Alcohol consumption and 5-year change in left atrial volume among patients with coronary heart disease: results from the Heart and Soul study.

BACKGROUND: Heavy alcohol consumption is a risk factor for developing atrial fibrillation, but whether chronic alcohol use affects left atrial volume is unknown. We evaluated the association of self-reported alcohol consumption with 5-year change in left atrial volume among patients with coronary heart disease (CHD). METHODS: We studied 601 participants with stable CHD who underwent 2-dimensional echocardiography at baseline (2000-2002) and after 5 years of follow-up (2005-2007). Alcohol consumption was determined at baseline with the use of the Alcohol Use Disorders Identification Test consumption questions (AUDIT-C), with a standard cutoff point of ≥3 used to define at-risk drinking. We used logistic regression to evaluate the association of baseline alcohol use with 5-year increase in left atrial end-systolic volume index (defined as being in the highest tertile of percent change). RESULTS: After adjustment for covariates, each standard deviation (2.4-point) increase in AUDIT-C score was associated with a 24% greater odds of experiencing a 5-year increase in left atrial volume index (adjusted odds ratio [OR] 1.24, 95% confidence interval [CI] 1.04-1.48; P = .02). Compared with the 369 participants who had AUDIT-C scores of <3, the 171 participants with scores of 3-5 had a 51% greater odds (OR 1.51, 95% CI, 1.11-2.25) and the 61 participants with scores of >5 a 98% greater odds (OR 1.98, 95% CI, 1.10-3.56) of experiencing a 5-year increase in left atrial volume index. CONCLUSIONS: In patients with CHD, heavier alcohol consumption is associated with a 5-year increase in left atrial volume. Whether greater left atrial volume contributes to the increased risk of atrial fibrillation associated with alcohol use deserves further study.

Lifetime trauma exposure and prospective cardiovascular events and all-cause mortality: findings from the Heart and Soul Study.

OBJECTIVE: Little is known about the effect of cumulative psychological trauma on health outcomes in patients with cardiovascular disease. The objective of this study was to prospectively examine the association between lifetime trauma exposure and recurrent cardiovascular events or all-cause mortality in patients with existing cardiovascular disease. METHODS: A total of 1021 men and women with cardiovascular disease were recruited in 2000 to 2002 and followed annually. Trauma history and psychiatric comorbidities were assessed at baseline using the Computerized Diagnostic Interview Schedule for DSM-IV. Health behaviors were assessed using standardized questionnaires. Outcome data were collected annually, and all medical records were reviewed by two independent, blinded physician adjudicators. We used Cox proportional hazards models to evaluate the association between lifetime trauma exposure and the composite outcome of cardiovascular events and all-cause mortality. RESULTS: During an average of 7.5 years of follow-up, there were 503 cardiovascular events and deaths. Compared with the 251 participants in the lowest trauma exposure quartile, the 256 participants in the highest exposure quartile had a 38% greater risk of adverse outcomes (hazard ratio = 1.38, 95% confidence interval = 1.06-1.81), adjusted for age, sex, race, income, education, depression, posttraumatic stress disorder, generalized anxiety disorder, smoking, physical inactivity, and illicit drug abuse. CONCLUSIONS: Cumulative exposure to psychological trauma was associated with an increased risk of recurrent cardiovascular events and mortality, independent of psychiatric comorbidities and health behaviors. These data add to a growing literature showing enduring effects of repeated trauma exposure on health that are independent of trauma-related psychiatric disorders such as depression and posttraumatic stress disorder.

First-degree atrioventricular block is associated with heart failure and death in persons with stable coronary artery disease: data from the Heart and Soul Study.

AIMS: First-degree atrioventricular block (AVB) has traditionally been considered a benign electrocardiographic finding in healthy individuals. However, the clinical significance of first-degree AVB has not been evaluated in patients with stable coronary heart disease. We investigated whether first-degree AVB is associated with heart failure (HF) and mortality in a prospective cohort study of outpatients with stable coronary artery disease (CAD). METHODS AND RESULTS: We measured the P-R interval in 938 patients with stable CAD and classified them into those with (P-R interval ≥ 220 ms) and without (P-R interval <220 ms) first-degree AVB. Hazard ratios (HRs) and 95% confidence intervals were calculated for HF hospitalization and all-cause mortality. During 5 years of follow-up, there were 123 hospitalizations for HF and 285 deaths. Compared with patients who had normal atrioventricular conduction, those with first-degree AVB were at increased risk for HF hospitalization (age-adjusted HR 2.33: 95% CI 1.49-3.65; P= 0.0002), mortality [age-adjusted HR 1.58; 95% CI (1.13-2.20); P = 0.008], cardiovascular (CV) mortality [age-adjusted HR 2.33; 95% CI (1.28-4.22); P= 0.005], and the combined endpoint of HF hospitalization or CV mortality (age-adjusted HR 2.43: 95% CI 1.64-3.61; P ≤ 0.0001). These associations persisted after multivariable adjustment for heart rate, medication use, ischaemic burden, and QRS duration. Adjustment for left ventricular systolic and diastolic function partially attenuated the effect, but first-degree AVB remained associated with the combined endpoint of HF or CV death (HR 1.61, CI 1.02-2.54; P= 0.04). CONCLUSION: In a large cohort of patients with stable coronary artery disease, first-degree AVB is associated with HF and death.

The CHADS2 score predicts ischemic stroke in the absence of atrial fibrillation among subjects with coronary heart disease: data from the Heart and Soul Study.

BACKGROUND: We sought to evaluate the prognostic performance of the CHADS(2) score for prediction of ischemic stroke/transient ischemic attack (TIA) in subjects with coronary heart disease (CHD) without atrial fibrillation (AF). METHODS: In 916 nonanticoagulated outpatients with stable CHD and no AF by baseline electrocardiogram, we calculated CHADS(2) scores (congestive heart failure, hypertension, age ≥75 years, diabetes [1 point each], and prior stroke or TIA [2 points]). The primary outcome was time to ischemic stroke or TIA over a mean follow-up of 6.4 ± 2.3 years. RESULTS: Over 5,821 person-years of follow-up, 40 subjects had an ischemic stroke/TIA (rate 0.69/100 person-years, 95% CI 0.50-0.94). Compared with subjects with low (0-1) CHADS(2) scores, those with intermediate (2-3) and high (4-6) CHADS(2) scores had an increased rate of stroke/TIA, even after adjustment for age, tobacco, antiplatelet therapy, statins, and angiotensin inhibitors (CHADS(2) score 2-3: HR 2.4, 95% CI 1.1-5.3, P = .03; CHADS(2) score 4-6: HR 4.0, 95% CI 1.5-10.6, P = .006). Model discrimination (c-statistic = 0.65) was comparable with CHADS(2) model fit in published AF-only cohorts. CONCLUSIONS: The CHADS(2) score predicts ischemic stroke/TIA in subjects with stable CHD and no baseline AF. The event rate in non-AF subjects with high CHADS(2) scores (5-6) was comparable with published rates in AF patients with moderate CHADS(2) scores (1-2), a population known to derive benefit from stroke prevention therapies. These findings should inform efforts to determine whether stroke prevention therapies or screening for silent AF may benefit subjects with stable CHD and high CHADS(2) scores.

Association of resistin with heart failure and mortality in patients with stable coronary heart disease: data from the heart and soul study.

BACKGROUND: Resistin is a pro-inflammatory signaling molecule that is thought to contribute to atherosclerosis. We sought to evaluate whether resistin is predictive of worse cardiovascular outcomes among ambulatory patients with stable coronary heart disease (CHD). METHODS AND RESULTS: We measured baseline serum resistin in 980 participants with documented CHD. After a mean follow-up of 6.1 (range, 0.1 to 9.0) years, 358 (36.5%) were hospitalized for myocardial infarction or heart failure or had died. As compared with participants who had resistin levels in the lowest quartile, those with resistin levels in the highest quartile were at an increased risk of heart failure (hazard ratio [HR], 2.06; 95% confidence interval [CI], 1.26-3.39) and death (HR, 1.56; 95% CI, 1.11-2.18), adjusted for age, sex, and race. Further adjustments for obesity, hypertension, insulin resistance, dyslipidemia, and renal dysfunction eliminated these associations. Resistin levels were not associated with an increased risk of non-fatal myocardial infarction (unadjusted HR, 1.18; 95% CI, 0.68-2.05). CONCLUSIONS: Elevated serum resistin is associated with higher rates of mortality and hospitalization for heart failure. However, this appears to be explained by the association of resistin with traditional measures of cardiovascular risk. Thus, serum resistin does not add prognostic information among high-risk persons with established CHD.

Association between a serotonin transporter gene variant and hopelessness among men in the Heart and Soul Study.

BACKGROUND: Hopelessness is associated with mortality in patients with cardiac disease even after accounting for severity of depression. We sought to determine whether a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) is associated with increased hopelessness, and whether this effect is modified by sex, age, antidepressant use or depression in patients with coronary heart disease. METHODS: We conducted a cross-sectional study of 870 patients with stable coronary heart disease. Our primary outcomes were hopelessness score (range 0-8) and hopeless category (low, moderate and high) as measured by the Everson hopelessness scale. Analysis of covariance and ordinal logistic regression were used to examine the independent association of genotype with hopelessness. RESULTS: Compared to patients with l/l genotype, adjusted odds of a higher hopeless category increased by 35% for the l/s genotype and 80% for s/s genotype (p-value for trend = 0.004). Analysis of covariance demonstrated that the effect of 5-HTTLPR genotype on hopelessness was modified by sex (.04), but not by racial group (p = 0.63). Among men, odds of higher hopeless category increased by 40% for the l/s genotype and by 2.3-fold for s/s genotype (p-value p < 0.001), compared to no effect in the smaller female sample (p = 0.42). Results stratified by race demonstrated a similar dose-response effect of the s allele on hopelessness across racial groups. CONCLUSIONS: We found that the 5-HTTLPR is independently associated with hopelessness among men with cardiovascular disease.

Psychological risk factors and the metabolic syndrome in patients with coronary heart disease: findings from the Heart and Soul Study.

Psychological factors, such as depression and anxiety, are independently associated with an increased risk of both diabetes mellitus and cardiovascular disease, but the reasons for these associations are unknown. We sought to determine whether psychological factors were associated with a greater prevalence of the metabolic syndrome in patients with coronary heart disease, and the extent to which such an association may be explained by socioeconomic status, health behaviors, and biological mediators. We conducted a cross-sectional study of 1024 outpatients with stable coronary heart disease. Psychological factors, including depressive and anxiety symptoms, hostility, anger, and optimism-pessimism, were assessed using validated standardized questionnaires. The presence or absence of the metabolic syndrome was determined using the criteria outlined by the National Cholesterol Education Program, Adult Treatment Panel III. Higher levels of depression, anger expression, hostility, and pessimism were significantly associated with increased prevalence of the metabolic syndrome. These associations were explained by differences in socioeconomic status and health behaviors. Additional adjustment for potential biological mediators had little impact. Further research is needed to determine whether addressing socioeconomic and behavioral factors in people with depression or high levels of anger or hostility could reduce the burden of the metabolic syndrome.

Prevalence and prognostic significance of incidental cardiac troponin T elevation in ambulatory patients with stable coronary artery disease: data from the Heart and Soul study.

BACKGROUND: The significance of troponin elevation and clinical utility of troponin testing in ambulatory patients with coronary artery disease (CAD) have not been examined. We sought to investigate the prevalence and prognostic value of cardiac troponin T (cTnT) elevation in a population with stable CAD. METHODS: We studied 987 patients with stable CAD enrolled in the Heart & Soul study who had plasma cTnT measurements before performing exercise treadmill testing. RESULTS: Of the studied population, 58 patients or 6.2% had detectable cTnT levels, >or=0.01 ng/mL (0.01-0.72 ng/mL). During a mean follow-up period of 4.3 (0.1-6.5) years, 58.6% of participants with detectable cTnT had cardiovascular events compared with 22.5% of those without detectable cTnT (hazard ratio [HR] 3.8, 95% CI 2.6-5.4, P < .001). This association remained strong after adjustment for traditional risk factors and C-reactive protein (HR 2.0, 95% CI 1.3-3.1, P = .002). However, after further adjustment for N-terminal pro-B-type natriuretic peptide and echocardiographic parameters of left ventricular function, cTnT elevation was not an independent predictor of cardiovascular events (HR 1.3, 95% CI, 0.8-2.3, P = .28). CONCLUSIONS: In ambulatory patients with stable CAD, the prevalence of cTnT elevation was 6.2%. Cardiac troponin T elevation detected using the conventional troponin assay was associated with increased risk of adverse cardiovascular outcomes, but its prognostic value was not incremental over N-terminal pro-B-type natriuretic peptide and echocardiographic evidence of cardiac abnormalities.

Depressive symptoms and perceived doctor-patient communication in the Heart and Soul study.

BACKGROUND: Doctor-patient communication is an important marker of health-care quality. Little is known about the extent to which medical comorbidities, disease severity and depressive symptoms influence perceptions of doctor-patient communication in patients with chronic disease. METHODS: In a cross-sectional study of 703 outpatients with chronic coronary disease, we evaluated the extent to which patient reports of doctor-patient communication were influenced by medical comorbidities, disease severity and depressive symptoms. We assessed patient reports of doctor-patient communication using the Explanations of Condition and Responsiveness to Patient Preferences subscales from the "Interpersonal Processes of Care" instrument. Poor doctor-patient communication was defined as a score of <4 (range 1 to 5) on either subscale. All patients completed the nine-item Patient Health Questionnaire (PHQ) for measurement of depressive symptoms and underwent an extensive evaluation of medical comorbidities and cardiac function. RESULTS: In univariate analyses, the following patient characteristics were associated with poor reported doctor-patient communication on one or both subscales: female sex, white or Asian race and depressive symptoms. After adjusting for demographic factors, medical comorbidities and disease severity, each standard deviation (5.4-point) increase in depressive symptom score was associated with a 50% greater odds of poor reported explanations of condition (OR 1.5, 95% CI, 1.2-1.8; p < 0.001) and a 30% greater odds of poor reported responsiveness to patient preferences (OR 1.3, 95% CI, 1.1-1.5; p = 0.01). In contrast, objective measures of disease severity (left ventricular ejection fraction, exercise capacity, inducible ischemia) and medical comorbidities (hypertension, diabetes, myocardial infarction) were not associated with reports of doctor-patient communication. CONCLUSIONS: In outpatients with chronic coronary heart disease, depressive symptoms are associated with perceived deficits in doctor-patient communication, while medical comorbidities and disease severity are not. These findings suggest that patient reports of doctor-patient communication may partly reflect the psychological state of the patient.

Prognostic value of leukocyte telomere length in patients with stable coronary artery disease: data from the Heart and Soul Study.

BACKGROUND: Telomere shortening has been proposed as a marker of biological aging. Whether leukocyte telomere length is associated with mortality among patients with stable coronary artery disease (CAD) is unknown. METHODS AND RESULTS: We measured leukocyte telomere length in 780 patients with stable CAD in a prospective cohort study. Participants were categorized by quartiles of telomere length. Hazard Ratios (HRs) and 95% confidence intervals were calculated for all-cause mortality, heart failure (HF) hospitalization, and cardiovascular (CV) events. After 4.4 years of follow-up there were 166 deaths. Compared with participants in the highest telomere length quartile, those in the lowest quartile were at increased risk of death (age-adjusted HR 1.8; 95% CI 1.2 to 2.9). After multivariate adjustment for clinical (HR 2.1; CI 1.3 to 3.3), inflammatory (HR 2.0; CI 1.2 to 3.2), and echocardiographic (HR 1.9; CI 1.0 to 3.5) risk factors, patients in the lowest quartile of telomere length remained at significantly increased risk of death compared to those in the highest quartile. Patients in the lowest quartile of telomere length were also at significantly increased risk of HF hospitalization (HR 2.6; CI 1.1 to 6.0) but not CV events (HR 1.7; CI 0.9 to 3.5). CONCLUSIONS: Reduced leukocyte telomere length is associated with all-cause mortality in patients with stable CAD. The prognostic value of short telomeres in predicting death is not completely captured by existing clinical, inflammatory, and echocardiographic markers of risk.

Left-ventricular power-to-mass ratio at peak exercise predicts mortality, heart failure, and cardiovascular events in patients with stable coronary artery disease: data from the Heart and Soul Study.

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 x heart rate x mean arterial pressure x 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.

Usefulness of noninvasive estimate of pulmonary vascular resistance to predict mortality, heart failure, and adverse cardiovascular events in Patients With stable coronary artery disease (from the Heart and Soul Study).

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/VTI RVOT 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/VTI RVOT 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/VTI RVOT ratio) predicts mortality, heart failure hospitalization, and adverse cardiovascular events in patients with stable coronary artery disease.

Self-reported medication adherence and cardiovascular events in patients with stable coronary heart disease: the heart and soul study.

BACKGROUND: Nonadherence to physician treatment recommendations is an increasingly recognized cause of adverse outcomes and increased health care costs, particularly among patients with cardiovascular disease. Whether patient self-report can provide an accurate assessment of medication adherence in outpatients with stable coronary heart disease is unknown. METHODS: We prospectively evaluated the risk of cardiovascular events associated with self-reported medication nonadherence in 1015 outpatients with established coronary heart disease from the Heart and Soul Study. We asked participants a single question: "In the past month, how often did you take your medications as the doctor prescribed?" Nonadherence was defined as taking medications as prescribed 75% of the time or less. Cardiovascular events (coronary heart disease death, myocardial infarction, or stroke) were identified by review of medical records during 3.9 years of follow-up. We used Cox proportional hazards analysis to determine the risk of adverse cardiovascular events associated with self-reported medication nonadherence. RESULTS: Of the 1015 participants, 83 (8.2%) reported nonadherence to their medications, and 146 (14.4%) developed cardiovascular events. Nonadherent participants were more likely than adherent participants to develop cardiovascular events during 3.9 years of follow-up (22.9% vs 13.8%, P = .03). Self-reported nonadherence remained independently predictive of adverse cardiovascular events after adjusting for baseline cardiac disease severity, traditional risk factors, and depressive symptoms (hazards ratio, 2.3; 95% confidence interval, 1.3-4.3; P = .006). CONCLUSIONS: In outpatients with stable coronary heart disease, self-reported medication nonadherence is associated with a greater than 2-fold increased rate of subsequent cardiovascular events. A single question about medication adherence may be a simple and effective method to identify patients at higher risk for adverse cardiovascular events.

Depressive symptoms, health behaviors, and risk of cardiovascular events in patients with coronary heart disease.

CONTEXT: Depressive symptoms predict adverse cardiovascular outcomes in patients with coronary heart disease, but the mechanisms responsible for this association are unknown. OBJECTIVE: To determine why depressive symptoms are associated with an increased risk of cardiovascular events. DESIGN AND PARTICIPANTS: The Heart and Soul Study is a prospective cohort study of 1017 outpatients with stable coronary heart disease followed up for a mean (SD) of 4.8 (1.4) years. SETTING: Participants were recruited between September 11, 2000, and December 20, 2002, from 12 outpatient clinics in the San Francisco Bay Area and were followed up to January 12, 2008. MAIN OUTCOME MEASURES: Baseline depressive symptoms were assessed using the Patient Health Questionnaire (PHQ). We used proportional hazards models to evaluate the extent to which the association of depressive symptoms with subsequent cardiovascular events (heart failure, myocardial infarction, stroke, transient ischemic attack, or death) was explained by baseline disease severity and potential biological or behavioral mediators. RESULTS: A total of 341 cardiovascular events occurred during 4876 person-years of follow-up. The age-adjusted annual rate of cardiovascular events was 10.0% among the 199 participants with depressive symptoms (PHQ score > or = 10) and 6.7% among the 818 participants without depressive symptoms (hazard ratio [HR], 1.50; 95% confidence interval, [CI], 1.16-1.95; P = .002). After adjustment for comorbid conditions and disease severity, depressive symptoms were associated with a 31% higher rate of cardiovascular events (HR, 1.31; 95% CI, 1.00-1.71; P = .04). Additional adjustment for potential biological mediators attenuated this association (HR, 1.24; 95% CI, 0.94-1.63; P = .12). After further adjustment for potential behavioral mediators, including physical inactivity, there was no significant association (HR, 1.05; 95% CI, 0.79-1.40; P = .75). CONCLUSION: In this sample of outpatients with coronary heart disease, the association between depressive symptoms and adverse cardiovascular events was largely explained by behavioral factors, particularly physical inactivity.

Prevalence and prognosis of asymptomatic left ventricular diastolic dysfunction in ambulatory patients with coronary heart disease.

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>or=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.

N-terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP), cardiovascular events, and mortality in patients with stable coronary heart disease.

CONTEXT: Identification of individuals at high risk for cardiovascular events is important for the optimal use of primary and secondary prevention measures. OBJECTIVE: To determine whether plasma levels of amino terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP) predict cardiovascular events or death independent of other available prognostic tests. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study (2000-2002) of 987 individuals in California with stable coronary heart disease in the Heart and Soul Study, who were followed up for a mean of 3.7 (range, 0.1-5.3) years. MAIN OUTCOME MEASURES: The association of baseline NT-proBNP levels with death or cardiovascular events (myocardial infarction, stroke, or heart failure). Traditional clinical risk factors, echocardiographic measures, ischemia, other biomarkers, and New York Heart Association classification were adjusted for to determine whether NT-proBNP levels were independent of other prognostic factors. Receiver operating characteristic (ROC) curves were used to assess the incremental prognostic value of adding NT-proBNP level to these other measures. RESULTS: A total of 256 participants (26.2%) had a cardiovascular event or died. Each increasing quartile of NT-proBNP level (range of quartile 1, 8.06-73.95 pg/mL; quartile 2, 74-174.5 pg/mL; quartile 3, 175.1-459 pg/mL; quartile 4, > or =460 pg/mL) was associated with a greater risk of cardiovascular events or death, ranging from 23 of 247 (annual event rate, 2.6%) in the lowest quartile to 134 of 246 (annual event rate, 19.6%) in the highest quartile (unadjusted hazard ratio [HR] for quartile 4 vs quartile 1, 7.8; 95% confidence interval [CI], 5.0-12.1; P<.001). Each SD increase in log NT-proBNP level (1.3 pg/mL) was associated with a 2.3-fold increased rate of adverse cardiovascular outcomes (unadjusted HR, 2.3; 95% CI, 2.0-2.6; P<.001), and this association persisted after adjustment for all of the other prognostic measures (adjusted HR, 1.7; 95% CI, 1.3-2.2; P<.001). The addition of NT-proBNP level to standard clinical assessment and complete echocardiographic parameters significantly improved the area under the ROC curves for predicting subsequent adverse cardiovascular outcomes (0.80 for clinical risk factors and echocardiographic parameters plus log NT-proBNP vs 0.76 for clinical risk factors and echocardiographic parameters only; P = .006). CONCLUSIONS: Elevated levels of NT-proBNP predict cardiovascular morbidity and mortality, independent of other prognostic markers, and identify at-risk individuals even in the absence of systolic or diastolic dysfunction by echocardiography. Level of NT-proBNP may help guide risk stratification of high-risk individuals, such as those with coronary heart disease.

Hostility, health behaviors, and risk of recurrent events in patients with stable coronary heart disease: findings from the Heart and Soul Study.

BACKGROUND: Hostility is a significant predictor of mortality and cardiovascular events in patients with coronary heart disease (CHD), but the mechanisms that explain this association are not well understood. The purpose of this study was to evaluate potential mechanisms of association between hostility and adverse cardiovascular outcomes. METHODS AND RESULTS: We prospectively examined the association between self-reported hostility and secondary events (myocardial infarction, heart failure, stroke, transient ischemic attack, and death) in 1022 outpatients with stable CHD from the Heart and Soul Study. Baseline hostility was assessed using the 8-item Cynical Distrust scale. Cox proportional hazard models were used to determine the extent to which candidate biological and behavioral mediators changed the strength of association between hostility and secondary events. During an average follow-up time of 7.4 ± 2.7 years, the age-adjusted annual rate of secondary events was 9.5% among subjects in the highest quartile of hostility and 5.7% among subjects in the lowest quartile (age-adjusted hazard ratio [HR]: 1.68, 95% confidence interval [CI]: 1.30 to 2.17; P < 0.0001). After adjustment for cardiovascular risk factors, participants with hostility scores in the highest quartile had a 58% greater risk of secondary events than those in the lowest quartile (HR: 1.58, 95% CI: 1.19 to 2.09; P = 0.001). This association was mildly attenuated after adjustment for C-reactive protein (HR: 1.41, 95% CI, 1.06 to 1.87; P = 0.02) and no longer significant after further adjustment for smoking and physical inactivity (HR: 1.25, 95% CI: 0.94 to 1.67; P = 0.13). CONCLUSIONS: Hostility was a significant predictor of secondary events in this sample of outpatients with baseline stable CHD. Much of this association was moderated by poor health behaviors, specifically physical inactivity and smoking.

Depressive symptoms and white blood cell count in coronary heart disease patients: prospective findings from the Heart and Soul Study.

BACKGROUND: Depression has been associated with elevated white blood cell (WBC) count - indicative of systemic inflammation - in cross-sectional studies, but no longitudinal study has evaluated whether depressive symptoms predict subsequent WBC count or vice versa. We sought to evaluate the bidirectional association between depressive symptoms and WBC count in patients with coronary heart disease (CHD). METHODS: Depressive symptoms were assessed at baseline and annually during 5 consecutive years of follow-up in 667 outpatients with stable CHD from the Heart and Soul Study. The presence of significant depressive symptoms was defined as a score of ≥10 on the Patient Health Questionnaire (PHQ-9) at one or more assessments. WBC count was measured in blood samples collected at baseline and after 5 years of follow-up. RESULTS: Of the 667 participants, 443 (66%) had no depressive symptoms (PHQ-9<10), 86 (13%) had depressive symptoms (PHQ-9≥10) at 1 assessment, and 138 (21%) had depressive symptoms at 2 or more annual assessments. Across the three groups, participants with recurrent depressive symptoms had higher WBC levels after 5 years of follow-up (p<.001). This relationship was essentially unchanged after adjustment for demographics, traditional cardiovascular risk factors, cardiac disease severity, inflammatory cytokine levels, and health behaviors (p=.009). Baseline WBC count was not associated with subsequent depressive symptoms (p=.18). CONCLUSIONS: Depressive symptoms independently predicted higher subsequent WBC count in patients with stable CHD, but baseline WBC count did not predict subsequent depressive symptoms. These findings support a unidirectional relationship in which depression is a risk-factor for inflammation.

Adiponectin is associated with increased mortality and heart failure in patients with stable ischemic heart disease: data from the Heart and Soul Study.

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.

Mitral annular calcium, inducible myocardial ischemia, and cardiovascular events in outpatients with coronary heart disease (from the Heart and Soul Study).

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.