Faculty Bibliography

BACKGROUND: Preoperative anemia is a well-established risk factor for short-term mortality in patients undergoing non-cardiac surgery, but appropriate thresholds for transfusion remain uncertain. The objective of this study was to determine long-term outcomes associated with anemia, hemorrhage and red blood cell transfusion in patients undergoing non-cardiac surgery. METHODS: We performed a long-term follow-up study of consecutive subjects undergoing hip, knee, and spine surgery between November 1, 2008 and December 31, 2009. Clinical data were obtained from administrative and laboratory databases, and retrospective record review. Pre-operative anemia was defined as baseline hemoglobin <13 g/dL for men and <12 g/dL for women. Hemorrhage was defined by ICD-9 coding. Data on long-term survival were queried from the Social Security Death Index (SSDI) database. Logistic regression models were used to identify factors associated with long-term mortality. RESULTS: 3,050 subjects underwent orthopedic surgery. Pre-operative anemia was present in 17.6% (537) of subjects, hemorrhage occurred in 33 (1%), and 766 (25%) received >/=1 red blood cell transfusion. Over 9,015 patient-years of follow up, 111 deaths occurred. Anemia (HR 3.91, CI 2.49 - 6.15) and hemorrhage (HR 5.28, CI 2.20 - 12.67) were independently associated with long-term mortality after multivariable adjustment. Red blood cell transfusion during the surgical hospitalization was associated with long-term mortality (HR 3.96, CI 2.47 - 6.34), which was attenuated by severity of anemia (no anemia [HR 4.39], mild anemia [HR 2.27], and moderate/severe anemia [HR 0.81], P for trend 0.0015). CONCLUSIONS: Preoperative anemia, perioperative bleeding and red blood cell transfusion are associated with increased mortality at long-term follow up after non-cardiac surgery. Strategies to minimize anemia and bleeding should be considered for all patients and restrictive transfusion strategies may be advisable. Further investigation into mechanisms of these adverse events is warranted.

The evolution of the management of acute myocardial infarction (MI) has been one of the crowning achievements of modern medicine. At the turn of the twentieth century, MI was an often-fatal condition. Prolonged bed rest served as the principal treatment modality. Over the past century, insights into the pathophysiology of MI revolutionized approaches to management, with the sequential use of surgical coronary artery revascularization, thrombolytic therapy, and percutaneous coronary intervention (PCI) with primary coronary angioplasty, and placement of intracoronary stents. The benefits of prompt revascularization inspired systems of care to provide rapid access to PCI. This review provides a historical context for our current approach to primary PCI for acute MI.

BACKGROUND: Ischemic heart disease (IHD) mortality has been on the decline in the United States for decades. However, declines in IHD mortality have been slower in certain groups, including young women and black individuals. HYPOTHESIS: Trends in IHD vary by age, sex, and race in New York City (NYC). Young female minorities are a vulnerable group that may warrant renewed efforts to reduce IHD. METHODS: IHD mortality trends were assessed in NYC 1980-2008. NYC Vital Statistics data were obtained for analysis. Age-specific IHD mortality rates and confidence bounds were estimated. Trends in IHD mortality were compared by age and race/ethnicity using linear regression of log-transformed mortality rates. Rates and trends in IHD mortality rates were compared between subgroups defined by age, sex and race/ethnicity. RESULTS: The decline in IHD mortality rates slowed in 1999 among individuals aged 35-54 years but not >/=55. IHD mortality rates were higher among young men than women age 35-54, but annual declines in IHD mortality were slower for women. Black women age 35-54 had higher IHD mortality rates and slower declines in IHD mortality than women of other race/ethnicity groups. IHD mortality trends were similar in black and white men age 35-54. CONCLUSIONS: The decline in IHD mortality rates has slowed in recent years among younger, but not older, individuals in NYC. There was an association between sex and race/ethnicity on IHD mortality rates and trends. Young black women may benefit from targeted medical and public health interventions to reduce IHD mortality.

BACKGROUND: Certain proton pump inhibitors (PPIs) interfere with clopidogrel metabolism, potentially attenuating P2Y12 receptor inhibition. Previous observational and randomized trials report conflicting results regarding the clinical significance of this pharmacological interaction. We examined the interaction between concomitant administration of PPI and clopidogrel on platelet reactivity and clinical outcomes in the large-scale, prospective Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents study. METHODS AND RESULTS: On-treatment P2Y12 platelet reactivity testing was performed using the VerifyNow assay after clopidogrel loading and successful drug-eluting stent implantation at 11 sites in the United States and Germany. PPIs were prescribed at the discretion of treating physicians; patients were followed for 2 years. High platelet reactivity was defined as P2Y12 reactivity units >208. Of 8582 enrolled patients, 2697 (31.4%) were taking a PPI at the time of coronary intervention. After adjustment for differences in baseline characteristics, PPI use was independently associated with high platelet reactivity (odds ratio, 1.38: 95% confidence interval, 1.25-1.52, P=0.0001). A total of 2162 (25.2%) patients were prescribed a PPI at hospital discharge. In a propensity-adjusted multivariable analysis, discharge PPI use was independently associated with increased risk for postdischarge major adverse cardiac events (cardiac death, myocardial infarction, or ischemia-driven target lesion revascularization) at 2-year follow-up (hazard ratio, 1.21; 95% confidence interval, 1.04-1.42, P=0.02). CONCLUSIONS: In patients treated with clopidogrel after successful drug-eluting stents implantation, the concomitant administration of PPI was associated with high platelet reactivity and a greater rate of adverse outcomes during long-term follow-up. Additional studies are warranted to determine the risk-benefit ratio of PPIs in patients with drug-eluting stents treated with clopidogrel. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00433966.

In addition to aggressive lifestyle and nonlipid risk factor modification, statin therapy improves cardiovascular disease outcomes following acute coronary syndromes. Despite established benefits of treatment, contemporary registries reveal substantial underutilization of and nonadherence to statin therapy for secondary prevention. In randomized controlled trials investigating statin therapy, including moderate-intensity statin plus ezetimibe therapy, rates of nonadherence are reported in up to 40% of subjects. Durable strategies to address gaps in lipid lowering for secondary prevention are essential to maximize reduction in cardiovascular disease risk.

Myocardial necrosis in the perioperative period of noncardiac surgery is associated with short-term mortality, but long-term outcomes have not been characterized. We investigated the association between perioperative troponin elevation and long-term mortality in a retrospective study of consecutive subjects who underwent hip, knee, and spine surgery. Perioperative myocardial necrosis and International Classification of Disease, Ninth Revision-coded myocardial infarction (MI) were recorded. Long-term survival was assessed using the Social Security Death Index database. Logistic regression models were used to identify independent predictors of long-term mortality. A total of 3,050 subjects underwent surgery. Mean age was 60.8 years, and 59% were women. Postoperative troponin was measured in 1,055 subjects (34.6%). Myocardial necrosis occurred in 179 cases (5.9%), and MI was coded in 20 (0.7%). Over 9,015 patient-years of follow-up, 111 deaths (3.6%) occurred. Long-term mortality was 16.8% in subjects with myocardial necrosis and 5.8% with a troponin in the normal range. Perioperative troponin elevation (hazard ratio 2.33, 95% confidence interval 1.33 to 4.10) and coded postoperative MI (adjusted hazard ratio 3.51, 95% confidence interval 1.44 to 8.53) were significantly associated with long-term mortality after multivariable adjustment. After excluding patients with coronary artery disease and renal dysfunction, myocardial necrosis remained associated with long-term mortality. In conclusion, postoperative myocardial necrosis is common after orthopedic surgery. Myocardial necrosis is independently associated with long-term mortality at 3 years and may be used to identify patients at higher risk for events who may benefit from aggressive management of cardiovascular risk factors.

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.

Type 2 myocardial infarction (type 2 MI) is defined as myocardial necrosis that results from an imbalance of myocardial oxygen supply and demand. Although type 2 MI is highly prevalent and strongly associated with mortality, the pathophysiology remains poorly understood. Discrepancies in definitions, frequency of screening, diagnostic approaches, and methods of adjudication lead to confusion and misclassification. To date, there is no consensus on the diagnostic criteria for type 2 MI. No guidelines exist for the optimal management of this condition, and further investigation is urgently needed. This review explores the existing evidence on the pathophysiology, diagnosis, prognosis, and management of type 2 MI.