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Abstract: Objective: Recent large-scale genome-wide association studies have identified a novel susceptibility locus on chromosome 9p21.3 that contributes a significant attributable risk for myocardial infarction. The phenotypic significance of this locus in patients with established coronary artery disease is unknown. We sought to compare cardiovascular structure and function in carriers and non-carriers of the risk haplotype in a cross-sectional study. Methods: We genotyped the rs1333049 single-nucleotide polymorphism in 593 Caucasian individuals with stable coronary artery disease recruited in the Heart and Soul Study. All study subjects underwent resting and stress echocardiography. Linear and logistic regression models were used to examine the association between the rs1333049 polymorphism and echocardiographic parameters of cardiovascular structure and function. Results: There was no association between rs1333049 genotype and echocardiographic phenotype (left ventricular hypertrophy, systolic dysfunction, diastolic dysfunction, inducible ischemia, exercise capacity, mitral annular calcification, and aortic plaque). Conclusions: In a cross-sectional study of individuals with stable coronary artery disease, there was no association of chromosome 9p21.3 genotype with cardiovascular structure and function. [Copyright &y& Elsevier]

Obesity is an independent risk factor for recurrent events among patients with established coronary heart disease (CHD). The goal of the present study was to identify potential mechanisms underlying this association. We measured the waist-to-hip ratio and body mass index in 979 outpatients with stable CHD and followed them for a mean of 4.9 years. We used proportional hazards models to evaluate the extent to which the association of obesity with subsequent heart failure (HF) hospitalization or cardiovascular (CV) events (myocardial infarction, stroke, or CHD death) was explained by baseline co-morbidities, cardiac disease severity, inflammation, insulin resistance, neurohormones and adipokines. Of the 979 participants, 128 (13%) were hospitalized for HF and 152 (16%) developed a CV event. Each standard deviation (SD) increase in the waist-to-hip ratio was associated with a 30% increased risk of HF hospitalization (unadjusted hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.1 to 1.6). This association was not attenuated after adjustment for potential mediators (HR 1.6, 95% CI 1.2 to 2.1). Likewise, each SD increase in the waist-to-hip ratio was associated with a 20% greater risk of CV events (unadjusted HR 1.2, 95% CI 1.0 to 1.4), and this remained unchanged after adjustment for potential mediators (adjusted HR 1.3, 95% CI 1.0 to 1.5). The body mass index was not associated with the risk of HF or CV events. In conclusion, abdominal obesity is an independent predictor of HF hospitalization and recurrent CV events in patients with stable CHD. This association does not appear to be mediated by co-morbid conditions, cardiac disease severity, insulin resistance, inflammation, neurohormones, or adipokines. [Copyright &y& Elsevier]

Abstract: Objective: Elevated concentrations of adiponectin are associated with a favorable metabolic profile but also with adverse cardiovascular outcomes. This apparent discrepancy has raised questions about whether adiponectin is associated with an increased or decreased risk of coronary heart disease (CHD). We sought to determine whether higher adiponectin levels are associated with exercise-induced ischemia in patients with stable CHD. Methods and results: We measured total serum adiponectin concentrations and evaluated exercise-induced ischemia by stress echocardiography in a cross-sectional study of 899 outpatients with documented stable CHD. Of these, 217 (24%) had inducible ischemia. Although adiponectin levels correlated negatively with diabetes prevalence, body mass index, serum insulin, fasting glucose, low-density lipoprotein cholesterol, and triglycerides and positively with high-density lipoprotein cholesterol (all P <0.005), elevated adiponectin concentrations were also associated with a greater risk of inducible ischemia. Each standard deviation (0.08μg/mL) increase in log adiponectin was associated with a 35% greater odds of inducible ischemia (unadjusted odds ratio 1.35; 95% confidence interval 1.15–1.57; P =0.0002). Although attenuated, this association remained present after multivariable adjustment for traditional cardiovascular risk factors and other measures of cardiac function (adjusted odds ratio 1.21; 95% confidence interval 1.02–1.43; P =0.03). Conclusions: Elevated concentrations of adiponectin are independently associated with inducible ischemia in patients with stable CHD. These findings raise the possibility that the presence of chronic inducible ischemia may alter the cardio-protective effects afforded by adiponectin secretion in the healthy population. [Copyright &y& Elsevier]

Diastolic dysfunction is usually identified by the combination of characteristic mitral and pulmonary vein flow patterns. However, obtaining a complete set of echocardiographic parameters can be technically difficult and data may conflict. We hypothesized that as a stand-alone variable, (ventricular) diastolic dominant pulmonary vein flow would predict heart failure (HF) hospitalizations and cardiovascular death. Standard transthoracic echocardiograms were obtained in 906 subjects from the Heart and Soul Study, a prospective study of the effects of depression on coronary heart disease. Pulmonary vein flow pattern was determined using the dominant velocity–time integral. Cardiac events were determined by 2 independent adjudicators, and Cox proportional hazards models were used. Systolic dominant pulmonary vein flow was present in 89% of subjects, and diastolic dominant, in the remaining 11%. During an average 4.1 years of follow-up, subjects with diastolic dominant pulmonary vein flow had a 25% rate of HF hospitalization and 9% rate of cardiovascular death. After multivariate adjustment including left ventricular ejection fraction, diastolic pulmonary vein flow was associated with a 3-fold risk of HF hospitalization (p = 0.001) and a 2-fold risk of HF hospitalization or death (p = 0.004). In conclusion, diastolic dominant pulmonary vein flow pattern was a stand-alone predictor of adverse cardiac events, and its presence was associated with significantly higher rates of HF hospitalizations and cardiovascular death. [Copyright &y& Elsevier]

The article presents the results from a clinical study that examined whether plasma levels of amino terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP) could be used to predict death or cardiovascular events, such as myocardial infarction, stroke, or heart failure. Patients in the study had coronary heart disease. The authors found that, independent of other prognostic markers, elevated levels of NT-proBNP could be used to predict cardiovascular morbidity and mortality and help identify individuals at risk for cardiovascular events.