Shuaib Abdullah

Prevalence and Determinants of Troponin T Elevation in the General Population

Background— The prevalence and determinants of cardiac troponin T (cTnT) elevation in the general population are unknown, and the significance of minimally increased cTnT remains controversial. Our objective was to determine the prevalence and determinants of cTnT elevation in a large, representative sample of the general population. Methods and Results— cTnT was measured from stored plasma samples in 3557 subjects of the Dallas Heart Study, a population-based sample. cTnT elevation (≥0.01 &mgr;g/L) was correlated with clinical variables and cardiac MRI findings. The sample weight-adjusted prevalence of cTnT elevation in the general population was 0.7%. In univariable analyses, cTnT elevation was associated with older age, black race, male sex, coronary artery calcium by electron beam CT, a composite marker of congestive heart failure (CHF), left ventricular hypertrophy (LVH), diabetes mellitus (DM), and chronic kidney disease (CKD) (P<0.001 for each). Subjects with minimally increased (0.01 to 0.029 &mgr;g/L) and increased (≥0.03 &mgr;g/L) cTnT had a similar prevalence of these characteristics. In multivariable logistic regression analysis, LVH, CHF, DM, and CKD were independently associated with cTnT elevation. Conclusions— In the general population, cTnT elevation is rare in subjects without CHF, LVH, CKD, or DM, suggesting that the upper limit of normal for the immunoassay should be <0.01 &mgr;g/L. Even minimally increased cTnT may represent subclinical cardiac injury and have important clinical implications, a hypothesis that should be tested in longitudinal outcome studies.

Impact of body mass and body composition on circulating levels of natriuretic peptides: results from the Dallas Heart Study.

Background— The association between higher body mass index (BMI) and lower B-type natriuretic peptide (BNP) level is thought to be mediated by expression of the natriuretic peptide clearance receptor (NPR-C) in adipose tissue. To explore this association, we tested 2 hypotheses: (1) that N-terminal (NT)-proBNP, which is not believed to bind NPR-C, would not be associated with BMI and (2) that lower BNP would be more closely associated with fat mass than with lean mass. Methods and Results— Measurements of BNP, NT-proBNP, and body composition by direct dual energy x-ray absorptiometry (DEXA) were performed in 2707 subjects from the Dallas Heart Study. The associations between obesity and low BNP (<4 ng/L) or low NT-proBNP (lowest sex-specific quartile) were evaluated with multivariable logistic regression models stratified by sex and adjusted for age, race/ethnicity, hypertension, left ventricular mass, and end-diastolic volume. Higher BMI was independently associated with lower BNP and NT-proBNP (all P<0.001). When BMI was replaced with both DEXA-derived lean and fat mass, greater lean mass, but not fat mass, was associated with low BNP and NT-proBNP levels. Conclusions— In a large, population-based cohort, we confirm the previously described association between higher BMI and lower BNP and demonstrate a similar inverse association between BMI and NT-proBNP. Interestingly, both BNP and NT-proBNP are more closely associated with lean mass than with fat mass. These findings do not support the hypothesis that the lower BNP levels seen in obesity are driven by enhanced BNP clearance mediated via NPR-C.

Angiographic Success and Procedural Complications in Patients Undergoing Percutaneous Coronary Chronic Total Occlusion Interventions : A Weighted Meta-Analysis of 18,061 Patients From 65 Studies

OBJECTIVES This study sought to perform a weighted meta-analysis of the complication risk during chronic total occlusion (CTO) percutaneous coronary intervention (PCI). BACKGROUND The safety profile of CTO PCI has received limited study. METHODS We conducted a meta-analysis of 65 studies published between 2000 and 2011 reporting procedural complications of CTO PCI. Data on the frequency of death, emergent coronary artery bypass graft surgery, stroke, myocardial infarction, perforation, tamponade, stent thrombosis, major vascular or bleeding events, contrast nephropathy, and radiation skin injury were collected. RESULTS A total of 65 studies with 18,061 patients and 18,941 target CTO vessels were included. Pooled estimates of outcomes were as follows: angiographic success 77% (95% confidence interval [CI]: 74.3% to 79.6%); death 0.2% (95% CI: 0.1% to 0.3%); emergent coronary artery bypass graft surgery 0.1% (95% CI: 0.0% to 0.2%); stroke <0.01% (95% CI: 0.0% to 0.1%); myocardial infarction 2.5% (95% CI: 1.9% to 3.0%); Q-wave myocardial infarction 0.2% (95% CI: 0.1% to 0.3%); coronary perforation 2.9% (95% CI: 2.2% to 3.6%); tamponade 0.3% (95% CI: 0.2% to 0.5%); and contrast nephropathy 3.8% (95% CI: 2.4% to 5.3%). Compared with successful procedures, unsuccessful procedures had higher rates of death (0.42% vs. 1.54%, p < 0.0001), perforation (3.65% vs. 10.70%, p < 0.0001), and tamponade (0% vs. 1.65%, p < 0.0001). Among 886 lesions treated with the retrograde approach, success rate was 79.8% with no deaths and low rates of emergent coronary artery bypass graft surgery (0.17%) and tamponade (1.2%). CONCLUSIONS CTO PCI carries low risk for procedural complications despite high success rates.

Women have higher left ventricular ejection fractions than men independent of differences in left ventricular volume : The dallas heart study

Background— Although gender-specific criteria are common for defining cardiac traits such as left ventricular hypertrophy, left ventricular ejection fraction (LVEF) thresholds widely used in clinical practice have traditionally been the same for women and men, perhaps because it remains uncertain whether there is a systematic difference in LVEF between genders. Methods and Results— Using cardiac magnetic resonance imaging in a probability-based sample of Dallas County residents aged 30 to 65 years (1435 women and 1183 men), we compared LVEF in women and men. The association of gender with stroke volume independent of end-diastolic volume (EDV) or other potential confounders was assessed by multivariable analysis. Gender-specific thresholds for a low LVEF were defined at the 2.5th percentile in women and men from a healthy reference subpopulation. The median (25th, 75th percentile) LVEF was higher in women than in men (75% [70%, 79%] in women versus 70% [65%, 75%] in men, P<0.001). Left ventricular EDV and end-systolic volume indexed to body surface area were smaller in women than in men (P<0.001 for both). Gender remained significantly associated with stroke volume, independent of EDV and other potential confounders in multivariable analysis. A low LVEF was defined as below 61% in women and below 55% in men. Conclusions— Women have a higher LVEF than men in the general population, secondary to a higher stroke volume for a given EDV independent of known potential confounders.

Interleukin-18, the Metabolic Syndrome, and Subclinical Atherosclerosis Results From the Dallas Heart Study

Objective—Although IL-18 promotes atherogenesis in animal studies and predicts cardiovascular risk in humans, it is unknown whether elevated IL-18 levels are associated with coronary atherosclerosis in the general population. Methods and Results—IL-18 plasma levels were determined by ELISA in 2231 subjects from the Dallas Heart Study. In univariable analysis, IL-18 levels associated with traditional cardiovascular risk factors and particularly with components of the metabolic syndrome (MS, P<0.01 for trend across the number of MS components); IL-18 also associated with coronary artery calcium (CAC) scores measured by electron beam computed tomography and aortic plaque measured by MRI (P<0.01 for each). In multivariable analyses, IL-18 remained associated with multiple components of the MS but not with CAC or aortic plaque. Conclusions—In a large population-based sample, elevated IL-18 plasma levels associated with risk factors for atherosclerosis and with the metabolic syndrome. The association between IL-18 and atherosclerosis diminished after accounting for traditional cardiovascular risk factors. These data suggest that IL-18 does not add independently to detection of atherosclerotic burden in asymptomatic individuals.

Meta-analysis of clinical outcomes of patients who underwent percutaneous coronary interventions for chronic total occlusions

Successful percutaneous coronary intervention (PCI) for chronic total occlusions (CTOs) has been associated with clinical benefit. There are no randomized controlled trials on long-term clinical outcomes after CTO PCI, limiting the available evidence to observational cohort studies. We sought to perform a weighted meta-analysis of the long-term outcomes of successful versus failed CTO PCI. A total of 25 studies, published from 1990 to 2014, with 28,486 patients (29,315 CTO PCI procedures) were included. We analyzed data on mortality, subsequent coronary artery bypass grafting (CABG), myocardial infarction, major adverse cardiac events, angina pectoris, stroke, and target vessel revascularization using random-effects models. Procedural success was 71% (range 51% to 87%). During a weighted mean follow-up of 3.11 years, compared with unsuccessful, successful CTO PCI was associated with lower mortality (odds ratio [OR] 0.52, 95% confidence interval [CI] 0.43 to 0.63), less residual angina (OR 0.38, 95% CI 0.24 to 0.60), lower risk for stroke (OR 0.72, 95% CI 0.60 to 0.88), less need for subsequent coronary artery bypass grafting (OR 0.18, 95% CI 0.14 to 0.22), and lower risk for major adverse cardiac events (0.59, 95% CI 0.44 to 0.79). There was no difference in the incidence of target vessel revascularization (OR 0.66, 95% CI 0.36 to 1.23) or myocardial infarction (OR 0.73, 95% CI 0.52 to 1.03). Outcomes were similar in patients who underwent balloon angioplasty only or stenting with bare metal or drug-eluting stents. Compared with failed procedures, successful CTO PCIs are associated with a lower risk of death, stroke, and coronary artery bypass grafting and less recurrent angina pectoris.

Stress myocardial perfusion imaging by CMR provides strong prognostic value to cardiac events regardless of patient's sex.

OBJECTIVES The major aim of this study is to test the hypothesis that stress cardiac magnetic resonance (CMR) imaging can provide robust prognostic value in women presenting with suspected ischemia, to the same extent as in men. BACKGROUND Compelling evidence indicates that women with coronary artery disease (CAD) experience worse outcomes than men owing to a lack of early diagnosis and management. Numerous clinical studies have shown that stress CMR detects evidence of myocardial ischemia and infarction at high accuracy. Compared to nuclear scintigraphy, CMR is free of ionizing radiation, has high spatial resolution for imaging small hearts, and overcomes breast attenuation artifacts, which are substantial advantages when imaging women for CAD. METHODS We performed stress CMR in 405 patients (168 women, mean age 58 ± 14 years) referred for ischemia assessment. CMR techniques included cine cardiac function, perfusion imaging during vasodilating stress, and late gadolinium enhancement imaging. All patients were followed for major adverse cardiac events (MACE). RESULTS At a median follow-up of 30 months, MACE occurred in 36 patients (9%) including 21 cardiac deaths and 15 acute myocardial infarctions. In women, CMR evidence of ischemia (ISCHEMIA) demonstrated strong association with MACE (unadjusted hazard ratio: 49.9, p < 0.0001). While women with ISCHEMIA(+) had an annual MACE rate of 15%, women with ISCHEMIA(-) had very low annual MACE rate (0.3%), which was not statistically different from the low annual MACE rate in men with ISCHEMIA(-) (1.1%). CMR myocardial ischemia score was the strongest multivariable predictor of MACE in this cohort, for both women and men, indicating robust cardiac prognostication regardless of sex. CONCLUSIONS In addition to avoiding exposure to ionizing radiation, stress CMR myocardial perfusion imaging is an effective and robust risk-stratifying tool for patients of either sex presenting with possible ischemia.

Prevalence and management of coronary chronic total occlusions in a tertiary veterans affairs hospital

We sought to determine the contemporary prevalence and management of coronary chronic total occlusions (CTO) in a veteran population.

Receptor for advanced glycation end-products (RAGE) and soluble RAGE (sRAGE): cardiovascular implications

Disorders of glucose metabolism are associated with increased risk for cardiovascular disease (CVD) complications, including coronary, peripheral and cerebral arterial disease, that account for the majority of morbidity and mortality among patients with diabetes mellitus (DM). These associations between glucose and CVD risk extend continuously well below the glycaemic thresholds established for the diagnosis of diabetes, including significantly increased risk associated with impaired fasting glucose, impaired glucose tolerance, and even high normal glucose concentrations. While these epidemiological observations have established a clear association between cardiovascular disease and dysglycaemia and suggest a direct causal link, the mechanisms by which hyperglycaemia may contribute to the development, progression and instability of atherosclerosis remain unclear. A number of recent advances in the realm of vascular biology have identified several novel, plausible pathways that might link hyperglycaemia with atherosclerosis, individually or in aggregate. Key among them are the interaction between advanced glycation end-products (AGEs) and the receptor for AGEs (RAGE), which exists as a trans-membrane signalling receptor and as a circulating form, soluble RAGE (sRAGE). The purpose of this review is to provide an overview of the present understanding of RAGE and sRAGE, their plausible role linking perturbed glucose metabolism with the development, progression and instability of atherosclerosis, and the potential therapeutic implications of modulation of this biological system.

Angiographic success and procedural complications in patients undergoing retrograde percutaneous coronary chronic total occlusion interventions: A weighted meta-analysis of 3482 patients from 26 studies

BACKGROUND The efficacy and safety profile of retrograde chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. We sought to perform a weighted meta-analysis of the success and complication rates of retrograde CTO PCI. METHODS We conducted a meta-analysis of 26 studies published between 2006 and April 2013 reporting in-hospital outcomes of retrograde CTO PCI. Data on procedural success, frequency of death, emergent coronary artery bypass graft surgery (CABG), stroke, myocardial infarction (MI), perforation, tamponade, stent thrombosis, major vascular or bleeding events, contrast nephropathy, and radiation skin injury were collected. RESULTS A total of 26 studies with 3482 patients and 3493 target CTO lesions were included. Primary retrograde CTO PCI was attempted in 52.4%. Pooled estimates of outcomes were as follows: procedural success 83.3% [95% confidence interval (CI): 79.0% to 87.7%]; death 0.7% (95% CI: 0.5% to 1.2%); urgent CABG 0.7% (95% CI: 0.4% to 1.2%); tamponade 1.4% (95% CI: 1.0% to 2.2%); collateral perforation 6.9% (95% CI: 4.6% to 10.4%); coronary perforation 4.3% (95% CI: 1.2% to 15.4%); donor vessel dissection 2% (95% CI: 0.9% to 4.5%); stroke 0.5% (95% CI: 0.2% to 1.0%); MI 3.1% (95% CI: 0.2% to 5.0%); Q wave MI 0.6% (95% CI: 0.4% to 1.1%); vascular access complications 2% (95% CI: 0.9% to 4.5%); contrast nephropathy 1.8% (95% CI: 0.8% to 3.7%); and wire fracture and equipment entrapment 1.2% (95% CI: 0.6% to 2.5%). CONCLUSIONS Retrograde CTO PCI is associated with high procedural success rate and acceptable risk for procedural complications.