Saul Blecker

Everolimus-Eluting Stents or Bypass Surgery for Multivessel Coronary Disease

BACKGROUND Results of trials and registry studies have shown lower long-term mortality after coronary-artery bypass grafting (CABG) than after percutaneous coronary intervention (PCI) among patients with multivessel disease. These previous analyses did not evaluate PCI with second-generation drug-eluting stents. METHODS In an observational registry study, we compared the outcomes in patients with multivessel disease who underwent CABG with the outcomes in those who underwent PCI with the use of everolimus-eluting stents. The primary outcome was all-cause mortality. Secondary outcomes were the rates of myocardial infarction, stroke, and repeat revascularization. Propensity-score matching was used to assemble a cohort of patients with similar baseline characteristics. RESULTS Among 34,819 eligible patients, 9223 patients who underwent PCI with everolimus-eluting stents and 9223 who underwent CABG had similar propensity scores and were included in the analyses. At a mean follow-up of 2.9 years, PCI with everolimus-eluting stents, as compared with CABG, was associated with a similar risk of death (3.1% per year and 2.9% per year, respectively; hazard ratio, 1.04; 95% confidence interval [CI], 0.93 to 1.17; P=0.50), higher risks of myocardial infarction (1.9% per year vs. 1.1% per year; hazard ratio, 1.51; 95% CI, 1.29 to 1.77; P<0.001) and repeat revascularization (7.2% per year vs. 3.1% per year; hazard ratio, 2.35; 95% CI, 2.14 to 2.58; P<0.001), and a lower risk of stroke (0.7% per year vs. 1.0% per year; hazard ratio, 0.62; 95% CI, 0.50 to 0.76; P<0.001). The higher risk of myocardial infarction with PCI than with CABG was not significant among patients with complete revascularization but was significant among those with incomplete revascularization (P=0.02 for interaction). CONCLUSIONS In a contemporary clinical-practice registry study, the risk of death associated with PCI with everolimus-eluting stents was similar to that associated with CABG. PCI was associated with a higher risk of myocardial infarction (among patients with incomplete revascularization) and repeat revascularization but a lower risk of stroke. (Funded by Abbott Vascular.).

The Association of Hemoglobin A1c With Incident Heart Failure Among People Without Diabetes: The Atherosclerosis Risk in Communities Study

OBJECTIVE This study sought to investigate an association of HbA1c (A1C) with incident heart failure among individuals without diabetes and compare it to fasting glucose. RESEARCH DESIGN AND METHODS We studied 11,057 participants of the Atherosclerosis Risk in Communities (ARIC) Study without heart failure or diabetes at baseline and estimated hazard ratios of incident heart failure by categories of A1C (<5.0, 5.0–5.4 [reference], 5.5–5.9, and 6.0–6.4%) and fasting glucose (<90, 90–99 [reference], 100–109, and 110–125 mg/dl) using Cox proportional hazards models. RESULTS A total of 841 cases of incident heart failure hospitalization or deaths (International Classification of Disease, 9th/10th Revision, 428/I50) occurred during a median follow-up of 14.1 years (incidence rate 5.7 per 1,000 person-years). After the adjustment for covariates including fasting glucose, the hazard ratio of incident heart failure was higher in individuals with A1C 6.0–6.4% (1.40 [95% CI, 1.09–1.79]) and 5.5–6.0% (1.16 [0.98–1.37]) as compared with the reference group. Similar results were observed when adjusting for insulin level or limiting to heart failure cases without preceding coronary events or developed diabetes during follow-up. In contrast, elevated fasting glucose was not associated with heart failure after adjustment for covariates and A1C. Similar findings were observed when the top quartile (A1C, 5.7–6.4%, and fasting glucose, 108–125 mg/dl) was compared with the lowest quartile (<5.2% and <95 mg/dl, respectively). CONCLUSIONS Elevated A1C (≥5.5–6.0%) was associated with incident heart failure in a middle-aged population without diabetes, suggesting that chronic hyperglycemia prior to the development of diabetes contributes to development of heart failure.

Physician Decision Making and Trends in the Use of Cardiac Stress Testing in the United States: An Analysis of Repeated Cross-sectional Data

Background Cardiac stress testing, particularly with imaging, has been the focus of debates about rising health care costs, inappropriate use, and patient safety in the context of radiation exposure.

High-Normal Albuminuria and Risk of Heart Failure in the Community

BACKGROUND Albuminuria has been associated with cardiovascular risk, but the relationship of high-normal albuminuria to subsequent heart failure has not been well established. STUDY DESIGN Prospective observational study, the Atherosclerosis Risk in Communities (ARIC) Study. SETTING & PARTICIPANTS 10,975 individuals free from heart failure were followed up from the fourth ARIC Study visit (1996-1998) through January 2006. PREDICTOR Urinary albumin-creatinine ratio (UACR), analyzed continuously and categorically as optimal (<5 mg/g), intermediate-normal (5-9 mg/g), high-normal (10-29 mg/g), microalbuminuria (30-299 mg/g), and macroalbuminuria (≥300 mg/g). OUTCOMES & MEASUREMENTS Incident heart failure was defined as a heart failure-related hospitalization or death. Cox proportional hazard models were used to calculate the HR of heart failure after adjustment for age, race, sex, estimated glomerular filtration rate (eGFR), and other cardiovascular risk factors. RESULTS Individuals were followed up for a median of 8.3 years and experienced 344 heart failure events. Compared with normal UACR, albuminuria was associated with a progressively increased risk of heart failure from intermediate-normal (adjusted HR, 1.54; 95% CI, 1.12-2.11) and high-normal UACR (adjusted HR, 1.91; 95% CI, 1.38-2.66) to microalbuminuria (adjusted HR, 2.49; 95% CI, 1.77-3.50) and macroalbuminuria (adjusted HR, 3.47; 95% CI, 2.10-5.72). Results were similar in secondary analyses of participants censored at the time of coronary heart disease event and along a range of eGFRs. LIMITATIONS UACR was measured as a single random sample. CONCLUSIONS Albuminuria is associated with subsequent heart failure, even in individuals with few cardiovascular risk factors and UACR within the normal range. Our results suggest that the association between albuminuria and heart failure may not be mediated fully by ischemic heart disease or kidney disease, measured using eGFR.

Revascularization in Patients With Multivessel Coronary Artery Disease and Chronic Kidney Disease: Everolimus-Eluting Stents Versus Coronary Artery Bypass Graft Surgery

BACKGROUND Randomized trials of percutaneous coronary intervention (PCI) versus coronary artery bypass graft (CABG) routinely exclude patients with chronic kidney disease (CKD). OBJECTIVES This study evaluated outcomes of PCI versus CABG in patients with CKD. METHODS Patients with CKD who underwent PCI using everolimus-eluting stents were propensity-score matched to patients who underwent isolated CABG for multivessel coronary disease in New York. The primary outcome was all-cause mortality. Secondary outcomes were myocardial infarction (MI), stroke, and repeat revascularization. RESULTS Of 11,305 patients with CKD, 5,920 patients were propensity-score matched. In the short term, PCI was associated with a lower risk of death (hazard ratio [HR]: 0.55; 95% confidence interval [CI]: 0.35 to 0.87), stroke (HR: 0.22; 95% CI: 0.12 to 0.42), and repeat revascularization (HR: 0.48; 95% CI: 0.23 to 0.98) compared with CABG. In the longer term, PCI was associated with a similar risk of death (HR: 1.07; 95% CI: 0.92 to 1.24), higher risk of MI (HR: 1.76; 95% CI: 1.40 to 2.23), a lower risk of stroke (HR: 0.56; 95% CI: 0.41 to 0.76), and a higher risk of repeat revascularization (HR: 2.42; 95% CI: 2.05 to 2.85). In the subgroup with complete revascularization with PCI, the increased risk of MI was no longer statistically significant (HR: 1.18; 95% CI: 0.67 to 2.09). In the 243 matched pairs of patients with end-stage renal disease on hemodialysis, PCI was associated with significantly higher risk of death (HR: 2.02; 95% CI: 1.40 to 2.93) and repeat revascularization (HR: 2.44; 95% CI: 1.50 to 3.96) compared with CABG. CONCLUSIONS In patients with CKD, CABG is associated with higher short-term risk of death, stroke, and repeat revascularization, whereas PCI with everolimus-eluting stents is associated with a higher long-term risk of repeat revascularization and perhaps MI, with no long-term mortality difference. In the subgroup on dialysis, the results favored CABG over PCI.

Airflow obstruction, lung function, and incidence of atrial fibrillation: the Atherosclerosis Risk in Communities (ARIC) study.

Background— Reduced low forced expiratory volume in 1 second (FEV1) is reportedly associated with an increased risk of atrial fibrillation (AF). Extant reports do not provide separate estimates for never smokers or for blacks, who incongruously have lower AF incidence than whites. Methods and Results— We examined 15 004 middle-aged blacks and whites enrolled in the Atherosclerosis Risk in Communities (ARIC) cohort study. Standardized spirometry data were collected at the baseline examination. Incident AF was identified from the first among the following: International Classification of Diseases codes for AF on hospital discharge records or death certificates or 12-lead ECGs performed during 3 triennial follow-up visits. Over an average follow-up of 17.5 years, a total of 1691 participants (11%) developed new-onset AF. The rate of incident AF was inversely associated with FEV1 in each of the 4 race and sex groups. After multivariable adjustment for traditional cardiovascular disease risk factors and height, hazard ratios of AF comparing the lowest with the highest quartile of FEV1 were 1.37 (95% confidence interval, 1.02–1.83) for white women, 1.49 (95% confidence interval, 1.16–1.91) for white men, 1.63 (95% confidence interval, 1.00–2.66) for black women, and 2.36 (95% confidence interval, 1.30–4.29) for black men. The above associations were observed across all smoking status categories. Moderate/severe airflow obstruction (FEV1/forced vital capacity <0.70 and FEV1 < 80% of predicted value) was also associated with higher AF incidence. Conclusions— In this large population-based study with a long-term follow-up, reduced FEV1 and obstructive respiratory disease were associated with a higher AF incidence after adjustment for measured confounders.

Diabetes and Risk of Fracture-Related Hospitalization: The Atherosclerosis Risk in Communities Study

OBJECTIVE To examine the association between diabetes, glycemic control, and risk of fracture-related hospitalization in the Atherosclerosis Risk in Communities (ARIC) Study. RESEARCH DESIGN AND METHODS Fracture-related hospitalization was defined using International Classification of Diseases, 9th revision, codes (733.1–733.19, 733.93–733.98, or 800–829). We calculated the incidence rate of fracture-related hospitalization by age and used Cox proportional hazards models to investigate the association of diabetes with risk of fracture after adjustment for demographic, lifestyle, and behavioral risk factors. RESULTS There were 1,078 incident fracture-related hospitalizations among 15,140 participants during a median of 20 years of follow-up. The overall incidence rate was 4.0 per 1,000 person-years (95% confidence interval [CI], 3.8–4.3). Diagnosed diabetes was significantly and independently associated with an increased risk of fracture (adjusted hazard ratio [HR], 1.74; 95% CI, 1.42–2.14). There also was a significantly increased risk of fracture among persons with diagnosed diabetes who were treated with insulin (HR, 1.87; 95% CI, 1.15–3.05) and among persons with diagnosed diabetes with hemoglobin A1c (HbA1c) ≥8% (1.63; 1.09–2.44) compared with those with HbA1c <8%. Undiagnosed diabetes was not significantly associated with risk of fracture (HR, 1.12; 95% CI, 0.82–1.53). CONCLUSIONS This study supports recommendations from the American Diabetes Association for assessment of fracture risk and implementation of prevention strategies in persons with type 2 diabetes, particularly those persons with poor glucose control.

Revascularization in Patients With Multivessel Coronary Artery Disease and Severe Left Ventricular Systolic Dysfunction Everolimus-Eluting Stents Versus Coronary Artery Bypass Graft Surgery

Background— Guidelines recommend coronary artery bypass graft surgery (CABG) over percutaneous coronary intervention (PCI) for multivessel disease and severe left ventricular systolic dysfunction. However, CABG has not been compared with PCI in such patients in randomized trials. Methods and Results— Patients with multivessel disease and severe left ventricular systolic dysfunction (ejection fraction ⩽35%) who underwent either PCI with everolimus-eluting stent or CABG were selected from the New York State registries. The primary outcome was long-term all-cause death. Secondary outcomes were individual outcomes of myocardial infarction, stroke, and repeat revascularization. Among the 4616 patients who fulfilled our inclusion criteria (1351 everolimus-eluting stent and 3265 CABG), propensity score matching identified 2126 patients with similar propensity scores. In the short term, PCI was associated with a lower risk of stroke (hazard ratio [HR], 0.05; 95% confidence interval [CI], 0.01–0.39; P=0.004) in comparison with CABG. At long-term follow-up (median, 2.9 years), PCI was associated with a similar risk of death (HR, 1.01; 95% CI, 0.81–1.28; P=0.91), a higher risk of myocardial infarction (HR, 2.16; 95% CI, 1.42–3.28; P=0.0003), a lower risk of stroke (HR, 0.57; 95% CI, 0.33–0.97; P=0.04), and a higher risk of repeat revascularization (HR, 2.54; 95% CI, 1.88–3.44; P<0.0001). The test for interaction was significant (P=0.002) for completeness of revascularization, such that, in patients in whom complete revascularization was achieved with PCI, there was no difference in myocardial infarction between PCI and CABG. Conclusions— Among patients with multivessel disease and severe left ventricular systolic dysfunction, PCI with everolimus-eluting stent had comparable long-term survival in comparison with CABG. PCI was associated with higher risk of myocardial infarction (in those with incomplete revascularization) and repeat revascularization, and CABG was associated with higher risk of stroke.

Airflow Obstruction, Lung Function, and Incidence of Atrial Fibrillation

Background— Reduced low forced expiratory volume in 1 second (FEV1) is reportedly associated with an increased risk of atrial fibrillation (AF). Extant reports do not provide separate estimates for never smokers or for blacks, who incongruously have lower AF incidence than whites. Methods and Results— We examined 15 004 middle-aged blacks and whites enrolled in the Atherosclerosis Risk in Communities (ARIC) cohort study. Standardized spirometry data were collected at the baseline examination. Incident AF was identified from the first among the following: International Classification of Diseases codes for AF on hospital discharge records or death certificates or 12-lead ECGs performed during 3 triennial follow-up visits. Over an average follow-up of 17.5 years, a total of 1691 participants (11%) developed new-onset AF. The rate of incident AF was inversely associated with FEV1 in each of the 4 race and sex groups. After multivariable adjustment for traditional cardiovascular disease risk factors and height, hazard ratios of AF comparing the lowest with the highest quartile of FEV1 were 1.37 (95% confidence interval, 1.02–1.83) for white women, 1.49 (95% confidence interval, 1.16–1.91) for white men, 1.63 (95% confidence interval, 1.00–2.66) for black women, and 2.36 (95% confidence interval, 1.30–4.29) for black men. The above associations were observed across all smoking status categories. Moderate/severe airflow obstruction (FEV1/forced vital capacity <0.70 and FEV1 < 80% of predicted value) was also associated with higher AF incidence. Conclusions— In this large population-based study with a long-term follow-up, reduced FEV1 and obstructive respiratory disease were associated with a higher AF incidence after adjustment for measured confounders.

Clinical Implications of Referral Bias in the Diagnostic Performance of Exercise Testing for Coronary Artery Disease

Background Exercise testing with echocardiography or myocardial perfusion imaging is widely used to risk‐stratify patients with suspected coronary artery disease. However, reports of diagnostic performance rarely adjust for referral bias, and this practice may adversely influence patient care. Therefore, we evaluated the potential impact of referral bias on diagnostic effectiveness and clinical decision‐making. Methods and Results Searching PubMed and EMBASE (1990–2012), 2 investigators independently evaluated eligibility and abstracted data on study characteristics and referral patterns. Diagnostic performance reported in 4 previously published meta‐analyses of exercise echocardiography and myocardial perfusion imaging was adjusted using pooled referral rates and Bayesian methods. Twenty‐one studies reported referral patterns in 49 006 patients (mean age 60.7 years, 39.6% women, and 0.8% prior history of myocardial infarction). Catheterization referral rates after normal and abnormal exercise tests were 4.0% (95% CI, 2.9% to 5.0%) and 42.5% (36.2% to 48.9%), respectively, with odds ratio for referral after an abnormal test of 14.6 (10.7 to 19.9). After adjustment for referral, exercise echocardiography sensitivity fell from 84% (80% to 89%) to 34% (27% to 41%), and specificity rose from 77% (69% to 86%) to 99% (99% to 100%). Similarly, exercise myocardial perfusion imaging sensitivity fell from 85% (81% to 88%) to 38% (31% to 44%), and specificity rose from 69% (61% to 78%) to 99% (99% to 100%). Summary receiver operating curve analysis demonstrated only modest changes in overall discriminatory power but adjusting for referral increased positive‐predictive value and reduced negative‐predictive value. Conclusions Exercise echocardiography and myocardial perfusion imaging are considerably less sensitive and more specific for coronary artery disease after adjustment for referral. Given these findings, future work should assess the comparative ability of these and other tests to rule‐in versus rule‐out coronary artery disease.