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The article offers information on a study that deals with the prognostic value of the 6-minute walk test (6MWT) in patients with stable coronary heart disease. The study aims to assess the role played by the 6MWT in predicting cardiovascular events in ambulatory patients with coronary heart disease. It found improvement in risk prediction with the addition of a 6MWT.

Criticizes the common mistake of attributing casualty to associations in observational studies. Example of associating hormone replacement therapy (HRT) and coronary heart disease (CHD); Suggested choice of words in pointing out HRT and CHD.

Background: Patients with posttraumatic stress disorder (PTSD) are at increased risk for cardiovascular disease (CVD), but few studies have included objective measures of CVD and how PTSD causes CVD remains unknown. We sought to determine the association between PTSD and objectively assessed CVD and examine potential underlying mechanisms. Methods: Outpatients from two Veterans Affairs Medical Centers were enrolled from 2008 to 2010. Posttraumatic stress disorder was identified using the Clinician Administered PTSD Scale, and standardized exercise treadmill tests were performed to detect myocardial ischemia. Results: Of the 663 participants with complete data, ischemia was present in 17% of patients with PTSD versus 10% of patients without PTSD (p = .006). The association between PTSD and ischemia remained significant after adjusting for potential confounders (age, sex, prior CVD) and mediators (traditional cardiac risk factors, C-reactive protein, obesity, alcohol use, sleep quality, social support, and depression), adjusted odds ratio (OR) 2.42, 95% confidence interval (CI) 1.39 to 4.22, p = .002. Findings remained significant when those with prior CVD were excluded (fully adjusted OR 2.24, 95% CI 1.20–4.18, p = .01) and when continuous PTSD symptom score was used as the predictor (fully adjusted OR per 10-point change in Clinician Administered PTSD Scale score 1.12, 95% CI 1.03–1.22, p = .01). Conclusions: Posttraumatic stress disorder was associated with ischemic changes on exercise treadmill tests independent of traditional cardiac risk factors, C-reactive protein, and several health behaviors and psychosocial risk factors, suggesting additional mechanisms linking PTSD and ischemia should be explored. The association of PTSD and ischemia among patients without known CVD highlights an opportunity for early interventions to prevent progression of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Resistin is an adipocytokine involved in insulin resistance, inflammation, and atherosclerosis. Its role in the development and progression of coronary heart disease (CHD) is not yet well-characterized. We performed a cross-sectional study to evaluate the association between serum resistin levels, exercise capacity, and exercise-induced cardiac ischemia among patients with stable CHD. Methods and results: We measured serum resistin concentrations and determined treadmill exercise capacity and inducible ischemia by stress echocardiography in 899 outpatients with documented CHD. Of these, 215 (24%) had poor exercise capacity (<5 metabolic equivalent tasks), and 217 (24%) had inducible ischemia. As compared with participants who had resistin levels in the lowest quartile, those with resistin levels in the highest quartile were more likely to have poor exercise capacity (33% versus 16%, odds ratio [OR] 2.68, P <0.0001) and inducible ischemia (30% versus 17%, OR 2.08, P =0.001). Both associations remained robust after adjusting for numerous clinical risk factors, metabolic variables, and markers of insulin resistance (poor exercise capacity adjusted OR 1.73, P =0.04; inducible ischemia adjusted OR 1.82, P =0.01). However, further adjustments for C-reactive protein, interleukin-6, and tumor necrosis factor-α eliminated the association with poor exercise capacity (adjusted OR 1.50, P =0.14) and substantially weakened the association with inducible ischemia (adjusted OR 1.72, P =0.03). Conclusions: Elevated serum resistin is associated with poor exercise capacity and exercise-induced cardiac ischemia in patients with stable coronary disease. Adjustment for inflammatory markers attenuated these associations, suggesting a possible role for resistin in inflammation and CHD pathophysiology. [ABSTRACT FROM AUTHOR]

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]

Background: Serial increases in high-sensitivity cardiac troponin (hs-cTnT) have been associated with death in community-dwelling adults, but the association remains uninvestigated in those with coronary artery disease (CAD). Methods: We measured hs-cTnT at baseline and after 5 years in 635 ambulatory Heart and Soul Study patients with CAD. We also performed echocardiography at rest and after treadmill exercise at baseline and after 5 years. Participants were subsequently followed for the outcome of death. We used a multivariable-adjusted Cox proportional hazards model to evaluate the association between 5-year change in hs-cTnT and subsequent all-cause mortality. Results: Of the 635 subjects, there were 386 participants (61%) who had an increase in hs-cTnT levels between baseline and year 5 measurements (median increase 5.6 pg/mL, IQR 3.2–9.9 pg/mL). There were 182 deaths after a mean 4.2-year follow-up after the year 5 visit. After adjusting for clinical variables, a >50% increase in hs-cTnT between baseline and year 5 was associated with a nearly 2-fold increased risk of death from any cause (hazard ratio 1.7, 95% confidence interval 1.1–2.7). When addition of year 5 hs-cTnT was compared to a model including clinical variables and baseline hs-cTnT, there was a modest but statistically significant increase in C-statistic from 0.82 to 0.83 (p = 0.04). Conclusion: In ambulatory patients with CAD, serial increases in hs-cTnT over time are associated with an increased risk of death. [ABSTRACT FROM AUTHOR]

Familial combined hyperlipidemia (FCH) is a complex and common familial dyslipidemia characterized by elevated total cholesterol and/or triglyceride levels with over five-fold risk of coronary heart disease. The genetic architecture and contribution of rare Mendelian and common variants to FCH susceptibility is unknown. In 53 Finnish FCH families, we genotyped and imputed nine million variants in 715 family members with DNA available. We studied the enrichment of variants previously implicated with monogenic dyslipidemias and/or lipid levels in the general population by comparing allele frequencies between the FCH families and population samples. We also constructed weighted polygenic scores using 212 lipid-associated SNPs and estimated the relative contributions of Mendelian variants and polygenic scores to the risk of FCH in the families. We identified, across the whole allele frequency spectrum, an enrichment of variants known to elevate, and a deficiency of variants known to lower LDL-C and/or TG levels among both probands and affected FCH individuals. The score based on TG associated SNPs was particularly high among affected individuals compared to non-affected family members. Out of 234 affected FCH individuals across the families, seven (3%) carried Mendelian variants and 83 (35%) showed high accumulation of either known LDL-C or TG elevating variants by having either polygenic score over the 90th percentile in the population. The positive predictive value of high score was much higher for affected FCH individuals than for similar sporadic cases in the population. FCH is highly polygenic, supporting the hypothesis that variants across the whole allele frequency spectrum contribute to this complex familial trait. Polygenic SNP panels improve identification of individuals affected with FCH, but their clinical utility remains to be defined. [ABSTRACT FROM AUTHOR]

Background While changes in the left ventricular end-diastolic pressure-volume relationship ( LV- EDPVR) can be estimated using echocardiography, their prognostic utility in stable coronary artery disease ( CAD) is unknown. Methods Using echo-estimated LV end-diastolic volume index and diastolic function category, the relative position of the LV- EDPVR was defined in 901 participants with stable CAD as: (1) left-shifted, (2) right-shifted, or (3) intermediate. We then evaluated the association of LV- EDPVR position relative to the intermediate category with time to hospitalization for heart failure ( HF) or cardiovascular ( CV) death using Cox proportional hazards models. Results During 7.0 ± 3.1 years of follow-up, there were 207 admissions for HF or CV deaths. Both leftward and rightward shifts of LV- EDPVR were associated with a significantly higher risk of HF or CV death ( HR 1.73, 95% CI 1.15-2.62 and HR 6.75, 95% CI 4.02-11.31, respectively). In multivariable-adjusted models, these associations were attenuated but remained significant ( HR 1.66, 95% CI 1.08-2.55 for left-shifted and HR 4.19, 95% CI 2.32-7.55 for right-shifted). The association of LV- EDPVR with HF or CV death was no longer significant after inclusion of N-terminal pro-brain natriuretic peptide level as a covariate. Conclusions In stable CAD, echo-estimated leftward and rightward shifts in the LV- EDPVR are associated with HF and CV death. The loss of these associations after adjustment for N-terminal pro-brain natriuretic peptide level suggests that echo-estimated LV- EDPVR captures changes in LV filling pressure at any given LV end-diastolic volume. [ABSTRACT FROM AUTHOR]

The predictive ability of the CHADS2 index to stratify stroke risk may be mechanistically linked to severity of left atrial (LA) dysfunction. This study investigated the association between the CHADS2 score and LA function. We performed resting transthoracic echocardiography in 970 patients with stable coronary heart disease and normal ejection fraction and calculated baseline LA functional index (LAFI) using a validated formula: (LA emptying fraction 3 left ventricular outflow tract velocity time integral)/LA end-systolic volume indexed to body surface area. We performed regression analyses to evaluate the association between risk scores and LAFI. Among 970 subjects, mean CHADS2 was 1.7±1.2. Mean LAFI decreased across tertiles of CHADS2 (42.8±18.1, 37.8±19.1, 36.7±19.4, p <0.001). After adjustment for age, sex, race, systolic blood pressure, hyperlipidemia, myocardial infarction, revascularization, body mass index, smoking, and alcohol use, high CHADS2 remained associated with the lowest quartile of LAFI (odds ratio 2.34, p [ 0.001). In multivariable analysis of component co-morbidities, heart failure, age, and creatinine clearance <60 ml/min were strongly associated with LA dysfunction. For every point increase in CHADS2, the LAFI decreased by 4.0%. Secondary analyses using CHA2DS2-VASc and R2CHADS2 scores replicated these results. Findings were consistent when excluding patients with baseline atrial fibrillation. In conclusion, CHADS2, CHA2DS2-VASc, and R2CHADS2 scores are associated with LA dysfunction, even in patients without baseline atrial fibrillation. These findings merit further study to determine the role of LA dysfunction in cardioembolic stroke and the value of LAFI for risk stratification. [ABSTRACT FROM AUTHOR]

We sought to determine whether mitral annular calcium (MAC) is associated with inducible myocardial ischemia and adverse cardiovascular outcomes in ambulatory patients with coronary artery disease (CAD). MAC is associated with cardiovascular disease (CVD) in the general population, but its association with CVD outcomes in patients with CAD has not been evaluated. We examined the association of MAC with inducible ischemia and subsequent cardiovascular events in 1,020 ambulatory patients with CAD who were enrolled in the Heart and Soul Study. We used logistic regression to determine the association of MAC with inducible ischemia and Cox proportional hazards models to determine the association with CVD events (myocardial infarction, heart failure, stroke, transient ischemic attack or death). Models were adjusted for age, gender, race, smoking, history of heart failure, blood pressure, high-density lipoprotein, and estimated glomerular filtration rate. Of the 1,020 participants 192 (19%) had MAC. Participants with MAC were more likely than those without MAC to have inducible ischemia (adjusted odds ratio 2.06, 95% confidence interval 1.41 to 3.01, p = 0.0002). During an average of 6.26 ± 2.11 years of follow-up, there were 310 deaths, 161 hospitalizations for heart failure, 118 myocardial infarctions, and 55 cerebrovascular events. MAC was associated with an increased rate of cardiovascular events (adjusted hazard ratio 1.39, 95% confidence interval 1.08 to 1.79, p = 0.01). In conclusion, we found that MAC was associated with inducible ischemia and subsequent CVD events in ambulatory patients with CAD. MAC may indicate a high atherosclerotic burden and identify patients at increased risk for adverse cardiovascular outcomes. [Copyright &y& Elsevier]

Objectives: This study sought to determine whether left atrial (LA) dysfunction predicts heart failure (HF) hospitalization in subjects with preserved baseline ejection fraction (EF). Background: Among patients with preserved EF, factors leading to HF are not fully understood. Cross-sectional studies have demonstrated LA dysfunction at the time of HF, but longitudinal data on antecedent atrial function are lacking. Methods: We performed resting transthoracic echocardiography in 855 subjects with coronary heart disease and EF ≥50%. Left atrial functional index (LAFI) was calculated as ([LA emptying fraction × left ventricular outflow tract-velocity time integral] / [indexed LA end-systolic volume]), where LA emptying fraction was defined as (LA end-systolic volume − LA end-diastolic volume) / LA end-systolic volume. We used Cox models to evaluate the association between LAFI and HF hospitalization. Results: Over a median follow-up of 7.9 years, 106 participants (12.4%) were hospitalized for HF. Rates of HF hospitalization were inversely proportional to quartile (Q) of LAFI: Q1, 47 per 1,000 person-years; Q2, 18.3; Q3, 9.6; and Q4, 5.3 (p < 0.001). Each standard deviation decrease in LAFI was associated with a 2.6-fold increased hazard of adverse cardiovascular outcomes (unadjusted hazard ratio: 2.6, 95% confidence interval: 2.1 to 3.3, p < 0.001), and the association persisted even after adjustment for clinical risk factors, N-terminal pro–B-type natriuretic peptide, and a wide range of echocardiographic parameters (adjusted hazard ratio: 1.5, 95% confidence interval: 1.0 to 2.1, p = 0.05). Conclusions: Left atrial dysfunction independently predicts HF hospitalization in subjects with coronary heart disease and preserved baseline EF. The LAFI may be useful for HF risk stratification, and LA dysfunction may be a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Serum adiponectin protects against incident ischemic heart disease (IHD). However, in patients with existing IHD, higher adiponectin levels are paradoxically associated with worse outcomes. We investigated this paradox by evaluating the relationship between adiponectin and cardiovascular events in patients with existing IHD. Methods: We measured total serum adiponectin and cardiac disease severity by stress echocardiography in 981 outpatients with stable IHD who were recruited for the Heart and Soul Study between September 2000 and December 2002. Subsequent heart failure hospitalizations, myocardial infarction, and death were recorded. Results: During an average of 7.1 years of follow-up, patients with adiponectin levels in the highest quartile were more likely than those in the lowest quartile to be hospitalized for heart failure (23% vs. 13%; demographics-adjusted hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.04–2.56, p =0.03) or die (49% vs. 31%; HR 1.67, 95% CI 1.24–2.26, p <0.008), but not more likely to have a myocardial infarction (12% vs. 17%; HR 0.64, 95% CI 0.38–1.06, p =0.08). The combined outcome of myocardial infarction, heart failure, or death occurred in 56% (136/245) of participants in the highest quartile of adiponectin vs. 38% (94/246) of participants in the lowest quartile (HR 1.54, 95% CI 1.31–2.21, p <0.002). Adjustment for left ventricular ejection fraction, diastolic dysfunction, inducible ischemia, C-reactive protein, and NT-proBNP attenuated the association between higher adiponectin and increased risk of subsequent events (HR 1.43, 95% CI 0.98–2.09, p =0.06). Conclusions: Higher concentrations of adiponectin were associated with heart failure and mortality among patients with existing IHD. [Copyright &y& Elsevier]

Concentric remodeling (CR) is defined as increased left ventricular (LV) wall thickness with normal total LV mass. When encountered in populations with hypertension or patients undergoing aortic valve replacement, some studies have shown that CR predicts cardiovascular (CV) events and stroke. To expand our understanding of the prognostic implications of this common echocardiographic finding, we examined the association of CR and adverse CV events in ambulatory patients with coronary artery disease (CAD). We tested the hypothesis that finding CR on echocardiogram in ambulatory CAD independently predicts heart failure hospitalizations and CV death. Transthoracic echocardiograms were recorded in 973 participants from the Heart and Soul Study. Participants were divided into 4 groups: normal, CR, concentric LV hypertrophy, and eccentric LV hypertrophy. CV events were determined by 2 independent adjudicators and these were analyzed by Cox proportional hazards models. After mean 4.9 ± 1.5 years of follow-up, adverse outcomes occurred more frequently in those with concentric and eccentric LV hypertrophy but not in those with CR. After multivariate adjustment, concentric and eccentric LV hypertrophies were associated with increased risk of death and heart failure hospitalization, whereas CR was not. In conclusion, our hypothesis was not supported because CR was not associated with adverse CV events in our cohort of patients with stable CAD. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a common public health problem, and many new cases are now recognized to occur in patients with preserved left ventricular ejection fraction. β Blockers improve the outcomes of patients with known left ventricular systolic dysfunction, but whether β blockers provide similar protection among patients with left ventricular diastolic dysfunction is unclear. We studied the association between use of β blockers and subsequent hospitalization for HF in patients with diastolic dysfunction and stable coronary heart disease. We evaluated medication use and performed echocardiography at baseline in a prospective cohort of 911 outpatients with known coronary heart disease from the Heart and Soul Study. Hospitalizations for HF were assessed by blinded review of the medical records during an average follow-up of 5.2 years. Of the 911 participants, 118 (13%) had diastolic dysfunction, of whom 2 were lost to follow-up. Of the 116 remaining patients, 19 (25%) of the 77 using β blockers were hospitalized for HF compared to 16 (41%) of the 39 not using β blockers (age-adjusted hazard ratio 0.51, 95% confidence interval 0.26 to 1.00; p = 0.05). This association remained after additional adjustment for gender, smoking, history of myocardial infarction, diabetes, and creatinine (hazard ratio 0.46, 95% confidence interval 0.23 to 0.93; p = 0.03). The results were similar after excluding 31 participants with a history of self-reported HF (hazard ratio 0.33, 95% confidence interval 0.13 to 0.86; p = 0.02) and 24 participants with concurrent systolic dysfunction (hazard ratio 0.36, 95% confidence interval 0.14 to 0.89; p = 0.03). In conclusion, the use of β blockers is associated with a decreased risk of hospitalization for HF in patients with diastolic dysfunction and stable coronary heart disease. [Copyright &y& Elsevier]

Background: Quantitative stress echocardiography enables calculation of left-ventricular power-to-mass ratio (LVPMR) at peak exercise, a novel measure of cardiac performance per unit mass of myocardial tissue. We hypothesized that LVPMR at peak exercise provides prognostic information beyond established echocardiographic indices such as left-ventricular ejection fraction (LVEF) and left-ventricular mass index (LVMI). Methods: LVPMR (watts/kilogram) at peak exercise was defined as (k × heart rate × mean arterial pressure × stroke volume)/LV mass. We measured LVPMR in 918 adults with stable ambulatory coronary artery disease recruited for the Heart and Soul Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for all-cause mortality, cardiovascular death, nonfatal myocardial infarction, heart failure hospitalization, and combined adverse cardiovascular events. Multivariate adjustments were made for established risk factors including LVEF and LVMI. The prognostic value of LVPMR was also compared with established exercise parameters using receiver-operating characteristic curve analysis. Results: Compared with patients in the highest LVPMR quartile, those in the lowest quartile were at increased risk of all-cause mortality (adjusted HR 1.9; 95% CI 1.1–3.3), heart failure hospitalization (adjusted HR 2.9; 95% CI 1.2–6.9), and combined adverse cardiovascular events (adjusted HR 1.9; 95% CI 1.1–3.4). In comparison with the rate-pressure product and the Duke treadmill score, LVPMR did not add significant prognostic value (p > 0.1 for c-statistic comparisons). Conclusions: In patients with stable ambulatory coronary artery disease, LVPMR at peak exercise predicts mortality, heart failure hospitalization, and adverse cardiovascular events. However, LVPMR does not add significant prognostic information beyond established exercise test parameters. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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]

The article discusses a study aimed at conducting a genome-wide association analysis to identify common genetic variants associated with C-reactive protein (CRP) levels and coronary heart disease. A mendelian randomization study of the most closely associated single-nucleotide polymorphism (SNP) in the CRP locus was conducted by the researchers. Findings were compared with that predicted from meta-analysis of observational studies of CRP levels. It was concluded that there was no causal association between CRP levels and coronary heart disease.

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 reports on the inducible ischemia and the risks of recurring cardiovascular consequences with outpatients. It discusses that readmission after HF hospitalization is the increasing focus for physicians and policy makers, and that the statistical models are needed to assess patient risk and to compare hospital performance. It infers that more systematic recognition and integration of visit companions in health care processes may benefit the quality of care for a vulnerable patient population.

The predictive value of left atrial (LA) dilatation in ambulatory adults with coronary artery disease is not known. It was hypothesized that echocardiographic LA volume index (LAVI) predicts heart failure (HF) hospitalization and mortality with similar statistical power as left ventricular ejection fraction (LVEF) in ambulatory adults with coronary artery disease. We measured LAVI in 935 adults without atrial fibrillation, atrial flutter, or significant mitral valve disease in the Heart and Soul Study. LAVI was calculated using the biplane method of disks. Outcomes included HF hospitalization and mortality. Logistic regression odds ratios (ORs) were calculated and adjusted for age, demographics, medical history, left ventricular mass, diastolic function, and LVEF. Mean LAVI was 32 ± 11 ml/m2, and mean LVEF was 62 ± 10%. Sixty-six patients (7%) had LAVI >50 ml/m2. There were 108 HF hospitalizations and 180 deaths at 4.3 years of follow-up. C statistics calculated as the area under the receiver-operator characteristic curve were the same (0.60) for LAVI and LVEF in predicting mortality. The unadjusted OR for HF hospitalization was 4.4 for LAVI >50 ml/m2 and 5.3 for LVEF <45% (p <0.001). In those with normal LVEF, the ORs for LAVI >50 ml/m2 were 5.2 for HF hospitalization (p <0.0001) and 2.5 for mortality (p = 0.006). After multivariate adjustment, LAVI >50 ml/m2 was predictive of HF hospitalization (OR 2.4, p = 0.02), and LAVI >40 ml/m2 was predictive of mortality (OR 1.9, p = 0.005). In conclusion, LAVI had similar predictability as LVEF for HF hospitalization and mortality in ambulatory adults with coronary artery disease. [Copyright &y& Elsevier]

Pulmonary vascular resistance (PVR) is an important hemodynamic variable that affects prognosis and therapy in a wide range of cardiovascular and pulmonary conditions. We sought to determine whether a noninvasive estimate of PVR predicts adverse outcomes in patients with stable coronary artery disease. Using Doppler echocardiography we measured the estimated PVR (defined as the ratio of the tricuspid regurgitant velocity [TRV] to the velocity–time integral [VTI] of the right ventricular outflow tract [RVOT]) in 795 ambulatory patients with stable coronary artery disease. Participants were categorized by quartiles of the TRV/VTIRVOT ratio. Hazard ratios (HRs) and 95% confidence intervals were calculated for all-cause mortality, heart failure hospitalization, and adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or stroke). After 4.3 years of follow-up there were 161 deaths, 44 deaths from cardiovascular causes, 103 heart failure hospitalizations, and 120 adverse cardiovascular events. Compared with patients in the lowest TRV/VTIRVOT quartile, those in the highest quartile were at increased risk of all-cause mortality (unadjusted HR 1.8, 95% confidence interval 1.3 to 2.5), heart failure hospitalization (unadjusted HR 2.9, 95% confidence interval 2.0 to 4.3), and adverse cardiovascular events (unadjusted HR 2.0, 95% confidence interval 1.4 to 2.9). After multivariate adjustment, patients in the highest quartile were at increased risk of heart failure hospitalizations (adjusted HR 2.5, 95% confidence interval 1.3 to 4.7). In conclusion, a noninvasive estimate of PVR (TRV/VTIRVOT ratio) predicts mortality, heart failure hospitalization, and adverse cardiovascular events in patients with stable coronary artery disease. [Copyright &y& Elsevier]

Abstract: Background: High-sensitivity C-reactive protein (CRP) is an inflammatory marker that predicts coronary heart disease (CHD) and, in recent studies, incident heart failure (HF). Whether the association of inflammation with incident HF is explained by worse baseline left ventricular dysfunction or by underlying CHD is unknown. Methods and results: Serum CRP was measured in a cohort of 985 outpatients with established CHD from the Heart and Soul Study. During 3 years of follow-up, 15% of the participants with elevated CRP levels (>3 mg/L) were hospitalised for HF, compared with 7% of those with CRP ≤3 mg/L. In multivariate analysis, elevated CRP was associated with HF after adjustment for traditional risk factors, baseline CHD severity and interim MI (adjusted HR 2.1, 95% CI, 1.2–3.6; p =0.009). However, elevated CRP was no longer associated with HF after further adjustment for the presence of diastolic dysfunction on echocardiography (adjusted HR 1.6, 95% CI, 0.8–3.2; p =0.1). Conclusions: Among outpatients with stable CHD, elevated CRP levels predict hospitalisation for heart failure, independent of baseline heart failure, medication use, CHD severity, and subsequent MI events. This relationship appears to be at least partly explained by abnormal diastolic function in patients with elevated CRP levels. [Copyright &y& Elsevier]

The association of asymptomatic left ventricular (LV) diastolic dysfunction with cardiovascular outcomes in ambulatory patients with coronary heart disease (CHD) and no history of heart failure (HF) was examined. LV diastolic HF predicts adverse cardiovascular outcomes. However, the prevalence and prognosis of asymptomatic LV diastolic dysfunction in patients with established CHD in the absence of clinical HF is unknown. Six hundred ninety-three patients with stable CHD, normal systolic function (LV ejection fraction ≥50%), and no history of HF were evaluated. Echocardiography was used to classify LV diastolic function, and Cox proportional hazards models were used to evaluate the association of LV diastolic dysfunction with cardiovascular outcomes during 3 years of follow-up. Of 693 subjects with normal systolic function and no history of HF, 455 (66%) had normal LV diastolic function, 166 (24%) had mild LV diastolic dysfunction, and 72 (10%) had moderate to severe LV diastolic dysfunction. After multivariable adjustment, the presence of moderate to severe LV diastolic dysfunction was strongly predictive of incident hospitalization for HF (hazard ratio 6.3, 95% confidence interval 2.4 to 16.1, p = 0.0003) and death from heart disease (HR 3.9, 95% confidence interval 1.0 to 14.8, p = 0.05). In conclusion, moderate to severe LV diastolic dysfunction was present in 10% of patients with stable CHD with normal ejection fraction and no history of HF and predicts subsequent hospitalization for HF and death from heart disease. Patients with asymptomatic LV diastolic dysfunction may benefit from more aggressive therapy to prevent or delay the development of HF. [Copyright &y& Elsevier]

Aortic sclerosis is associated with cardiovascular events in patients without coronary heart disease (CHD), but it is unclear whether this association exists in patients with established CHD or is independent of baseline cardiac disease severity. It is also unclear whether statins modify this association. In a prospective cohort study of 814 outpatients with established CHD and no evidence of aortic stenosis, the association of aortic sclerosis with subsequent cardiovascular events was examined using a multivariable Cox proportional hazards model. Of 814 participants, 324 (40%) had aortic sclerosis. During 4 years of follow-up, 10% with aortic sclerosis experienced a myocardial infarction (MI) compared with 5% of those without aortic sclerosis (hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.1 to 3.1, p = 0.02). This association was unchanged after adjustment for potential confounders and mediators (HR 2.4, 95% CI 1.3 to 4.8, p = 0.009). However, the association between aortic sclerosis and MI appeared to differ by statin use (p = 0.15 for interaction). Aortic sclerosis predicted subsequent MI in subjects not administered statins (adjusted HR 4.1, 95% CI 1.1 to 15.7, p = 0.04), but not in those administered statins (adjusted HR 1.7, 95% CI 0.8 to 3.9, p = 0.18). In conclusion, aortic sclerosis was present in 40% of patients with CHD and is independently associated with a 2.4-fold increased rate of subsequent MI. Statins may attenuate the increased risk of future MI in patients with aortic sclerosis. [Copyright &y& Elsevier]

The article examines the benefits and limitations of using N-Terminal Pro-B-Type natriuretic peptide as a diagnostic test for ventricular dysfunction in patients with coronary heart disease (CHD). The results indicate that NT-proBNP levels lower than 100 pg/ml effectively rule out ventricular dysfunction with a negative likelihood ratio of 0.28 in patients with stable CHD and no history of heart failure.

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.

Objectives: We compared the predictive ability of tricuspid regurgitation (TR) and end-diastolic pulmonary regurgitation (EDPR) gradients in outpatients with coronary artery disease. Background: The TR and EDPR gradients, in conjunction with right atrial pressure, provide Doppler estimates of pulmonary artery systolic and diastolic pressures. We hypothesized that increases in TR or EDPR gradients in stable coronary artery disease would predict heart failure (HF) hospitalization or cardiovascular (CV) death. Methods: We measured TR and EDPR gradients in 717 adults with completed outcome adjudications who were recruited for the Heart and Soul Study. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for HF hospitalization, CV death, all-cause death, and the combined end point. Multivariate adjustments were made for age, gender, race, history of CV or pulmonary disease, functional class, and left ventricular ejection fraction. Results: There were 63 HF hospitalizations, 19 CV deaths, and 86 all-cause deaths at the 3-year follow-up. There were 466 measurable EDPR gradients and 573 measurable TR gradients. Age-adjusted ORs for EDPR >5 mm Hg predicted HF hospitalization (2.7, 95% CI 1.3 to 5.5, p = 0.006), all-cause death (2.5, 95% CI 1.4 to 4.4, p = 0.002), and HF hospitalization or CV death (2.7, 95% CI 1.4 to 5.2, p = 0.004). Age-adjusted OR for TR >30 mm Hg predicted HF hospitalization (3.4, 95% CI 1.9 to 6.2, p < 0.0001) and HF hospitalization or CV death (3.0, 95% CI 1.7 to 5.3, p = 0.0001). Multivariate adjusted OR per 5-mm Hg incremental increases in EDPR predicted HF hospitalization or CV death (1.9, 95% CI 1.01 to 3.6, p = 0.046) and all-cause death (1.7, 95% CI 1.05 to 2.8, p = 0.03). Multivariate adjusted OR per 10-mm Hg incremental increases in TR predicted HF hospitalization or CV death (1.6, 95% CI 1.1 to 2.4, p = 0.008). Conclusions: Increases in EDPR or TR gradients predict HF hospitalization or CV death among ambulatory adults with coronary artery disease. [Copyright &y& Elsevier]

It is not known whether the metabolic syndrome is associated with poor exercise capacity among patients who have established coronary heart disease. We evaluated the association of the metabolic syndrome with treadmill exercise capacity and heart rate recovery among patients who had coronary heart disease. We measured treadmill exercise capacity (METs) and heart rate recovery (beats per minute) in 943 subjects who had known coronary heart disease. Of these, 377 (40%) had the metabolic syndrome as defined by criteria of the National Cholesterol Education Program. Participants who had the metabolic syndrome were more likely to have poor exercise capacity (METs &#60;5, 33% vs 18%, p &#60;0.0001) and poor heart rate recovery (≤16 beats/min, 34% vs 21%, p &#60;0.0001) than those who did not have the metabolic syndrome. In ordinal logistic regression analyses, the metabolic syndrome was associated with decreased exercise capacity (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.7 to 2.8, p &#60;0.0001) and decreased heart rate recovery (OR 1.8, 95% CI 1.4 to 2.3, p &#60;0.0001). These associations remained strong after adjusting for potential confounding variables (OR 1.6, 95% CI 1.2 to 2.1, p = 0.003 for decreased exercise capacity; OR 1.4, 95% CI 1.1 to 1.9, p = 0.02 for decreased heart rate recovery). The metabolic syndrome is independently associated with poor exercise capacity and poor heart rate recovery in patients who have established coronary heart disease. Decreased exercise capacity may contribute to the adverse outcomes associated with the metabolic syndrome. [Copyright &y& Elsevier]

: BackgroundWhether B-type natriuretic peptide (BNP) levels can be used to screen for ventricular dysfunction in patients at risk of heart failure but without overt symptoms is not known. We examined the characteristics of a BNP test for identifying systolic and diastolic dysfunction in outpatients with stable coronary disease.: MethodsIn a cross-sectional study of 293 outpatients who had stable coronary disease and no history of heart failure, we compared elevations in plasma BNP levels with echocardiography for the diagnosis of systolic dysfunction (ejection fraction <55%) and diastolic dysfunction (diastolic dominant pulmonary vein flow with ejection fraction ≥55%).: ResultsA total of 48 patients (16%) had systolic dysfunction, and among the remaining 245 with preserved systolic function, 31 (13%) had diastolic dysfunction. At the standard cutpoint of >100 pg/mL, an elevated BNP level was 38% sensitive (80% specific) for systolic dysfunction and 55% sensitive (85% specific) for diastolic dysfunction. Negative likelihood ratios were 0.8 (95% confidence interval [CI]: 0.6 to 1.0) for systolic dysfunction and 0.5 (95% CI: 0.4 to 0.8) for diastolic dysfunction. Positive likelihood ratios were 1.9 (95% CI: 1.2 to 2.9) for systolic dysfunction and 3.8 (95% CI: 2.4 to 5.9) for diastolic dysfunction. Areas under the receiver operating characteristic curves were 0.59 (95% CI: 0.49 to 0.69) for systolic dysfunction and 0.79 (95% CI: 0.71 to 0.87) for diastolic dysfunction.: ConclusionThese data suggest that BNP is not a useful screening test for asymptomatic ventricular dysfunction in patients with stable coronary disease. [Copyright &y& Elsevier]

We hypothesized that assessment of hyperemic myocardial blood flow (MBF) velocity using myocardial contrast echocardiography (MCE) can detect coronary artery disease (CAD). We also postulated that only a single MCE study during stress is required for the detection of CAD in patients with normal function at rest. Patients with known or suspected CAD referred for dipyridamole stress technetium-99m sestamibi single-photon emission computed tomographic (SPECT) studies were enrolled. MCE was performed concurrently with SPECT using continuous infusions of PB127 during intermittent harmonic power Doppler imaging at multiple pulsing intervals. MCE and SPECT were compared in 43 of 54 patients who had adequate studies using both techniques. In 15 of the 43 patients, coronary angiography was performed within 30 days of the MCE/SPECT tests. Overall concordance for classification of patients as normal versus abnormal was 84% (κ = 0.63) between the 2 tests. When false-negative SPECT scans were corrected for results of angiography, concordance increased to 93% (κ = 0.82). For territorial analysis, concordance between MCE and SPECT for location of perfusion defects was 65% (κ = 0.41) and 74% (κ = 0.61) after SPECT was corrected by angiography. In patients with normal function at rest, a single stress MCE perfusion study allowed identification of CAD with the same concordance as rest/stress perfusion studies. In conclusion, visual assessment of regional differences in MBF velocity using PB127 allows detection of CAD with good concordance compared with technetium-99m sestamibi SPECT. In patients with normal left ventricular function at rest, a single stress PB127 MCE perfusion study is adequate for the detection of CAD. [Copyright &y& Elsevier]

To determine whether self-reported angina pectoris is associated with objective evidence of myocardial ischemia, we assessed angina symptoms, using the Seattle Angina Questionnaire, and measured ischemia using stress echocardiography in 933 patients with known coronary artery disease. We observed no association between self-reported angina pectoris and objective evidence of inducible ischemia. [Copyright &y& Elsevier]

Introduction: Serial increases in high-sensitivity cardiac troponin (hs-cTnT) have been associated with death in community-dwelling adults, but the association remains uninvestigated in those with ambulatory coronary artery disease (CAD). Hypothesis: An increase in hs-cTnT over 5 years predicts subsequent all-cause mortality in ambulatory CAD. Methods: We measured hs-cTnT at baseline and after 5 years in 635 participants with ambulatory CAD. We defined "undetectable" levels of hs-cTnT as < 5 pg/mL, "detectable" as between 5 and 14 pg/mL, and "elevated" as >14 pg/mL. We used an unadjusted and a multivariable-adjusted Cox proportional hazards model to evaluate the association between 5-year change in hs-cTnT and subsequent all-cause mortality. Results: There were 386 participants (61%) who had an increase in hs-cTnT levels between baseline and year 5 measurements (median increase 5.6 pg/mL, IQR 3.2-9.9 pg/mL). There were 182 deaths after a mean 4.2 years of follow-up after year 5. After adjusting for clinical variables, a > 50% increase in hs-cTnT between baseline and year 5 was associated with a nearly 2-fold increased risk of death from any cause (HR 1.7, 95% CI 1.1-2.7). Additional hazard ratios for death from any cause, categorized by levels of baseline and year 5 hs-cTnT, are displayed in the figure. Conclusion: In ambulatory CAD, serial increases in hs-cTnT predict death, suggesting that preventive strategies may be warranted in this setting. Figure: Hazard ratios for death from any cause, categorized by levels of baseline and year 5 high-sensitivity cardiac troponin (hs-cTnT), adjusted for clinical variables. Error bars represent 95% confidence intervals. Data for patients who had detectable baseline but undetectable year 5 levels, as well as patients with elevated baseline but undetectable year 5 levels are not displayed due to small numbers of deaths in these categories. [ABSTRACT FROM AUTHOR]

Introduction: C-reactive protein (CRP) level stratifies risk for events in coronary heart disease (CHD) and is independently associated with increased risk of heart failure (HF). It is unknown how CHD-associated risk of stroke, HF, and all-cause mortality is affected by CRP and if it is modifiable. Hypothesis: The risk associated with elevated CRP in patients with CHD can be modified by beta blocker and statin use. Methods: A cohort of outpatients with CHD from the Heart and Soul Study (N = 985) had serum CRP measured. Outcomes after 7.1 years ± 3.2 years including non-fatal MI, HF, stroke, cardiovascular death, and all-cause mortality were analyzed and modifying factors were compared using Kaplan Meier estimates. Results: Elevated CRP level > 3mg/L (CRPH) was associated with an increased risk of stroke (hazard ratio (HR) 2.4, p = 0.01), HF (HR 1.9, p = 0.001), and all-cause mortality (HR 1.4, p = 0.005), compared to low CRP level < 3mg/L (CRPL). CRPH patients not taking a statin had more HF events (HR 2.9, p = 0.001) and increased risk of all-cause mortality (HR 1.5, p = 0.045) compared to CRPL patients not taking a statin. CRPH patients not taking a beta blocker had more HF events (HR 2.5, p = 0.001) and increased risk of all-cause mortality (HR 1.7, p = 0.003) compared to CRPL patients not taking a beta-blocker. CRPH patients on neither beta blocker nor statin had more HF events (HR 2.7, p = 0.002) and increased risk of all-cause mortality (HR 2.0, p = 0.004) compared to CRPH patients on both medications. CRPL patients on both beta blocker and statin had reduced risk of all-cause mortality (HR 0.6, p = 0.04) compared to CRPL patients on neither medication. Conclusions: Among outpatients with CHD, CRPH is associated with an increased risk of adverse CHD outcomes including stroke, HF, and all-cause mortality. The risk of HF and all-cause mortality is considerable but modified by beta blockers and statins. Among those with CRPL, the use of beta blockers and statin reduces risk of all-cause mortality. [ABSTRACT FROM AUTHOR]