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.

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.

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.

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.

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.

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.

Depression and heart rate variability in patients with stable coronary heart disease: findings from the Heart and Soul Study.

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.

beta-Blocker use, BMD, and fractures in the study of osteoporotic fractures.

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.

C-reactive protein and ischemia in users and nonusers of beta-blockers and statins: data from the Heart and Soul Study.

BACKGROUND: Elevated levels of C-reactive protein (CRP) are associated with an increased risk of coronary events, but whether inflammation is associated with inducible ischemia in patients with stable coronary disease is unknown. METHODS AND RESULTS: We recruited patients with known coronary disease from 2 VA Medical Centers and 1 University-based medical center for the Heart and Soul Study. We measured CRP levels in 118 participants who had exercise-induced ischemia and in 111 who did not have inducible ischemia, as determined by stress echocardiography. We used logistic regression to examine the risk of exercise-induced ischemia associated with elevated CRP. We found that 75% (39/52) of participants in the highest CRP category (>0.38 mg/dL) had inducible ischemia, compared with 45% (79/177) in the lower 4 categories combined (adjusted odds ratio 4.2; 95% confidence interval 1.6 to 11; P=0.004). However, this association differed in users and nonusers of beta-blockers and statins. Among 89 participants who did not use beta-blockers, 93% in the highest CRP category had exercise-induced ischemia, compared with 42% in the lower 4 categories (P=0.03). Among 67 participants who did not use statins, 94% in the highest CRP category had exercise-induced ischemia, compared with 44% in the lower 4 categories (P=0.009). We did not observe a significant association between CRP and ischemia among participants who were treated with either of these medications. CONCLUSION: Elevated CRP levels are associated with inducible ischemia in patients with stable coronary disease, particularly among those not treated with beta-blockers or statins.

Improving guideline adherence: a randomized trial evaluating strategies to increase beta-blocker use in heart failure.

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.

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.

Using the coronary artery calcium score to predict coronary heart disease events: a systematic review and meta-analysis.

BACKGROUND: Primary prevention of coronary heart disease is most appropriate for patients at relatively high risk. Measurement of coronary artery calcium has been proposed as a way to improve risk assessment, but it is unknown whether it adds predictive information to standard risk factor assessment. METHODS: We systematically searched electronic databases for relevant articles published between January 1, 1980, and March 19, 2003, and hand searched bibliographies. We included studies that reported measuring the coronary artery calcium score by electron beam computed tomography in asymptomatic subjects and subsequent follow-up of those patients for coronary events and that presented score-specific relative risks, adjusted for established risk factors. Two abstractors verified inclusion criteria and abstracted data from each study. We estimated adjusted relative risks associated with 3 standard categories of coronary artery calcium scores (1-100, 101-400, and >400), compared with a score of 0, and used a random-effects model for meta-analysis. RESULTS: Meta-analysis of the 4 studies meeting inclusion criteria yielded a summary adjusted relative risk of 2.1 (95% confidence interval, 1.6-2.9) for a coronary artery calcium score of 1 to 100. Relative risk estimates for higher calcium scores were higher, ranging from 3.0 to 17.0 but varied significantly among studies. Subgroup analyses suggested that differences among studies in outcome adjudication (blinded or not), measurement of other risk factors (direct or by patient history), tomographic slice thickness (3 or 6 mm), and/or proportion of female study subjects may account for this heterogeneity. CONCLUSION: The coronary artery calcium score is an independent predictor of coronary heart disease events.

Association of renal insufficiency with treatment and outcomes after myocardial infarction in elderly patients.

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.

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.

BMD at multiple sites and risk of fracture of multiple types: long-term results from the Study of Osteoporotic Fractures.

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.

Depression and 24-hour urinary cortisol in medical outpatients with coronary heart disease: The Heart and Soul Study.

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.

What does my patient's coronary artery calcium score mean? Combining information from the coronary artery calcium score with information from conventional risk factors to estimate coronary heart disease risk.

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.