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Objective

The short allele of a functional polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) has been shown to interact with stressful life events to predict depression in otherwise healthy individuals. Whether the short allele increases risk for depression associated with the stress of a chronic illness has not been established.

Method

In a cross-sectional genetic association study, the authors examined the association of 5-HTTLPR with current depression (measured by the Computerized Diagnostic Interview Schedule), perceived stress (measured by the Perceived Stress Scale), and 24-hour urinary norepinephrine excretion in 557 outpatients with chronic coronary disease.

Results

Among individuals carrying an s allele, 25% (97 of 383) had current depression, compared with 17% (29 of 174) of l/l homozygotes. The unadjusted odds ratio was 1.6, with a 95% confidence interval (CI) of 1.0–2.6; the age- and gender-adjusted odds ratio was also 1.6 (95% CI= 1.0–2.5). Participants carrying an s allele had a higher mean score for perceived stress than l/l homozygotes (5.4 versus 4.7) and a higher rate of moderate or high perceived stress (adjusted odds ratio=1.6, 95% CI=1.1–2.3). Mean 24-hour norepinephrine excretion was higher in s allele carriers (55.6 versus 50.2 μg/day), who were more likely to have norepinephrine values in the highest quartile (adjusted odds ratio=1.7, 95% CI=1.0–3.0).

Conclusions

Among patients with chronic illness, carriers of the s allele of 5-HTTLPR are more vulnerable to depression, perceived stress, and high norepinephrine secretion. These factors may contribute to worse cardiovascular outcomes in these patients.

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.

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 (0.08 μg/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.

Objective

To determine whether depression is associated with worse cardiac disease severity in patients with stable coronary heart disease (CHD). There is considerable evidence that depression is a risk factor for adverse cardiovascular events in patients with CHD. However, a frequent criticism of this literature is that the association between depression and adverse cardiovascular outcomes may be confounded by worse baseline cardiac disease severity in depressed patients.

Method

In a sample of 1020 outpatients with stable CHD, we examined the association between major depression (assessed using the Computerized National Institute of Mental Health Diagnostic Interview Schedule) with measures of cardiac disease severity, including systolic dysfunction, diastolic dysfunction, exercise-induced ischemia, and cardiac wall motion abnormalities. Cross-sectional univariate and multivariate models controlling for demographic and clinical variables were computed.

Results

Of the 1020 participants, 224 (22%) had current (past month) major depression. After adjustment for age, major depression was not associated with systolic dysfunction, diastolic dysfunction, inducible ischemia, or cardiac wall motion abnormalities. Similarly, multivariate models revealed no significant relationship between major depression and cardiac disease severity.

Conclusions

Overall, we found little evidence that depression is associated with worse cardiac disease severity. This suggests that greater baseline cardiac disease severity is unlikely to be responsible for the increased risk of CHD events in depressed patients.

Background

Previous studies suggest that markers of inflammation are elevated in patients with atrial fibrillation (AF). However, because inflammation has been implicated in contributing to risk of both AF and coronary artery disease (CAD), which are often present in the same populations, it is important to control for confounding by the presence of CAD. We therefore examined several biomarkers of inflammation and ultimately genotyped IL-6 polymorphisms in AF patients in a cohort of subjects with known CAD.

Methods

We performed a cross-sectional analysis of 971 participants in the Heart and Soul Study, 46 of whom had AF. IL-6, CRP, tumor necrosis factor-α, CD-40 ligand, monocyte chemoattractant protein-1, and fibrinogen levels were measured.

Results

In both unadjusted and adjusted analyses, IL-06 was the only biomarker significantly associated with AF (median IL-6 3.76 pg/ml and 2.52 pg/ml in those with and without AF, respectively, p=0.0005; adjusted odds ratio [OR] 1.77 p=0.032). The IL-6 –174CC genotype was significantly associated with the presence of AF in the adjusted analysis (OR 2.34, p=0.04) and with higher IL-6 levels (p=0.002).

Conclusions

In this cohort of subjects with CAD, AF was significantly associated with elevated IL-6 levels and the IL-6 –174CC genotype. No associations were found with other biomarkers, including CRP. This suggests that IL-6 is a uniquely important mediator in the pathophysiology of AF.

We performed a cross-sectional study to evaluate the association of anemia with diastolic dysfunction and left ventricular hypertrophy (LVH) in outpatients who had coronary artery disease. Logistic regression was used to examine the association of blood hemoglobin (Hb) concentrations with diastolic dysfunction and LVH in 822 participants in the Heart and Soul Study who had normal sinus rhythm and preserved systolic function (left ventricular ejection fraction ≥50%). Using transthoracic echocardiography, diastolic dysfunction was defined as diastolically dominant pulmonary vein flow, and LVH was defined as left ventricular mass index >90 g/m2. Anemia (Hb <13 g/dl) was present in 24% of participants (197 of 822). The prevalence of diastolic dysfunction ranged from 8% in participants who did not have anemia (Hb ≥13 g/dl) to 13% in those who had moderate anemia (Hb 11 to 13 g/dl) to 24% in those who had severe anemia (Hb < 11 g/dl, p = 0.004 for trend). After multivariable adjustment, moderate anemia (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.1 to 3.6) and severe anemia (OR 6.6, 95% CI 1.9 to 24.9) remained strongly associated with diastolic dysfunction. In contrast, moderate anemia (OR 1.4, 95% CI 1.0 to 2.1) and severe anemia (OR 1.6, 95% CI 0.6 to 4.6) were not significantly associated with LVH. We found anemia to be strongly associated with diastolic dysfunction but not with LVH in this community-based sample of outpatients who had established coronary disease.

Sacred values, such as those associated with religious or ethnic identity, underlie many important individual and group decisions in life, and individuals typically resist attempts to trade off their sacred values in exchange for material benefits. Deontological theory suggests that sacred values are processed based on rights and wrongs irrespective of outcomes, while utilitarian theory suggests that they are processed based on costs and benefits of potential outcomes, but which mode of processing an individual naturally uses is unknown. The study of decisions over sacred values is difficult because outcomes cannot typically be realized in a laboratory, and hence little is known about the neural representation and processing of sacred values. We used an experimental paradigm that used integrity as a proxy for sacredness and which paid real money to induce individuals to sell their personal values. Using functional magnetic resonance imaging (fMRI), we found that values that people refused to sell (sacred values) were associated with increased activity in the left temporoparietal junction and ventrolateral prefrontal cortex, regions previously associated with semantic rule retrieval. This suggests that sacred values affect behaviour through the retrieval and processing of deontic rules and not through a utilitarian evaluation of costs and benefits.

The SOUL protein is known to induce apoptosis by provoking the mitochondrial permeability transition, and a sequence homologous with the BH3 (Bcl-2 homology 3) domains has recently been identified in the protein, thus making it a potential new member of the BH3-only protein family. In the present study, we provide NMR, SPR (surface plasmon resonance) and crystallographic evidence that a peptide spanning residues 147–172 in SOUL interacts with the anti-apoptotic protein Bcl-xL. We have crystallized SOUL alone and the complex of its BH3 domain peptide with Bcl-xL, and solved their three-dimensional structures. The SOUL monomer is a single domain organized as a distorted β-barrel with eight anti-parallel strands and two α-helices. The BH3 domain extends across 15 residues at the end of the second helix and eight amino acids in the chain following it. There are important structural differences in the BH3 domain in the intact SOUL molecule and the same sequence bound to Bcl-xL.

Galen's three souls incorporate previously existing ideas of soul. Soul is matter – cum – energy. As matter it is airlike, the finest by nature and as movement, like sound, the form of energy most subtle of its kind. Creator is depicted with Creation as the Cosmic egg and snake as Cosmic soul and the syllable Om, as the word incorporating creative energy. Om as humming sound is symbolized by Bees which produce such sound.

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.

Objective

The authors sought to evaluate the association of self-efficacy with objective measures of cardiac function, subsequent hospitalization for heart failure (HF), and all-cause mortality.

Design

Observational cohort of ambulatory patients with stable CHD. The authors measured self-efficacy using a published, validated, 5-item summative scale, the Sullivan Self-Efficacy to Maintain Function Scale. The authors also performed a cardiac assessment, including an exercise treadmill test with stress echocardiography.

Main Outcome Measures

Hospitalizations for HF, as determined by blinded review of medical records, and all-cause mortality, with adjustment for demographics, medical history, medication use, depressive symptoms, and social support.

Results

Of the 1,024 predominately male, older CHD patients, 1013 (99%) were available for follow-up, 124 (12%) were hospitalized for HF, and 235 (23%) died during 4.3 years of follow-up. Mean cardiac self-efficacy score was 9.7 (SD 4.5, range 0–20), corresponding to responses between “not at all confident” and “somewhat confident” for ability to maintain function. Lower self-efficacy predicted subsequent HF hospitalization (OR per SD decrease = 1.4, p = 0006), and all-cause mortality (OR per SD decrease = 1.4, p < .0001). After adjustment, the association of cardiac self-efficacy with both HF hospitalization and mortality was explained by worse baseline cardiac function.

Conclusion

Among patients with CHD, self-efficacy was a reasonable proxy for predicting HF hospitalizations. The increased risk of HF associated with lower baseline self-efficacy was explained by worse cardiac function. These findings indicate that measuring cardiac self-efficacy provides a rapid and potentially useful assessment of cardiac function among outpatients with CHD.

BACKGROUND

Clinical guidelines recommend depression screening in patients with coronary artery disease (CAD), but how to accomplish this is unclear.

OBJECTIVE

We evaluated the test characteristics of the two-item Patient Health Questionnaire (PHQ-2), the nine-item Patient Health Questionnaire (PHQ-9), and a two-step screening approach (PHQ-2 then PHQ-9 if positive on PHQ-2), compared with the Computerized Diagnostic Interview Schedule (C-DIS) for major depression. We also evaluated a “PHQ diagnosis” of depression, requiring five of nine symptoms “more than half the days,” compared with the C-DIS.

DESIGN

Cross-sectional study of 1,024 outpatients with CAD.

MAIN RESULTS

Two hundred twenty-four patients (22%) had current major depression. Optimal cutpoints were ≥2 for the PHQ-2 (82% sensitive, 79% specific) and ≥6 for the PHQ-9 (83% sensitive, 76% specific). The two-step screening approach was less sensitive (75%), but more specific (84%), than the PHQ-2 or PHQ-9 alone. The “PHQ diagnosis” had low sensitivity (28%), but high specificity (96%).

CONCLUSIONS

Cutpoints of ≥2 on the PHQ-2 and ≥6 on the PHQ-9 had similar test characteristics. A two-step approach using the PHQ-2 followed by the PHQ-9 was no better than either instrument alone. A “PHQ diagnosis” of depression had high specificity, but poor sensitivity.

Traditional cardiac risk factors only partially explain the biological mechanisms by which persons of lower socioeconomic status (SES) have higher cardiovascular risk. Dietary factors, resulting in lower circulating levels of (n-3) fatty acids, may also contribute to the increased risk of cardiovascular disease (CVD) in patients with low SES. We tested whether low SES is associated with RBC levels of (n-3) fatty acids in patients with coronary heart disease. We performed a cross-sectional analysis of 987 adults with stable coronary artery disease (CAD) recruited from San Francisco area outpatient clinics. Four SES measures (household income, education, occupation, and housing status) were assessed by self-report. RBC fatty acid levels of 2 (n-3) fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), were measured in venous blood samples from fasting subjects. Participants with lower household income, education, occupation, and housing status had lower RBC levels of (n-3) fatty acids (P < 0.001 for all 4 measures). In multivariable models, household income, education, and occupation remained strongly associated with DHA and EPA levels after adjustment for demographic factors, BMI, physical activity, statin use, and kidney function (P < 0.001 for all 3 measures). Housing status was not associated with DHA or EPA after multivariable adjustment. Among patients with CAD, 3 indicators of low SES, household income, education, and occupation, were strongly associated with lower RBC levels of (n-3) fatty acids. Our results raise the possibility that (n-3) fatty acids may be an important mediating factor in the association between low SES and CVD.

Objective

To evaluate whether depression is associated with whole blood serotonin in outpatients with stable coronary heart disease (CHD). Depression is associated with incident CHD and with adverse cardiovascular outcomes. Dysregulation of peripheral serotonin, common to both depression and CHD, may contribute to this association.

Methods

We performed a cross-sectional study of 791 participants with stable CHD enrolled in the Heart and Soul Study and not taking antidepressant medication. We assessed major depression using the Computerized Diagnostic Interview Schedule (CDIS-IV) and measured whole blood serotonin (WBS) from fasting venous samples.

Results

Of the 791 participants, 114 (14%) had current (past month) major depression, 186 (24%) had past (but not current) major depression, and 491 (62%) had no history of depression. Age-adjusted mean WBS was higher in participants with current major depression (139 ± 6.5 ng/ml) than in those with past depression (120 ± 5.0 ng/ml) or no history of depression (119 ± 3.1 ng/ml) (p= .02). This association was unchanged after adjustment for demographic characteristics, medical comorbidities, medication use, and cardiac disease severity (p = .02). When serotonin was analyzed as a dichotomous variable, current depression was associated with a 70% greater odds of having WBS in the highest quartile (adjusted odds ratio = 1.71; 95% Confidence Interval = 1.03–2.83; p = .04).

Conclusions

In this sample of patients with stable CHD, current major depression was independently associated with higher mean WBS levels. Future studies should examine whether elevated WBS may contribute to adverse outcomes in patients with depression and CHD.

Objective

To examine the relationship between cardiac self-efficacy and health status, including symptom burden, physical limitation, quality of life, and overall health among outpatients with stable coronary heart disease (CHD). We hypothesized that lower self-efficacy would predict worse health status, independent of CHD severity and depression.

Methods

We performed a cross-sectional study of 1024 outpatients with CHD, who were recruited between 2000 and 2002 for the Heart and Soul Study. We administered a validated measure of cardiac self-efficacy, assessed cardiac function using exercise treadmill testing with stress echocardiography, and measured depressive symptoms using the Patient Health Questionnaire. Health status outcomes (symptom burden, physical limitation, and quality of life) were assessed using the Seattle Angina Questionnaire, and overall health was measured as fair or poor (versus good, very good, or excellent).

Results

After adjustment for CHD severity and depressive symptoms, each standard deviation (4.5-point) decrease in self-efficacy score was independently associated with greater symptom burden (adjusted odds ratio (OR) = 2.1, p = .001), greater physical limitation (OR = 1.8, p < .0001), worse quality of life (OR = 1.6, p < .0001), and worse overall health (OR = 1.9, p < .0001). Depressive symptoms and poor treadmill exercise capacity were also associated with poor health status, but left ventricular ejection fraction and ischemia were not.

Conclusions

Among patients with CHD, low cardiac self-efficacy is associated with poor health status, independent of CHD severity and depressive symptoms. Further study should examine if self-efficacy constitutes a useful target for cardiovascular disease management interventions.

Chronic renal insufficiency (CRI) is a predictor of stroke, cardiovascular, and all-cause mortality, but the mechanisms responsible for these associations are unclear. Whether CRI was associated with severity of coronary artery disease (CAD) as measured by exercise stress echocardiography among outpatients with stable CAD was evaluated. This study is a cross-sectional analysis of the Heart and Soul study, a prospective cohort of patients with known CAD. Renal function was assessed by 24-h urine collection, and CRI was defined as measured creatinine clearance ≤60 ml/min. Exercise stress echocardiography was used to identify inducible ischemia, defined as any wall motion abnormality seen at stress but not at rest. Logistic regression was used to evaluate the association of CRI with exercise-induced ischemia after adjustment for cardiovascular risk factors. Participants with CRI composed 97 (23%) of the 431 participants and were characterized by older age, worse CAD, lower ejection fraction, greater left ventricular mass and higher C-reactive protein values. The prevalence of exercise-induced ischemia was also substantially greater in the participants with CRI (42% versus 23%; odds ratio [OR], 2.3; 95% confidence interval [CI], 1.4 to 3.8; P < 0.001). This association was minimally changed by adjustment for traditional cardiovascular risk factors and coronary disease history (OR, 2.0; 95% CI, 1.3 to 3.3; P < 0.01) and remained strong even after adjustment for C-reactive protein (OR, 2.3; 95% CI, 1.0 to 5.1; P < 0.04). CRI is strongly associated with exercise-induced ischemia in patients with CAD. The greater severity of atherosclerotic disease observed in patients with CRI may in part explain the association of CRI with increased cardiovascular risk among individuals with CAD.

Summary

Alterations of glucocorticoid receptor sensitivity have been associated with depression. Thus, variation in the glucocorticoid receptor gene that determines glucocorticoid sensitivity may influence risk for depression.

In a cross-sectional genetic association study of 526 white outpatients with chronic coronary heart disease, we examined whether haplotypes of the glucocorticoid receptor gene (NR3C1) are associated with depression. Participants were genotyped for four common glucocorticoid receptor gene polymorphisms (ER22/23EK, BclI C/G, N363S, and 9beta A/G) and haplotype analyses were conducted. Depression was assessed by an interview (Computerized Diagnostic Interview Schedule).

Of the 526 participants, 355 (67.5%) were non-carriers, 153 (29.1%) had one copy, and 17 (3.2%) had 2 copies of the haplotype 3 allele, which includes the minor allele of the 9beta A/G polymorphism and which has been associated with reduced glucocorticoid sensitivity. The prevalence of depression ranged from 24.4% in the non-carriers to 34.4% in heterozygotes to 52.9% in participants homozygous for the haplotype 3 allele (p < 0.01). In logistic regression analyses, carriers of one haplotype 3 allele had an odds ratio of 1.64 (95% CI 1.1–2.5, p = 0.02) for depression, while the odds ratio of homozygous haplotype 3 carriers was 3.52 (95% CI 1.3–9.4, p = 0.01). These associations persisted after adjusting for potentially confounding variables.

Background

B-type natriuretic peptide (BNP) is predictive of inducible ischemia in patients with coronary heart disease (CHD). Whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) has a comparable strength of association with ischemia is uncertain.

Hypothesis

Resting NT-proBNP levels are associated with inducible ischemia in patients with stable CHD.

Methods

We performed a cross-sectional study of 901 outpatients with stable CHD. NT-proBNP was measured in all patients prior to exercise treadmill testing and stress echocardiography. In addition, plasma BNP was measured in a subset of 355 participants. Logistic regression was used to examine the association of NT-proBNP and BNP quartiles with inducible ischemia.

Results

Inducible ischemia was found in 216 (24%) patients. The proportion with inducible ischemia ranged from 42% (95/225) in the highest quartile of NT-proBNP levels (>410 pg/ml) to 9% (21/226) in the lowest quartile (0–72 pg/ml). The highest quartile had a 7-fold greater odds of inducible ischemia than the lowest quartile (odds ratio [OR]: 7.1, 95% confidence interval [CI]: 4.2–12; P<0.0001). This association remained robust after adjustment for traditional cardiovascular risk factors, left ventricular ejection fraction, and diastolic dysfunction (OR: 3.6, 95% CI: 1.4–9.1; P = 0.009). In the subgroup with measurements of both NT-proBNP and BNP, both natriuretic peptides were predictive of ischemia. The multivariable-adjusted c-statistics for inducible ischemia were 0.71 for NT-proBNP and 0.62 for BNP (entered as continuous variables).

Conclusions

Resting NT-proBNP levels are independently associated with inducible ischemia in outpatients with stable CHD. Baseline elevations of natriuretic peptide may indicate subclinical inducible ischemia in high risk patients with CHD.

Background

The effect of mild chronic kidney disease (CKD) on depression, stress, quality of life (QOL), and health status is not well understood. We compared these outcomes in subjects with and without CKD.

Methods

We performed a cross-sectional study of 967 outpatients enrolled in the Heart and Soul Study. CKD was defined as a measured creatinine clearance <60 ml/min. Outcome measures included depressive symptoms measured using the Patient Health Questionnaire (PHQ), stress measured using the Perceived Stress Scale (PSS), and QOL and overall health rated as excellent, very good, good, fair, or poor.

Results

The prevalence of depressive symptoms (17 vs. 19%, p = 0.4) or perceived stress (11 vs. 16%, p = 0.09) did not vary significantly by CKD. The prevalence of fair or poor QOL was not significantly different in subjects with CKD, compared with those without CKD (24 vs. 23%, p = 0.65). Age-adjusted analyses revealed a significant association of CKD with QOL (p = 0.003), however, this association no longer reached statistical significance after adjustment for confounders (p = 0.06). Subjects with CKD were more likely to report poor or fair overall health than subjects without CKD (42 vs. 34%, p = 0.03). After multivariate adjustment, CKD remained significantly associated with worse overall health (OR = 1.65, 95% CI 1.21–2.24, p = 0.001), and modestly associated with QOL (OR = 1.31, 95% CI 0.99–1.75, p = 0.06), but had no association with depression (p = 0.48) or stress (p = 0.24).

Conclusion

In this study of persons with coronary artery disease, subjects with CKD had reduced overall health and modestly reduced QOL; however, mental health was similar in those with and without CKD. These findings suggest that self-assessed overall health may decline at earlier stages of renal dysfunction than mental health outcomes or QOL.

Context

Little is known regarding the extent to which patient-reported health status, including symptom burden, physical limitation, and quality of life, is determined by psychosocial vs physiological factors among patients with chronic disease.

Objective

To compare the contributions of depressive symptoms and measures of cardiac function to the health status of patients with coronary artery disease.

Design, Setting, and Participants

Cross-sectional study of 1024 adults with stable coronary artery disease recruited from outpatient clinics in the San Francisco Bay Area between September 2000 and December 2002.

Main Measures

Measurement of depressive symptoms using the Patient Health Questionnaire (PHQ); assessment of cardiac function by measuring left ventricular ejection fraction on echocardiography, exercise capacity on treadmill testing, and ischemia on stress echocardiography; and measurement of a range of health status outcomes, including symptom burden, physical limitation, and quality of life, using the Seattle Angina Questionnaire. Participants were also asked to rate their overall health as excellent, very good, good, fair, or poor.

Results

Of the 1024 participants, 201 (20%) had depressive symptoms (PHQ score ≥10). Participants with depressive symptoms were more likely than those without depressive symptoms to report at least mild symptom burden (60% vs 33%; P<.001), mild physical limitation (73% vs 40%; P<.001), mildly diminished quality of life (67% vs 31%; P<.001), and fair or poor overall health (66% vs 30%; P<.001). In multivariate analyses adjusting for measures of cardiac function and other patient characteristics, depressive symptoms were strongly associated with greater symptom burden (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.3-2.7; P=.002), greater physical limitation (OR, 3.1; 95% CI, 2.1-4.6; P<.001), worse quality of life (OR, 3.1; 95% CI, 2.2-4.6; P<.001), and worse overall health (OR, 2.0; 95% CI, 1.3-2.9; P<.001). Although decreased exercise capacity was associated with worse health status, left ventricular ejection fraction and ischemia were not.

Conclusions

Among patients with coronary disease, depressive symptoms are strongly associated with patient-reported health status, including symptom burden, physical limitation, quality of life, and overall health. Conversely, 2 traditional measures of cardiac function—ejection fraction and ischemia—are not. Efforts to improve health status should include assessment and treatment of depressive symptoms.

Background

Whether 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.

Methods

In 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%).

Results

A 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.

Conclusion

These data suggest that BNP is not a useful screening test for asymptomatic ventricular dysfunction in patients with stable coronary disease.

Low socioeconomic status (SES) is associated with poor health outcomes in patients who have coronary heart disease (CHD). Inflammation is a potential mechanism by which low SES may lead to adverse cardiovascular outcomes, but it is not known whether low SES is associated with inflammation in patients who have CHD. We measured high-sensitivity C-reactive protein (CRP) levels in a cross-sectional study of 985 adults who had CHD. Income and education were determined by self-report. We used ordinal logistic regression to examine the association of income and education with CRP. Of the 985 participants, 390 had high CRP levels (>3 mg/dl). The proportion of participants who had high CRP levels ranged from 30% (103 of 340) in those who had a college degree to 51% (65 of 127) in those who had less than a high school degree (p <0.0001). The proportion of subjects who had a high CRP level ranged from 28% (52 of 183) in those who had annual income >$50,000 to 42% (199 of 974) in those who had an annual income <$20,000 (p <0.001). After adjustment for traditional cardiovascular risk factors and other potential confounding variables, lower income and education remained associated with higher CRP levels. In conclusion, low SES is associated with high CRP levels in patients who have CHD. This observation raises the possibility that inflammation may contribute to the adverse cardiovascular outcomes associated with low SES.

We examined the association between anemia (hemoglobin ≤12 g/dl) and 6 indexes of heart rate variability (HRV) as measured by 24-hour ambulatory electrocardiography in a cross-sectional study of 874 outpatients who had stable coronary heart disease. Of 90 participants who had anemia, 29% to 41% had low HRV, defined as the lowest quartile of each HRV index, compared with 23% to 25% of the 784 participants who did not have anemia (comparison p values <0.05 for all HRV indexes except high-frequency power). With the exception of high-frequency power, each 1 g/dl decrease in hemoglobin was associated with increased odds of having low HRV. This association remained strong after adjustment for potential confounding variables, including ischemia, left ventricular mass, left ventricular ejection fraction, and diastolic dysfunction. Thus, anemia is associated with low HRV in ambulatory patients who have stable coronary heart disease. Low HRV could potentially mediate the association of anemia with increased cardiac risk.

To examine the association between depressive symptoms and exercise capacity, we performed a cross-sectional study of 944 outpatients with stable coronary artery disease and found that the presence of depressive symptoms was independently associated with poor exercise capacity (<5 MET tasks achieved; adjusted odds ratio 1.8, 95% confidence interval 1.1 to 2.7, p = 0.01). Depressive symptoms should be considered in the differential diagnosis of poor exercise capacity.

Chronic kidney disease (CKD) and anemia are common conditions in the outpatient setting, but their independent and additive effects on physical capacity have not been well characterized. The association of CKD and anemia with self-reported physical function was evaluated and exercise capacity was measured in patients with coronary disease. A cross-sectional study of 954 outpatients enrolled in the Heart and Soul study was performed. CKD was defined as a measured creatinine clearance <60 ml/min, and anemia was defined as a hemoglobin level of <12g/dl. Physical function was self-assessed using the physical limitation subscale of the Seattle Angina Questionnaire (0 to 100), and exercise capacity was defined as metabolic equivalent tasks achieved at peak exercise. In unadjusted analyses, CKD was associated with lower self-reported physical function (67.6 versus 74.9; P < 0.001) and lower exercise capacity (5.5 versus 7.9; P < 0.001). Similarly, anemia was associated with lower self-reported physical function (62.6 versus 74.3; P < 0.001) and exercise capacity (5.7 versus 7.5; P < 0.001). After multivariate adjustment, CKD (69.4 versus 74.2; P = 0.003) and anemia (67.5 versus 73.6; P = 0.009) each remained associated with lower mean self-reported physical function. In addition, patients with CKD (6.3 versus 7.7; P < 0.001) or anemia (6.5 versus 7.4; P = 0.004) had lower adjusted mean exercise capacities. Participants with both CKD and anemia had lower self-reported physical function and exercise capacity than those with either alone. CKD and anemia are independently associated with physical limitation and reduced exercise capacity in outpatients with coronary disease, and these effects are additive. The broad impact of these disease conditions merits further study.