Faculty Bibliography

OBJECTIVES: This study assessed whether the results of major, potentially practice-altering cardiovascular trials were influenced by the authors' self-declared financial conflicts of interest (FCOI). Secondary objectives included assessment of trial outcomes by source of funding, by FCOI subtype, and by trial endpoints. BACKGROUND: Financial conflicts of interest, ubiquitous in cardiovascular medicine because of significant investigator-industry collaborations, potentially can influence trial outcomes. METHODS: A MEDLINE search was performed using the MeSH term cardiovascular disease limited to randomized controlled trials and clinical trials published from January 1, 2000, through April 15, 2008, in 3 high-impact journals. Two reviewers independently abstracted data from the published article. Chi-square tests, Fisher exact tests, and multivariate logistic regression were used to assess the associations between FCOI and study characteristics and between FCOI and trial outcomes. RESULTS: Of the 550 articles reviewed, 51.1% satisfied FCOI criteria, including at least one of the following: stock ownership, employee, speaker's bureau, and consultant). Of the 538 articles providing sponsorship information, 34.6% reported funding solely by nonprofit organizations, 48.3% reported funding solely by industry, and 17.1% reported funding by a combination. Prevalence of FCOI significantly increased with level of industry funding: 21.5% (none), 50.0% (shared), 75.0% (industry solely, n = 281, p < 0.0001). However, no differences in reporting of favorable results were detected when articles were analyzed by self-declared FCOI (60.5% vs. 59.5% in those with and without, odds ratio: 1.04, p = 0.81). This result was upheld in multivariate analysis. CONCLUSIONS: Authors' self-declared FCOI and source of funding do not seem to impact outcomes in major cardiovascular clinical trials.

Current models incompletely risk-stratify patients with acute chest pain. In this study, N-terminal pro-B-type natriuretic peptide and cystatin C were incorporated into a contemporary chest pain triage algorithm in a clinically stratified population to improve acute coronary syndrome discrimination. Adult patients with chest pain presenting without myocardial infarction (n = 382) were prospectively enrolled from 2008 to 2009. After clinical risk stratification, N-terminal pro-B-type natriuretic peptide and cystatin C were measured and standard care was performed. The primary end point was the result of a clinical stress test. The secondary end point was any major adverse cardiac event at 6 months. Associations were determined through multivariate stratified analyses. In the low-risk group, 76 of 78 patients with normal levels of the 2 biomarkers had normal stress test results (negative predictive value 97%). Normal biomarkers predicted normal stress test results with an odds ratio of 10.56 (p = 0.006). In contrast, 26 of 33 intermediate-risk patients with normal levels of the 2 biomarkers had normal stress test results (negative predictive value 79%). Biomarkers and stress test results were not associated in the intermediate-risk group (odds ratio 2.48, p = 0.09). There were 42 major adverse cardiac events in the overall cohort. No major adverse cardiac events occurred at 6 months in the low-risk subgroup that underwent stress testing. In conclusion, N-terminal pro-B-type natriuretic peptide and cystatin C levels predict the results of stress tests in low-risk patients with chest pain but should not be substituted for stress testing in intermediate-risk patients. There is potential for their use in the early discharge of low-risk patients after clinical risk stratification.

Although electrocardiographic criteria for diagnosing left ventricular hypertrophy have a low sensitivity in the general population, their test characteristics have not been evaluated in the high-prevalence group of American Americans with chronic kidney disease. The purpose of the current study was to evaluate these test characteristics among African Americans (n = 645) with hypertensive kidney disease as part of the African-American Study of Kidney Disease and Hypertension cohort. Electrocardiograms were read by 2 cardiologists at an independent core laboratory using the 2 Sokolow-Lyon criteria and the Cornell criteria. Left ventricular hypertrophy on echocardiography was defined as left ventricular mass index greater than 49.2 and greater than 46.7 g/m(2.7) in men and women, respectively. Sixty-nine percent of the population had left ventricular hypertrophy on echo, whereas 34% had left ventricular hypertrophy by any of the electrocardiographic criteria. Sensitivity by individual electrocardiographic criteria was 16.5% by Sokolow-Lyon-1, 19.3% by Sokolow-Lyon-2, and 24.7% by Cornell criteria, with specificity ranging from 89% to 92%. When using any of the 3 criteria, sensitivity increased to 40.4% with a decrease in specificity to 78.0%. Consistent with findings in a general population, left ventricular hypertrophy by electrocardiography had low sensitivity and high specificity in this cohort of African Americans with hypertensive kidney disease.

Chest pain and other symptoms that may represent acute coronary syndromes (ACS) are common reasons for emergency department (ED) presentations, accounting for over six million visits annually in the United States [1]. Chest pain is the second most common ED presentation in the United States. Delays in diagnosis and inaccurate risk stratification of chest pain can result in serious morbidity and mortality from ACS, pulmonary embolism (PE), aortic dissection and other serious pathology. Because of the high morbidity, mortality, and liability issues associated with both recognized and unrecognized cardiovascular pathology, an aggressive approach to the evaluation of this patient group has become the standard of care. Clinical history, physical examination and electrocardiography have a limited diagnostic and prognostic role in the evaluation of possible ACS, PE, and aortic dissection, so clinicians continue to seek more accurate means of risk stratification. Recent advances in diagnostic imaging techniques particularly computed-tomography of the coronary arteries and aorta, have significantly improved our ability to diagnose life-threatening cardiovascular disease. In an era where health care utilization and cost are major considerations in how disease is managed, it is crucial to risk-stratify patients quickly and efficiently. Historically, biomarkers have played a significant role in the diagnosis and risk stratification of several cardiovascular disease states including myocardial infarction, congestive heart failure, and pulmonary embolus. Multiple biomarkers have shown early promise in answering questions of risk stratification and early diagnosis of cardiovascular pathology however many do not yet have wide clinical availability. The goal of this review will be to discuss these novel biomarkers and describe their potential role in direct patient care.

Although current literature demonstrates metabolic abnormalities are associated with mortality, obese patients who tend to have more metabolic abnormalities paradoxically have lower overall mortality rates compared to their normal-weight counterparts. In this study, we examined the prevalence of metabolic abnormality clustering and its relation to mortality in obese and normal-weight patients after percutaneous coronary intervention (PCI). Patients (n = 9,673) undergoing elective PCI from October 2003 through December 2006 at a single urban hospital were categorized by body mass index (BMI) levels of 18.5 to 24.9, 25.0 to 29.9, 30.0 to 34.9, and >/=35 kg/m(2) and by number of metabolic abnormalities possessed (hypertension, impaired fasting glucose/diabetes, triglycerides >/=150 mg/dl, high-density lipoprotein cholesterol < 40 mg/dl, and C-reactive protein >/=2.0 mg/L). All-cause mortality was assessed through June 30, 2007. Mean age of patients was 65.9 years and 66% were men. Prevalences of 4 or 5 metabolic abnormalities were 12%, 18%, 24%, and 31% in patients with BMI levels of 18.5 to 24.9, 25.0 to 29.9, 30 to 34.9, and >/=35 kg/m(2), respectively. In patients with BMI of 30.0 to 34.9 kg/m(2), hazard ratios (95% confidence intervals) for mortality associated with 2, 3, and 4 to 5 metabolic abnormalities versus 0 to 1 metabolic abnormality were 1.31 (0.79 to 2.17), 1.42 (0.83 to 2.43), and 2.39 (1.24 to 4.59), respectively. Analogous hazard ratios for patients with BMI >/=35 kg/m(2) were 1.94 (0.90 to 4.20), 1.44 (0.63 to 3.28), and 2.17 (0.91 to 5.18). All-cause mortality rates per 1,000 person-years were 55.5, 33.7, 28.3, and 33.8 in patients with BMI levels of 18.5 to 24.9, 25 to 29.9, 30 to 34.9, and >/=35 kg/m(2), respectively. In conclusion, BMI levels of 25.0 to 29.9 and 30 to 34.9 kg/m(2) were associated with lower all-cause mortality after PCI. However, an increased number of metabolic abnormalities translated into increased all-cause mortality.