Epidemiology of Sarcoidosis in U.S. Veterans from 2003 to 2019.

Rationale: United States veterans represent an important population to study sarcoidosis. Their unique history of environmental exposures, wide geographic distribution, and long-term enrollment in a single integrated healthcare system provides an unparalleled opportunity to understand the incidence, prevalence, and risk factors for sarcoidosis. Objectives: To determine the epidemiology, patient characteristics, geographic distribution, and associated risk factors of sarcoidosis among U.S. veterans. Methods: We used data from the Veterans Health Administration (VHA) electronic health record system between 2003 and 2019 to evaluate the annual incidence, prevalence, and geographic distribution of sarcoidosis (defined using the International Classification of Diseases codes). We used multivariate logistic regression to examine patient characteristics associated with sarcoidosis incidence. Results: Among more than 13 million veterans who received care through or paid for by the VHA, 23,747 (0.20%) incident diagnoses of sarcoidosis were identified. Compared with selected VHA control subjects using propensity score matching, veterans with sarcoidosis were more likely to be female (13.5% vs. 9.0%), of Black race (52.2% vs. 17.0%), and ever-tobacco users (74.2% vs. 64.5%). There was an increase in the annual incidence of sarcoidosis between 2004 and 2019 (from 38 to 52 cases/100,000 person-years) and the annual prevalence between 2003 and 2019 (from 79 to 141 cases/100,000 persons). In a multivariate logistic regression model, Black race (odds ratio [OR], 4.49; 95% confidence interval [CI], 4.33-4.65), female sex (OR, 1.64; 95% CI, 1.56-1.73), living in the Northeast compared with the western region (OR, 1.57; 95% CI, 1.48-1.67), history of tobacco use (OR, 1.36; 95% CI, 1.31-1.41), and serving in the Army, Air Force, or multiple branches compared with the Navy (OR, 1.08; 95% CI, 1.03-1.13; OR, 1.10; 95% CI, 1.04-1.17; OR, 1.27; 95% CI, 1.16-1.39, respectively) were significantly associated with incident sarcoidosis (P < 0.0001). Conclusions: The incidence and prevalence of sarcoidosis are higher among veterans than in the general population. Alongside traditionally recognized risk factors such as Black race and female sex, we found that a history of tobacco use within the Veterans Affairs population and serving in the Army, Air Force, or multiple service branches were associated with increased sarcoidosis risk.

Implantable cardioverter-defibrillator placement among patients with left ventricular ejection fraction ≤35 % at least 40 days after acute myocardial infarction.

Background: Implantable cardioverter-defibrillators (ICDs) reduce the risk of sudden cardiac death among patients with persistently reduced (≤35 %) left ventricular ejection fraction (LVEF) at least 40 days following acute myocardial infarction (AMI). Few prior studies have used LVEF measured after the 40-day waiting period to examine primary prevention ICD placement. Methods: We sought to determine factors associated with ICD placement among patients who met LVEF criteria post-MI within a large integrated health care system in the U.S by conducting a retrospective cohort study of Veteran patients hospitalized for AMI from 2004 to 2017 who had documented LVEF ≤35 % from echocardiograms performed between 40 and 455 (90 days +1 year) days post-MI. We used multivariable logistic regression to examine factors associated with ICD placement. Results: Of 12,893 patients with LVEF ≤35 % at least 40 days post-MI, 2176 (16.9 %) received an ICD between 91- and 455-days post-MI. Younger age, fewer comorbidities, revascularization with PCI, and greater use of GDMT were associated with increased odds of receiving an ICD. However, half of patients treated with a beta-blocker, ACE inhibitor or angiotensin receptor blocker, and mineralocorticoid receptor antagonist prior to LVEF assessment did not receive an ICD. Eligible Black patients were less likely (odds ratio 0.80, 95 % confidence interval 0.69-0.92) to receive an ICD than White patients. Conclusion: Many factors affect ICD placement among Veteran patients with a confirmed LVEF ≤35 % at least 40 days post-MI. Greater understanding of factors influencing ICD placement would help clinicians ensure guideline-concordant care.

Social integration and mortality in patients with coronary heart disease: findings from the Heart and Soul Study.

OBJECTIVE: To determine why lower social integration predicts higher mortality in patients with coronary heart disease (CHD). METHODS: The association between social integration and mortality was examined prospectively in 1019 outpatients with stable CHD from the Heart and Soul Study. Baseline social integration was assessed with the Berkman Social Network Index. Cox proportional hazards models were used to determine the extent to which demographic and disease-relevant confounders and potential biological, behavioral, and psychological mediators explained the association between social integration and mortality. RESULTS: During a mean (standard deviation) follow-up period of 6.7 (2.3) years, the age-adjusted annual rate of mortality was 6.3% among socially isolated patients and 4.1% among nonisolated patients (age-adjusted hazard ratio [HR] = 1.61, 95% confidence interval [CI] = 1.26-2.05, p < .001). After adjustment for demographic and disease-relevant confounders, socially isolated patients had a 50% greater risk of death than did nonisolated patients (HR = 1.50, 95% CI = 1.07-2.10). Separate adjustment for potential biological (HR = 1.53, CI = 1.05-2.25) and psychological mediators (HR = 1.52, CI = 1.08-2.14) did not significantly attenuate this association, whereas adjustment for potential behavioral mediators did (HR = 1.30, CI = 0.91-1.86). C-reactive protein and hemoglobin A1c were identified as important biological and omega-3 fatty acids, smoking, and medication adherence as important behavioral potential mediators, with smoking making the largest contribution. CONCLUSIONS: In this sample of outpatients with baseline stable CHD, the association between social integration and mortality was largely explained by health-related behavioral pathways, particularly smoking.

Vitamin D deficiency and cardiovascular events in patients with coronary heart disease: data from the Heart and Soul Study.

A growing body of evidence supports an association between vitamin D and cardiovascular disease. However, the mechanisms underlying this association are unknown. From 2000 to 2002, we identified 946 participants with stable cardiovascular disease in San Francisco, California, and followed them prospectively for cardiovascular events (heart failure, myocardial infarction, stroke, or cardiovascular death). We then examined the extent to which the association was attenuated by adjustment for poor health behaviors, comorbid health conditions, and potential biological mediators. During a median follow-up period of 8.0 years (through August 24, 2012), 323 subjects (34.1%) experienced a cardiovascular event. Following adjustment for sociodemographic factors, season of blood measurement, health behaviors, and comorbid conditions, 25-hydroxyvitamin D levels under 20 ng/mL remained independently associated with cardiovascular events (hazard ratio = 1.30, 95% confidence interval: 1.01, 1.67). However, after further adjustment for potential biological mediators, the independent association was no longer present (hazard ratio = 1.11, 95% confidence interval: 0.85, 1.44). Parathyroid hormone, a potentially modifiable biological factor downstream from 25-hydroxyvitamin D, was responsible for the majority of this attenuation. These findings highlight the need for randomized controlled trials to determine whether vitamin D supplementation in persons with deficiency could be beneficial for the primary or secondary prevention of cardiovascular events.

Selenium exposure and depressive symptoms: the Coronary Artery Risk Development in Young Adults Trace Element Study.

Selenium is an essential trace element important to neurotransmission, but toxic at high levels. Some studies suggest beneficial effects on mood. We assessed the association of selenium exposure with presence of depressive symptoms. Selenium exposure was measured in toenail samples collected in 1987 from 3735 US participants (age 20-32 years) and depressive symptoms assessed in 1990, 1995, 2000, 2005, and 2010 using the Center for Epidemiologic Studies Depression Scale (CES-D). Binary and polytomous logistic regression models were used to assess the relation of log2(selenium) and selenium quintiles with presence of depressive symptoms (CES-D score≥27 or on antidepressant medication). Relative to selenium quintile 1, the adjusted odds ratio (OR) for having depressive symptoms in 1990 for quintile 5 was 1.59 (95% CI: 1.01, 2.51) and a unit increase in log2(selenium), which represents a doubling of the selenium level, was associated with an OR=2.03 (95% CI: 1.12, 3.70). When examining 1, 2 or 3+ exams vs. no exams with symptoms, the OR for quintile 5 was 1.73 (1.04, 2.89) for 3+ exams and for one exam and two exams, there were no associations. In a generalized estimating equations longitudinal model, a doubling of the selenium level was associated with a 56% higher odds of having depressive symptoms at an exam. Contrary to previously reported findings related to mood, higher level of selenium exposure was associated with presence of elevated depressive symptoms. More research is needed to elucidate the role of selenium in depressive disorders.

Positive affect and survival in patients with stable coronary heart disease: findings from the Heart and Soul Study.

OBJECTIVE: Positive affect can improve survival, but the mechanisms responsible for this association are unknown. We sought to evaluate the association between positive affect and mortality in patients with stable coronary heart disease and to determine biological and behavioral factors that might explain this association. METHOD: The Heart and Soul Study is a prospective cohort study of 1,018 outpatients with stable coronary heart disease. Participants were recruited between September 11, 2000, and December 20, 2002, and were followed up to June 2011. Baseline positive affect was assessed by using the 10-item positive affect subscale of the Positive and Negative Affect Schedule. Cox proportional hazards regression was used to estimate the risk of mortality (primary outcome measure) and cardiovascular events (heart failure, myocardial infarction, stroke, transient ischemic attack) associated with positive affect, adjusting for baseline cardiac disease severity and depression. We also evaluated the extent to which these associations were explained by potential biological and behavioral mediators. RESULTS: A total of 369 patients (36%) died during a mean ± SD follow-up period of 7.1 ± 2.5 years. Positive affect was not significantly associated with cardiovascular events (hazard ratio [HR]: 0.89; 95% CI, 0.79-1.00; P = .06). However, each standard deviation (8.8-point) increase in positive affect score was associated with a 16% decreased risk of all-cause mortality (HR: 0.84; 95% CI, 0.76-0.92; P = .001). After adjustment for cardiac disease severity and depressive symptoms, positive affect remained significantly associated with improved survival (HR: 0.87; 95% CI, 0.78-0.97; P = .01). The association was no longer significant after adjustment for behavioral factors, and particularly physical activity (HR: 0.92; 95% CI, 0.82-1.03; P = .16). Further adjustment for C-reactive protein and omega-3 fatty acids did not result in any meaningful changes (HR: 0.94; 95% CI, 0.84-1.06; P = .31). CONCLUSIONS: In this sample of outpatients with coronary heart disease, positive affect was associated with improved survival. This association was largely explained by physical activity.

Depression and cardiovascular disease.

Approximately one out of every five patients with cardiovascular disease (CVD) suffers from major depressive disorder (MDD). Both MDD and depressive symptoms are risk factors for CVD incidence, severity and outcomes. Great progress has been made in understanding potential mediators between MDD and CVD, particularly focusing on health behaviors. Investigators have also made considerable strides in the diagnosis and treatment of depression among patients with CVD. At the same time, many research questions remain. In what settings is depression screening most effective for patients with CVD? What is the optimal screening frequency? Which therapies are safe and effective? How can we better integrate the care of mental health conditions with that of CVD? How do we motivate depressed patients to change health behaviors? What technological tools can we use to improve care for depression? Gaining a more thorough understanding of the links between MDD and heart disease, and how best to diagnose and treat depression among these patients, has the potential to substantially reduce morbidity and mortality from CVD.

24-hour urine phosphorus excretion and mortality and cardiovascular events.

BACKGROUND AND OBJECTIVES: Higher morning serum phosphorus has been associated with cardiovascular disease (CVD) in patients with or without CKD. In patients with CKD and a phosphorous level >4.6 mg/dl, the Kidney Disease Improving Global Outcomes guidelines recommend dietary phosphorus restriction. However, whether phosphorus restriction influences serum phosphorus concentrations and whether dietary phosphorus is itself associated with CVD or death are uncertain. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Among 880 patients with stable CVD and normal kidney function to moderate CKD, 24-hour urine phosphorus excretion (UPE) and serum phosphorus were measured at baseline. Participants were followed for a median of 7.4 years for CVD events and all-cause mortality. RESULTS: Mean ± SD age was 67±11 years, estimated GFR (eGFR) was 71±22 ml/min per 1.73 m(2), and serum phosphorus was 3.7±0.6 mg/dl. Median UPE was 632 (interquartile range, 439, 853) mg/d. In models adjusted for demographic characteristics and eGFR, UPE was weakly and nonsignificantly associated with serum phosphorus (0.03 mg/dl higher phosphorus per 300 mg higher UPE; P=0.07). When adjusted for demographics, eGFR, and CVD risk factors, each 300-mg higher UPE was associated with 17% lower risk of CVD events. The association of UPE with all-cause mortality was not statistically significant (hazard ratio, 0.93; 95% confidence interval, 0.82 to 1.05). Results were similar irrespective of CKD status (P interactions > 0.87). CONCLUSIONS: Among outpatients with stable CVD, the magnitude of the association of UPE with morning serum phosphorus is modest. Greater UPE is associated with lower risk for CVD events. The association was similar for all-cause mortality but was not statistically significant.

Fractional excretion of phosphorus modifies the association between fibroblast growth factor-23 and outcomes.

Fibroblast growth factor-23 (FGF23) induces phosphaturia through its effects on renal tubules. Higher levels of FGF23 associate with cardiovascular disease (CVD) events and all-cause mortality, but it is unknown whether these associations differ by the degree of phosphaturia. Here, we measured serum FGF23 and 24-hour urine fractional excretion of phosphorus (FePi) in 872 outpatients with stable CVD and a mean estimated GFR of 71 ml/min per 1.73 m(2). During an average 7.5 years of follow-up, there were 337 deaths and 199 CVD events. Urinary FePi significantly modified the association of FGF23 with each outcome (P interaction<0.001 for all-cause mortality and P interaction<0.05 for CVD events). In models adjusted for CVD risk factors, kidney function, and PTH, those patients who had FGF23 above the median (≥ 42.3 relative units [RU]/ml) but FePi below the median (<15.7%) had the highest risks of both all-cause mortality (HR=1.98, 95% CI=1.42-2.77) and CVD events (HR=1.92, 95% CI=1.25-2.94) compared with those patients who had low concentrations of FGF23 and low FePi. In summary, associations of FGF23 with mortality and CVD events are stronger in persons with lower FePi independent of PTH and kidney function. In such individuals, the renal tubular response to FGF23 may be suboptimal.

Urine calcium excretion, cardiovascular events, and mortality in outpatients with stable coronary artery disease (from the Heart and Soul study).

We sought to evaluate the association of urine calcium excretion (UCaE), which reflects systemic calcium absorption, with cardiovascular (CV) events and mortality in outpatients with prevalent coronary heart disease (CHD). Calcium supplementation is associated with vascular calcification and adverse CV outcomes in patients with end-stage renal disease. Recent studies have raised concern that this phenomenon may also extend to the general population. However, previous studies have assessed oral calcium intake, which correlates poorly with systemic calcium absorption. We measured UCaE from 24-hour urine collections provided by 903 outpatients who were recruited from 2000 to 2002. We used Cox proportional hazard models to evaluate the association of baseline UCaE with a primary end point of any CV event (myocardial infarction [MI], heart failure, stroke, or CV mortality). During a mean follow-up of 6 ± 3 years, 287 subjects (32%) had a CV event. After multivariate adjustment for demographics, traditional CV risk factors, and kidney function, there was no association between UCaE and the primary end point of any CV event (per 10-mg/day greater UCaE, hazard ratio 1.00, 95% confidence interval 0.98 to 1.02). Evaluation of individual CV outcomes revealed a lower rate of MI with higher UCaE (hazard ratio 0.97, 95% confidence interval 0.94 to 1.00). In conclusion, greater UCaE is not associated with higher overall CV event rates or mortality in outpatients with stable CHD. On the contrary, greater UCaE is associated with a modestly lower rate of MI. These findings suggest that greater systemic calcium absorption does not confer CV harm in outpatients with prevalent CHD.

Statin use and risk of depression in patients with coronary heart disease: longitudinal data from the Heart and Soul Study.

BACKGROUND: Statins are among the most commonly prescribed medications worldwide. Although their benefits for cardiovascular disease are well established, the effects of statins on depressive symptoms are unknown. METHOD: We examined the association between baseline statin use (2000-2002) and subsequent depressive symptoms in a prospective cohort study of 965 outpatients with coronary disease from 12 outpatient clinics in the San Francisco Bay Area. Depressive symptoms were assessed annually for 6 years using the Patient Health Questionnaire (PHQ) (primary outcome measure). We evaluated the cross-sectional association between statin use and risk of depressive symptoms at baseline and the longitudinal association between baseline statin use and risk of depressive symptoms during follow-up. RESULTS: Of the 965 participants, 629 (65%) used statins. At baseline, statin users had lower mean ± SE PHQ depression scores than nonusers (4.8 ± 0.2 vs 5.9 ± 0.3, P < .01). Statin users were less likely than nonusers to have depression (PHQ score ≥ 10) at baseline (17% vs 24%; P = .02) and during follow-up (28% vs 40%; P < .01). Among the 776 patients without depressive symptoms at baseline (PHQ < 10), statin use was associated with a 48% decreased odds of developing depression during follow-up (odds ratio [OR], 0.52; 95% CI, 0.38-0.73; P < .01). After we adjusted for potentially confounding variables, statin use remained associated with a 38% decreased odds of subsequent depression (adjusted OR, 0.62; 95% CI, 0.41-0.95; P = .02). CONCLUSIONS: We found that statin use was associated with a decreased risk of subsequent depressive symptoms in patients with coronary heart disease. Whether use of statins prevents depressive symptoms deserves further study.

Relation of sex and estrogen therapy to serum fibroblast growth factor 23, serum phosphorus, and urine phosphorus: the Heart and Soul Study.

BACKGROUND: Menopause is associated with urine phosphorus retention, which is mitigated by estrogen therapy. Fibroblast growth factor 23 (FGF-23) is a hormone originating from bone that regulates urine phosphorus excretion. Whether sex or estrogen therapy is associated with different FGF-23 levels is unknown. STUDY DESIGN & SETTING: Cross-sectional study of ambulatory individuals with prevalent cardiovascular disease. PREDICTORS: Sex and, in women, use or nonuse of estrogen. OUTCOMES: Serum phosphorus, tubular maximum reabsorption of phosphorus indexed to glomerular filtration rate (TMP/GFR), and plasma FGF-23 concentrations. RESULTS: For 987 participants, mean age was 67 ± 11 years, 182 (18%) were women, and 46 (25%) were using estrogen. Mean estimated GFR was 71 ± 23 (SD) mL/min/1.73 m(2). Compared with women who were not using estrogen, both women on estrogen therapy and men had significantly lower serum phosphorus concentrations, lower TMP/GFR values (indicating higher urine phosphorus excretion), and lower FGF-23 concentrations with adjustment for age, demographics, and kidney function (P < 0.001 for each). Mean FGF-23 levels were 68.7 (95% CI, 59.7-79.0) relative units (RU)/mL in non-estrogen-using women, 43.8 (95% CI, 41.2-46.5) RU/mL in men, and 45.1 (95% CI, 35.2-57.4) RU/mL in women using estrogen in adjusted analysis (P < 0.001). LIMITATIONS: Most participants were men. Estrogen therapy was not randomly assigned. CONCLUSIONS: Older women who are not using estrogen have higher FGF-23 levels than either men or women using estrogen. In the context of prior literature, these data suggest that postmenopausal phosphorus retention may stimulate higher FGF-23 concentrations after menopause.

Relation of whole blood n-3 fatty acid levels to exercise parameters in patients with stable coronary artery disease (from the heart and soul study).

Dietary intake of n-3 polyunsaturated fatty acids is associated with a lower incidence of cardiovascular events. Mechanisms underlying this association are poorly understood but may include beneficial effects on physical conditioning and vagal tone. We investigated the association of n-3 fatty acid levels to exercise parameters in 992 subjects with stable coronary artery disease. Cross-sectional associations of heart rate recovery time, treadmill exercise capacity, and exercise time with docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) levels were evaluated in multivariable linear and logistic regression models adjusted for demographics, cardiovascular risk factors, co-morbidities, self-reported physical activity, medication use, and left ventricular function. After multivariable adjustment, n-3 fatty acid levels (DHA + EPA) were strongly associated with heart rate recovery (beta 2.1, p = 0.003), exercise capacity (beta 0.8, p <0.0001), and exercise time (beta 0.9, p <0.0001). Increasing levels of (DHA + EPA) were also associated with decreased risk of impaired heart rate recovery (odds ratio 0.8, p = 0.004) and exercise time (odds ratio 0.7, p = 0.01) and trended toward significance for exercise capacity (odds ratio 0.8, p = 0.07). These associations were not modified by demographics, body mass index, smoking, co-morbid conditions, statin use, or ß-blocker use (p for interaction >0.1 for all comparisons). In conclusion, an independent association exists between n-3 fatty acid levels and important exercise parameters in patients with stable coronary artery disease. These findings support the hypothesis that n-3 fatty acids may increase vagal tone and physical conditioning.

Association of serum phosphorus with left ventricular mass in men and women with stable cardiovascular disease: data from the Heart and Soul Study.

BACKGROUND: Higher serum phosphorus levels are associated with cardiovascular disease (CVD) events in the general population, an association that may be stronger in men. Estradiol has phosphaturic properties. Whether higher serum phosphorus levels are associated with left ventricular (LV) mass in persons without end-stage renal disease and whether the association is modified by sex is unknown. STUDY DESIGN: Cross-sectional observational study. SETTING & PARTICIPANTS: 978 outpatients with stable CVD. PREDICTOR: The primary predictor variable was serum phosphorus level. Sex was evaluated as an effect modifier. OUTCOME & MEASUREMENTS: LV mass using transthoracic echocardiography. RESULTS: The association of serum phosphorus level with LV mass differed by sex (interaction P=0.04). In models adjusted for age, race, kidney function, smoking, diabetes, blood pressure, cholesterol level, C-reactive protein level, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use, each 1-mg/dL higher serum phosphorus level was associated with 4.52-g/m2 greater LV mass (95% CI, 1.04-8.01; P=0.01) in men. Conversely, in women, no statistically significant association was found between serum phosphorus level and LV mass. LIMITATIONS: Older adult population with stable CVD; 19% were women. CONCLUSIONS: In outpatients with stable CVD, higher serum phosphorus levels are associated with greater LV mass in men, but not women. Whether sex hormones may account for these differences requires future study.

Association of marine omega-3 fatty acid levels with telomeric aging in patients with coronary heart disease.

CONTEXT: Increased dietary intake of marine omega-3 fatty acids is associated with prolonged survival in patients with coronary heart disease. However, the mechanisms underlying this protective effect are poorly understood. OBJECTIVE: To investigate the association of omega-3 fatty acid blood levels with temporal changes in telomere length, an emerging marker of biological age. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 608 ambulatory outpatients in California with stable coronary artery disease recruited from the Heart and Soul Study between September 2000 and December 2002 and followed up to January 2009 (median, 6.0 years; range, 5.0-8.1 years). MAIN OUTCOME MEASURES: We measured leukocyte telomere length at baseline and again after 5 years of follow-up. Multivariable linear and logistic regression models were used to investigate the association of baseline levels of omega-3 fatty acids (docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]) with subsequent change in telomere length. RESULTS: Individuals in the lowest quartile of DHA+EPA experienced the fastest rate of telomere shortening (0.13 telomere-to-single-copy gene ratio [T/S] units over 5 years; 95% confidence interval [CI], 0.09-0.17), whereas those in the highest quartile experienced the slowest rate of telomere shortening (0.05 T/S units over 5 years; 95% CI, 0.02-0.08; P < .001 for linear trend across quartiles). Levels of DHA+EPA were associated with less telomere shortening before (unadjusted beta coefficient x 10(-3) = 0.06; 95% CI, 0.02-0.10) and after (adjusted beta coefficient x 10(-3) = 0.05; 95% CI, 0.01-0.08) sequential adjustment for established risk factors and potential confounders. Each 1-SD increase in DHA+EPA levels was associated with a 32% reduction in the odds of telomere shortening (adjusted odds ratio, 0.68; 95% CI, 0.47-0.98). CONCLUSION: Among this cohort of patients with coronary artery disease, there was an inverse relationship between baseline blood levels of marine omega-3 fatty acids and the rate of telomere shortening over 5 years.

Higher dietary intake of long-chain omega-3 polyunsaturated fatty acids is inversely associated with depressive symptoms in women.

OBJECTIVE: Experimental and observational data suggest that a higher dietary intake of long-chain omega-3 polyunsaturated acids may lead to a decreased risk of depressive disorders. We assessed multivariable-adjusted associations of fish consumption and dietary intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) with depressive symptoms in a population-based sample of 3317 African-American and Caucasian men and women from the Coronary Artery Risk Development in Young Adults study. METHODS: Diet was assessed in year 7 (1992-1993) and depressive symptoms were measured in years 10 (1995-1996), 15 (2000-2001), and 20 (2005-2006) by the 20-item Center for Epidemiological Studies Depression Scale. Depressive symptoms were defined as a Center for Epidemiological Studies Depression Scale score > or =16 or self-reported use of antidepressant medication. RESULTS: In the entire cohort, the highest quintiles of intakes of EPA (> or =0.03% energy), DHA (> or =0.05% energy), and EPA + DHA (> or =0.08% energy) were associated with a lower risk of depressive symptoms at year 10 (P for trends = 0.16, 0.10, and 0.03, respectively). The observed inverse associations were more pronounced in women. For the total number of occasions with depressive symptoms, the multivariable adjusted odds ratios (95% confidence interval) in women were 0.75 (0.55-1.01) for fish intake, 0.66 (0.50-0.89) for EPA, 0.66 (0.49-0.89) for DHA, and 0.71 (0.52-0.95) for EPA + DHA when comparing the highest with the lowest quintiles. Analyses of continuous Center for Epidemiological Studies Depression Scale scores revealed inverse associations with fourth-root-transformed omega-3 variables in women. CONCLUSION: Our findings suggest that dietary intakes of fish and long-chain omega-3 fatty acids may be inversely associated with chronic depressive symptoms in women.

Inverse association of erythrocyte n-3 fatty acid levels with inflammatory biomarkers in patients with stable coronary artery disease: The Heart and Soul Study.

OBJECTIVE: Dietary intake of polyunsaturated n-3 fatty acids has been associated with a reduced incidence of adverse cardiovascular events. The protective mechanisms involved are not fully understood, but may include anti-inflammatory factors. We sought to investigate the relationship between n-3 fatty acid levels in erythrocyte membranes and markers of systemic inflammation in 992 individuals with stable coronary artery disease. METHODS: Cross-sectional associations of C-reactive protein (CRP) and Interleukin-6 (Il-6) with docosahexaenoic acid (DHA) and eicosapentaenoic acid (EHA) were evaluated in multivariable linear regression models adjusted for demographics, cardiovascular risk factors, medication use, exercise capacity, body-mass index, and waist-to-hip ratio. RESULTS: After multivariable adjustment, n-3 fatty acid levels (DHA+EPA) were inversely associated with CRP and IL-6. The inverse association of n-3 fatty acids with CRP and IL-6 was not modified by demographics, body-mass index, smoking, LDL-cholesterol, or statin use (p values for interaction>0.1). CONCLUSIONS: In patients with stable coronary artery disease, an independent and inverse association exists between n-3 fatty acid levels and inflammatory biomarkers. These findings suggest that inhibition of systemic inflammation may be a mechanism by which n-3 fatty acids prevent recurrent cardiovascular events.

Fetuin-A and kidney function in persons with coronary artery disease--data from the Heart and Soul Study.

BACKGROUND: Fetuin-A is a serum protein that inhibits ectopic vascular calcification and is present in lower concentrations in end-stage renal disease than in healthy controls. Whether fetuin-A concentrations are also lower in the setting of mild-to-moderate chronic kidney disease (CKD) is unknown. METHODS: We evaluated the associations of several parameters of kidney function including measured 24 h urinary creatinine clearance (CrCl), estimated glomerular filtration rate (GFR) by the Mayo Clinic quadratic GFR equation (qGFR), serum cystatin-C concentrations, and urinary albumin-to-creatinine ratio with serum fetuin-A concentrations in 970 outpatients with coronary artery disease. We used general linear models to determine the adjusted mean fetuin-A concentrations within each kidney function category. RESULTS: The mean age of the study sample was 67 years, 82% were male, 71% had hypertension and 26% had diabetes mellitus. In adjusted analysis, we observed no significant differences in mean fetuin-A concentrations across groups defined by CrCl, qGFR, or albumin-to-creatinine ratio groups. For example, adjusted mean fetuin-A concentrations were 0.66 g/l in participants with CrCl > 90, 60-90 and 45-60 ml/min/1.73 m(2), and 0.65 g/l in participants with CrCl < 45 ml/min/1.73 m(2). Higher serum cystatin-C (indicating worse kidney function) was associated with higher adjusted mean serum fetuin-A concentrations (lowest quartile 0.62 g/l, highest quartile 0.68 g/l; P for trend <0.001). CONCLUSIONS: Among ambulatory patients with coronary artery disease, there is no evidence that mild-to-moderate CKD is associated with lower concentrations of serum fetuin-A compared with persons with normal renal function. The mechanisms explaining the association between CKD and vascular calcification remain elusive.