Nathaniel R. Smilowitz

Women have less severe and extensive coronary atherosclerosis in fatal cases of ischemic heart disease: an autopsy study.

OBJECTIVE The study aims to evaluate sex differences in extent and severity of coronary artery disease (CAD) and myocardial findings at autopsy among young people with fatal ischemic heart disease (IHD). BACKGROUND Women with acute coronary syndrome are less likely than men to display obstructive CAD at angiography. This suggests unique mechanisms of acute coronary syndrome exist in women or may reflect prehospital death of women with the most severe CAD. METHODS Reports of autopsies by the Office of the Chief Medical Examiner of New York City on people aged 21 to 54 years who died between January 1, 2006, and December 31, 2008, were reviewed. A total of 639 cases of death due to atherosclerotic or arteriosclerotic cardiovascular disease according to the medical examiner were analyzed. Significant CAD was defined as ≥75% cross-sectional area stenosis in an epicardial vessel or ≥50% left main. RESULTS Women were less likely to have obstructive CAD (63% vs 77% of men, P = .002). There was pathologic evidence of myocardial infarction (MI) in 43% of cases, 17% of which had nonobstructive CAD. Frequency of MI did not vary by sex overall (38% of women vs 45% of men, P = .18) or among those without significant CAD (23% vs 29%, P = .45). CONCLUSIONS Among young people determined at autopsy to have died of IHD, fewer women had obstructive CAD, consistent with angiographic data in other IHD syndromes. Pathologic evidence of MI may exist in the absence of obstructive CAD.

Utilization of and Adherence to Guideline-Recommended Lipid-Lowering Therapy After Acute Coronary Syndrome: Opportunities for Improvement.

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.

Perioperative Major Adverse Cardiovascular and Cerebrovascular Events Associated With Noncardiac Surgery

Importance Major adverse cardiovascular and cerebrovascular events (MACCE) are a significant source of perioperative morbidity and mortality following noncardiac surgery. Objective To evaluate national trends in perioperative cardiovascular outcomes and mortality after major noncardiac surgery and to identify surgical subtypes associated with cardiovascular events using a large administrative database of United States hospital admissions. Design, Setting, Participants Patients who underwent major noncardiac surgery from January 2004 to December 2013 were identified using the National Inpatient Sample. Main Outcomes and Measures Perioperative MACCE (primary outcome), defined as in-hospital, all-cause death, acute myocardial infarction (AMI), or acute ischemic stroke, were evaluated over time. Results Among 10 581 621 hospitalizations (mean [SD] patient age, 65.74 [12.32] years; 5 975 798 female patients 56.60%]) for major noncardiac surgery, perioperative MACCE occurred in 317 479 hospitalizations (3.0%), corresponding to an annual incidence of approximately 150 000 events after applying sample weights. Major adverse cardiovascular and cerebrovascular events occurred most frequently in patients undergoing vascular (7.7%), thoracic (6.5%), and transplant surgery (6.3%). Between 2004 and 2013, the frequency of MACCE declined from 3.1% to 2.6% (P for trend <.001; adjusted odds ratio [aOR], 0.95; 95% CI, 0.94-0.97) driven by a decline in frequency of perioperative death (aOR, 0.79; 95% CI, 0.77-0.81) and AMI (aOR, 0.87; 95% CI, 0.84-0.89) but an increase in perioperative ischemic stroke from 0.52% in 2004 to 0.77% in 2013 (P for trend <.001; aOR 1.79; CI 1.73-1.86). Conclusions and Relevance Perioperative MACCE occurs in 1 of every 33 hospitalizations for noncardiac surgery. Despite reductions in the rate of death and AMI among patients undergoing major noncardiac surgery in the United States, perioperative ischemic stroke increased over time. Additional efforts are necessary to improve cardiovascular care in the perioperative period of patients undergoing noncardiac surgery.

Association Between Anemia, Bleeding, and Transfusion with Long-term Mortality Following Noncardiac Surgery

BACKGROUND Preoperative anemia is a well-established risk factor for short-term mortality in patients undergoing noncardiac 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 noncardiac 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. Preoperative anemia was defined as baseline hemoglobin < 13 g/dL for men and < 12 g/dL for women. Hemorrhage was defined by International Classification of Diseases, Ninth Revision coding. Data on long-term survival were collected from the Social Security Death Index database. Logistic regression models were used to identify factors associated with long-term mortality. RESULTS There were 3050 subjects who underwent orthopedic surgery. Preoperative anemia was present in 17.6% (537) of subjects, hemorrhage occurred in 33 (1%), and 766 (25%) received at least one red blood cell transfusion. Over 9015 patient-years of follow-up, 111 deaths occurred. Anemia (hazard ratio [HR] 3.91; confidence interval [CI], 2.49-6.15) and hemorrhage (HR 5.28; 95% 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; 95% 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 .0015). CONCLUSIONS Preoperative anemia, perioperative bleeding, and red blood cell transfusion are associated with increased mortality at long-term follow-up after noncardiac 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.

Glucagon-Like Peptide-1 Receptor Agonists for Diabetes Mellitus A Role in Cardiovascular Disease

Diabetes mellitus, defined as a fasting plasma glucose of ≥126 mg/dL or a glycosylated hemoglobin A1c level (HbA1c) of ≥6.5%, afflicts ≈12.9% of adults in the United States and nearly 285 million adults worldwide.1,2 Diabetes mellitus is a major risk factor for the development of cardiovascular disease, independently conferring a 2-fold excess risk of coronary heart disease and stroke.3 Macrovascular events in diabetes mellitus remain the leading cause of mortality, and the burden of cardiovascular disease attributable to diabetes mellitus has increased over the past decade.4 An increase in the prevalence of obesity has contributed to the rise in diabetes mellitus. Additionally, obesity independently increases the risk of cardiovascular disease in patients with diabetes mellitus.5 Although strict glycemic control unequivocally reduces the microvascular complications of diabetes mellitus, the macrovascular benefits of intensive therapy have been difficult to establish, with conflicting results from large clinical trials.6–9 Multifactorial strategies are recommended to reduce cardiovascular risk in diabetes mellitus through enhanced glycemic control, blood pressure reduction, lipid management, weight loss, and physical activity.10 Unfortunately, despite aggressive interventions for hyperglycemia, <50% of patients achieve standard HbA1c targets with conventional therapy.11 Polypharmacy is required to achieve glycemic control in the majority of patients within 3 years of diagnosis.12 Although combinations of drug classes can synergistically target multiple pathophysiological defects, novel therapies are required to manage diabetes mellitus and mitigate cardiovascular risks. Dipeptidyl-peptidase IV (DPP-IV) inhibitor and glucagon-like peptide-1 (GLP-1) receptor agonist incretin therapies were developed to complement conventional treatment options for diabetes mellitus. Despite promising initial reports of cardioprotective effects, DPP-IV inhibitors have failed to demonstrate improved cardiovascular outcomes in large clinical trials.13–15 Randomized studies to evaluate cardiovascular outcomes associated with GLP-1 receptor agonists are currently underway. This review presents …

Perioperative Management to Reduce Cardiovascular Events

C ase Presentation: A 75-year-old man with hypertension and a history of stable coronary artery disease (CAD) presents to your office 1 month before an elective total knee replacement. He states that he underwent percutaneous coronary intervention (PCI) with a drug-eluting stent (DES) to his left anterior descending coronary artery 2 years ago. His medication regimen includes daily aspirin 81, clopidogrel 75 mg, amlodipine 10 mg, lisinopril 5 mg, and atorvastatin 40 mg. He does not smoke cigarettes. Recent laboratory data reveal normal renal function. He asks what he can do to reduce the cardiovascular risks of noncardiac surgery. Perioperative cardiovascular complications are a source of morbidity and mortality for >200 million patients worldwide who undergo noncardiac surgery each year. In large cohorts and randomized trials, perioperative myocardial infarction (MI) occurs in up to 6.2% of surgeries.1–4 The pathogenesis of cardiovascular events in the postoperative period is complex (Figure). Induction of anesthesia, surgical trauma, bleeding, anemia, hypoxia, and postoperative pain lead to surges in catecholamines, cortisol production, and a hypercoaguable state. Inflammatory cytokines, including tumor necrosis factor-α, interleukin-1, interleukin-6, and C-reactive protein, rise in the postoperative period. Increased platelet activation contributes to the thrombotic milieu.5 Tachycardia and elevations in blood pressure increase coronary artery sheer stress and can precipitate coronary plaque destabilization, plaque rupture, coronary thrombosis, and type 1 MI. Postoperative myocardial necrosis and infarction may also be caused by imbalances in myocardial oxygen supply and demand from tachycardia, hypotension, hypoxia, or anemia in the setting of stable CAD (type 2 MI). Microvascular coronary disease, endothelial dysfunction, and excess activation of inflammatory pathways may be contributing mechanisms but require further study. Figure. Pathogenesis of perioperative cardiovascular events. Multiple perioperative events and cardiovascular factors may contribute to the development of myocardial necrosis and infarction. CAD indicates coronary artery …

Diagnosis and management of type II myocardial infarction: increased demand for a limited supply of evidence.

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.

Proton Pump Inhibitors, Platelet Reactivity, and Cardiovascular Outcomes After Drug-Eluting Stents in Clopidogrel-Treated Patients The ADAPT-DES Study

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.

Perioperative acute myocardial infarction associated with non-cardiac surgery

Aims Acute myocardial infarction (AMI) is a significant cardiovascular complication following non-cardiac surgery. We sought to evaluate national trends in perioperative AMI, its management, and outcomes. Methods and results Patients who underwent non-cardiac surgery from 2005 to 2013 were identified using the United States National Inpatient Sample. Perioperative AMI was evaluated over time. Propensity score matching was used to compile a cohort of AMI patients managed invasively (defined as cardiac catheterization or coronary revascularization) vs. conservatively. The primary outcome was in-hospital all-cause mortality. Among 9 566 277 hospitalizations for major non-cardiac surgery, perioperative AMI occurred in 84 093 (0.88%). Over time, the rate of perioperative AMI per 100 000 surgeries declined by 170 [95% confidence intervals (95% CI) 158-181], from 898 in 2005 to 729 in 2013 (P for trend <0.0001). Perioperative AMI occurred most frequently in patients undergoing vascular (2.0%), transplant (1.6%), and thoracic (1.5%) surgery. In-hospital mortality was higher in patients with perioperative AMI than those without AMI [18.0% vs. 1.5%, P < 0.0001; adjusted odds ratio (OR) 5.76, 95% CI 5.65-5.88]. Mortality associated with perioperative AMI declined over time (adjusted OR 0.86, 95% CI 0.84-0.88). In a propensity-matched cohort of 34 650 patients with perioperative AMI, invasive management was associated with lower mortality than conservative management (8.9% vs. 18.1%, P < 0.001; OR 0.44, 95% CI 0.41-0.47). Conclusion In an observational cohort study from the USA, perioperative AMI occurs in 0.9% of patients undergoing major non-cardiac surgery and is strongly associated with in-hospital mortality. Invasive management of such patients may mitigate some of this excess risk, and further research on the management of perioperative AMI is warranted.

Mortality of Myocardial Infarction by Sex, Age, and Obstructive Coronary Artery Disease Status in the ACTION Registry–GWTG (Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With the Guidelines)

Background— Sex differences in early mortality after myocardial infarction (MI) vary by age. MI with nonobstructive coronary arteries (MINOCA [<50% stenosis]) is more common among younger patients and women, and MINOCA has a better prognosis than MI with obstructive coronary artery disease (MI-CAD). The relationship between age, sex, and obstructive CAD status and outcomes post-MI has not been established. Methods and Results— Adults who underwent coronary angiography for acute ST-segment–elevation and non–ST-segment–elevation MI in the National Cardiovascular Data Registry ACTION Registry-GWTG (Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With the Guidelines) from 2007 to 2014 were identified. Patients with cardiac arrest, thrombolytic therapy, prior revascularization, or missing demographic or angiographic data were excluded. The primary outcome was all-cause, in-hospital mortality. Secondary outcomes included major adverse cardiovascular events. Demographics, clinical history, presentation, and in-hospital treatments were compared by sex and CAD status (MI-CAD or MINOCA). Mortality and major adverse cardiovascular outcomes were analyzed by age, sex, and CAD status. Among 322 523 patients with MI, MINOCA occurred in 18 918 (5.9%). MINOCA was more common in women than men (10.5% versus 3.4%; P<0.0001), and women had higher mortality than men overall (3.6% versus 2.4%; P<0.0001). In-hospital mortality was lower after MINOCA than MI-CAD (1.1% versus 2.9%; P<0.0001). Among patients with MI-CAD, women had higher mortality than men (3.9% versus 2.4%; P<0.0001) while no sex difference in mortality was observed with MINOCA (1.1% versus 1.0%; P=0.84). The higher risk of post-MI death among women with MI-CAD was most pronounced at younger ages. Conclusions— MINOCA was associated with lower mortality than MI-CAD. Higher risk of post-MI death among women in comparison to men was restricted to patients with MI-CAD.