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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 > or =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. [ABSTRACT FROM AUTHOR]

Context: Transgenic animal experiments suggest that increased expression of transforming growth factor beta1 (TGF-beta1) is protective against early tumor development, particularly in breast cancer. A T-->C (thymine to cytosine) transition in the 29th nucleotide in the coding sequence results in a leucine to proline substitution at the 10th amino acid and is associated with increased serum levels of TGF-beta1.Objective: To determine whether an association exists between this TGF-beta1 polymorphism and breast cancer risk.Design, Setting, and Participants: The Study of Osteoporotic Fractures, a prospective cohort study of white, community-dwelling women aged 65 years or older who were recruited at 4 US centers between 1986 and 1988. Three thousand seventy-five women who provided sufficient clinical information, buffy coat samples, and adequate consent for genotyping are included in this analysis.Main Outcome Measure: Breast cancer cases during a mean (SD) follow-up of 9.3 (1.9) years, verified by medical chart review and compared by genotype.Results: Risk of breast cancer was similar in the 1124 women with the T/T genotype (56 cases; 5.4 per 1000 person-years) and the 1493 women with the T/C genotype (80 cases; 5.8 per 1000 person-years) but was significantly lower (P =.01) in the 458 women with the C/C genotype (10 cases; 2.3 per 1000 person-years). In analyses that adjusted for age, age at menarche, age at menopause, estrogen use, parity, body mass index, and bone mineral density, women with the C/C genotype had a significantly lower risk of developing breast cancer compared with women with the T/T or T/C genotype (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.17-0.75). There was no significant difference between the risk for women with the T/C genotype compared with women with the T/T genotype (adjusted HR, 1.04; 95% CI, 0.73-1.48).Conclusions: Our findings suggest that TGF-beta1 genotype is associated with risk of breast cancer in white women aged 65 years or older. Because the T allele is the common variant and confers an increased risk, it may be associated with a large proportion of breast cancer cases. [ABSTRACT FROM AUTHOR]

Context: Calcium deposits in coronary and extracoronary arterial beds may indicate the extent of atherosclerosis. However, the incremental predictive value of vascular calcification, beyond traditional coronary risk factors, is not clearly established.Objective: To evaluate risk factors for aortic arch calcification and its long-term association with cardiovascular diseases in a population-based sample.Design and Setting: Cohort study conducted at a health maintenance organization in northern California.Participants: A total of 60,393 women and 55,916 men, aged 30 to 89 years at baseline who attended multiphasic health checkups between 1964 and 1973 and for whom incidence of hospitalizations and/or mortality data were ascertained using discharge diagnosis codes and death records through December 31, 1997 (median follow-up, 28 years).Main Outcome Measure: Hospitalization for or death due to coronary heart disease, ischemic stroke, hemorrhagic stroke, or peripheral vascular disease, as associated with aortic arch calcification found on chest radiograph at checkup from 1964-1973.Results: Aortic arch calcification was present in 1.9% of men and 2.6% of women. It was independently associated with older age, no college education, current smoking, and hypertension in both sexes, but it was inversely related to body mass index and family history of myocardial infarction. In women, aortic arch calcification was also associated with black race and elevated serum cholesterol level. After adjustment for age, educational attainment, race/ethnicity, cigarette smoking, alcohol consumption, body mass index, serum cholesterol level, hypertension, diabetes, and family history of myocardial infarction, aortic arch calcification was associated with an increased risk of coronary heart disease (in men, relative risk [RR], 1.27; 95% confidence interval [CI], 1.11-1.45; in women, RR, 1. 22; 95% CI, 1.07-1.38). Among women, it was also independently associated with a 1.46-fold increased risk of ischemic stroke (95% CI, 1.28-1.67).Conclusion: In our population-based cohort, aortic arch calcification was independently related to coronary heart disease risk in both sexes as well as to ischemic stroke risk in women. JAMA. 2000;283:2810-2815 [ABSTRACT FROM AUTHOR]

Context: A patient's coronary heart disease (CHD) risk must be correctly classified to successfully apply risk-based guidelines for treatment of hypercholesterolemia.Objective: To determine the classification accuracy of the National Cholesterol Education Program (NCEP) CHD risk-stratification system and compare it with a simple revised system that gives greater weight to age as a CHD risk factor.Design: Modeling of 10-year CHD risk, using equations from the Framingham Heart Study applied to a cross-sectional survey of the US population.Subjects: The 3284 subjects aged 20 to 74 years surveyed in the Second National Health and Nutrition Examination Survey (1978-1982) who had fasting lipid levels measured.Main Outcome Measures: The area under the receiver operating characteristic curve (AUC) for 10-year CHD risk for the NCEP and revised scales.Results: Among all adults with a low-density lipoprotein cholesterol value of at least 4.1 mmol/L (160 mg/dL), the NCEP system showed fairly good discrimination (AUC=0.90), though there was a substantial decline among men 35 to 74 years old and women 55 to 74 years old (AUC=0.81). By contrast, the revised system showed superior performance in all hypercholesterolemic adults (AUC=0.94-0.97) as well as in the subgroup of men 35 to 74 years old and women 55 to 74 years old (AUC=0.94-0.96).Conclusions: Simple modifications of the NCEP treatment criteria result in a substantially improved ability to discriminate between higher and lower CHD risk groups. Unlike the NCEP system, this revised system retains its classification ability in all age groups studied. [ABSTRACT FROM AUTHOR]

Background: Vitamin K deficiency may be associated with osteoporosis.Objective: To assess the effects of warfarin on bone.Design: Prospective observational study.Setting: Four centers in the United States.Participants: 6201 elderly, postmenopausal women.Measurements: Self-reported warfarin use, bone mineral density at the hip and the heel, hip bone loss over 2 years, and fractures during 3.5 years of follow-up. Analyses were adjusted for baseline differences, age, weight, and estrogen use.Results: Compared with warfarin nonusers (n = 6052), warfarin users (n = 149) more frequently had poor health, involuntary weight loss, nonthiazide diuretic use, and frailty but had similar bone mineral density at the hip (difference, 1.6% [95% CI, -0.7% to 4.1%]) and heel (difference, 2.1% [CI, -1.6% to 5.6%]). Users and nonusers had similar rates of bone loss (1.1% and 0.8%; P = 0.18) and fractures (relative hazard, 1.0 [CI, 0.60 to 1.71).Conclusion: In this population, warfarin use did not decrease bone mineral density or increase fracture rates. [ABSTRACT FROM AUTHOR]

Objective: To assess the role of serum lipid levels as screening tests in adults.Design: Pooled analysis of clinical trials, supplemented by analysis of data from the Framingham Heart Study, to estimate the effect of cholesterol reduction in patient groups stratified by cardiac risk.Study Selection: Published randomized controlled trials of cholesterol reduction, meta-analyses of such trials, prospective cohort studies of the association between cholesterol levels and morbidity and death related to coronary heart disease, and cost-effectiveness analyses of cholesterol reduction.Data Analysis: Two-stage logistic regression on cardiac risk factors and outcomes in the Framingham Heart Study. The first stage predicted the risk for death from coronary heart disease using standard risk factors but not cholesterol; the second stage predicted the risk for death from coronary heart disease and all causes as functions of age and cholesterol level, stratified by the risk predicted from the first stage.Results: Randomized clinical trials show that cholesterol reduction confers survival benefits in patients with symptomatic coronary disease. In asymptomatic middle-aged men, who are at lower risk for death from coronary disease, cholesterol reduction prevents coronary disease but has not been shown to prolong life. The risk model based on analysis of the data from the Framingham Heart Study is consistent with the randomized trial data and shows that in the demographic groups excluded from trials, the hypothetical benefits of cholesterol reduction are greatest when the underlying risk for coronary disease is greatest.Conclusions: Screening with total cholesterol levels is most likely to be useful when done in populations at high short-term risk for dying of coronary heart disease, such as survivors of myocardial infarction and middle-aged men with multiple cardiac risk factors. In these populations, cholesterol reduction appears to be both effective and cost-effective. In other populations, the benefits of reduction are much smaller or are uncertain. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that bone mineral density (BMD) is associated with the risk of developing breast cancer in older women.Design: Prospective cohort study with mean (SD) follow-up of 3.2 (1.6) years.Setting: Four clinical centers, one each located in the following areas: Baltimore, Md; Minneapolis, Minn; Portland, Ore; and the Monongahela Valley in Pennsylvania.Participants: A total of 6854 nonblack women who were 65 years of age or older and enrolled in the Study of Osteoporotic Fractures.Measurements: Radius and calcaneus BMD by single photon absorptiometry at baseline; hip and spine BMD by dual-energy x-ray absorptiometry 2 years later.Main Outcome Measure: Breast cancer confirmed by medical record review.Results: A total of 97 women developed breast cancer. In the multivariate model, adjusting for age, the degree of obesity, and other important covariates, the risk of breast cancer was about 30% to 50% higher per 1 SD increase in BMD (relative risk, distal radius BMD=1.50; 95% confidence interval, 1.16-1.95). The age-adjusted incidence rate of breast cancer per 1000 person-years among women in the lowest quartile of distal radius BMD was 2.46, compared with 5.99 among women with the highest BMD. Women with BMD above the 25th percentile were at 2.0 to 2.5 times increased risk of breast cancer compared with women below the 25th percentile. Results were consistent across all BMD sites.Conclusions: Bone mineral density predicts the risk of breast cancer in older women. The magnitude of the association is similar to that observed between BMD and all fractures. Our findings suggest a link between 2 of the most common conditions affecting a woman's health. Identifying a common denominator for these conditions should substantially improve our understanding of their etiology and prevention. [ABSTRACT FROM AUTHOR]

Objective: To determine the incidence, predictors, and cost of atrial fibrillation and flutter (AFIB) following coronary artery bypass graft (CABG) surgery.Design: Prospective observational study (MultiCenter Study of Perioperative Ischemia).Setting: Twenty-four university-affiliated hospitals in the United States from 1991 to 1993.Subjects: A total of 2417 patients undergoing CABG with or without concurrent valvular surgery selected using a systematic sampling interval.Measurements: Detailed preoperative, intraoperative, and postoperative data collected on standardized reporting forms.Results: The overall incidence of postoperative AFIB was 27 percent. Independent predictors of postoperative AFIB included advanced age (odds ratio [OR], 1.24 per 5-year increase; 95 percent confidence interval [CI], 1.18-1.31); male sex (OR, 1.41; 95 percent CI, 1.09-1.81); a history of AFIB (OR, 2.28; 95 percent CI, 1.74-3.00); a history of congestive heart failure (OR, 1.31; 95 percent CI, 1.04-1.64); and a precardiopulmonary bypass heart rate of more than 100 beats per minute (OR, 1.59; 95 percent CI, 1.00-2.55). Surgical practices such as pulmonary vein venting (OR, 1.44; 95 percent CI, 1.13-1.83); bicaval venous cannulation (OR, 1.40; 95 percent CI, 1.04-1.89); postoperative atrial pacing (OR, 1.27; 95 percent CI, 1.00-1.62); and longer cross-clamp times (OR, 1.06 per 15 minutes; 95 percent CI, 1.00-1.11) also were identified as independent predictors of postoperative AFIB. Patients with postoperative AFIB remained an average of 13 hours longer in the intensive care unit and 2.0 days longer in the ward when compared with patients without AFIB.Conclusion: Postoperative AFIB is common after CABG surgery and has a significant effect on both intensive care unit and overall hospital length of stay. In addition to expected demographic factors, certain surgical practices increase the risk of postoperative AFIB. Randomized controlled trials are necessary to determine if modification of these surgical practices, especially in patients at high risk, would decrease the incidence of postoperative AFIB. [ABSTRACT FROM AUTHOR]

Focuses on a study from the University of California in San Francisco which reported that the regular intake of warfarin sodium (Coumadin, Panwarfin, Sofarin) does not decrease bone mass in older women or need special surveillance or treatment for osteoporosis. Reference to the study by S.A. Jamal, W.S. Browner and others in the May 1998 issue of the `Annals Internal Medicine' periodical; Measurement of bone mineral density; Treatment of fractures in the aged women.

Background: Red cell distribution width (RDW), an index for variation of red blood cell (RBC) size, has been proposed as a potential marker for poorer outcomes in several aging-related diseases and conditions. We tested whether greater variability of RBC size, presented as a higher RDW value, predicts poor prognoses among hospitalized patients over 60 years old., Methods: We retrospectively collected data from older hospitalized patients aged ≥60 years between January 2013 to December 2017 at Sutter Health, a large integrated health system in Northern California. The RDW was measured during hospital admission and categorized with 1% intervals (≤13.9, 14.0-14.9, 15.0-15.9, 16.0-16.9, 17.0-17.9 and ≥18.0%). The primary outcome was the rate of in-hospital mortality and secondary outcomes included 30-day re-admission rate and length of hospital stay (in days)., Results: A total of 167,292 admissions from 94,617 patients were included. The overall in-hospital mortality rate was 6.3%. As the RDW value increased, the rate of in-hospital mortality gradually increased from 2.7% for the lowest RDW category to 12.2% in the highest category (p-trend <0.001). The overall 30-day re-admission rate after discharge was 12.5% and the rate of 30-day re-admission also increased with increasing RDW categories (7.4% in the lowest group vs. 15.8% in the highest group, p-trend <0.001). Patients with the highest RDW values at admission stayed 1.5-2.0 times longer in the hospital than patients with lower RDW values who were admitted for the same causes., Conclusions: Greater variability of RBC size is significantly associated with worse prognosis in hospitalized elderly patients, indicating higher mortality, greater risk of early re-admission, and longer hospital stay days. Risk stratification strategies for hospitalized elderly should include RDW value., (© 2022 The American Geriatrics Society.)

Background: US hospitals have reported compliance with the SEP-1 quality measure to Medicare since 2015. Finding an association between compliance and outcomes is essential to gauge measure effectiveness., Research Question: What is the association between compliance with SEP-1 and 30-day mortality among Medicare beneficiaries?, Study Design and Methods: Studying patient-level data reported to Medicare by 3,241 hospitals from October 1, 2015, to March 31, 2017, we used propensity score matching and a hierarchical general linear model (HGLM) to estimate the treatment effects associated with compliance with SEP-1. Compliance was defined as completion of all qualifying SEP-1 elements including lactate measurements, blood culture collection, broad-spectrum antibiotic administration, 30 mL/kg crystalloid fluid administration, application of vasopressors, and patient reassessment. The primary outcome was a change in 30-day mortality. Secondary outcomes included changes in length of stay., Results: We completed two matches to evaluate population-level treatment effects. In standard match, 122,870 patients whose care was compliant were matched with the same number whose care was noncompliant. Compliance was associated with a reduction in 30-day mortality (21.81% vs 27.48%, respectively), yielding an absolute risk reduction (ARR) of 5.67% (95% CI, 5.33-6.00; P < .001). In stringent match, 107,016 patients whose care was compliant were matched with the same number whose care was noncompliant. Compliance was associated with a reduction in 30-day mortality (22.22% vs 26.28%, respectively), yielding an ARR of 4.06% (95% CI, 3.70-4.41; P < .001). At the subject level, our HGLM found compliance associated with lower 30-day risk-adjusted mortality (adjusted conditional OR, 0.829; 95% CI, 0.812-0.846; P < .001). Multiple elements correlated with lower mortality. Median length of stay was shorter among cases whose care was compliant (5 vs 6 days; interquartile range, 3-9 vs 4-10, respectively; P < .001)., Interpretation: Compliance with SEP-1 was associated with lower 30-day mortality. Rendering SEP-1 compliant care may reduce the incidence of avoidable deaths., (Copyright © 2021 American College of Chest Physicians. All rights reserved.)

Background: We tested whether greater variation in red blood cell size, measured by red cell distribution width (RDW), may predict aging-related degenerative conditions and therefore, serve as a marker of biological aging., Methods: Three thousand six hundred and thirty-five community-dwelling older men were enrolled in the prospective Osteoporotic Fractures in Men Study. RDW was categorized into 4 groups (≤13.0%, 13.1%-14.0%, 14.1%-15.0%, and ≥15.1%). Functional limitations, frailty, strength, physical performance, and cognitive function were measured at baseline and 7.4 years later. Falls were recorded in the year after baseline; hospitalizations were obtained for 2 years after baseline. Mortality was assessed during a mean of 8.3 years of follow-up., Results: Participants with greater variability in red cell size were weaker, walked more slowly, and had a worse cognitive function. They were more likely to have functional limitations (35.2% in the highest RDW category vs 16.0% in the lowest, p < .001) and frailty (30.3% vs 11.3%, p < .001). Those with greater variability in red cell size were more likely to develop new functional limitations and to become frail. The risk of having 2 or more falls was also greater (highest 19.2% vs lowest 10.3%, p < .001). The risk of hospitalization was higher in those with the highest variability (odds ratio [95% confidence interval], 1.8 [1.3-2.5]) compared with the lowest. Variability in red cell size was related to total and cause-specific mortality., Conclusion: Greater variability in red cell size is associated with diverse aging-related outcomes, suggesting that it may have potential value as a marker for biological aging., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Mitochondrial DNA (mtDNA) heteroplasmy is a mixture of normal and mutated mtDNA molecules in a cell. High levels of heteroplasmy at specific mtDNA sites lead to inherited mitochondrial diseases with neurological, sensory, and movement impairments. Here we test the hypothesis that heteroplasmy levels in elderly adults are associated with impaired function resembling mild forms of mitochondrial disease., Methods: We examined platelet mtDNA heteroplasmy at 20 disease-causing sites for associations with neurosensory and mobility function among 137 participants from the community-based Health, Aging, and Body Composition Study., Results: Elevated mtDNA heteroplasmy at four mtDNA sites in complex I and tRNA genes was nominally associated with reduced cognition, vision, hearing, and mobility: m.10158T>C with Modified Mini-Mental State Examination score (p = .009); m.11778G>A with contrast sensitivity (p = .02); m.7445A>G with high-frequency hearing (p = .047); and m.5703G>A with 400 m walking speed (p = .007)., Conclusions: These results indicate that increased mtDNA heteroplasmy at disease-causing sites is associated with neurosensory and mobility function in older persons. We propose the novel use of mtDNA heteroplasmy as a simple, noninvasive predictor of age-related neurologic, sensory, and movement impairments., (© The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Fractures have been associated with subsequent increases in mortality, but it is unknown how long that increase persists., Methods: A total of 5580 women from a large community-based, multicenter US prospective cohort of 9704 (Study of Osteoporotic Fractures) were observed prospectively for almost 20 years. We age-matched 1116 hip fracture cases with 4 control participants (n = 4464). To examine the effect of health status, we examined a healthy older subset (n = 960) 80 years or older who attended the 10-year follow-up examination and reported good or excellent health. Incident hip fractures were adjudicated from radiology reports by study physicians. Death was confirmed by death certificates., Results: Hip fracture cases had 2-fold increased mortality in the year after fracture compared with controls (16.9% vs 8.4%; multivariable adjusted odds ratio [OR], 2.4; 95% CI, 1.9-3.1]. When examined by age and health status, short-term mortality was increased in those aged 65 to 69 years (16.3% vs 3.7%; OR, 5.0; 95% CI, 2.6-9.5), 70 to 79 years (16.5% vs 8.9%; OR, 2.4; 95% CI, 1.8-3.3), and only in those 80 years or older with good or excellent health (15.1% vs 7.2%; multivariable adjusted OR, 2.8; 95% CI, 1.5-5.2). After the first year, survival of hip fracture cases and controls was similar except in those aged 65 to 69 years, who continued to have increased mortality., Conclusions: Short-term mortality is increased after hip fracture in women aged 65 to 79 years and in exceptionally healthy women 80 years or older. Women 70 years or older return to previous risk levels after a year. Interventions are needed to decrease mortality in the year after hip fracture, when mortality risk is highest.

The insulin/IGF1 signaling pathways affect lifespan in several model organisms, including worms, flies and mice. To investigate whether common genetic variation in this pathway influences lifespan in humans, we genotyped 291 common variants in 30 genes encoding proteins in the insulin/IGF1 signaling pathway in a cohort of elderly Caucasian women selected from the Study of Osteoporotic Fractures (SOF). The cohort included 293 long-lived cases (lifespan > or = 92 years (y), mean +/- standard deviation (SD) = 95.3 +/- 2.2y) and 603 average-lifespan controls (lifespan < or = 79y, mean = 75.7 +/- 2.6y). Variants were selected for genotyping using a haplotype-tagging approach. We found a modest excess of variants nominally associated with longevity. Nominally significant variants were then replicated in two additional Caucasian cohorts including both males and females: the Cardiovascular Health Study and Ashkenazi Jewish Centenarians. An intronic single nucleotide polymorphism in AKT1, rs3803304, was significantly associated with lifespan in a meta-analysis across the three cohorts (OR = 0.78 95%CI = 0.68-0.89, adjusted P = 0.043); two intronic single nucleotide polymorphisms in FOXO3A demonstrated a significant lifespan association among women only (rs1935949, OR = 1.35, 95%CI = 1.15-1.57, adjusted P = 0.0093). These results demonstrate that common variants in several genes in the insulin/IGF1 pathway are associated with human lifespan.

Background: It is uncertain whether evidence supports routinely estimating a postmenopausal woman's risk of breast cancer and intervening to reduce risk., Methods: We systematically reviewed prospective studies about models and sex hormone levels to assess breast cancer risk and used meta-analysis with random effects models to summarize the predictive accuracy of breast density. We also reviewed prospective studies of the effects of exercise, weight management, healthy diet, moderate alcohol consumption, and fruit and vegetable intake on breast cancer risk, and used random effects models for a meta-analyses of tamoxifen and raloxifene for primary prevention of breast cancer. All studies reviewed were published before June 2008, and all statistical tests were two-sided., Results: Risk models that are based on demographic characteristics and medical history had modest discriminatory accuracy for estimating breast cancer risk (c-statistics range = 0.58-0.63). Breast density was strongly associated with breast cancer (relative risk [RR] = 4.03, 95% confidence interval [CI] = 3.10 to 5.26, for Breast Imaging Reporting and Data System category IV vs category I; RR = 4.20, 95% CI = 3.61 to 4.89, for >75% vs <5% of dense area), and adding breast density to models improved discriminatory accuracy (c-statistics range = 0.63-0.66). Estradiol was also associated with breast cancer (RR range = 2.0-2.9, comparing the highest vs lowest quintile of estradiol, P < .01). Most studies found that exercise, weight reduction, low-fat diet, and reduced alcohol intake were associated with a decreased risk of breast cancer. Tamoxifen and raloxifene reduced the risk of estrogen receptor-positive invasive breast cancer and invasive breast cancer overall., Conclusions: Evidence from this study supports screening for breast cancer risk in all postmenopausal women by use of risk factors and breast density and considering chemoprevention for those found to be at high risk. Several lifestyle changes with the potential to prevent breast cancer should be recommended regardless of risk.

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.

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.

Objective: In an international, prospective, observational study, we contrasted adverse vascular outcomes among four countries and then assessed practice pattern differences that may have contributed to these outcomes., Methods: A total of 5065 patients undergoing coronary artery bypass graft surgery were analyzed at 70 international medical centers, and from this pool, 3180 patients from the 4 highest enrolling countries were selected. Fatal and nonfatal postoperative ischemic complications related to the heart, brain, kidney, and gastrointestinal tract were assessed by blinded investigators., Results: In-hospital mortality was 1.5% (9/619) in the United Kingdom, 2.0% (9/444) in Canada, 2.7% (34/1283) in the United States, and 3.8% (32/834) in Germany (P = .03). The rates of the composite outcome (morbidity and mortality) were 12% in the United Kingdom, 16% in Canada, 18% in the United States, and 24% in Germany (P < .001). After adjustment for difference in case-mix (using the European System for Cardiac Operative Risk Evaluation) and practice, country was not an independent predictor for mortality. However, there was an independent effect of country on composite outcome. The practices that were associated with adverse outcomes were the intraoperative use of aprotinin, intraoperative transfusion of fresh-frozen plasma or platelets, lack of use of early postoperative aspirin, and use of postoperative heparin., Conclusions: Significant between-country differences in perioperative outcome exist and appear to be related to hematologic practices, including administration of antifibrinolytics, fresh-frozen plasma, platelets, heparin, and aspirin. Understanding the mechanisms for these observations and selection of practices associated with improved outcomes may result in significant patient benefit.

Objectives: To determine whether older women with abdominal aortic calcification had a greater cardiovascular and all-cause mortality, as such data are limited in older adults., Design: Prospective cohort study with a mean follow-up of 13 years., Setting: Community-based sample with four US clinical centres., Subjects: A total of 2056 women aged > or =65 years with abdominal aortic calcification assessed on baseline radiographs., Main Outcome Measure: Mortality rate (all, cardiovascular, cancer or other cause) adjudicated from death certificates and hospital records., Results: The prevalence of abdominal aortic calcification increased with age, ranging from 60% at age 65-69 years to 96% at 85 years and older. Participants with aortic calcification were more likely to die during follow-up of any cause (47% vs. 27%) or a cardiovascular-specific cause (18% vs. 11%, both P < 0.001) than those without aortic calcification. In age-adjusted analyses, aortic calcification was associated with a greater rate of all-cause and cause-specific mortality (cardiovascular, cancer, and other, all P < or = 0.01). In analyses adjusted for age and cardiovascular risk factors, aortic calcification was associated with an increased rate of all-cause mortality (HR: 1.37, 95% CI: 1.15-1.64), and noncardiovascular noncancer mortality (HR: 1.57, 95% CI: 1.17-2.11). The associations between aortic calcification and cancer mortality (HR: 1.44, 95% CI: 1.00-2.08) or cardiovascular mortality (HR: 1.18, 95% CI: 0.88-1.57) showed a similar pattern without reaching statistical significance, but was slightly stronger for mortality from coronary heart disease (HR: 1.53, 95% CI: 0.91-2.56)., Conclusions: Abdominal aortic calcification in older women is associated with increased mortality. Future research should examine potential mechanisms for this association.