Higher red cell distribution width and poorer hospitalization-related outcomes in elderly patients.

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

Effects of Compliance With the Early Management Bundle (SEP-1) on Mortality Changes Among Medicare Beneficiaries With Sepsis: A Propensity Score Matched Cohort Study.

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

Association Between Variation in Red Cell Size and Multiple Aging-Related Outcomes.

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

Mitochondrial DNA Heteroplasmy Associations With Neurosensory and Mobility Function in Elderly Adults.

BACKGROUND: Mitochondrial DNA (mtDNA) heteroplasmy is a mixture of normal and mutated mtDNA molecules in a cell. High levels of heteroplasmy at specific mtDNA sites lead to inherited mitochondrial diseases with neurological, sensory, and movement impairments. Here we test the hypothesis that heteroplasmy levels in elderly adults are associated with impaired function resembling mild forms of mitochondrial disease. METHODS: We examined platelet mtDNA heteroplasmy at 20 disease-causing sites for associations with neurosensory and mobility function among 137 participants from the community-based Health, Aging, and Body Composition Study. RESULTS: Elevated mtDNA heteroplasmy at four mtDNA sites in complex I and tRNA genes was nominally associated with reduced cognition, vision, hearing, and mobility: m.10158T>C with Modified Mini-Mental State Examination score (p = .009); m.11778G>A with contrast sensitivity (p = .02); m.7445A>G with high-frequency hearing (p = .047); and m.5703G>A with 400 m walking speed (p = .007). CONCLUSIONS: These results indicate that increased mtDNA heteroplasmy at disease-causing sites is associated with neurosensory and mobility function in older persons. We propose the novel use of mtDNA heteroplasmy as a simple, noninvasive predictor of age-related neurologic, sensory, and movement impairments.

Hip fracture and increased short-term but not long-term mortality in healthy older women.

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

A comparison of prediction models for fractures in older women: is more better?

BACKGROUND: A Web-based risk assessment tool (FRAX) using clinical risk factors with and without femoral neck bone mineral density (BMD) has been incorporated into clinical guidelines regarding treatment to prevent fractures. However, it is uncertain whether prediction with FRAX models is superior to that based on parsimonious models. METHODS: We conducted a prospective cohort study in 6252 women 65 years or older to compare the value of FRAX models that include BMD with that of parsimonious models based on age and BMD alone for prediction of fractures. We also compared FRAX models without BMD with simple models based on age and fracture history alone. Fractures (hip, major osteoporotic [hip, clinical vertebral, wrist, or humerus], and any clinical fracture) were ascertained during 10 years of follow-up. Area under the curve (AUC) statistics from receiver operating characteristic curve analysis were compared between FRAX models and simple models. RESULTS: The AUC comparisons showed no differences between FRAX models with BMD and simple models with age and BMD alone in discriminating hip (AUC, 0.75 for the FRAX model and 0.76 for the simple model; P = .26), major osteoporotic (AUC, 0.68 for the FRAX model and 0.69 for the simple model; P = .51), and clinical fracture (AUC, 0.64 for the FRAX model and 0.63 for the simple model; P = .16). Similarly, performance of parsimonious models containing age and fracture history alone was nearly identical to that of FRAX models without BMD. The proportion of women in each quartile of predicted risk who actually experienced a fracture outcome did not differ between FRAX and simple models (P > or = .16). CONCLUSION: Simple models based on age and BMD alone or age and fracture history alone predicted 10-year risk of hip, major osteoporotic, and clinical fracture as well as more complex FRAX models.

Association of common genetic variation in the insulin/IGF1 signaling pathway with human longevity.

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

Prevention of breast cancer in postmenopausal women: approaches to estimating and reducing risk.

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

A meta-analysis of candidate gene polymorphisms and ischemic stroke in 6 study populations: association of lymphotoxin-alpha in nonhypertensive patients.

BACKGROUND AND PURPOSE: Ischemic stroke is a multifactorial disease with a strong genetic component. Pathways, including lipid metabolism, systemic chronic inflammation, coagulation, blood pressure regulation, and cellular adhesion, have been implicated in stroke pathophysiology, and candidate gene polymorphisms in these pathways have been proposed as genetic risk factors. METHODS: We genotyped 105 simple deletions and single nucleotide polymorphisms from 64 candidate genes in 3550 patients and 6560 control subjects from 6 case-control association studies conducted in the United States, Europe, and China. Genotyping was performed using the same immobilized probe typing system and meta-analyses were based on summary logistic regressions for each study. The primary analyses were fixed-effects meta-analyses adjusting for age and sex with additive, dominant, and recessive models of inheritance. RESULTS: Although 7 polymorphisms showed a nominal additive association, none remained statistically significant after adjustment for multiple comparisons. In contrast, after stratification for hypertension, 2 lymphotoxin-alpha polymorphisms, which are in strong linkage disequilibrium, were significantly associated among nonhypertensive individuals: LTA 252A>G (additive model; OR, 1.41 with 95% CI, 1.20 to 1.65; P=0.00002) and LTA 26Thr>Asn (OR, 1.19 with 95% CI, 1.06 to 1.34; P=0.003). LTA 252A>G remained significant after adjustment for multiple testing using either the false discovery rate or by permutation testing. The 2 single nucleotide polymorphisms showed no association in hypertensive subjects (eg, LTA 252A>G, OR, 0.93; 95% CI, 0.84 to 1.03; P=0.17). CONCLUSIONS: These observations may indicate an important role of LTA-mediated inflammatory processes in the pathogenesis of ischemic stroke.

Depressive symptoms, health behaviors, and risk of cardiovascular events in patients with coronary heart disease.

CONTEXT: Depressive symptoms predict adverse cardiovascular outcomes in patients with coronary heart disease, but the mechanisms responsible for this association are unknown. OBJECTIVE: To determine why depressive symptoms are associated with an increased risk of cardiovascular events. DESIGN AND PARTICIPANTS: The Heart and Soul Study is a prospective cohort study of 1017 outpatients with stable coronary heart disease followed up for a mean (SD) of 4.8 (1.4) years. SETTING: Participants were recruited between September 11, 2000, and December 20, 2002, from 12 outpatient clinics in the San Francisco Bay Area and were followed up to January 12, 2008. MAIN OUTCOME MEASURES: Baseline depressive symptoms were assessed using the Patient Health Questionnaire (PHQ). We used proportional hazards models to evaluate the extent to which the association of depressive symptoms with subsequent cardiovascular events (heart failure, myocardial infarction, stroke, transient ischemic attack, or death) was explained by baseline disease severity and potential biological or behavioral mediators. RESULTS: A total of 341 cardiovascular events occurred during 4876 person-years of follow-up. The age-adjusted annual rate of cardiovascular events was 10.0% among the 199 participants with depressive symptoms (PHQ score > or = 10) and 6.7% among the 818 participants without depressive symptoms (hazard ratio [HR], 1.50; 95% confidence interval, [CI], 1.16-1.95; P = .002). After adjustment for comorbid conditions and disease severity, depressive symptoms were associated with a 31% higher rate of cardiovascular events (HR, 1.31; 95% CI, 1.00-1.71; P = .04). Additional adjustment for potential biological mediators attenuated this association (HR, 1.24; 95% CI, 0.94-1.63; P = .12). After further adjustment for potential behavioral mediators, including physical inactivity, there was no significant association (HR, 1.05; 95% CI, 0.79-1.40; P = .75). CONCLUSION: In this sample of outpatients with coronary heart disease, the association between depressive symptoms and adverse cardiovascular events was largely explained by behavioral factors, particularly physical inactivity.

Prognostic value of leukocyte telomere length in patients with stable coronary artery disease: data from the Heart and Soul Study.

BACKGROUND: Telomere shortening has been proposed as a marker of biological aging. Whether leukocyte telomere length is associated with mortality among patients with stable coronary artery disease (CAD) is unknown. METHODS AND RESULTS: We measured leukocyte telomere length in 780 patients with stable CAD in a prospective cohort study. Participants were categorized by quartiles of telomere length. Hazard Ratios (HRs) and 95% confidence intervals were calculated for all-cause mortality, heart failure (HF) hospitalization, and cardiovascular (CV) events. After 4.4 years of follow-up there were 166 deaths. Compared with participants in the highest telomere length quartile, those in the lowest quartile were at increased risk of death (age-adjusted HR 1.8; 95% CI 1.2 to 2.9). After multivariate adjustment for clinical (HR 2.1; CI 1.3 to 3.3), inflammatory (HR 2.0; CI 1.2 to 3.2), and echocardiographic (HR 1.9; CI 1.0 to 3.5) risk factors, patients in the lowest quartile of telomere length remained at significantly increased risk of death compared to those in the highest quartile. Patients in the lowest quartile of telomere length were also at significantly increased risk of HF hospitalization (HR 2.6; CI 1.1 to 6.0) but not CV events (HR 1.7; CI 0.9 to 3.5). CONCLUSIONS: Reduced leukocyte telomere length is associated with all-cause mortality in patients with stable CAD. The prognostic value of short telomeres in predicting death is not completely captured by existing clinical, inflammatory, and echocardiographic markers of risk.

Delineando a pesquisa clínica: uma abordagem epidemiológica / Designing clinical research: an epidemiologic approach

Um guia prático para o planejamento e a implementação da pesquisa clínica. Direto e de fácil leitura, o texto oferece a médicos e a investigadores clínicos descrições rigorosas dos componentes básicos, enfatizando o bom senso como o ingrediente fundamental do sucesso. Diferenciais dessa segunda edição: exemplos e idéias sobre o que há de novo na pesquisa clínica; expansão dos tópicos relativos ao delineamento e à implementação de ensaios clínicos randomizados; novas abordagens para estimativas de tamanho de amostra, abrangendo novas opções de delineamento; atualização nas questões éticas e na condução responsável da pesquisa clínica; novos capítulos sobre estudos de testes médicos, dados secundários (incluindo estudos suplementares e metanálise), gerenciamento de dados e pesquisa comunitária e internacional.

Coronary artery bypass graft surgery--care globalization: the impact of national care on fatal and nonfatal outcome.

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

Physical examination: Mallampati score as an independent predictor of obstructive sleep apnea.

STUDY OBJECTIVE: To assess the clinical usefulness of the Mallampati score in patients with obstructive sleep apnea. Mallampati scoring of the orophyarynx is a simple noninvasive method used to assess the difficulty of endotracheal intubation, but its clinical usefulness has not been validated in patients with sleep-disordered breathing. DESIGN: Prospective multivariate assessment of a predictor variable. SETTING: The UCSF Sleep Disorders Center. PATIENTS OR PARTICIPANTS: One hundred thirty-seven adult patients who were evaluated for possible obstructive sleep apnea. INTERVENTIONS: Prospective determination of the Mallampati score, assessment of other variables for multivariate analysis, and subsequent overnight polysomnography. MEASUREMENTS AND RESULTS: The Mallampati score was an independent predictor of both the presence and severity of obstructive sleep apnea. On average, for every 1-point increase in the Mallampati score, the odds of having obstructive sleep apnea (apnea-hypopnea index> or = 5) increased more than 2-fold (odds ratio [per 1-point increase] = 2.5; 95% confidence interval: 1.2-5.0; p = .01), and the apnea-hypopnea index increased by more than 5 events per hour (coefficient = 5.2; 95% confidence interval: 0.2-10; p = .04). These results were independent of more than 30 variables that reflected airway anatomy, body habitus, symptoms, and medical history. CONCLUSION: Our results indicate that Mallampati scoring is a useful part of the physical examination of patients prior to polysomnography. The independent association between Mallampati score and presence and severity of obstructive sleep apnea suggests that this scoring system will have practical value in clinical settings and prospective studies of sleep-disordered breathing.

Association of phosphodiesterase 4D polymorphisms with ischemic stroke in a US population stratified by hypertension status.

BACKGROUND AND PURPOSE: Phosphodiesterase 4D (PDE4D) underlies the STRK1 linkage peak for stroke on chromosome 5q12 identified in Iceland. We tested association of 13 single-nucleotide polymorphisms (SNPs) and 1 microsatellite in a nested case-control sample of elderly white women (>65 years of age) from the Study of Osteoporotic Fractures (SOF) in the United States. METHODS: The genotypes of 248 women who experienced an incident ischemic stroke during an average of 5.4 years of follow-up were compared with 560 controls. RESULTS: Marginal associations with stroke (P<0.10) were found for 3 polymorphisms. Stratification of the population by hypertension markedly strengthened the association. SNPs 9 (hazard ratio [HR], 0.48; 95% CI, 0.26 to 0.91), 42 (HR, 1.73; 95% CI, 1.10 to 2.70), 219 (HR, 1.73; 95% CI, 1.13 to 2.64), and 220 (HR, 1.56; 95% CI, 1.05 to 2.32) showed significant association with stroke (P<0.05) under a dominant model in subjects without hypertension at baseline, and SNP 175 was significantly associated with stroke under an additive model (HR, 0.76; 95% CI, 0.59 to 0.98) in subjects with hypertension. Furthermore, the microsatellite AC008818-1 showed association with stroke only in the nonhypertensive subjects. Based on results in Iceland, specific haplotypes were tested in SOF, and stratification by hypertension also affected these association results. CONCLUSIONS: These data are consistent with an association of the PDE4D gene with stroke in a non-Icelandic sample and suggest an effect of hypertension status.

Depressive symptoms and 24-hour urinary norepinephrine excretion levels in patients with coronary disease: findings from the Heart and Soul Study.

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.

Common promoter polymorphisms of inflammation and thrombosis genes and longevity in older adults: the cardiovascular health study.

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.