Seattle Epidemiologic Information and Research Center

We derived and tested a short form of the Center for Epidemio-logic Studies Depression Scale (CES-D) for reliability and validity among a sample of well older adults in a large Health Maintenance Organization. The 10-item screening questionnaire, the CESD-10, showed good predictive accuracy when compared to the full-length 20-item version of the CES-D (x = .97, P < .001). Cutoff scores for depressive symptoms were ≥16 for the full-length questionnaire and ≥10 for the 10-item version. We discuss other potential cutoff values. The CESD-10 showed an expected positive correlation with poorer health status scores (r = .37) and a strong negative correlation with positive affect (r = —.63). Retest correlations for the CESD-10 were comparable to those in other studies (r = .71). We administered the CESD-10 again after 12 months, and scores were stable with strong correlation of r — .59.

OBJECTIVE: We conducted a prospective study among Japanese Americans of diabetes incidence in relation to visceral and regional adiposity, fasting insulin and C-peptide, and a measure of insulin secretion, because little prospective data exist on these associations. RESEARCH DESIGN AND METHODS: Baseline variables included plasma glucose, C-peptide, and insulin measured after an overnight fast and 30 and 120 min after a 75-g oral glucose tolerance test; abdominal, thoracic, and thigh fat areas by computed tomography (CT); BMI (kg/m2); and insulin secretion (incremental insulin response [IIR]). RESULTS: Study subjects included 290 second-generation (nisei) and 230 third-generation (sansei) Japanese Americans without diabetes, of whom 65 and 13, respectively, developed diabetes. Among nisei, significant predictors of diabetes risk for a 1 SD increase in continuous variables included intra-abdominal fat area (IAFA) (odds ratio, 95% CI) (1.6, 1.1-2.3), fasting plasma C-peptide (1.4, 1.1-1.8), and the IIR (0.5, 0.3-0.9) after adjusting for age, sex, impaired glucose tolerance, family diabetes history, and CT-measured fat areas other than intra-abdominal. Intra-abdominal fat area remained a significant predictor of diabetes incidence even after adjustment for BMI, total body fat area, and subcutaneous fat area, although no measure of regional or total adiposity was related to development of diabetes. Among sansei, all adiposity measures were related to diabetes incidence, but, in adjusted models, only IAFA remained significantly associated with higher risk (2.7, 1.4-5.4, BMI-adjusted). CONCLUSIONS: Greater visceral adiposity precedes the development of type 2 diabetes in Japanese Americans and demonstrates an effect independent of fasting insulin, insulin secretion, glycemia, total and regional adiposity, and family history of diabetes.

In older adults, measurements of physical performance assess physical function and associate with mortality and disability. Muscle wasting and diminished physical performance often accompany CKD, resembling physiologic aging, but whether physical performance associates with clinical outcome in CKD is unknown. We evaluated 385 ambulatory, stroke-free participants with stage 2-4 CKD enrolled in clinic-based cohorts at the University of Washington and University of Maryland and Veterans Affairs Maryland Healthcare systems. We compared handgrip strength, usual gait speed, timed up and go (TUAG), and 6-minute walking distance with normative values and constructed Cox proportional hazards models and receiver operating characteristic curves to test associations with all-cause mortality. Mean age was 61 years and the mean estimated GFR was 41 ml/min per 1.73 m(2). Measures of lower extremity performance were at least 30% lower than predicted, but handgrip strength was relatively preserved. Fifty deaths occurred during the median 3-year follow-up period. After adjustment, each 0.1-m/s decrement in gait speed associated with a 26% higher risk for death, and each 1-second longer TUAG associated with an 8% higher risk for death. On the basis of the receiver operating characteristic analysis, gait speed and TUAG more strongly predicted 3-year mortality than kidney function or commonly measured serum biomarkers. Adding gait speed to a model that included estimated GFR significantly improved the prediction of 3-year mortality. In summary, impaired physical performance of the lower extremities is common in CKD and strongly associates with all-cause mortality.

CONTEXT: Low testosterone levels in men have been associated with increased mortality. However, the influence of testosterone treatment on mortality in men with low testosterone levels is not known. OBJECTIVE: The objective of the study was to examine the association between testosterone treatment and mortality in men with low testosterone levels. DESIGN: This was an observational study of mortality in testosterone-treated compared with untreated men, assessed with time-varying, adjusted Cox proportional hazards regression models. Effect modification by age, diabetes, and coronary heart disease was tested a priori. SETTING: The study was conducted with a clinical database that included seven Northwest Veterans Affairs medical centers. PATIENTS: Patients included a cohort of 1031 male veterans, aged older than 40 yr, with low total testosterone [≤250 ng/dl (8.7 nmol/liter)] and no history of prostate cancer, assessed between January 2001 and December 2002 and followed up through the end of 2005. MAIN OUTCOME MEASURE: Total mortality in testosterone-treated compared with untreated men was measured. RESULTS: Testosterone treatment was initiated in 398 men (39%) during routine clinical care. The mortality in testosterone-treated men was 10.3% compared with 20.7% in untreated men (P<0.0001) with a mortality rate of 3.4 deaths per 100 person-years for testosterone-treated men and 5.7 deaths per 100 person-years in men not treated with testosterone. After multivariable adjustment including age, body mass index, testosterone level, medical morbidity, diabetes, and coronary heart disease, testosterone treatment was associated with decreased risk of death (hazard ratio 0.61; 95% confidence interval 0.42-0.88; P = 0.008). No significant effect modification was found by age, diabetes, or coronary heart disease. CONCLUSIONS: In an observational cohort of men with low testosterone levels, testosterone treatment was associated with decreased mortality compared with no testosterone treatment. These results should be interpreted cautiously because residual confounding may still be a source of bias. Large, randomized clinical trials are needed to better characterize the health effects of testosterone treatment in older men with low testosterone levels.

BACKGROUND: Most previous attempts to determine the psychological cost of military deployment have been limited by reliance on convenience samples, lack of pre-deployment data or confidentiality and cross-sectional designs. AIMS: This study addressed these limitations using a population-based, prospective cohort of U.S. military personnel deployed in support of the operations in Iraq and Afghanistan. METHOD: The sample consisted of U.S. military service members in all branches including active duty, reserve and national guard who deployed once (n = 3393) or multiple times (n = 4394). Self-reported symptoms of post-traumatic stress were obtained prior to deployment and at two follow-ups spaced 3 years apart. Data were examined for longitudinal trajectories using latent growth mixture modelling. RESULTS: Each analysis revealed remarkably similar post-traumatic stress trajectories across time. The most common pattern was low-stable post-traumatic stress or resilience (83.1% single deployers, 84.9% multiple deployers), moderate-improving (8.0%, 8.5%), then worsening-chronic post-traumatic stress (6.7%, 4.5%), high-stable (2.2% single deployers only) and high-improving (2.2% multiple deployers only). Covariates associated with each trajectory were identified. CONCLUSIONS: The final models exhibited similar types of trajectories for single and multiple deployers; most notably, the stable trajectory of low post-traumatic stress preto post-deployment, or resilience, was exceptionally high. Several factors predicting trajectories were identified, which we hope will assist in future research aimed at decreasing the risk of post-traumatic stress disorder among deployers.

IMPORTANCE: Beginning in 2005, the incidence of suicide deaths in the US military began to sharply increase. Unique stressors, such as combat deployments, have been assumed to underlie the increasing incidence. Previous military suicide studies, however, have relied on case series and cross-sectional investigations and have not linked data during service with postservice periods. OBJECTIVE: To prospectively identify and quantify risk factors associated with suicide in current and former US military personnel including demographic, military, mental health, behavioral, and deployment characteristics. DESIGN, SETTING, AND PARTICIPANTS: Prospective longitudinal study with accrual and assessment of participants in 2001, 2004, and 2007. Questionnaire data were linked with the National Death Index and the Department of Defense Medical Mortality Registry through December 31, 2008. Participants were current and former US military personnel from all service branches, including active and Reserve/National Guard, who were included in the Millennium Cohort Study (N = 151,560). MAIN OUTCOMES AND MEASURES: Death by suicide captured by the National Death Index and the Department of Defense Medical Mortality Registry. RESULTS: Through the end of 2008, findings were 83 suicides in 707,493 person-years of follow-up (11.73/100,000 person-years [95% CI, 9.21-14.26]). In Cox models adjusted for age and sex, factors significantly associated with increased risk of suicide included male sex, depression, manic-depressive disorder, heavy or binge drinking, and alcohol-related problems. None of the deployment-related factors (combat experience, cumulative days deployed, or number of deployments) were associated with increased suicide risk in any of the models. In multivariable Cox models, individuals with increased risk for suicide were men (hazard ratio [HR], 2.14; 95% CI, 1.17-3.92; P = .01; attributable risk [AR], 3.5 cases/10,000 persons), and those with depression (HR, 1.96; 95% CI, 1.05-3.64; P = .03; AR, 6.9/10,000 persons), manic-depressive disorder (HR, 4.35; 95% CI, 1.56-12.09; P = .005; AR, 35.6/10,000 persons), or alcohol-related problems (HR, 2.56; 95% CI, 1.56-4.18; P <.001; AR, 7.7/10,000 persons). A nested, matched case-control analysis using 20:1 control participants per case confirmed these findings. CONCLUSIONS AND RELEVANCE: In this sample of current and former military personnel observed July 1, 2001-December 31, 2008, suicide risk was independently associated with male sex and mental disorders but not with military-specific variables. These findings may inform approaches to mitigating suicide risk in this population.

AIMS: While most patients with myocardial infarction (MI) have underlying coronary atherosclerosis, not all patients with coronary artery disease (CAD) develop MI. We sought to address the hypothesis that some of the genetic factors which establish atherosclerosis may be distinct from those that predispose to vulnerable plaques and thrombus formation. METHODS AND RESULTS: We carried out a genome-wide association study for MI in the UK Biobank (n∼472 000), followed by a meta-analysis with summary statistics from the CARDIoGRAMplusC4D Consortium (n∼167 000). Multiple independent replication analyses and functional approaches were used to prioritize loci and evaluate positional candidate genes. Eight novel regions were identified for MI at the genome wide significance level, of which effect sizes at six loci were more robust for MI than for CAD without the presence of MI. Confirmatory evidence for association of a locus on chromosome 1p21.3 harbouring choline-like transporter 3 (SLC44A3) with MI in the context of CAD, but not with coronary atherosclerosis itself, was obtained in Biobank Japan (n∼165 000) and 16 independent angiography-based cohorts (n∼27 000). Follow-up analyses did not reveal association of the SLC44A3 locus with CAD risk factors, biomarkers of coagulation, other thrombotic diseases, or plasma levels of a broad array of metabolites, including choline, trimethylamine N-oxide, and betaine. However, aortic expression of SLC44A3 was increased in carriers of the MI risk allele at chromosome 1p21.3, increased in ischaemic (vs. non-diseased) coronary arteries, up-regulated in human aortic endothelial cells treated with interleukin-1β (vs. vehicle), and associated with smooth muscle cell migration in vitro. CONCLUSIONS: A large-scale analysis comprising ∼831 000 subjects revealed novel genetic determinants of MI and implicated SLC44A3 in the pathophysiology of vulnerable plaques.

OBJECTIVES: The effect of national exercise recommendations on adiposity is unknown and may differ by sex. We examined long-term effects of aerobic exercise on adiposity in women and men. RESEARCH METHODS AND PROCEDURES: This was a 12-month randomized, controlled clinical trial testing exercise effect on weight and body composition in men (N = 102) and women (N = 100). Sedentary/unfit persons, 40 to 75 years old, were recruited through physician practices and media. The intervention was facility- and home-based moderate-to-vigorous intensity aerobic activity, 60 min/d, 6 days/wk vs. controls (no intervention). RESULTS: Exercisers exercised a mean 370 min/wk (men) and 295 min/wk (women), and seven dropped the intervention. Exercisers lost weight (women, -1.4 vs. +0.7 kg in controls, p = 0.008; men, -1.8 vs. -0.1 kg in controls, p = 0.03), BMI (women, -0.6 vs. +0.3 kg/m(2) in controls, p = 0.006; men, -0.5 kg/m(2) vs. no change in controls, p = 0.03), waist circumference (women, -1.4 vs. +2.2 cm in controls, p < 0.001; men, -3.3 vs. -0.4 cm in controls, p = 0.003), and total fat mass (women, -1.9 vs. +0.2 kg in controls, p = 0.001; men, -3.0 vs. +0.2 kg in controls, p < 0.001). Exercisers with greater increases in pedometer-measured steps per day had greater decreases in weight, BMI, body fat, and intra-abdominal fat (all p trend < 0.05 in both men and women). Similar trends were observed for increased minutes per day of exercise and for increases in maximal oxygen consumption. DISCUSSION: These data support the U.S. Department of Agriculture and Institute of Medicine guidelines of 60 min/d of moderate-to-vigorous physical activity.

OBJECTIVE: To examine whether the presence of diabetes alters the risk of acute urinary tract infection (UTI) in postmenopausal women. RESEARCH DESIGN AND METHODS: A case-control study of the Group Health Cooperative of Puget Sound (GHC), a staff-model nonprofit health maintenance organization in Washington State, was conducted. Subjects were women aged 55-75 years who had been members of GHC for at least 1 year and who had had an acute symptomatic UTI within the preceding month. Laboratory files were used to identify women with a urine culture that grew > or =10(5) colonies of a urinary pathogen. Medical records were reviewed to confirm the presence of acute, clinically symptomatic UTI. Control subjects were randomly selected from the GHC enrollment file, screened to remove women with recent UTI, and frequency matched to cases by age within 2 years. An interviewer ascertained self-reported clinician-diagnosed diabetes. Diagnosis of diabetes was confirmed by the GHC diabetes registry. A subsample of women underwent measurement of postvoid residual bladder volume (n = 748) and culture of vaginal flora (n = 454). RESULTS: Of the 901 case and 913 control subjects, diabetes was reported in 13.1 and 6.8%, respectively. The health plan diabetes registry confirmed the diagnosis in 92% of women who self-reported the condition. The age-adjusted odds ratio (OR) for UTI in relation to self-reported clinician-diagnosed diabetes was 2.2 (95% CI 1.6-3.0). Adjustment for frequency of sexual intercourse and history of UTI had little effect on this estimate. Compared with nondiabetic women, higher UTI odds were seen in subjects who used oral hypoglycemic agents (OR 2.9 [95% CI 1.7-5.1]) and insulin (2.6 [1.5-4.6]) but not in subjects with untreated diabetes or diabetes treated by lifestyle changes (1.3 [0.7-2.3]). No significant difference was seen in the OR for UTI in diabetic women with disease of shorter duration (<10 years, OR 1.9) or longer duration (> or =10 years, OR 2.6) or in relation to HbA(1c) level. Similar microbiologic pathogens were seen in diabetic and nondiabetic women. No significant differences were seen by diabetes status in mean postvoid residual bladder volume or vaginal flora. CONCLUSIONS: Diabetes under pharmacologic treatment is associated with increased risk of clinically apparent UTI in postmenopausal women.

This study examines the association of individual and familial risk factors with exposure to trauma and posttraumatic stress disorder (PTSD) in male twins (N = 6744) from the Vietnam Era Twin Registry. Independent reports of familial psychopathology from co-twins were used to avoid the potential biases of the family history method. Risk for exposure to traumatic events was increased by service in Southeast Asia, preexisting conduct disorder, preexisting substance dependence, and a family history of mood disorders whose effects appear to be partly genetic. Preexisting mood disorders in the individual were associated with decreased odds of traumatic exposure. Risk of developing PTSD following exposure was increased by an earlier age at first trauma, exposure to multiple traumas, paternal depression, less than high school education at entry into the military, service in Southeast Asia, and preexisting conduct disorder, panic disorder or generalized anxiety disorder, and major depression. Results suggest the association of familial psychopathology and PTSD may be mediated by increased risk of traumatic exposure and by preexisting psychopathology.

Most clinicians currently in practice did not receive the evidence-based communication skills training they need to provide high-quality communication for seriously ill older adults and their families. Clinician communication skills are a critical factor in achieving a patient and family understanding of their illness that enables them to share in decision making that will result in medical treatments and social supports that are aligned with their goals and values. Research demonstrates that existing clinician competence in communication skills is extremely variable, that most clinicians need specific communication training to have an adequate level of skill, and that evidence-based training is efficacious. A conservative estimate suggests that more than 219,000 physicians and advance practice providers (APPs) (50% of physicians in high-contact subspecialties and 25% of all APPs) could benefit from training. Combining evidence-based clinician training with health system workflow redesign would likely maximize the impact of this training. We conclude with recommendations designed to address gaps in communication skills through effective training and health system changes in the service of enabling all patients with serious illness and their families to receive care aligned with their personal priorities. J Am Geriatr Soc 67:S435-S441, 2019.

STUDY OBJECTIVES: To better understand the relationships of insomnia, sleepiness, and obesity. DESIGN: Classic twin study. SETTING: A community-based twin registry in Washington State. PATIENTS OR PARTICIPANTS: One thousand forty-two monozygotic and 828 dizygotic twin pairs participating in the University of Washington Twin Registry. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Twins were, on average, 32 years old; 61% were women, and 19.5% were obese, defined as a body mass index > or = 28. Insomnia and sleepiness were endorsed by 19.3% and 3.7% of twins, respectively. Twin correlations were higher in monozygotic than dizygotic twins for insomnia (0.47 versus 0.15), sleepiness (0.37 versus 0.14), and obesity (0.82 versus 0.46). Heritability estimates were 57% for insomnia (p < .001; 95% confidence interval 47-63), 38% for sleepiness (p < .01; 95% confidence interval 16-46), and 73% for obesity (p < .001; 95% confidence interval 49-87). Multivariate genetic model fitting revealed that common additive genetic effects comprised 12.8% of the phenotypic correlation between insomnia and sleepiness (p < .01) and 10% of the phenotypic correlation between insomnia and obesity (p < .01). The phenotypic correlation between sleepiness and obesity was not due to common additive genetic effects. CONCLUSIONS: Insomnia, sleepiness, and obesity are under strong genetic influence. Common genetic effects were observed between insomnia and both sleepiness and obesity, suggesting shared genetic contributions to these phenomena.

Back pain is the #1 cause of years lived with disability worldwide, yet surprisingly little is known regarding the biology underlying this symptom. We conducted a genome-wide association study (GWAS) meta-analysis of chronic back pain (CBP). Adults of European ancestry were included from 15 cohorts in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and from the UK Biobank interim data release. CBP cases were defined as those reporting back pain present for ≥3-6 months; non-cases were included as comparisons ("controls"). Each cohort conducted genotyping using commercially available arrays followed by imputation. GWAS used logistic regression models with additive genetic effects, adjusting for age, sex, study-specific covariates, and population substructure. The threshold for genome-wide significance in the fixed-effect inverse-variance weighted meta-analysis was p<5×10(-8). Suggestive (p<5×10(-7)) and genome-wide significant (p<5×10(-8)) variants were carried forward for replication or further investigation in the remaining UK Biobank participants not included in the discovery sample. The discovery sample comprised 158,025 individuals, including 29,531 CBP cases. A genome-wide significant association was found for the intronic variant rs12310519 in SOX5 (OR 1.08, p = 7.2×10(-10)). This was subsequently replicated in 283,752 UK Biobank participants not included in the discovery sample, including 50,915 cases (OR 1.06, p = 5.3×10(-11)), and exceeded genome-wide significance in joint meta-analysis (OR 1.07, p = 4.5×10(-19)). We found suggestive associations at three other loci in the discovery sample, two of which exceeded genome-wide significance in joint meta-analysis: an intergenic variant, rs7833174, located between CCDC26 and GSDMC (OR 1.05, p = 4.4×10(-13)), and an intronic variant, rs4384683, in DCC (OR 0.97, p = 2.4×10(-10)). In this first reported meta-analysis of GWAS for CBP, we identified and replicated a genetic locus associated with CBP (SOX5). We also identified 2 other loci that reached genome-wide significance in a 2-stage joint meta-analysis (CCDC26/GSDMC and DCC).

Abstract Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755 ), expression quantitative trait loci (eQTLs) (influencing GNG11 , RGS6 and NEO1 ), or are located in genes preferentially expressed in the sinoatrial node ( GNG11 , RGS6 and HCN4) . Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (−0.74&lt; r g &lt;−0.55) and blood pressure (−0.35&lt; r g &lt;−0.20). These findings provide clinically relevant biological insight into heritable variation in vagal heart rhythm regulation, with a key role for genetic variants ( GNG11 , RGS6) that influence G-protein heterotrimer action in GIRK-channel induced pacemaker membrane hyperpolarization.

COVID-19 has placed enormous stress on hospitals and health care providers worldwide. Limitations in hospital capacity may result in difficult decisions in how life-sustaining technologies are allocated among patients. The authors of this essay provide guidance on how to communicate with patients who are seriously ill from COVID-19 infection.

The vaginal ecology of 463 community-dwelling postmenopausal women was characterized. Vaginal lactobacilli were present in 62% of the women and were significantly more prevalent among women receiving hormone replacement therapy during the previous year. Vaginal Escherichia coli and enterococci were each present in 39% of women and were significantly more frequent in women with a history of urinary tract infection. Heavy growth of lactobacilli was associated with a lower frequency of vaginal colonization with E. coli. Thus, postmenopausal women have a relative depletion of vaginal lactobacilli and an increase in vaginal E. coli compared with premenopausal women.

BACKGROUND: The Mediterranean diet is protective against cardiovascular disease; a proposed mechanism is through a reduction in systemic inflammation. It is unknown to what extent the association between the Mediterranean diet and inflammation is due to genetic or other familial factors. METHODS AND RESULTS: We administered the Willett food frequency questionnaire to 345 middle-aged male twins and assessed adherence to the Mediterranean diet using a published adherence score. Fasting plasma levels of interleukin-6, C-reactive protein, and known cardiovascular risk factors were measured. Mixed-effect regression analyses were used to examine the relationship between diet score and inflammatory biomarkers after accounting for known cardiovascular risk factors. Adherence to the Mediterranean diet was associated with reduced levels of interleukin-6 (P<0.001) but not C-reactive protein (P=0.10) after adjustment for total energy intake, other nutritional factors, known cardiovascular risk factors, and use of supplements and medications. When the overall association of adherence to the diet with interleukin-6 levels was partitioned into between- and within-pair effects, the between-pair effect was not significant (P=0.9) and the within-pair effect was highly significant (P<0.0001). A 1-unit within-pair absolute difference in the diet score was associated with a 9% (95% CI, 4.5 to 13.6) lower interleukin-6 level. CONCLUSIONS: Shared environmental and genetic factors are unlikely to play a major role in the association between adherence to the Mediterranean diet and systemic inflammation. These results support the hypothesis that reduced inflammation is an important mechanism linking Mediterranean diet to reduced cardiovascular risk.

PURPOSE: We reviewed the current state of knowledge about urinary tract infection in patients with diabetes from the clinical and basic science perspectives. We identified key knowledge gaps and areas for further research. MATERIALS AND METHODS: We performed a focused literature search on certain topics, including clinical studies related to etiology and pathophysiology of urinary tract infection in patients with diabetes, urinary tract infection studies in animal models of diabetes and basic science studies of the molecular mechanisms of urinary tract infection. RESULTS: Individuals with diabetes are at higher risk for urinary tract infection. Increased susceptibility in patients with diabetes is positively associated with increased duration and severity of diabetes. Clinical epidemiological data identifying mechanisms of increased urinary tract infection susceptibility in patients with diabetes are generally lacking and indicate only that urinary tract infections in women with and without diabetes are qualitatively similar in bacterial etiology and morbid sequelae. Existing animal models for diabetes have not been well characterized for urinary tract infection research. The increased incidence, prevalence and severity of urinary tract infection in patients with diabetes argue for aggressive antibacterial chemotherapy but novel therapies resulting from urinary tract infection research in nondiabetic animal models are still not available. CONCLUSIONS: Future clinical investigations of urinary tract infection in patients with diabetes should focus on how the disease differs from that in patients without diabetes, notably on the role of glycosuria and urinary tract infection risk. Basic science research priorities for urinary tract infection in patients with diabetes should emphasize further development of diabetic animal models for urinary tract infection research and clinical translation of known important virulence determinants into new therapies.

CONTEXT: Low testosterone (T) is associated with prevalent cardiovascular disease (CVD) and mortality. DHT, a more potent androgen, may also be associated with CVD and mortality, but few studies have examined this. OBJECTIVE: The study objective was to examine whether T and DHT are risk factors for incident CVD and mortality. DESIGN: In a longitudinal cohort study, we evaluated whether total T, calculated free T (cFT), DHT, and calculated free DHT were associated with incident CVD and mortality in men in the Cardiovascular Health Study (mean age 76, range 66-97 years) who were free of CVD at the time of blood collection. MAIN OUTCOME: The main outcomes were incident CVD and all-cause mortality. RESULTS: Among 1032 men followed for a median of 9 years, 436 incident CVD events and 777 deaths occurred. In models adjusted for cardiovascular risk factors, total T and cFT were not associated with incident CVD or all-cause mortality, whereas DHT and calculated free DHT had curvilinear associations with incident CVD (P < .002 and P = .04, respectively) and all-cause mortality (P < .001 for both). CONCLUSIONS: In a cohort of elderly men, DHT and calculated free DHT were associated with incident CVD and all-cause mortality. Further studies are needed to confirm these results and to clarify the underlying physiologic mechanisms.

BACKGROUND: Treatment preferences established before life-threatening Illness occurs may differ from actual decisions because of changes in preferences or poor understanding of the link between prospective preferences and outcomes. OBJECTIVES: To evaluate the validity of prospective treatment preferences by examining their concordance with ratings of health states. DESIGN: Survey of seven cohorts of persons with diverse health status. Home- and hospital-based interviews were conducted at baseline and at 6, 18, and 30 months. SETTING: The greater Seattle area. PARTICIPANTS: Younger and older well adults; persons with chronic conditions, terminal cancer, or AIDS; stroke survivors; and nursing home residents. MEASUREMENTS: Concordance between six treatment preferences and five health state ratings (on a seven-point scale) was assessed by using logistic regression to measure the increase in odds of treatment refusal for each one-point change in health state rating. Preferences were considered concordant if treatments were refused in health states rated as worse than death and were accepted in health states rated as better than death. Reasons for discordance were elicited at the final interview. RESULTS: The probability of refusal of prospective treatment was strongly related to health state ratings. Odds ratios ranged from 1.7 to 1.9 (P < 0.001) for every treatment. When patients were shown their discordant preferences, they had a coherent explanation or changed their health state rating or treatment preference to make the two concordant. CONCLUSIONS: Prospective life-sustaining treatment preferences show high convergent validity. For most persons, treatment preferences are grounded in a consistent belief system. Concordance and discordance between treatment preferences and health state ratings offer clinicians the opportunity to explore patients' values and reasoning.