Faculty Bibliography

BACKGROUND: Over the past decade, ischemic heart disease (IHD) mortality trends have been less favorable among adults age 25-54 than age >/=55 years. HYPOTHESIS: Disorders associated with IHD such as diabetes, chronic inflammatory and infectious diseases, and cocaine use are important contributors to premature IHD mortality. METHODS: Multiple-cause-of-death analysis was performed using the New York City (NYC) Vital Statistics database. Frequencies of selected contributing causes on death records with IHD as the underlying cause for decedents age >/=25 were assessed (n = 418,151; 1990-2008). Concurrent Telephone risk-factor surveys (NYC Community Health Survey, Centers for Disease Control Behavioral Risk Factor Survey in New York State) were analyzed. RESULTS: In sum, a prespecified contributing cause was identified on 13.6% of death certificates for IHD decedents age 25-54. Diabetes was reported more frequently for younger IHD decedents (15% of females and 10% of males age 25-54 vs 6% of both sexes age >/= 55). In contrast, concurrent diabetes prevalence in New York State was 3.4% for those age 25-54 and 13.6% for those age >55 (P < 0.0001). Systemic lupus erythematosus, human immunodeficiency virus, and cocaine were also more likely to contribute to IHD death among younger than older people. CONCLUSIONS: Diabetes may be a potent risk factor for IHD death in young people, particularly young women, in whom it was reported on IHD death records at a rate 5x higher than local prevalence. The high frequency of reporting of studied contributing causes in younger IHD decedents may provide a focus for further IHD mortality-reduction efforts in younger adults.

Background: Type 2 myocardial infarction (MI) is defined as myocardial necrosis due to an imbalance in supply and demand. Clinical characteristics predisposing to Type 2 MI and medical therapy use remain uncertain. Methods: Charts of patients admitted to NYU Langone Medical Center in 2013 with a diagnosis of secondary myocardial ischemia (ICD9 411.89) or non-primary diagnosis of non-ST-elevation MI (ICD9 410.71) were retrospectively reviewed, following hospital standardization of acute MI ICD9 coding. Cases with suspected/confirmed Type 1 MI or without rise and fall of troponin were excluded. Results: Charts of 104 inpatients with Type 2 MI have been reviewed to date, with evaluation of additional cases ongoing. Conditions associated with and possibly provoking Type 2 MI included sepsis (defined as SIRS with an infectious source, 39%), surgery (37%), anemia (Hgb < 7 mg/dL), bleeding, or transfusion >1 PRBCs (34%), respiratory failure (28%), tachyarrhythmia (21%), hypotension (17%), hypertensive crisis (8%), and bradycardia (2%). Multiple provoking conditions were identified in 74% of cases. See Table for risk factors, procedure use and results and in-hospital outcomes. Inpatient mortality was 3%. Among 92 patients discharged alive and not to hospice, medical regimens included aspirin (65%), statin (66%), ACE inhibition (ACEi) (38%), and beta blocker (65%). Patients with a peak troponin >1.0 ng/mL (35%) were more likely to be discharged on aspirin (p=0.004) and beta-blocker (p=0.027), but not statin or ACEi. Conclusions: Type 2 MI occurs most frequently in the setting of sepsis, surgery, and/or anemia in patients with cardiovascular risk factors, but mechanisms of Type 2 MI remain poorly understood. Rates of outpatient antiplatelet and statin prescription are low at hospital discharge, reflecting physician uncertainty about the role of secondary prevention. Further research into mechanisms is needed to inform management of patients with Type 2 MI

Noninvasive carotid measurements have proven value in the estimation of future cardiovascular (CV) outcomes in systemic lupus erythematosus (SLE). Natural IgM-antibodies to phosphorylcholine (PC) epitopes can enhance apoptotic-cell clearance and induce anti-inflammatory pathways. Herein, we show that subclinical CV disease, as detected by carotid ultrasound, in a cross-sectional SLE cohort was associated with lower levels of IgM anti-PC, as well as lower levels of the ratio of IgM anti-PC/total IgM, compared to patients without plaque (p=0.004 and p=0.02, respectively). The IgM anti-PC/total IgM association remained significant after adjusting for age, cholesterol and hypertension. Adiponectin and sE-selectin were significantly elevated in patients with plaque, and statistical models showed that combining adiponectin, sE-selectin and IgM anti-PC/total IgM was better for predicting plaque than either test alone. These results support the hypothesis that IgM-natural autoantibodies may inhibit atherogenesis, and confirm the utility of IgM anti-PC levels as a biomarker for subclinical CV disease.

BACKGROUND: The Occluded Artery Trial (OAT) randomized stable patients (n=2201) >24h (calendar days 3-28) after myocardial infarction (MI) with totally occluded infarct-related arteries (IRA), to percutaneous coronary intervention (PCI) with optimal medical therapy, or optimal medical therapy alone (MED). PCI had no impact on the composite of death, reinfarction, or class IV heart failure over extended follow-up of up to 9years. We evaluated the impact of early and late reinfarction and definition of MI on subsequent mortality. METHODS AND RESULTS: Reinfarction was adjudicated according to an adaptation of the 2007 universal definition of MI and the OAT definition (>/=2 of the following - symptoms, EKG and biomarkers). Cox regression models were used to analyze the effect of post-randomization reinfarction and baseline variables on time to death. After adjustment for baseline characteristics the 169 (PCI: n=95; MED: n=74) patients who developed reinfarction by the universal definition had a 4.15-fold (95% CI 3.03-5.69, p<0.001) increased risk of death compared to patients without reinfarction. This risk was similar for both treatment groups (interaction p=0.26) and when MI was defined by the stricter OAT criteria. Reinfarctions occurring within 6months of randomization had similar impact on mortality as reinfarctions occurring later, and the impact of reinfarction due to the same IRA and a different epicardial vessel was similar. CONCLUSIONS: For stable post-MI patients with totally occluded infarct arteries, reinfarction significantly independently increased the risk of death regardless of the initial management strategy (PCI vs. MED), reinfarction definition, location and early or late occurrence.

The lack of standardized reporting of the magnitude of ischemia on noninvasive imaging contributes to variability in translating the severity of ischemia across stress imaging modalities. We identified the risk of coronary artery disease (CAD) death or myocardial infarction (MI) associated with >/=10% ischemic myocardium on stress nuclear imaging as the risk threshold for stress echocardiography and cardiac magnetic resonance. A narrative review revealed that >/=10% ischemic myocardium on stress nuclear imaging was associated with a median rate of CAD death or MI of 4.9%/year (interquartile range: 3.75% to 5.3%). For stress echocardiography, >/=3 newly dysfunctional segments portend a median rate of CAD death or MI of 4.5%/year (interquartile range: 3.8% to 5.9%). Although imprecisely delineated, moderate-severe ischemia on cardiac magnetic resonance may be indicated by >/=4 of 32 stress perfusion defects or >/=3 dobutamine-induced dysfunctional segments. Risk-based thresholds can define equivalent amounts of ischemia across the stress imaging modalities, which will help to translate a common understanding of patient risk on which to guide subsequent management decisions.

BACKGROUND: In a prospective study, we previously identified plaque disruption (PD: plaque rupture or ulceration) in 38% of women with myocardial infarction (MI) without angiographically obstructive coronary artery disease (CAD), using intravascular ultrasound (IVUS). Underlying plaque morphology has not been described in these patients and may provide insight into the mechanisms of MI without obstructive CAD. METHODS: Forty-two women with MI and <50% angiographic stenosis underwent IVUS (n = 114 vessels). Analyses were performed by a blinded core laboratory. Sixteen patients had PD (14 ruptures and 5 ulcerations in 18 vessels). Plaque area, % plaque burden, lumen area stenosis, eccentricity, and remodeling index were calculated for disrupted plaques and largest plaque by area in each vessel. RESULTS: Disrupted plaques had lower % plaque burden than the largest plaque in the same vessel (31.9% vs 49.8%, P = .005) and were rarely located at the site of largest plaque (1/19). Disrupted plaques were typically fibrous and were not more eccentric or remodeled than the largest plaque in the same vessel. CONCLUSIONS: Plaque disruption was often identifiable on IVUS in women with MI without obstructive CAD. Plaque disruption in this patient population occurred in fibrous or fibrofatty plaques and, contrary to expectations based on prior studies of plaque vulnerability, did not typically occur in eccentric, outwardly remodeled, or soft plaque in these patients. Plaque disruption rarely occurred at the site of the largest plaque in the vessel. These findings suggest that the pathophysiology of PD in women with MI without angiographically obstructive CAD may be different from MI with obstructive disease and requires further investigation.