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Objective: Depressive symptoms are associated with an increased risk of cardiac events in patients with heart disease. Elevated catecholamine levels may contribute to this association, but whether depressive symptoms are associated with catecholamine levels in patients with heart disease is unknown., Method: The authors examined the association between depressive symptoms (defined by a Patient Health Questionnaire score > or =10) and 24-hour urinary norepinephrine, epinephrine, and dopamine excretion levels in 598 subjects with coronary disease., Results: A total of 106 participants (18%) had depressive symptoms. Participants with depressive symptoms had greater mean norepinephrine excretion levels than those without depressive symptoms (65 microg/day versus 59 mug/day, with adjustment for age, sex, body mass index, smoking, urinary creatinine levels, comorbid illnesses, medication use, and cardiac function). In logistic regression analyses, participants with depressive symptoms were more likely than those without depressive symptoms to have norepinephrine excretion levels in the highest quartile and above the normal range. Depressive symptoms were not associated with dopamine or epinephrine excretion levels., Conclusions: In patients with coronary disease, depressive symptoms are associated with elevated norepinephrine excretion levels. Future longitudinal studies are needed to determine whether elevations in norepinephrine contribute to adverse cardiac outcomes in patients with depressive symptoms.

Inflammatory response genes may influence life span or quality at advanced ages. Using data from the population-based cardiovascular health study (CHS) cohort, we examined the associations between promoter polymorphisms of several inflammation and thrombosis genes with longevity. We ascertained genotypes for interleukin (IL)-6 -174 G/C, beta-fibrinogen -455 G/A, plasminogen activator inhibitor (PAI)-1 -675 4G/5G, and thrombin-activatable fibrinolysis inhibitor (TAFI) -438 G/A in 2224 men and women > or = 65 years old at baseline. During 10 years of follow-up, men with the TAFI -438 A/A genotype had decreased mortality due to all causes, and lived, on average, 0.9 more years of life, or 1.1 more years of healthy life, than men with the -438 G allele. The effects of TAFI -438 G/A in women were smaller and not statistically significant. PAI-1 4G/4G genotype appeared to be associated with lower non-cardiovascular mortality in men, but with greater cardiovascular mortality in women. In exploratory analyses, we observed a possible interaction among anti-inflammatory drugs, interleukin-6 -174 C/C genotype, and longevity. These findings suggest that modulators of fibrinolytic activity may have a generalized influence on aging, and merit further investigation in studies of genetic determinants of human longevity.

Context: Depression is associated with low heart rate variability (HRV) in patients following myocardial infarction, suggesting that alterations in the autonomic nervous system may contribute to the adverse cardiac outcomes associated with depression. Whether depression is associated with low HRV in patients with stable coronary heart disease (CHD) is not known., Objective: To examine the association between major depression and 24-hour HRV in patients with stable CHD., Design, Setting, and Participants: Cross-sectional study of 873 outpatients with stable CHD recruited from outpatient clinics in the San Francisco Bay Area, California., Main Outcome Measures: Major depression was assessed using the Computerized National Institute of Mental Health Diagnostic Interview Schedule. Heart rate variability was measured by 24-hour ambulatory electrocardiography., Results: A total of 195 participants (22%) had major depression. Overall, we observed no association between depression and HRV as measured by time domain or frequency domain variables. Mean HRV was similar in participants with and without depression (all P values >.10), and participants with depression were no more likely than those without depression to have low HRV (all P values >.10)., Conclusions: We found no evidence of an association between depression and HRV in 873 outpatients with stable CHD. These findings raise questions about the potential role of HRV in the association between depression and cardiovascular disease.

Unlabelled: A role for osteoblastic beta-adrenoreceptors in bone regulation is suggested by the finding that beta-blockers increase bone mass in mice. We studied the association of beta-blocker use with BMD and fractures in the Study of Osteoporotic Fractures. beta-blocker use and BMD are unrelated in this cohort, and associations with fracture risk are inconsistent., Introduction: The central nervous system has been shown to regulate bone mass in mice, possibly by way of the beta(2)-adrenoreceptors on osteoblasts. beta-blockers have been shown to increase bone mass in mice. Because these agents are widely used therapeutically, it is possible that they may influence fracture epidemiology in humans, and they are a potential therapy for osteoporosis., Materials and Methods: We have studied the association of beta-blocker use with BMD and fracture rates in the Study of Osteoporotic Fractures. beta-blocker use was recorded at the fourth visit, in 8412 women, of whom 1099 were users, and these women were followed for 7 years., Results: Users had significantly higher weight, more thiazide use, more estrogen use, less glucocorticoid use, more statin use, and more hypertension than nonusers, and they smoked less. Total hip BMD at the fourth visit was higher in the beta-blocker users (0.746 versus 0.735 g/cm(2), p = 0.02), but adjustment for weight alone, or together with these other variables, eliminated this difference (p = 0.62). There was no effect of beta-blocker use on loss of hip BMD over a mean follow-up of 4 years (p = 0.48). Os calcis BMD at visit 4 was also higher in those taking beta-blockers (0.385 versus 0.375 g/cm(2), p = 0.005), but weight adjustment eliminated this difference (p = 0.14). The frequencies of hip or any fracture (since age 50) were similar in users and nonusers (p = 0.80 and p = 0.51, respectively). Over a mean follow-up of 7 years, there were 2167 total fractures, including 431 at the wrist and 585 at the hip. Among beta-blocker users, hazards ratios were 0.92 (0.81, 1.05) for any fracture, 0.74 (0.54, 1.01) for wrist fracture, and 0.76 (0.58, 0.99) for hip fracture. Adjustment for weight and other factors previously shown to influence hip fracture incidence in this cohort made little difference to the outcome. When fracture data were analyzed for nonselective and beta(1)-selective agents separately, trends toward fewer fractures were confined to the users of selective beta(1)-blockers., Conclusions: beta-Blocker use and BMD are unrelated in this cohort, and associations with fracture risk are inconsistent. Therefore, a history of use of these drugs is not useful in assessing fracture risk, nor do they have a role in osteoporosis management at this time. The relationship between beta-blocker use and hip fracture deserves further study.

Many of the genes that affect aging and longevity in model organisms, such as mice, fruit flies, and worms, have human homologs. This article reviews several genetic pathways that may extend lifespan through effects on aging, rather than through effects on diseases such as atherosclerosis or cancer. These include some of the genes involved in the regulation of DNA repair and nuclear structure, which cause the progeroid syndromes when mutated, as well as those that may affect telomere length, since shorter telomeres have been associated with shorter survival. Other potential longevity genes, such as sirtuins, are involved in regulating the response to cellular stress, including caloric restriction. The best-studied pathway involves insulin and insulin-like growth factor 1 signaling; mutations in homologs of these genes have extended lifespan up to sixfold in model organisms. Other potential candidates include mitochondrial DNA and the genes that regulate the inflammatory response. Despite the challenges in study design and analysis that face investigators in this area, the identification of genetic pathways that regulate longevity may suggest potential targets for therapy.

Background: The coronary artery calcium (CAC) score is an independent predictor of coronary heart disease. We sought to combine information from the CAC score with information from conventional cardiac risk factors to produce post-test risk estimates, and to determine whether the score may add clinically useful information., Methods: We measured the independent cross-sectional associations between conventional cardiac risk factors and the CAC score among asymptomatic persons referred for non-contrast electron beam computed tomography. Using the resulting multivariable models and published CAC score-specific relative risk estimates, we estimated post-test coronary heart disease risk in a number of different scenarios., Results: Among 9341 asymptomatic study participants (age 35-88 years, 40% female), we found that conventional coronary heart disease risk factors including age, male sex, self-reported hypertension, diabetes and high cholesterol were independent predictors of the CAC score, and we used the resulting multivariable models for predicting post-test risk in a variety of scenarios. Our models predicted, for example, that a 60-year-old non-smoking non-diabetic women with hypertension and high cholesterol would have a 47% chance of having a CAC score of zero, reducing her 10-year risk estimate from 15% (per Framingham) to 6-9%; if her score were over 100, however (a 17% chance), her risk estimate would be markedly higher (25-51% in 10 years). In low risk scenarios, the CAC score is very likely to be zero or low, and unlikely to change management., Conclusion: Combining information from the CAC score with information from conventional risk factors can change assessment of coronary heart disease risk to an extent that may be clinically important, especially when the pre-test 10-year risk estimate is intermediate. The attached spreadsheet makes these calculations easy.

Background: In patients with coronary heart disease (CHD), depression leads to worse cardiovascular outcomes. Depression has been associated with increased cortisol in medically healthy patients, suggesting that cortisol may act as a mediator in the pathway between depression and cardiovascular events. However, it is not known whether depression is associated with elevated cortisol levels in patients with CHD., Methods: We examined the association between depression (assessed by the Computerized Diagnostic Interview Schedule) and 24-hour urinary cortisol in 693 medical outpatients with known CHD., Results: Of 693 participants, 138 (20%) had current depression. Depressed participants had greater mean cortisol levels than those without depression (42 +/- 25 vs. 36 +/- 20 microg/day, p <.01). With each increasing quartile of cortisol concentration the frequency of depression increased (p <.01). Participants in the highest quartile of cortisol had a twofold increased odds of having depression, compared with those in the lowest quartile (odds ratio [OR] 2.1, 95% confidence interval [CR] 1.2-3.6, p =.01). This association remained strong after adjusting for potential confounding variables (OR 2.4, 95% CI 1.3-4.4, p <.01). In this cross-sectional analysis, elevated cortisol was not associated with worse cardiac function., Conclusions: In patients with CHD,depression is associated with elevated cortisol levels.

Unlabelled: In a large cohort of U.S. women aged 65 and older, we report the relationships of BMD measured at several sites, and subsequent fracture risk at multiple sites over > 8 years of follow-up. Although we found almost all fracture types to be related to low BMD, the overall proportion of fractures attributable to low BMD is modest., Introduction: Although several studies have reported the relationship between bone mineral density (BMD) and subsequent fracture risk, most have been limited by short follow-up time, BMD measures at only one or two sites, or availability of data for only select fracture types., Materials and Methods: In the multicenter Study of Osteoporotic Fractures (SOF), we studied the relationship of several different BMD measures to fracture risk of multiple types in 9704 non-black women aged 65 and older. We previously reported on the relationship of peripheral BMD measures to risk of several types of fracture during an average 2.2-year follow-up period. In this expanded analysis, we present results of the relationship of both peripheral and central BMD measures and fractures of multiple types during 10.4 and 8.5 years of follow-up, respectively. We also report population attributable risk (PAR) estimates for osteoporosis and risk of several types of fracture., Results: Our results show that almost all types of fractures have an increased incidence in women with low BMD. However, hip BMD is somewhat more strongly related to most of the fracture types studied than spine or peripheral BMD measures. Nonetheless, the proportion of fractures attributable to osteoporosis (based on a standard definition of osteoporosis) is modest, ranging from < 10% to 44% based on the most commonly used definition of osteoporosis (BMD T-score < -2.5)., Conclusion: Finding effective prevention strategies for fractures in older women will require additional interventions beside preventions for bone loss, such as prevention of falls and other fracture risk factors.

Background: Osteoporosis is associated with aortic calcification and cardiovascular mortality. However, whether skeletal fractures predict the risk of coronary events is unknown., Methods: We used Cox proportional hazards models to determine whether postmenopausal fracture was associated with the risk of coronary heart disease events among the 2763 postmenopausal women with known coronary disease enrolled in the Heart and Estrogen/progestin Replacement Study. Because fractures occurred before enrollment (in 615 women) and during follow-up (in 276 women), we treated incident fracture as a time-dependent covariate in our models., Results: During a mean follow-up of 4.1 years, 361 women had coronary heart disease events. The risk of these events was 25% lower in women who sustained fractures than in those without fractures (hazard ratio [HR] = 0.74; 95% confidence interval [CI]: 0.57 to 0.96; P = 0.02). This association was not confounded by physical activity or by factors associated with both fracture and coronary heart disease events (HR = 0.75; 95% CI: 0.57 to 0.98; P = 0.04)., Conclusion: Postmenopausal women with heart disease who had skeletal fractures had a reduced risk of subsequent coronary events. This unexpected association, if confirmed in future studies, could influence risk-related treatment strategies for cardiovascular disease.

Background: The dissemination of clinical practice guidelines often has not been accompanied by desired improvements in guideline adherence. This study evaluated interventions for implementing a new practice guideline advocating the use of beta-blockers for heart failure patients., Methods and Results: This was a randomized controlled trial involving heart failure patients (n=169) with an ejection fraction < or =45% and no contraindications to beta-blockers. Patients' primary providers were randomized in a stratified design to 1 of 3 interventions: (1) control: provider education; (2) provider and patient notification: computerized provider reminders and patient letters advocating beta-blockers; and (3) nurse facilitator: supervised nurse to initiate and titrate beta-blockers. The primary outcome, the proportion of patients who were initiated or uptitrated and maintained on beta-blockers, analyzed by intention to treat, was achieved in 67% (36 of 54) of patients in the nurse facilitator group compared with 16% (10 of 64) in the provider/patient notification and 27% (14 of 51) in the control groups (P<0.001 for the comparisons between the nurse facilitator group and both other groups). The proportion of patients on target beta-blocker doses at the study end (median follow-up, 12 months) was also highest in the nurse facilitator group (43%) compared with the control (10%) and provider/patient notification groups (2%) (P<0.001). There were no differences in adverse events among groups., Conclusions: The use of a nurse facilitator was a successful approach for implementing a beta-blocker guideline in heart failure patients. The use of provider education, clinical reminders, and patient education was of limited value in this setting.

Background: Patients with end-stage renal disease are known to have decreased survival after myocardial infarction, but the association of less severe renal dysfunction with survival after myocardial infarction is unknown., Objectives: To determine how patients with renal insufficiency are treated during hospitalization for myocardial infarction and to determine the association of renal insufficiency with survival after myocardial infarction., Design: Cohort study., Setting: All nongovernment hospitals in the United States., Patients: 130 099 elderly patients with myocardial infarction hospitalized between April 1994 and July 1995., Measurements: Patients were categorized according to initial serum creatinine level: no renal insufficiency (creatinine level < 1.5 mg/dL [<132 micromol/L]; n = 82 455), mild renal insufficiency (creatinine level, 1.5 to 2.4 mg/dL [132 to 212 micromol/L]; n = 36 756), or moderate renal insufficiency (creatinine level, 2.5 to 3.9 mg/dL [221 to 345 micromol/L]; n = 10 888). Vital status up to 1 year after discharge was obtained from Social Security records., Results: Compared with patients with no renal insufficiency, patients with moderate renal insufficiency were less likely to receive aspirin, beta-blockers, thrombolytic therapy, angiography, and angioplasty during hospitalization. One-year mortality was 24% in patients with no renal insufficiency, 46% in patients with mild renal insufficiency, and 66% in patients with moderate renal insufficiency (P < 0.001). After adjustment for patient and treatment characteristics, mild (hazard ratio, 1.68 [95% CI, 1.63 to 1.73]) and moderate (hazard ratio, 2.35 [CI, 2.26 to 2.45]) renal insufficiency were associated with substantially elevated risk for death during the first month of follow-up. This increased mortality risk continued until 6 months after myocardial infarction., Conclusions: Renal insufficiency was an independent risk factor for death in elderly patients after myocardial infarction. Targeted interventions may be needed to improve treatment for this high-risk population.

Objective: To determine the predictors of hospital length of stay (LOS) after elective uncomplicated coronary artery bypass graft surgery., Design: Retrospective analysis of the EPI-1 database, 1991-1993., Setting: Multicenter; 24 academic, private, federal, and health maintenance institutions., Participants: Patients undergoing elective CABG surgery (n = 2,417)., Measurements and Main Results: Using a systematic sampling scheme at each site, each patient was evaluated to identify markers of chronic disease, perioperative test data, treatments, adverse outcomes, and LOS. Institutional differences in the care of patients free of complications were assessed using a multivariate model. LOS was the outcome variable selected to estimate cost. A total of 861 patients (37%) were free of any complication. The mean site LOS ranged from 5.4 to 9.0 days, with half of the 24 centers reporting a hospital LOS routinely >7.1 days. The predominant factor associated with a complication-free LOS was site per se, accounting for 32% of the variability in hospital LOS that could not be explained by any site characteristic (eg, size, geographic location, academic affiliation). Multivariable analysis identified 3 demographic predictors--age >75 years (increasing LOS by 1.3 days), admission from the emergency department (increasing LOS by 0.7 days), and uninsured or Medicaid-insured (increasing LOS by 0.4 days); 2 historical predictors--New York Heart Association class III or IV congestive heart failure (increasing LOS by 0.5 days) and history of arrhythmia (increasing LOS by 0.7 days); and 2 practice patterns--transfusion of blood products (increasing LOS by 0.3 days) and delayed extubation (increasing LOS by 0.5 days). Previous myocardial infarction, diabetes, chronic obstructive pulmonary disease, neurologic disease, and other historical factors were not associated with LOS in patients without a complication., Conclusion: A substantial variability in LOS after complication-free coronary artery bypass graft surgery was determined predominantly by site per se, even after adjustment for disease severity, site type or location, and surgical and anesthetic practices. The variability in LOS was likely due to practice style influences and represents an opportunity to decrease waste in the provision of a common and expensive procedure., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

There is substantial interest in the early identification of women at risk for osteoporotic fractures, so that preventive measures may be instituted early. We examined whether women with a history of fractures before menopause were at an increased risk of fractures after menopause. We obtained information about any lifetime fractures of the hip, arm, spine, wrist, leg, ankle, foot and finger from 9086 ambulatory white women ages 65 years and older participating in the Study of Osteoporotic Fractures. We also measured bone mineral density and recorded history of falls, maternal fracture history, drug use, diet, functional status, and other characteristics commonly associated with osteoporotic fractures. We used proportional hazards models to estimate the effects of fractures that occurred before menopause on the risk of fractures after menopause, in particular those that occurred during the 12 years of study follow-up. The risk of fractures of all types during the study period was greater among women with a premenopausal fracture of any type compared with women without a premenopausal fracture (hazard ratio (HR), 1.33; 95% confidence interval (CI), 1.14-1.56; p<0.001). Adjustment for possible confounders, including bone mineral density, had only a modest effect (HR, 1.25; 95% CI, 1.03-1.50; p<0.02). An increased risk of fracture among women with a premenopausal fracture was also seen after stratification by estrogen use, propensity to fall and maternal fracture history. Premenopausal fractures are therefore a risk factor for subsequent fractures independent of other risk factors for osteoporotic fractures, such as bone mineral density. A fracture history, including fractures before menopause, should be obtained when making decisions about preventive treatments.

Background and Purpose: An elevated serum level of C-reactive protein, an inflammatory marker, is an independent predictor of stroke and coronary artery disease. To determine whether chronic infection with Chlamydia pneumoniae, which has been identified in atherosclerotic plaques, is responsible for systemic inflammation, we studied the association between serum C-reactive protein levels and infection of carotid artery atherosclerotic plaque with viable C pneumoniae., Methods: Serum C-reactive protein levels were obtained before endarterectomy for carotid artery stenosis. Plaques were tested for C pneumoniae mRNA, an indicator of viability, and DNA by polymerase chain reaction of DNA and cDNA, respectively., Results: Forty-eight samples were studied, of which 18 (38%; 95% CI, 23 to 50) were infected with viable C pneumoniae as evidenced by isolated chlamydial mRNA. All 18 of these samples, plus 1 additional sample, were positive for chlamydial DNA. Serum C-reactive protein levels were higher in those with viable C pneumoniae compared with those without infection (median, 8 mg/L versus undetectable; P=0.045 by Wilcoxon rank-sum test). In multivariable models, the only independent predictor of the presence of viable C pneumoniae was a detectable C-reactive protein level (odds ratio, 4.2; 95% CI, 1.1 to 17; P=0.04)., Conclusions: Viable C pneumoniae are present in a substantial portion of carotid artery atherosclerotic plaques and are associated with increased serum C-reactive protein levels. These findings may explain the link between elevated C-reactive protein levels and the risk of cardiovascular disease and stroke but should be reproduced in a larger cohort.

Objective: To describe patterns of physical activity and to determine factors associated with engaging in regular exercise, especially walking, in elderly white women., Design: Cross-sectional study of 9,442 independently living elderly white women aged 65 years and over participating in the Study of Osteoporotic Fractures., Measurements and Main Results: We studied the association between lifestyle habits, social factors, health status and self-reported physical activity (assessed by modified Paffenbarger scale) during the past twelve months. Walking was the most common form of exercise: 4,837 (51%) women reported doing so a mean of 12 (SD = 10) blocks per day, 3.9 (SD = 2.9) times per week. Other common activities were gardening (35%), swimming (16%), and bicycling (13%). Less than a third of women reported engaging in medium- or high-intensity exercise in the past year. In a multivariate age-adjusted analysis, factors independently (P < .01) associated with walking for exercise included greater than high school education (52% vs 48%), history of physical activity for exercise at ages 30 years (51% vs 46%) and 50 years (51% vs 45%), and stronger social network (51% vs 47%). Women who were current smokers, obese, or depressed were less likely to take walks for exercise. Marital status, self-reported arthritis, current estrogen use, and a history of falls in the past year were not independently associated with taking walks for exercise., Conclusions: In this healthy cohort, walking for exercise is associated with other positive health behaviors. Given the mounting evidence about the health benefits of walking, and since many of these community dwelling women can and do walk for exercise, but rarely engage in other common prescribed physical activities, clinicians might best focus their efforts on encouraging walking.

Purpose: Angiotensin converting-enzyme (ACE) inhibitors decrease mortality after myocardial infarction among patients with depressed left ventricular function. Beta blockers may also improve survival in these patients. We compared the relative effects of these agents on the survival of elderly patients with a left ventricular ejection fraction less than 40% after myocardial infarction., Subjects and Methods: The Cooperative Cardiovascular Project collected data on patients aged 65 years and older who were admitted with myocardial infarction from April 1994 to July 1995, including 20,902 with a measured left ventricular ejection fraction less than 40% before discharge. Using proportional hazard regression models that adjusted for patient characteristics and in-hospital treatments, we compared survival among patients discharged on ACE inhibitors, beta blockers, both medications, or neither medication., Results: Among patients surviving hospitalization with reduced left ventricular function, 9,108 (44%) were discharged on ACE inhibitors, 2,613 (13%) on beta blockers, 3,309 (16%) on both medications, and 5,872 (28%) on neither medication. Patients treated with ACE inhibitors were more likely to have a prior diagnosis of heart failure and less likely to have undergone revascularization, whereas those treated with beta blockers were more often treated with thrombolytic therapy and aspirin. Patients treated with ACE inhibitors [hazard ratio (HR = 0.80), 0.80; 95% confidence interval (CI), 0.73 to 0.87] or beta blockers (HR = 0.76, 0.76; 95% CI, 0.64 to 0.90) had lower adjusted 1-year mortality than those who were not treated with either medication. The combination of both medications was associated with additional benefit (HR = 0.68, 0.68; 95% CI, 0.59 to 0.80). The relative benefit of each medication was greatest among patients with an ejection fraction less than 30%, a serum creatinine level 2.0 mg/dL or greater, or both. To prevent a death within a year, the number of patients who needed to be treated with both medications varied from 5 to 15, depending on ejection fraction and renal function., Conclusion: ACE inhibitors and beta blockers were associated with similar improvements in survival among elderly patients with reduced left ventricular ejection fraction after myocardial infarction. Our results suggest that patients who can tolerate both medications gain additional benefit from the combination.

Osteoprotegerin (OPG) and its ligand are cytokines that regulate osteoclastogenesis and that may be involved in the regulation of vascular calcification. We examined whether serum OPG levels were associated with stroke, mortality, and cardiovascular risk factors, including diabetes, as well as with bone mineral density and fractures in a sample of 490 participants in a prospective cohort of white women, at least 65 yr of age. We found that OPG levels, assayed blinded from serum obtained at baseline, were about 30% greater in women with diabetes (mean +/- SD, 0.30 +/- 0.17 ng/mL) than in those without diabetes (0.23 +/- 0.10 ng/mL; P = 0.0001). OPG levels were associated with all-cause mortality [age-adjusted odds ratio, 1.4/SD (0.11 ng/mL) increase in serum OPG level; 95% confidence interval, 1.2--1.8] and cardiovascular mortality (odds ratio, 1.4; 95% confidence interval, 1.1--1.8); these effects were not confounded by diabetes. OPG levels were not associated with baseline bone mineral density or with subsequent strokes or fractures. The association of serum OPG levels with diabetes and with cardiovascular mortality raises the possibility that OPG may be a cause of or a marker for vascular calcification.

Context: Racial disparities in health care delivery and outcomes may be due to differences in health care access and, therefore, may be mitigated in an equal-access health care system. Few studies have examined racial differences in health outcomes in such a system., Objective: To study racial differences in mortality among patients admitted to hospitals in the Veterans Affairs (VA) system, a health care system that potentially offers equal access to care., Design, Setting, and Participants: Cohort study of 28 934 white and 7575 black men admitted to 147 VA hospitals for 1 of 6 common medical diagnoses (pneumonia, angina, congestive heart failure, chronic obstructive pulmonary disease, diabetes, and chronic renal failure) between October 1, 1995, and September 30, 1996., Main Outcome Measures: The primary outcome measure was 30-day mortality among black compared with white patients. Secondary outcome measures were in-hospital mortality and 6-month mortality., Results: Overall mortality at 30 days was 4.5% in black patients and 5.8% in white patients (relative risk [RR], 0.77; 95% confidence interval [CI], 0.69-0.87; P =.001). Mortality was lower among blacks for each of the 6 medical diagnoses. Multivariate adjustment for patient and hospital characteristics had a small effect (RR, 0.75; 95% CI, 0.66-0.85; P<.001). Black patients also had lower adjusted in-hospital and 6-month mortality. These findings were consistent among all subgroups evaluated., Conclusions: Black patients admitted to VA hospitals with common medical diagnoses have lower mortality rates than white patients. The survival advantage of black patients is not readily explained; however, the absence of a survival disadvantage for blacks may reflect the benefits of equal access to health care and the quality of inpatient treatment at VA medical centers.

Context: Management of patients with acute transient ischemic attack (TIA) varies widely, with some institutions admitting all patients and others proceeding with outpatient evaluations. Defining the short-term prognosis and risk factors for stroke after TIA may provide guidance in determining which patients need rapid evaluation., Objective: To determine the short-term risk of stroke and other adverse events after emergency department (ED) diagnosis of TIA., Design and Setting: Cohort study conducted from March 1997 through February 1998 in 16 hospitals in a health maintenance organization in northern California. Patients A total of 1707 patients (mean age, 72 years) identified by ED physicians as having presented with TIA., Main Outcome Measures: Risk of stroke during the 90 days after index TIA; other events, including death, recurrent TIA, and hospitalization for cardiovascular events., Results: During the 90 days after index TIA, 180 patients (10.5%) returned to the ED with a stroke, 91 of which occurred in the first 2 days. Five factors were independently associated with stroke: age greater than 60 years (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.1-2.7; P=.01), diabetes mellitus (OR, 2.0; 95% CI, 1.4-2.9; P<.001), symptom duration longer than 10 minutes (OR, 2.3; 95% CI, 1.3-4.2; P=.005), weakness (OR, 1.9; 95% CI, 1.4-2.6; P<.001), and speech impairment (OR, 1.5; 95% CI, 1.1-2.1; P=.01). Stroke or other adverse events occurred in 428 patients (25.1%) in the 90 days after the TIA and included 44 hospitalizations for cardiovascular events (2.6%), 45 deaths (2.6%), and 216 recurrent TIAs (12.7%)., Conclusions: Our results indicate that the short-term risk of stroke and other adverse events among patients who present to an ED with a TIA is substantial. Characteristics of the patient and the TIA may be useful for identifying patients who may benefit from expeditious evaluation and treatment.

Older women with low bone density have an increased risk of fracture, cardiovascular disease, and mortality. However, it is not known whether this association is caused by ongoing bone loss or by lower bone mass earlier in life. To determine whether rate of bone loss is associated with total and cause-specific mortality, we prospectively studied 6046 women aged 65 years or older who had serial bone mineral density (BMD) measurements as a part of the Study of Osteoporotic Fractures. Rates (mean +/- SD) of loss of BMD at the heel (for a mean of 5.7 years) and hip (for a mean of 3.5 years) were estimated. Cause-specific mortality was ascertained from death certificates and hospital records. BMD loss at the heel was 5.9 +/- 6.0 mg/cm2 per year (1.5 +/- 1.5%) and BMD loss at the hip was 4.1 +/- 10.2 mg/cm2 per year (0.6 +/- 1.4%). During an average follow-up of 3.2 years after the second measurement of BMD, 371 deaths occurred. Each SD increase in BMD loss at the hip was associated with a 1.3-fold (95% CI, 1.1-1.4) increase in total mortality, adjusted for age, baseline BMD, diabetes, hypertension, incident fractures, smoking, physical activity, health status, weight loss, and calcium use. In particular, hip BMD loss was associated with increased mortality from coronary heart disease (relative hazard [RH] = 1.3 per SD; 95% CI, 1.0-1.8) and pulmonary diseases (RH = 1.6 per SD; 95% CI, 1.1-2.5). The findings were similar for bone loss at the heel, except there was no significant association with pulmonary mortality. These results raise the possibility that bone loss may share common etiologies with coronary and pulmonary diseases.

Context: Angiotensin-converting enzyme (ACE) inhibitors have been shown to decrease mortality in patients with myocardial infarction and depressed left ventricular function, but physicians may be reluctant to prescribe ACE inhibitors to patients with concomitant renal insufficiency., Objective: To evaluate whether patients with depressed left ventricular ejection fraction following acute myocardial infarction have a similar reduction in mortality from ACE inhibitors regardless of their renal function., Design: Retrospective cohort study using medical record data., Setting: All nonfederal acute care hospitals., Patients: A cohort of 20,902 Medicare beneficiaries aged 65 years and older directly admitted to the hospital from February 1, 1994, through July 30, 1995, and with a documented left ventricular ejection fraction of less than 40% measured by echocardiography, radionuclide scintigraphy, or angiography following a confirmed acute myocardial infarction., Main Outcome Measures: One-year survival for patients who received or who did not receive an ACE inhibitor at hospital discharge, stratified by the patient's level of renal function., Results: For the entire cohort, the receipt of an ACE inhibitor on hospital discharge was associated with greater 1-year survival (hazards ratio, 0.84; 95% confidence interval, 0.77-0.91) after adjusting for patient demographic characteristics, comorbidity, severity of illness (including left ventricular ejection fraction), and the receipt of other therapies. In stratified models, the receipt of an ACE inhibitor was associated with a 37% (16%-52%) lower mortality for patients who had poor renal function (serum creatinine level,<265 micromol/L [<3 mg/dL]) and a 16% (8%-23%) lower mortality for patients who had better renal function. Use of aspirin therapy attenuated the benefit of ACE inhibitors in patients with poor renal function., Conclusions: Moderate renal insufficiency should not be considered a contraindication to the use of ACE inhibitors in patients with depressed left ventricular ejection fraction following myocardial infarction. Use of aspirin therapy may attenuate the benefit of ACE inhibitors in patients with high serum creatinine levels; therefore, further studies are needed to determine whether treatment with aspirin, alternative antiplatelet agents, or anticoagulation is indicated for these patients.

Purpose: To review the cause, pathophysiologic characteristics, cost, and treatment of alcohol-induced hangover., Data Sources: A MEDLINE search of English-language reports (1966 to 1999) and a manual search of bibliographies of relevant papers., Study Selection: Related experimental, clinical, and basic research studies., Data Extraction: Data in relevant articles were reviewed, and relevant clinical information was extracted., Data Synthesis: The alcohol hangover is characterized by headache, tremulousness, nausea, diarrhea, and fatigue combined with decreased occupational, cognitive, or visual-spatial skill performance. In the United States, related absenteeism and poor job performance cost $148 billion annually (average annual cost per working adult, $2000). Although hangover is associated with alcoholism, most of its cost is incurred by the light-to-moderate drinker. Patients with hangover may pose substantial risk to themselves and others despite having a normal blood alcohol level. Hangover may also be an independent risk factor for cardiac death. Symptoms of hangover seem to be caused by dehydration, hormonal alterations, dysregulated cytokine pathways, and toxic effects of alcohol. Physiologic characteristics include increased cardiac work with normal peripheral resistance, diffuse slowing on electroencephalography, and increased levels of antidiuretic hormone. Effective interventions include rehydration, prostaglandin inhibitors, and vitamin B6. Screening for hangover severity and frequency may help early detection of alcohol dependency and substantially improve quality of life. Recommended interventions include discussion of potential therapies and reminders of the possibility for cognitive and visual-spatial impairment. No evidence suggests that alleviation of hangover symptoms leads to further alcohol consumption, and the discomfort caused by such symptoms may do so. Therefore, treatment seems warranted., Conclusions: Hangover, a common disorder, has substantial morbidity and societal cost. Appropriate management may relieve symptoms in many patients.

In patients with left bundle branch block (LBBB) and acute chest pain, the association between the clinical presentation and the diagnosis of myocardial infarction has not been investigated. We sought to identify features in the clinical history of patients with LBBB and acute cardiopulmonary symptoms that predict myocardial infarction among candidates for reperfusion therapy. We retrospectively studied a consecutive cohort of 75 patients (94 presentations) who presented to a university emergency department from 1994 to 1997 with LBBB on initial electrocardiogram (ECG) and acute chest pain of >/=20 min duration or acute pulmonary edema. Among the 94 presentations meeting criteria for the cohort, 26 (28%) had confirmed myocardial infarction. Coronary heart disease risk factors, past cardiac history, prior LBBB on the ECG, and presenting symptoms did not predict whether patients were having myocardial infarction. The clinical history was not effective at distinguishing LBBB patients with myocardial infarction among patients who appeared to be candidates for acute reperfusion therapy., (Copyright 2000 S. Karger AG, Basel)

Background: Studies to determine whether care by cardiologists improves the survival of patients with acute myocardial infarction (MI) have produced conflicting results, and it is not known what accounts for differences in patient outcome by physician specialty., Objectives: To evaluate whether cardiologists provide more recommended therapies to elderly patients with acute MI and, if so, to determine whether variations in processes of care account for differences in patient outcome., Design: Retrospective cohort study using medical chart data and administrative data files., Setting: All nonfederal acute care hospitals in California., Patients: A cohort of 7663 Medicare beneficiaries 65 years and older directly admitted to the hospital with a confirmed acute MI from April 1994 to July 1995 with complete data regarding potential contraindications to recommended therapies., Main Outcome Measures: Percentage of "good" and "ideal" candidates for a given acute MI therapy who actually received that therapy, percentage who received exercise stress testing or coronary angiography, percentage who underwent revascularization, and 1-year mortality, stratified by specialty of the attending physician., Results: During hospitalization, good candidates for aspirin were more likely to receive aspirin if they were treated by cardiologists (87%) than by medical subspecialists (73%; P<.001), general internists (84%; P = .003), or family practitioners (81%; P<.001). Cardiologists were also more likely to treat good candidates with thrombolytic therapy (51%) than were medical subspecialists (29%; P<.001), general internists (40%; P<.001), or family practitioners (27%; P<.001). Patients of cardiologists were 2- to 4-fold more likely to undergo a revascularization procedure. Despite these differences in utilization, we found similar 30-day mortality rates across physician specialties. However, 1-year mortality rates were greater for patients treated by medical subspecialists (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.6-2.3), general internists (OR, 1.4; 95% CI, 1.3-1.6), and family practitioners (OR, 1.7; 95% CI, 1.4-1.9) than for those treated by cardiologists. Adjusting for differences in patient and hospital characteristics markedly reduced the ORs for those treated by medical subspecialists (OR, 1.2; 95% CI, 0.9-1.4), general internists (OR, 1.1; 95% CI, 1.0-1.3), and family practitioners (OR, 1.3; 95% CI, 1.1-1.6), whereas further adjustment for medication use and revascularization procedures had little effect., Conclusions: Differences in the use of recommended therapies by physician specialty are generally small and do not explain differences in patient outcome. In comparison, differences among patients treated by physicians of various specialties (case mix) have a large impact on patient outcome and may account for the residual survival advantage of patients treated by cardiologists. With the exception of the in-hospital use of aspirin, recommended MI therapies are markedly underused, regardless of the specialty of the physician.

Background: Osteoporotic fractures, including clinically detected vertebral fractures, are associated with increased mortality. However, only one third of vertebral fractures are diagnosed. It is unknown whether vertebral fractures, whether clinically apparent or not, are associated with greater mortality., Objectives: To test the hypothesis that women with prevalent vertebral fractures have greater mortality than those without fractures and to describe causes of death associated with vertebral fractures., Design: Prospective cohort study with mean follow-up of 8.3 years., Setting: Four clinical centers in the United States., Participants: A total of 9575 women aged 65 years or older and enrolled in the Study of Osteoporotic Fractures., Measurements: Vertebral fractures by radiographic morphometry; calcaneal bone mineral density; demographic, medical history, and lifestyle variables; blood pressure; and anthropometric measures. In a subset of 606 participants, thoracic curvature was measured during a second clinic visit., Main Outcome Measures: Hazard ratios for mortality and cause-specific mortality., Results: At baseline, 1915 women (20.0%) were diagnosed as having vertebral fractures. Compared with women who did not have a vertebral fracture, women with 1 or more fractures had a 1.23-fold greater age-adjusted mortality rate (95% confidence interval, 1.10-1.37). Mortality rose with greater numbers of vertebral fractures, from 19 per 1000 woman-years in women with no fractures to 44 per 1000 woman-years in those with 5 or more fractures (P for trend, <.001). In particular, vertebral fractures were related to the risk of subsequent cancer (hazard ratio, 1.4;95% confidence interval, 1.1-1.7) and pulmonary death (hazard ratio, 2.1;95% confidence interval, 1.4-3.0). In the subset of women who underwent thoracic curvature measurements, severe kyphosis was also related to pulmonary deaths (hazard ratio, 2.6;95% confidence interval, 1.3-5.1)., Conclusion: Women with radiographic evidence of vertebral fractures have an increased mortality rate, particularly from pulmonary disease and cancer.

Background: The association between depressive disorders and subsequent cognitive decline is controversial. We tested the hypothesis that elderly women (aged 65 years and older) without dementia but with depressive symptoms have worse cognitive function and greater cognitive decline than women with few or no symptoms., Methods: As part of an ongoing prospective study, we evaluated 5781 elderly, mostly white, community-dwelling women. Women completed the Geriatric Depression Scale short form. Three cognitive tests--Trails B, Digit Symbol, and a modified Mini-Mental State Examination--were administered at baseline and approximately 4 years later. Baseline, follow-up, and change scores for the cognitive tests were analyzed by analysis of covariance and Kruskal-Wallis analysis; the odds of cognitive deterioration (> or =3-point decline on the modified Mini-Mental State Examination) were determined by logistic regression., Results: At baseline, 211 (3.6%) of the women had 6 or more depressive symptoms. Only 16 (7.6%) of these women were receiving antidepressant medication. Increasing symptoms of depression were associated with worse performance at baseline and follow-up on all 3 tests of cognitive function (P<.001 for all comparisons). For example, the baseline Digit Symbol score (mean +/- SD) was 45.5 +/- 10.7 among women with 0 to 2 symptoms of depression, 40.3 +/- 10.7 for women with 3 to 5 symptoms, and 39.0 +/- 11.3 for women with 6 or more symptoms. After adjusting for the baseline score, cognitive change scores were also inversely associated with the number of depressive symptoms (P<.001 for all comparisons). Odds ratios for cognitive deterioration using 0 to 2 symptoms as the reference were 1.6 (95% confidence interval, 1.3-2.1) for 3 to 5 symptoms and 2.3 (95% confidence interval, 1.6-3.3) for 6 or more symptoms. Results were similar after being adjusted for education, age, health status, exercise, alcohol use, functional status, and clinic site., Conclusions: Depressive symptoms in older women are associated with both poor cognitive function and subsequent cognitive decline. Mechanisms underlying the association between these 2 common conditions need further exploration.

Serum fructosamine levels can be used to estimate long-term serum glucose values and can be measured in frozen serum. The authors examined whether fructosamine levels were associated with mortality in a cohort of 9,704 white women (> or = 65 years of age) recruited from September 1986 to October 1988 at four clinical centers in the United States. A random sample of women who had died during a mean of 6 years of follow-up (n = 55) was compared with randomly selected controls (n = 276, 54 of whom had died). Fructosamine assays were performed blinded to vital status. Hazard ratios with 95% confidence intervals were adjusted for age, clinical center, smoking, hypertension, and serum albumin and cholesterol levels. Each standard deviation (46 micromol) increase in fructosamine level was associated with a 1.3-fold (95% confidence interval (CI) 1.0-1.6, p = 0.04) increased rate of all-cause mortality, including a 1.5-fold (95% CI 1.0-2.1, p = 0.03) increase in cardiovascular disease mortality. Elevated fructosamine levels (>285 micromol/liter) were associated with a 4.3-fold (95% CI 1.6-12, p = 0.004) increased rate of cardiovascular mortality; in women without a history of diabetes, the hazard ratio was 4.6 (95% CI 1.3-16, p = 0.02). Fructosamine level, or another indicator of glycemia, should be included when the risk of cardiovascular disease among older patients is evaluated.

Context: Recently, an algorithm based on the electrocardiogram (ECG) was reported to predict myocardial infarction (MI) in patients with left bundle-branch block (LBBB), but the clinical impact of this testing strategy is unknown., Objective: To determine the diagnostic test characteristics and clinical utility of this ECG algorithm for patients with suspected MI., Design: Retrospective cohort study to which an algorithm was applied, followed by decision analysis regarding thrombolysis made with or without the algorithm., Setting: University emergency department, 1994 through 1997., Patients: Eighty-three patients with LBBB who presented 103 times with symptoms suggestive of MI., Main Outcome Measures: Myocardial infarction determined by serial cardiac enzyme analyses and stroke-free survival., Results: Of 9 ECG findings assessed, none effectively distinguished the 30% of patients with MI from those with other diagnoses. The ECG algorithm indicated positive findings in only 3% of presentations and had a sensitivity of 10% (95% confidence interval, 2%-26%). The decision analysis showed that among 1000 patients with LBBB and chest pain, 929 would survive without major stroke if all received thrombolysis compared with 918 if the ECG algorithm was used as a screening test., Conclusions: The ECG is a poor predictor of MI in a community-based cohort of patients with LBBB and acute cardiopulmonary symptoms. Acute thrombolytic therapy should be considered for all patients with LBBB who have symptoms consistent with MI.

Purpose: While a high serum fructosamine level may be an indicator of undiagnosed diabetes, a low level may be indicative of poor nutrition or frailty. As malnutrition is a risk factor for osteoporosis, low serum fructosamine levels may be associated with an increased risk of osteoporotic fracture. We examined the association between serum fructosamine levels and the risk of subsequent hip and vertebral fracture., Subjects and Methods: We performed a case-cohort study within the Study of Osteoporotic Fractures. Subjects were elderly, ambulatory, community-dwelling, Caucasian, women. Fructosamine levels were measured in baseline serum. Incident vertebral fractures were identified by comparing baseline spinal radiographs to those obtained an average of 3.5 years later. Hip fractures were confirmed by radiograph. We randomly selected 101 women who suffered a hip fracture, 100 women who developed a vertebral fracture, and 276 controls. We compared fructosamine levels in women with subsequent osteoporotic fractures to controls. All analyses were adjusted for age, weight, and use of estrogens., Results: Women with fructosamine levels in the lowest decile (< or = 223 micromol/L) had a three-fold increase in the risk of hip fracture (95% confidence interval 1.4-6.4), compared with all other women. Adjustment for markers of frailty, including smoking, functional status, and serum albumin levels, reduced the strength of this association. No clear association was observed between serum fructosamine level and the risk of vertebral fracture., Conclusion: Low serum fructosamine levels, which likely reflect frailty or malnutrition, may be a useful clinical tool to identify women at risk for hip fracture.

Nitric oxide slows bone remodeling and bone loss in animals. Because nitroglycerin and other nitrates increase nitric oxide levels, we hypothesized that nitrate use may be associated with greater bone mineral density (BMD) and decreased risk of fracture in humans. Further, intermittent nitrate use may be associated with greater benefits than daily nitrate use, which results in tachyphylaxis. We tested this hypothesis using data from the Study of Osteoporotic Fractures. We prospectively studied 6201 elderly women of whom 317 took nitrates on a daily basis and 74 used them intermittently. We measured BMD at the hip and the heel and adjusted all comparisons for multiple potential confounders. We found that women taking daily nitrates had slightly greater hip BMD (difference, 13%; 95% confidence interval [CI], 0.14-4.1%) but the same heel BMD (difference, 0%; 95% CI -2.6-2.6%) as nonusers. By contrast, women using nitrates intermittently had substantially greater hip (difference, 2.6%; 95% CI, 0.4-6.8%) and heel BMD (difference, 53%; 95% CI, 2.6-11%) than nonusers. This study suggests that the intermittent administration of nitrates may enhance BMD.

To examine the relation between serum fatty acids and cancer, the authors conducted a nested case-control study of 108 middle-aged men who died of cancer and 215 men without cancer, who were enrolled in the Multiple Risk Factor Intervention Trial (MRFIT) between 1973 and 1976. Control subjects were matched to case subjects on age, smoking status, treatment assignment, date of randomization, and clinical center. After confirming the stability of the stored serum samples, the authors measured serum fatty acid levels by gas-liquid chromatography and analyzed their association with cancer. In stepwise logistic regression analyses that controlled for the MRFIT selection criteria variables and for alcohol consumption, no fatty acid was significantly associated with overall risk of cancer death (all p > 0.05). Serum levels of phospholipid dihomogammalinolenic acid (20:3), an essential fatty acid, were inversely associated with the risk of dying from lung cancer; a standard deviation increase was associated with a 32% decrease in risk (p = 0.05). Dietary cholesterol intake was associated with the risk of nonlung, non-digestive tract cancers; a standard deviation increase (331 mg/day) was associated with a 75% increase in risk (p = 0.02). The authors found no evidence to suggest that increased dietary intake or serum levels of polyunsaturated fatty acids were associated with an increased risk of fatal cancer among middle-aged men at high risk for coronary heart disease. The clinical significance of the inverse association between dihomogammalinolenic acid and lung cancer death is uncertain and requires confirmation.

Objective: To examine the effects of resident and attending physician gender on the evaluation of residents in an internal medicine training program., Design: Cross-sectional study., Setting: Large urban academic internal medicine residency program., Participants: During their first 2 years of training, 132 residents (85 men, 47 women) received a total of 974 evaluations from 255 attending physicians (203 men, 52 women) from 1989 to 1995., Measurements: The primary measurements were the numerical portions of the American Board of Internal Medicine evaluation form. Separate analyses were performed for each of the nine evaluation dimensions graded on a scale of 1 to 9. The primary outcome was the difference in the average scores received by each resident from male versus female attending physicians., Results: Compared with female trainees, male residents received significantly higher scores from male attending physicians than from female attending physicians in six of the nine dimensions: clinical judgment, history, procedures, relationships, medical care, and overall. Similar trends, not reaching conventional levels of statistical significance, were observed in the other three categories: medical knowledge, physical exam, and attitude. These differences ranged from 0.24 to 0.60 points, and were primarily due to higher grading of male residents by male attending physicians than by female attending physicians., Conclusions: In one academic training program, we found a significant interaction in the grading process between the gender of internal medicine residents and the gender of their attending evaluators. This study raises the possibility that subtle aspects of gender bias may exist in medical training programs.

Purpose: To determine if thyroid hormone deficiency, manifested by elevated serum thyrotropin (TSH), is associated with alterations in serum lipids in an unselected population of older women., Subjects and Methods: Population-based sampling of 279 ambulatory white women over age 65 studied at four US clinical centers, randomly selected from a cohort of 9,704 participants enrolled in the Study of Osteoporotic Fractures. A third-generation chemiluminescent TSH assay and serum lipid levels--total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides--were measured on fasting sera collected at the baseline visit. The cross-sectional relationships between TSH and lipid levels were analyzed., Results: TSH was high (>5.5 mU/L) in 19 women (6.8%), and was low (< or =0.1 mU/L) in 10 (3.6%). After multiple adjustment, LDL-C was 17 mg/dL or 13% higher (95% confidence interval [CI] 1%, 25%), and HDL-C was 6.5 mg/dL or 12% lower (CI -0.2%, -25%) in women with high TSH compared with those with normal TSH. The ratio of LDL-C to HDL-C was 29% greater (CI 4%, 53%) among women with elevated TSH. Although total cholesterol was 8% higher among women with high TSH, this difference was not statistically significant (CI -1%, 15%). High TSH was found in 12% of the women with the combination of high cholesterol (>240 mg/dL), high LDL-C (>160 mg/dL), and low HDL-C (<45 mg/dL); likelihood ratio = 1.8) whereas high TSH was found in only 2.2% of women with normal lipids (likelihood ratio = 0.3)., Conclusion: Among older white women, high TSH is associated with deleterious changes in serum lipids, particularly HDL-C, LDL-C, and the ratio of LDL-C to HDL-C cholesterol. Women with multiple lipid abnormalities are twice as likely to have an increased TSH.

To examine the relation between serum ascorbic acid level and the prevalence of cardiovascular disease, we analyzed data from 6,624 U.S. men and women enrolled in the Second National Health and Nutrition Examination Survey. We calculated odds ratios and 95% confidence intervals to estimate the relative prevalence of cardiovascular disease, defined as self-reported coronary heart disease or stroke, or a diagnosis of peripheral vascular disease based on physical examination. Serum ascorbic acid levels were independently associated with prevalence of coronary heart disease and stroke; a 0.5-mg per dl increase in serum ascorbic acid level was associated with an 11% reduction in coronary heart disease and stroke prevalence. We also analyzed the relation of ascorbic acid, grouped into low to marginal, normal, and saturation serum categories, to cardiovascular disease. Compared with participants with low to marginally low serum ascorbic acid levels, we found a 27% decreased prevalence of coronary heart disease (95% confidence interval = 10-41%) and a 26% decreased prevalence of stroke (95% confidence interval = 3-44%) among participants in the highest serum ascorbic acid category. Serum ascorbic acid levels were not consistently associated with prevalence of peripheral vascular disease. These results are consistent with the hypothesis that increased ascorbic acid intake may decrease the risk of coronary heart disease and stroke.

Objective: Although posttraumatic stress disorder (PTSD) is a highly prevalent and often chronic condition, the relationship between PTSD and functioning and quality of life remains incompletely understood., Method: The authors undertook an archival analysis of data from the National Vietnam Veterans Readjustment Study. The study subjects consisted of the nationally representative sample of male Vietnam veterans who participated in the National Vietnam Veterans Readjustment Study. The authors estimated PTSD at the time of the interview with the Mississippi Scale for Combat-Related Posttraumatic Stress Disorder. They examined the following outcomes: diminished well-being, physical limitations, bed day in the past 2 weeks, compromised physical health status, currently not working, and perpetration of violence. Logistic models were used to determine the association between PTSD and outcome; adjustment was made for demographic characteristics and comorbid psychiatric and other medical conditions., Results: The risks of poorer outcome were significantly higher in subjects with PTSD than in subjects without PTSD in five of the six domains. For the outcome domains of physical limitations, not working, compromised physical health, and diminished well-being, these significantly higher risks persisted even in the most conservative logistic models that removed the shared effects of comorbid psychiatric and other medical disorders., Conclusions: The suffering associated with combat related-PTSD extends beyond the signs and symptoms of the disorder to broader areas of functional and social morbidity. The significantly higher risk of impaired functioning and diminished quality of life uniquely attributable to PTSD suggests that PTSD may well be the core problem in this group of difficult to treat and multiply afflicted patients.

Objective: This investigation assessed whether current post-traumatic stress disorder (PTSD) was associated with impaired functioning in a nationally representative sample of female Vietnam veterans., Methods: Logistic models were used to determine the association between PTSD and outcome while adjusting for demographic characteristics and medical and psychiatric co-morbidities., Results: PTSD was associated with significantly elevated odds of poorer functioning in five of the six outcome domains; only the association between perpetration of violence in the past year and PTSD did not achieve statistical significance. After adjusting for demographics and medical and psychiatric co-morbidities, PTSD remained associated with significantly elevated odds of bed days, poorer physical health, and currently not working., Conclusions: Among female Vietnam veterans PTSD is associated with a broad profile of functional impairment. The significantly increased odds of impaired functioning and diminished quality of life suggest that PTSD may be the core problem of the set of problems afflicting female Vietnam veterans.

Background: Smoking is associated with lower body weight, but an increased risk of diabetes in some studies. Because smoking may increase waist-to-hip ratio (WHR), a risk factor for diabetes, we postulated that the relation between smoking and diabetes may be mediated in part by smoking-associated differences in body fat distribution., Methods: We conducted a cross-sectional analysis of baseline data from 9,435 elderly nonblack women enrolled in the Study of Osteoporotic Fractures. Data were collected by Self-report and physical examination. Linear and logistic models were used to determine the relation of smoking to WHR and prevalence of self-reported diabetes., Results: Current and past smokers had greater WHRs compared with never smokers. In multivariate models that adjusted for body mass index, the prevalence of diabetes was lower among smokers of < or = 10 cigarettes/day [odds ratio (OR) = 0.57, 95% confidence interval (CI) 0.31-1.03] and higher among smokers of > 10 cigarettes/day (OR = 1.38, 95% CI 0.99-1.92) compared with never smokers. The relation of smoking > 10 cigarettes/day to prevalence of diabetes was slightly attenuated after further adjustment for WHR., Conclusions: Smoking-associated differences in WHR may mediate, at least in part, the prevalence of diabetes among smokers of > 10 cigarettes/day. The decreased prevalence of diabetes that we observed among smokers of < or = 10 cigarettes/day was not explained by differences in obesity and requires confirmation.

Objective: To determine the validity of a two-question case-finding instrument for depression as compared with six previously validated instruments., Design: The test characteristics of a two-question case-finding instrument that asks about depressed mood and anhedonia were compared with six common case-finding instruments, using the Quick Diagnostic Interview Schedule as a criterion standard for the diagnosis of major depression., Setting: Urgent care clinic at the San Francisco Department of Veterans Affairs Medical Center., Participants: Five hundred thirty-six consecutive adult patients without mania or schizophrenia., Measurements and Main Results: Measurements were two questions from the Primary Care Evaluation of Mental Disorders patient questionnaire, both the long and short forms of the Center for Epidemiologic Studies Depression Scale, both the long and short forms of the Book Depression Inventory, the Symptom-Driven Diagnostic System for Primary Care, the Medical Outcomes Study depression measure, and the Quick Diagnostic Interview Schedule. The prevalence of depression, as determined by the standardized interview, was 18% (97 of 536). Overall, the case-finding instruments had sensitivities of 89% to 96% and specificities of 51% to 72% for diagnosing major depression. A positive response to the two-item instrument had a sensitivity of 96% (95% confidence interval [CI], 90-99%) and a specificity of 57% (95% CI 53-62%). Areas under the receiver operating characteristic curves were similar for all of the instruments, with a range of 0.82 to 0.89., Conclusions: The two-question case-finding instrument is a useful measure for detecting depression in primary care. It has similar test characteristics to other case-finding instruments and is less time-consuming.