission remains unclear. METHODS AND RESULTS: The Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (STS/ACC TVT) Registry was used to evaluate readmissions among patients undergoing transcatheter aortic valve replacement (2011-2015). Hospitals were divided into quartiles (Q1-Q4) based on the percentage of patients discharged directly home. We assessed patient and hospital level characteristics and used hierarchical logistic regression to analyze the association of discharge disposition with 30-day readmission. Our cohort included 18 568 transcatheter aortic valve replacement patients at 329 US hospitals, of whom 69% were discharged directly home. Hospitals in the highest quartile of direct home discharge (Q4) compared with hospitals in the lowest (Q1) were more likely to use femoral access (75.2% versus 60.1%, P<0.001), had fewer patients receiving transfusion (26.4% versus 40.9%, P<0.001), and were more likely to be located in the Southern United States (48.8% versus 18.3%, P<0.001). Median 30-day readmission rate was 17.9%. There was no significant difference in 30-day readmissions among quartiles (P=0.14), even after multivariable adjustment (odds ratio Q4 versus Q1=0.89, 95%CI 0.76-1.04; P=0.15). Factors most strongly associated with 30-day readmission were glomerular filtration rate, in-hospital stroke or transient ischemic attack, and nonfemoral access. CONCLUSIONS: There was no statistically significant association between hospital practice of direct home discharge post-transcatheter aortic valve replacement and 30-day readmission. Further research is needed to understand regional variations and optimum strategies for postdischarge care.
PMCID:5586454
PMID: 28862964
ISSN: 2047-9980
CID: 2679572
Women with stable coronary artery disease have better clinical outcomes than men, but this association is modified by degree of depression: Insights from the STABILITY trial [Meeting Abstract]
Background: Greater understanding of the differences in male and female patients with coronary heart disease (CHD) is needed. Purpose: To describe psychosocial factors, treatments, and outcomes of men versus women with stable CHD, and to explore the association of gender with psychosocial characteristics and cardiovascular risk. Methods: We analyzed the STABILITY trial database, which includes patients with stable CHD and age >=60 years or another risk factor. Kaplan-Meier event rates of clinical outcomes were compared between men and women. Cox proportional hazard models were used to assess the relationship between sex and outcomes. Interactions between sex, psychosocial factors, and the composite endpoint of cardiovascular death, myocardial infarction (MI), and stroke were tested. Results: Of the 15,828 patients, 2967 (19%) were women. At study entry, 22.4% of women and 11.3% of men were living alone, while 82.4% of women and 64.3% of men were not currently working. Among women, 21.2% felt often/always stressed at home (vs. 9.8% of men), while 19.2% felt often/always sad, low in spirits, or depressed (vs. 10.1% of men). The use of evidence-based medications for CHD, at baseline and at 24 months, was similar among sexes, as well event rates for all outcomes analyzed. In the multivariable model including psychosocial measures, female sex was associated with lower cardiovascular risk. There was a statistically significant interaction such that the lower risk in women varied by degree of depression, whereby women who were more depressed had similar risk as men (Figure). Conclusions: Female sex was independently associated with better clinical outcomes, although that association was modified by degree of depression. This suggests that emotional state may be an important target for improving outcomes in patients with CHD, specifically in women. (Figure Presented)
EMBASE:621234682
ISSN: 1522-9645
CID: 3006222
Use of troponin assay 99th percentile as the decision level for myocardial infarction diagnosis
BACKGROUND: The Universal Definition of Myocardial Infarction recommends the 99th percentile concentration of cardiac troponin in a normal reference population as part of the decision threshold to diagnose type 1 spontaneous myocardial infarction. Adoption of this recommendation in contemporary worldwide practice is not well known. METHODS: We performed a cohort study of 276 hospital laboratories in 31 countries participating in the National Heart, Lung, and Blood Institute-sponsored International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial. Each hospital laboratory's troponin assay manufacturer and model, the recommended assay's 99th percentile upper reference limit (URL) from the manufacturer's package insert, and the troponin concentration used locally as the decision level to diagnose myocardial infarction were ascertained. RESULTS: Twenty-one unique troponin assays from 9 manufacturers were used by the surveyed hospital laboratories. The ratio of the troponin concentration used locally to diagnose myocardial infarction to the assay manufacturer-determined 99th percentile URL was <1 at 19 (6.6%) laboratories, equal to 1 at 91 (31.6%) laboratories, >1 to 5 to 10 at 43 (14.9%) laboratories. The variability in troponin decision level for myocardial infarction relative to the assay 99th percentile URL was present for laboratories in and outside of the United States, as well as for high- and standard-sensitivity assays. CONCLUSIONS: There is substantial hospital-level variation in the troponin threshold used to diagnose myocardial infarction; only one-third of hospital laboratories currently follow the Universal Definition of Myocardial Infarction consensus recommendation for use of troponin concentration at the 99th percentile of a normal reference population as the decision level to diagnose myocardial infarction. This variability across laboratories has important implications for both the diagnosis of myocardial infarction in clinical practice as well as adjudication of myocardial infarction in clinical trials.
PMCID:5543710
PMID: 28760208
ISSN: 1097-6744
CID: 2655612
DIRECT HOME DISCHARGE AND LIKELIHOOD OF 30-DAY HOSPITAL READMISSION AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT (TAVR): FINDINGS FROM THE STS/ACC TVT REGISTRY [Meeting Abstract]
ISI:000397342301755
ISSN: 1558-3597
CID: 2528922
Stress Cardiac MRI in Women With Myocardial Infarction and Nonobstructive Coronary Artery Disease
BACKGROUND: In a prospective study, cardiac MRI (CMR) and intravascular ultrasound were performed in women with myocardial infarction (MI) and nonobstructive coronary artery disease (MINOCA). Forty participants underwent adenosine-stress CMR (sCMR). HYPOTHESIS: Abnormal perfusion may co-localize with ischemic late gadolinium enhancement (LGE) and T2-weighted signal hyperintensity (T2+), suggesting microvascular dysfunction contributed to MI. METHODS: Qualitative perfusion analysis was performed by 2 independent readers. Abnormal myocardial perfusion reserve index (MPRI) was defined as global average
PMID: 27459149
ISSN: 1932-8737
CID: 2191502
Rates of Invasive Management of Cardiogenic Shock in New York Before and After Exclusion From Public Reporting
Importance: Reduced rates of cardiac catheterization, percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG) are an unintended consequence of public reporting of cardiogenic shock outcomes in New York. Objectives: To evaluate whether the referral rates for cardiac catheterization, PCI, or CABG have improved in New York since cardiogenic shock was excluded from public reporting in 2008 and compare them with corresponding rates in Michigan, New Jersey, and California. Design, Setting, and Participants: Patients with cardiogenic shock complicating acute myocardial infarction from 2002 to 2011 were identified using the National Inpatient Sample. Propensity score matching was used to assemble a cohort of patients with cardiogenic shock with similar baseline characteristics in New York and Michigan. Main Outcomes and Measures: Percutaneous coronary intervention (primary outcome), invasive management (cardiac catheterization, PCI, or CABG), revascularization (PCI or CABG), and CABG were evaluated with reference to 3 calendar year periods: 2002-2005 (time 1: cardiogenic shock included in publicly reported outcomes), 2006-2007 (time 2: cardiogenic shock excluded on a trial basis), and 2008 and thereafter (time 3: cardiogenic shock excluded permanently) in New York and compared with Michigan. Results: Among 2126 propensity score-matched patients representing 10795 (weighted) patients with myocardial infarction complicated by cardiogenic shock in New York and Michigan, 905 (42.6%) were women and mean (SE) age was 69.5 (0.3) years. A significantly higher proportion of the patients underwent PCI (time 1 vs 2 vs 3: 31.1% vs 39.8% vs 40.7% [OR, 1.50; 95% CI, 1.12-2.01; P = .005 for time 3 vs 1]), invasive management (time 1 vs 2 vs 3: 59.7% vs 70.9% vs 73.8% [OR, 1.84; 95% CI, 1.37-2.47; P < .001 for time 3 vs 1]), or revascularization (43.1% vs 55.9% vs 56.3% [OR, 1.66; 95% CI, 1.26-2.20; P < .001 for time 3 vs 1]) after the exclusion of cardiogenic shock from public reporting in New York. However, during the same periods, a greater proportion of patients underwent PCI (time 1 vs 2 vs 3: 41.2% vs 52.6% vs 57.8% [OR, 1.93; 95% CI, 1.45-2.56; P < .001 for time 3 vs 1]), invasive management (time 1 vs 2 vs 3: 64.4% vs 80.5% vs 78.6% [OR, 2.01; 95% CI, 1.47-2.74; P < .001 for time 3 vs 1]), or revascularization (51.2% vs 65.8% vs 68.0% [OR, 2.00; 95% CI, 1.50-2.66; P < .001 for times 3 vs 1]) in Michigan. Results were largely similar in several sensitivity analyses comparing New York with New Jersey or California. Conclusions and Relevance: Although the rates of PCI, invasive management, and revascularization have increased substantially after the exclusion of cardiogenic shock from public reporting in New York, these rates remain consistently lower than those observed in other states without public reporting.
PMID: 27463590
ISSN: 2380-6591
CID: 2191552
