ST segment resolution as a tool for assessing the efficacy of reperfusion therapy

AbstractRapid, simple and inexpensive measures are needed to assess the efficacy of reperfusion therapy both in clinical practice and in clinical trials testing novel reperfusion regimens. In the last decade, several observations have led to a favorable reappraisal of the utility of ST segment monitoring as a simple means of assessing reperfusion in patients receiving fibrinolytic therapy for acute ST elevation myocardial infarction, and ST resolution is being used increasingly in clinical practice and in clinical research. This review focuses on four interrelated roles for ST segment monitoring: the assessment of epicardial reperfusion and the identification of candidates for rescue percutaneous coronary intervention; the evaluation of microvascular and tissue-level reperfusion; the determination of prognosis early after fibrinolytic therapy; and the use of ST segment resolution to compare different reperfusion regimens

Association among plasma levels of monocyte chemoattractant protein-1, traditional cardiovascular risk factors, and subclinical atherosclerosis

ObjectivesWe sought to evaluate the association between plasma levels of monocyte chemoattractant protein (MCP)-1 and the risk for subclinical atherosclerosis.BackgroundMonocyte chemoattractant protein is a chemokine that recruits monocytes into the developing atheroma and may contribute to atherosclerotic disease development and progression. Plasma levels of MCP-1 are independently associated with prognosis in patients with acute coronary syndromes, but few population-based data are available from subjects in earlier stages of atherosclerosis.MethodsIn the Dallas Heart Study, a population-based probability sample of adults in Dallas County ≤65 years old, plasma levels of MCP-1 were measured in 3,499 subjects and correlated with traditional cardiovascular risk factors, high-sensitivityC-reactive protein (hs-CRP), and coronary artery calcium (CAC) measured by electron beam computed tomography.ResultsHigher MCP-1 levels were associated with older age, white race, family history of premature coronary disease, smoking, hypertension, diabetes, hypercholesterolemia, and higher levels of hs-CRP (p < 0.01 for each). Similar associations were observed between MCP-1 and risk factors in the subgroup of participants without detectable CAC. Compared with the subjects in the lowest quartile of MCP-1, the odds of prevalent CAC (CAC score ≥10) for subjects in the second, third, and fourth quartiles were 1.30 (95% confidence interval [CI] 0.99 to 1.73), 1.60 (95% CI 1.22 to 2.11), and 2.02 (95% CI 1.54 to 2.63), respectively. The association between MCP-1 and CAC remained significant when adjusted for traditional cardiovascular risk factors, but not when further adjusted for age.ConclusionsIn a large population-based sample, plasma levels of MCP-1 were associated with traditional risk factors for atherosclerosis, supporting the hypothesis that MCP-1 may mediate some of the atherogenic effects of these risk factors. These findings support the potential role of MCP-1 as a biomarker target for drug development

Acute Decline in Renal Function, Inflammation, and Cardiovascular Risk after an Acute Coronary Syndrome

Background and objectives: Chronic kidney disease is associated with a higher risk of cardiovascular outcomes. The prognostic significance of worsening renal function has also been shown in various cohorts of cardiac disease; however, the predictors of worsening renal function and the contribution of inflammation remains to be established. Design, setting, participants, & measurements: Worsening renal function was defined as a 25% or more decrease in estimated GFR (eGFR) over a 1-mo period in patients after a non-ST or ST elevation acute coronary syndromes participating in the Aggrastat-to-Zocor Trial; this occurred in 5% of the 3795 participants. Results: A baseline C-reactive protein (CRP) in the fourth quartile was a significant predictor of developing worsening renal function (odds ratio, 2.48; 95% confidence interval, 1.49, 4.14). After adjusting for baseline CRP and eGFR, worsening renal function remained a strong multivariate predictor for the combined cardiovascular composite of CV death, recurrent myocardial infarction (MI), heart failure or stroke (hazard ratio, 1.6; 95% confidence interval, 1.1, 2.3). Conclusions: Patients with an early decline in renal function after an acute coronary syndrome are at a significant increased risk for recurrent cardiovascular events. CRP is an independent predictor for subsequent decline in renal function and reinforces the idea that inflammation may be related to the pathophysiology of progressive renal disease

Racial Differences in Cardiovascular Biomarkers in the General Population

Background-The incidence and clinical manifestations of cardiovascular disease (CVD) differ between blacks and whites. Biomarkers that reflect important pathophysiological pathways may provide a window to allow deeper understanding of racial differences in CVD. Methods and Results-The study included 2635 white and black participants from the Dallas Heart Study who were free from existing CVD. Cross-sectional associations between race and 32 biomarkers were evaluated using multivariable linear regression adjusting for age, traditional CVD risk factors, imaging measures of body composition, renal function, insulin resistance, left ventricular mass, and socioeconomic factors. In fully adjusted models, black women had higher lipoprotein(a), leptin, D-dimer, osteoprotegerin, antinuclear antibody, homoarginine, suppression of tumorigenicity-2, and urinary microalbumin, and lower adiponectin, soluble receptor for advanced glycation end products and N-terminal pro-B-type natriuretic peptide versus white women. Black men had higher lipoprotein(a), leptin, D-dimer, high-sensitivity C-reactive protein, antinuclear antibody, symmetrical dimethylarginine, homoarginine, high-sensitivity cardiac troponin T, suppression of tumorigenicity-2, and lower adiponectin, soluble receptor for advanced glycation end products, and N-terminal pro-B-type natriuretic peptide versus white men. Adjustment for biomarkers that were associated with higher CVD risk, and that differed between blacks and whites, attenuated the risk for CVD events in black women (unadjusted hazard ratio 2.05, 95% CI 1.32, 3.17 and adjusted hazard ratio 1.15, 95% CI 0.69, 1.92) and black men (unadjusted hazard ratio 2.39, 95% CI 1.64, 3.46, and adjusted hazard ratio 1.21, 95% CI 0.76, 1.95). Conclusions-Significant racial differences were seen in biomarkers reflecting lipids, adipokines, and biomarkers of endothelial function, inflammation, myocyte injury, and neurohormonal stress, which may contribute to racial differences in the development and complications of CVD

The prognostic value of serum myoglobin in patients with non–ST-segment elevation acute coronary syndromes Results from the TIMI 11B and TACTICS-TIMI 18 studies

AbstractObjectivesThe goal of this study was to define the prognostic value of serum myoglobin in patients with non–ST-elevation acute coronary syndromes (ACS).BackgroundWhile myoglobin is useful for the early diagnosis of myocardial infarction (MI), its role in the early risk-stratification of patients with ACS has not been established.MethodsMyoglobin, creatine kinase-MB subfraction (CK-MB) and troponin I (cTnI) were measured at randomization in 616 patients from the Thrombolysis In Myocardial Ischemia/Infarction (TIMI) 11B study and 1,841 patients from the Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Therapy-Thrombolysis In Myocardial Ischemia/Infarction (TACTICS-TIMI) 18 study. The risks for death and nonfatal MI through six months of follow-up were compared between patients with and without myoglobin elevation (>110 μg/l) in each study and in a dataset combining all eligible patients from both studies (n = 2,457).ResultsIn a multivariate model adjusting for baseline characteristics, ST changes and CK-MB and cTnI levels, an elevated baseline myoglobin was associated with increased six-month mortality in TIMI 11B (adjusted odds ratio [OR] 2.9 [95% confidence interval {CI} 1.2 to 7.1]), TACTICS-TIMI 18 (adjusted OR 3.0 [95% CI 1.5 to 5.9]) and the combined dataset (adjusted OR 3.0 [95% CI 1.8 to 5.0]). In contrast, there was no significant association between myoglobin elevation and nonfatal MI (combined dataset adjusted OR 1.55, 95% CI 0.9 to 2.6). In TACTICS-TIMI 18, patients with versus those without myoglobin elevation were more likely to have an occluded culprit artery (28% vs. 10%; p < 0.0001) and visible thrombus (49% vs. 34%; p = 0.006) and less likely to have TIMI 3 flow (53% vs. 68%; p = 0.009).ConclusionsA serum concentration of myoglobin above the MI detection threshold (>110 μg/l) is associated with an increased risk of six-month mortality, independent of baseline clinical characteristics, electrocardiographic changes and elevation in CK-MB and cTnI. These findings suggest that myoglobin may be a useful addition to cardiac biomarker panels for early risk-stratification in ACS

Lifetime Risks for Cardiovascular Disease Mortality by Cardiorespiratory Fitness Levels Measured at Ages 45, 55, and 65 Years in Men The Cooper Center Longitudinal Study

ObjectivesThe purpose of this study was to determine the association between fitness and lifetime risk for cardiovascular disease (CVD).BackgroundHigher levels of traditional risk factors are associated with marked differences in lifetime risks for CVD. However, data are sparse regarding the association between fitness and the lifetime risk for CVD.MethodsWe followed up 11,049 men who underwent clinical examination at the Cooper Institute in Dallas, Texas, before 1990 until the occurrence of CVD death, non-CVD death, or attainment of age 90 years (281,469 person-years of follow-up, median follow-up 25.3 years, 1,106 CVD deaths). Fitness was measured by the Balke protocol and categorized according to treadmill time into low, moderate, and high fitness, with further stratification by CVD risk factor burden. Lifetime risk for CVD death determined by the National Death Index was estimated for fitness levels measured at ages 45, 55, and 65 years, with non-CVD death as the competing event.ResultsDifferences in fitness levels (low fitness vs. high fitness) were associated with marked differences in the lifetime risks for CVD death at each index age: age 45 years, 13.7% versus 3.4%; age 55 years, 34.2% versus 15.3%; and age 65 years, 35.6% versus 17.1%. These associations were strongest among persons with CVD risk factors.ConclusionsA single measurement of low fitness in mid-life was associated with higher lifetime risk for CVD death, particularly among persons with a high burden of CVD risk factors

Associations Among Androgens, Estrogens, and Natriuretic Peptides in Young Women Observations From the Dallas Heart Study

ObjectivesWe sought to determine if natriuretic peptides are associated with estrogen and androgen status in a population study of young women without known cardiac disease.BackgroundCirculating concentrations of plasma B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are higher in women than in men, and they may be influenced by estrogens and androgens.MethodsCardiac magnetic resonance imaging, dual energy X-ray absorbtiometry, and measurements of BNP, NT-proBNP, follicle-stimulating hormone (FSH), total testosterone, and sex hormone-binding globulin (SHBG), were performed in 682 women (ages 35 to 49 years) participating in the Dallas Heart Study.ResultsIn multivariable analyses adjusting for age, race/ethnicity, body mass index (BMI), serum creatinine, left ventricular mass and left ventricular ejection fraction <55%, menopausal status, and FSH were not associated with BNP and NT-proBNP. In contrast, higher SHBG was associated with higher BNP and NT-proBNP, while the free androgen index and calculated free testosterone were inversely associated with BNP and NT-proBNP (p < 0.0001 for each). Addition of SHBG or any measure of free testosterone to the multivariable models modified the effect of BMI and lean mass, such that measures of body composition were no longer significantly associated with BNP or NT-proBNP.ConclusionsAmong young women, measures of free testosterone were independently and inversely associated with BNP and NT-proBNP. These results suggest that circulating free testosterone, not estradiol, mediates gender differences in natriuretic peptides. In addition, the association between higher BMI and lean body mass with natriuretic peptides may be mediated by testosterone