Serum dehydroepiandrosterone sulfate and adverse health outcomes in older men and women

Low serum dehydroepiandrosterone sulfate (DHEAS) is common in older persons with poor health. The geriatric syndrome of physical frailty is associated with a higher risk of developing fatal and nonfatal health outcomes. However, the association of DHEAS with frailty is uncertain. This study investigated the association of serum DHEAS with frailty and its related adverse outcomes in 416 men and 504 women aged ≥65 years from an Italian prospective population-based cohort study. At baseline, frailty status was defined according to the physical phenotype, and serum DHEAS was measured in a fasting venous blood sample. After 4 years, subjects were reassessed for incident frailty and occurrence of nonfatal frailty-related outcomes (hospital admission, nursing home placement, disability, falls, and fractures). All-cause mortality after 8 years was also recorded. Incident frailty was inversely associated with baseline log-transformed DHEAS in men (odds ratio [OR]=0.35, 95% confidence interval [CI] 0.14-0.88, p=0.026) but not in women. Independent of baseline frailty status, women in the lowest DHEAS quartile compared to the upper three quartiles had a higher risk of hospital admission (OR=0.44, 95% CI 0.21-0.91, p=0.027) and nursing home placement (OR=0.27, 95% CI 0.08-0.95, p=0.041). Baseline log-transformed serum DHEAS was also inversely associated with mortality risk, but limited to women with concurrent frailty (hazard ratio [HR]=0.27, 95% CI 0.11-0.68, p=0.005) or preexisting major diseases (HR=0.57, 95% CI 0.33-0.98, p=0.041). These findings suggest that DHEAS is associated with incident frailty in older men and with fatal and nonfatal frailty-related adverse outcomes in older women.     

Sex differences in the effect of heart rate on mortality in the elderly

OBJECTIVES: To examine the association between heart rate and mortality risk in the elderly. DESIGN: Longitudinal cohort. SETTING: Outpatient. PARTICIPANTS: Four hundred twenty-two people, aged 70 upon entry, were surveyed and followed for 6 years. MEASUREMENTS: Pulse rate was measured manually, while sitting and standing, and heart rate was measured from electrocardiogram recordings. The population was divided into quartiles of heart rate, with the top quartile comprising those with heart rate greater than 77 beats per minute (bpm) and the bottom quartile those with heart rate less than 60 bpm. RESULTS: After controlling for possible confounders, there was a clear correlation (r) between heart rate and all-cause mortality in elderly women (r=0.25, P=.0003). The correlation in women was observed using the three different methods for measuring heart rate. Heart rate was associated with all-cause and cardiovascular mortality. There was no relationship between heart rate and level of exercise or smoking status. In multiple regression analysis, the increased risk of death in the women was independent of previous cardiovascular or cerebrovascular disease, hypertension, anemia, congestive heart failure, smoking, and level of exercise or activities of daily living (relative odds ratio (ROR)=3.37, 95% confidence interval (CI)=0.96-11.8). When women using beta-blockers were excluded, this relationship became even stronger (ROR=8.5, 95% CI=1.19-60.1). CONCLUSION: Elevated heart rate is related to increased mortality in elderly women, thus representing a simple index of general health status in this population. Elevated heart rate did not predict mortality in elderly men.     

Measures of adiposity and risk of breast cancer in older postmenopausal women

OBJECTIVES: To determine whether higher adiposity is associated with greater breast cancer risk in older postmenopausal women. DESIGN: Prospective cohort study with mean follow-up of 11.3 years. SETTING: Four U.S. clinical centers. PARTICIPANTS: Seven thousand five hundred twenty-three women (mean age 73.5) enrolled in the Study of Osteoporotic Fractures. MEASUREMENTS: Weight, height, and waist and hip circumference were measured at baseline. Body composition was determined using bioelectrical impedance. Risk factor information was obtained by interview and questionnaire. Bone mineral density was measured using dual energy x-ray absorptiometry. The outcome was incident invasive breast cancer, confirmed using medical records. RESULTS: After adjustment for multiple risk factors, including bone density, women in the uppermost quartiles of weight, weight gain since age 25, body mass index, waist circumference, and percentage of body fat had higher breast cancer rates than women in the first quartiles of each measure. For example, breast cancer rates were 49% higher for women in the uppermost quartile of weight (hazard ratio (HR)=1.49, 95% confidence interval (CI)=1.05-2.10), 64% higher for women in the top quartile of weight gain since age 25 (HR=1.64, 95% CI=1.15-2.34), and 58% higher for women in the top quartile of percentage of body fat (HR=1.58, 95% CI=1.11-2.23) than for women in the lowest quartile of each measure. The associations between adiposity measures and breast cancer rates were not altered when the analyses were limited to very elderly women (> or = 70). CONCLUSION: Higher adiposity is an independent risk factor for breast cancer in elderly women.     

Hand grip strength and incident ADL disability in elderly Mexican Americans over a seven-year period

BACKGROUND AND AIMS: Little is known about muscle strength as a predictor of disability among older Mexican Americans. The aim of this study was to examine the association between hand grip strength and 7-year incidence of ADL disability in older Mexican American men and women. METHODS: A 7-year prospective cohort study of 2493 non-institutionalized Mexican American men and women aged 65 or older residing in five south-western states. Maximal hand grip strength test, body mass index, cognitive function, activities of daily living, self-reports of medical conditions (arthritis, diabetes, heart attack, stroke, cancer, hip fracture), and depressive symptoms were obtained. RESULTS: In a Cox proportional regression analysis, there was a linear relationship between hand grip strength at baseline and risk of incident ADL disability over a 7-year follow-up. Among non-disabled men at baseline, the hazard ratio of any new ADL limitation was 1.90 (95% CI 1.14-3.17) for those in the lowest quartile, when compared with men in the highest hand grip strength quartile, after controlling for age, marital status, medical conditions, high depressive symptoms, MMSE score, and BMI at baseline. Among non-disabled women at baseline, the hazard ratio of any new ADL limitation was 2.28 (95% CI 1.59-3.27) for those in the lowest quartile, when compared with women in the highest hand grip strength quartile. CONCLUSIONS: Hand grip strength is an independent predictor of ADL disability among older Mexican American men and women. The hand grip strength test is an easy, reliable, valid, inexpensive method of screening to identify older adults at risk of disability.     

Low serum micronutrient concentrations predict frailty among older women living in the community

BACKGROUND: Micronutrient deficiencies are common among older adults. We hypothesized that low serum micronutrient concentrations were predictive of frailty among older disabled women living in the community. METHODS: We studied 766 women, aged 65 and older, from the Women's Health and Aging Study I, a population-based study of moderately to severely disabled community-dwelling women in Baltimore, Maryland. Serum vitamins A, D, E, B(6), and B(12), carotenoids, folate, zinc, and selenium were measured at baseline. Frailty status was determined at baseline and during annual visits for 3 years of follow-up. RESULTS: At baseline, 250 women were frail and 516 women were not frail. Of 463 nonfrail women who had at least one follow-up visit, 205 (31.9%) became frail, with an overall incidence rate of 19.1 per 100 person-years. Compared with women in the upper three quartiles, women in the lowest quartile of serum carotenoids (hazard ratio [HR] 1.39; 95% confidence interval [CI], 1.01-1.92), alpha-tocopherol (HR 1.39; 95% CI, 1.02-1.92), and 25-hydroxyvitamin D (HR 1.34; 95% CI, 0.94-1.90) had an increased risk of becoming frail. The number of nutritional deficiencies (HR 1.10; 95% CI, 1.01-1.20) was associated with an increased risk of becoming frail, after adjusting for age, smoking status, and chronic pulmonary disease. Adjusting for potential confounders, we found that women in the lowest quartile of serum carotenoids had a higher risk of becoming frail (HR 1.54; 95% CI, 1.11-2.13). CONCLUSIONS: Low serum micronutrient concentrations are an independent risk factor for frailty among disabled older women, and the risk of frailty increases with the number of micronutrient deficiencies.     

Circadian Activity Rhythms and Mortality: The Study of Osteoporotic Fractures

OBJECTIVES: To determine whether circadian activity rhythms are associated with mortality in community‐dwelling older women. DESIGN: Prospective study of mortality. SETTING: A cohort study of health and aging. PARTICIPANTS: Three thousand twenty‐seven community‐dwelling women from the Study of Osteoporotic Fractures cohort (mean age 84). MEASUREMENTS: Activity data were collected using wrist actigraphy for a minimum of three 24‐hour periods, and circadian activity rhythms were computed. Parameters of interest included height of activity peak (amplitude), midline estimating statistic of rhythm (mesor), strength of activity rhythm (robustness), and time of peak activity (acrophase). Vital status, with cause of death adjudicated through death certificates, was prospectively ascertained. RESULTS: Over an average of 4.1 years of follow‐up, there were 444 (14.7%) deaths. There was an inverse association between peak activity height and all‐cause mortality rates, with higher mortality rates observed in the lowest activity quartile (hazard ratio (HR)=2.18, 95% confidence interval (CI)=1.63–2.92) than in the highest quartile after adjusting for age, clinic site, race, body mass index, cognitive function, exercise, instrumental activity of daily living impairments, depression, medications, alcohol, smoking, self‐reported health status, married status, and comorbidities. A greater risk of mortality from all causes was observed for those in the lowest quartiles of mesor (HR=1.71, 95% CI=1.29–2.27) and rhythm robustness (HR=1.97, 95% CI=1.50–2.60) than for those in the highest quartiles. Greater mortality from cancer (HR=2.09, 95% CI=1.04–4.22) and stroke (HR=2.64, 95% CI=1.11–6.30) was observed for later peak activity (after 4:33 p.m.; >1.5 SD from mean) than for the mean peak range (2:50–4:33 p.m.). CONCLUSION: Older women with weak circadian activity rhythms have higher mortality risk. If confirmed in other cohorts, studies will be needed to test whether interventions (e.g., physical activity, bright light exposure) that regulate circadian activity rhythms will improve health outcomes in older adults.     

Low Total Cholesterol and Increased Risk of Dying: Are Low Levels Clinical Warning Signs in the Elderly? Results from the Italian Longitudinal Study on Aging

OBJECTIVES: To analyze the relationship between serum total cholesterol (TC) and all-cause mortality, taking into account various potential confounders. DESIGN: Population-based prospective cohort study. SETTING: Older Italians residing in the general community. PARTICIPANTS: Four thousand five hundred twenty-one men and women aged 65-84. MEASUREMENTS: Vital status data were available for 1992-95. The hazard ratios of dying for subjects in the second, third, and fourth quartiles compared with the first quartile of TC were computed using Cox proportional hazards, adjusting for lifestyle factors, anthropomorphic and biochemical measures, preexisting medical conditions, and frailty indicators. RESULTS: Blood samples were obtained from 3,295 (73%) of the participants, of whom 399 died during almost 3 years of follow-up. Low TC was associated with a higher risk of death. Those with TC in the second, third, and fourth quartiles (TC>189 mg/dL or 4.90 mmol/L) had lower hazard ratios (HRs) of death than subjects in the first quartile (0.57, 95% confidence interval (CI) = 0.38-0.87; 0.56, 95% CI = 0.36-0.88; and 0.53, 95% CI = 0.33-0.84, respectively). Few subjects taking lipid-lowering drugs (LLDs) were in the lowest quartile of cholesterol, suggesting that these individuals have low TC values for reasons other than LLD use. CONCLUSION: Subjects with low TC levels (<189 mg/dL) are at higher risk of dying even when many related factors have been taken into account. Although more data are needed to clarify the association between TC and all-cause mortality in older individuals, physicians may want to regard very low levels of cholesterol as potential warning signs of occult disease or as signals of rapidly declining health.     

Effect of hypertension on anticoagulated patients with atrial fibrillation.

AIM: To test the hypothesis that stroke and systemic embolic events (SEE) in the Stroke Prevention using an ORal Thrombin Inhibitor in atrial Fibrillation (SPORTIF) III and V trials were related to blood pressure, and that differences in event rates (stroke and SEE, bleeding) could also be related to the degree of hypertension. METHODS AND RESULTS: A cross-sectional, longitudinal analysis was conducted, using data from the SPORTIF III and V trials. Results showed an increasing rate of stroke and SEE with increasing quartiles of systolic blood pressure (SBP) in AF patients. For the top quartile of SBP compared with the lowest quartile, the hazard ratio (HR) for stroke and SEE was 1.83 (95% confidence intervals [CI]: 1.22-2.74), whereas mortality was lower in the top quartile (HR 0.64; 95% CI: 0.49-0.83). In the combined SPORTIF III and V cohort, the event rate for stroke/SEE increased markedly at mean SBP of > 140 mmHg. There was no relationship between bleeding and quartiles of BP. The proportion of subjects with mean systolic BP > or = 140 mmHg was 35.8% (1220/3407) in SPORTIF III and 20.6% (807/3922) in SPORTIF V (P < 0.0001). CONCLUSION: Hypertension contributes to increased stroke and SEE in AF. Event rates markedly increase at SBP levels of > or = 140 mmHg. The higher stroke rates observed in SPORTIF III compared with SPORTIF V may be related to the greater proportion of subjects with SBP > or = 140 mmHg during the trial.     

Coagulation and activation of inflammatory pathways in the development of functional decline and mortality in the elderly

PURPOSE: This study was performed to determine the effects of markers of inflammation (interleukin 6) and coagulation (D-dimer) on mortality and functional status in older persons. METHODS: Subjects were selected for the Duke Established Populations for Epidemiologic Studies of the Elderly. In 1992, 2569 subjects (age >71 years) were interviewed, of whom 1,723 had interleukin-6 and D-dimer measurements. Values of interleukin 6 and D-dimer were categorized into quartiles. Outcomes were mortality (through 5 years) and functional status (through 4 years). Relative risks were estimated with proportional hazards models that adjusted for potential confounders. RESULTS: The relative risk of mortality was 1.28 (95% confidence interval [CI]: 0.98 to 1.69; P = 0.06) for those with only interleukin-6 levels in the highest quartile, 1.53 (95% CI: 1.18 to 1.97; P = 0.001) for subjects with only D-dimer levels in the highest quartile, and 2.00 (95% CI: 1.53 to 2.62; P = 0.0001) for those with levels of both in the highest quartile, as compared with those who were not in either of the highest quartiles. Those with high interleukin-6 and high D-dimer levels had the greatest declines in all measures of function. CONCLUSION: Activation of the coagulation and inflammatory pathways is associated with mortality and decline in function, and may be part of the explanation for the development of a frailty phenotype in the elderly.     

Handgrip strength and mortality in older Mexican Americans

OBJECTIVES: To examine the association between handgrip strength and mortality in older Mexican American men and women. DESIGN: A 5-year prospective cohort study. SETTING: Five southwestern states: Texas, New Mexico, Colorado, Arizona, and California. PARTICIPANTS: A population-based sample of 2,488 noninstitutionalized Mexican-American men and women aged 65 and older. MEASUREMENTS: Maximal handgrip strength, timed walk, and body mass index were assessed at baseline during 1993/94. Self-reports of functional disability, various medical conditions, and status at follow-up were obtained. RESULTS: Of the baseline sample with complete data, 507 persons were confirmed deceased 5 years later. Average handgrip strength +/- standard deviation was significantly higher in men (28.4 kg +/- 9.5) than in women (18.2g +/- 6.5). Of men who had a handgrip strength less than 22.01 kg and women who had a handgrip strength less than 14 kg, 38.2% and 41.5%, respectively, were dead 5 years later. In men in the lowest handgrip strength quartile, the hazard ratio of death was 2.10 (95% confidence interval (CI) = 1.31-3.38) compared with those in the highest handgrip strength quartile, after controlling for sociodemographic variables, functional disability, timed walk, medical conditions, body mass index, and smoking status at baseline. In women in the lowest handgrip strength quartile, the hazard ratio of death was 1.76 (95%I = 1.05-2.93) compared with those in the highest handgrip strength quartile. Poorer performance in the timed walk and the presence of diabetes mellitus, hypertension, and cancer were also significant predictors of mortality 5 years later. CONCLUSION: Handgrip strength is a strong predictor of mortality in older Mexican Americans, after controlling for relevant risk factors.     

Predictive value of C-reactive protein on 30-day and 1-year mortality in acute coronary syndromes: an analysis from the ACUITY trial

We sought to evaluate the association between C-reactive protein (CRP) sampled on admission and short- and long-term mortality in patients with acute coronary syndromes (ACS) undergoing early invasive treatment. Baseline levels of CRP were determined in 2,974 patients with moderate and high-risk ACS undergoing an early invasive treatment strategy in the large-scale randomized ACUITY trial. The relationship of CRP to 30-day and 1-year clinical outcomes were assessed according to quartiles of CRP values. Patients with CRP levels in the fourth quartile compared to the first quartile had significantly higher 30-day mortality (2.3 vs. 0.3%, P = 0.0004) and 1-year mortality (5.5 vs. 2.8%, P = 0.0003). CRP level as a continuous variable was associated with 30-day mortality (OR [95% CI] for one unit increase in logarithmically transformed CRP level = 1.42 [1.08-1.89], P = 0.01) and 1-year mortality (OR [95% CI] = 1.24, [1.04-1.47], P = 0.02). By multivariable analysis, higher baseline CRP levels independently predicted 30-day and 1-year mortality, a relationship that was particularly strong for patients with the highest quartile of CRP (OR [95% CI] = 5.19 [1.14-23.68], P = 0.009). In troponin-positive patients, increasing quartiles of CRP were associated with a trend for 30-day mortality (P (trend) = 0.08) and a significant increase in 1-year mortality (P (trend) = 0.02); this relationship was not present in troponin-negative patients. Baseline CRP level is a powerful independent predictor of both early and late mortality in patients with ACS being treated with an early invasive strategy, especially in troponin positive patients.     

Low micronutrient levels as a predictor of incident disability in older women

BACKGROUND: The role of nutritional status in the disablement process is still unclear. The objective of this study was to assess whether low concentrations of nutrients predict the development and course of disability. METHODS: Longitudinal study including community-dwelling women 65 years or older enrolled in the Women's Health and Aging Study I. In total, 643 women were assessed prospectively at 6-month intervals from 1992 to 1995. RESULTS: Incidence rates of disability in activities of daily living (ADLs) during 3 years of follow-up. Incidence rates in the lowest quartile of each selected nutrient were compared with those in the upper quartiles. The hazard ratios were estimated from Cox models adjusted for potential confounders. Women in the lowest quartile of serum concentrations of vitamin B(6) (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.03-1.67), vitamin B(12) (HR, 1.40; 95% CI, 1.12-1.74), and selenium (HR, 1.38; 95% CI, 1.12-1.71) had significantly higher risk of disability in ADLs during 3 years of follow-up compared with women in the upper 3 quartiles. CONCLUSIONS: Low serum concentrations of vitamins B(6) and B(12) and selenium predict subsequent disability in ADLs in older women living in the community. Nutritional status is one of the key factors to be considered in the development of strategies aimed at preventing or delaying the disablement process.     

Biomarkers of inflammation and malnutrition associated with early death in healthy elderly people

OBJECTIVES: To determine whether malnutrition and biomarkers of inflammation predict all-cause, cancer, and cardiovascular mortality in healthy elderly subjects.
DESIGN: Population-based study, prospective cohort.
SETTING: Sète, on the French Mediterranean coast.
PARTICIPANTS: Five hundred and fifty-three men and 888 women aged 60 and older from the Pathologies Oculaires Liées à l'Age cohort free of known comorbidities.
MEASUREMENTS: Plasma levels of cholesterol, albumin, transthyretin (TTR), C-reactive protein (CRP), and alpha 1-acid glycoprotein (AAG) were measured at baseline. To investigate the risks of 5-year (early) and 5- to 9-year (late) mortality, hazard ratios (HR) were evaluated using Cox models.
RESULTS: In men, early death was associated with high CRP and AAG and low albumin and TTR. In women, early death was associated with high AAG, low TTR and low cholesterol. For late death, the only significant association was with CRP in men. A synergistic effect was observed between biomarkers of inflammation and malnutrition. In men, the adjusted HR of early death was 4.98 (95% confidence interval (CI)=2.25–11.01) for both CRP in the highest quartile and albumin in the lowest. In men, this risk was greatest for both AAG in the highest quartile and TTR in the lowest (HR=6.86, 95% CI=3.20–14.71). In women, this risk was greatest for both AAG in the highest quartile and TTR in the lowest (HR=4.64, 95% CI=1.79–12.05). Cancer mortality was greater for high CRP and AAG and for low albumin and TTR in men but not in women.
CONCLUSION: Biomarkers of inflammation and malnutrition together predict early mortality. In healthy elderly subjects, TTR and AAG could be helpful in identifying elderly subjects at higher risk of death.     

Insulin-like growth factor (IGF) I, -II, and IGF binding protein-3 and risk of ischemic stroke

BACKGROUND: Low IGF-I levels may be associated with the development of stroke; however, prospective data appear to be unavailable. METHODS: This was a nested case-control study within a Danish follow-up study, including 57,053 men and women. Baseline data included circulating IGF-I, IGF-II, and IGF binding protein (IGFBP)-3 concentrations as well as lifestyle factors and medical history. We identified 254 cases with incident ischemic stroke and 254 gender- and age-matched controls. RESULTS: Participants in the bottom quartiles of IGF-I and IGFBP-3 levels (median concentrations, 72 and 2937 ng/ml, respectively) were at increased risk of ischemic stroke, e.g. adjusted odds ratios (ORs) of 2.06 [95% confidence interval (CI), 1.05-4.03] and 2.29 (95% CI, 1.17-4.49), respectively, when compared with participants in the top quartiles (median concentrations, 125 and 4835 ng/ml, respectively). A negative, although weaker, association was also found for IGF-II (adjusted OR 1.44, 95% CI 0.79-2.64) when comparing the bottom quartile with the top quartile. No substantial associations were seen for IGF-I and IGF-II when also adjusting for IGFBP-3; adjusting IGFBP-3 for IGF-I and -II had only a minor impact on the risk estimates. CONCLUSION: These findings give some support to the hypothesis that the IGF axis is involved in the pathogenesis of ischemic stroke.     

The relation of C-reactive protein levels to total and cardiovascular mortality in older U.S. women

PURPOSE: To determine whether serum C-reactive protein levels, a sensitive indicator of inflammation, are associated with the risk of cardiovascular mortality among older women. METHODS: We conducted a case-cohort study within the Study of Osteoporotic Fractures, a population-based study involving 9,704 women aged > or = 65 years from four U.S. centers. We randomly selected 400 women from the entire cohort plus an additional random sample of 92 women from the 1,125 women in the cohort who had died during the first 6 years of follow-up. Baseline serum C-reactive protein levels were measured using a high-sensitivity immunoassay. Cause-specific mortality was ascertained by review of death certificates and hospitalization records. Multivariable Cox proportional hazards regression was used to determine the association between C-reactive protein levels and cardiovascular mortality. RESULTS: During 6 years of follow-up, 150 of the 492 women died, including 52 who died of cardiovascular disease. After adjusting for potential confounders, women with C-reactive protein levels in the highest quartile (>3.0 mg/L) had a 8.0-fold (95% confidence interval [CI]: 2.2 to 29) greater risk of cardiovascular mortality than those in the lowest quartile (< or = 1.0 mg/L). The association remained strong in women who did not smoke or take estrogen, and when early deaths were excluded. Women who smoked and whose C-reactive protein levels were above the first quartile had a very high risk of cardiovascular mortality (relative risk [RR] = 13; 95% CI: 3.4 to 47). C-reactive protein levels were not associated with noncardiovascular mortality (RR = 0.92; 95% CI: 0.4 to 2.1). CONCLUSION: C-reactive protein level was an independent predictor of cardiovascular mortality in older women.     

Nonfasting plasma total homocysteine levels and stroke incidence in elderly persons: the Framingham Study.

BACKGROUND: Total homocysteine levels are associated with arteriosclerotic outcomes. OBJECTIVE: To determine whether total homocysteine levels predict incident stroke in elderly persons. DESIGN: Prospective population-based cohort study with 9.9 years of follow-up. SETTING: Framingham, Massachusetts. PATIENTS: 1947 Framingham Study participants (1158 women and 789 men; mean age +/- SD, 70 +/- 7 years). MEASUREMENTS: Baseline total homocysteine levels and 9.9-year stroke incidence. RESULTS: The quartiles of nonfasting total homocysteine levels were as follows: quartile 1, 4.13 to 9.25 micromol/L; quartile 2, 9.26 to 11.43 micromol/L; quartile 3, 11.44 to 14.23 micromol/L; quartile 4, 14.24 to 219.84 micromol/L. During follow-up, 165 incident strokes occurred. In proportional hazards models adjusted for age, sex, systolic blood pressure, diabetes, smoking, and history of atrial fibrillation and coronary heart disease, relative risk (RR) estimates comparing quartile 1 with the other three quartiles were as follows: quartile 2 compared with quartile 1--RR, 1.32 (95% CI, 0.81 to 2.14); quartile 3 compared with quartile 1--RR, 1.44 (CI, 0.89 to 2.34); quartile 4 compared with quartile 1--RR, 1.82 (CI, 1.14 to 2.91). The linear trend across the quartiles was significant (P < 0.001). CONCLUSION: Nonfasting total homocysteine levels are an independent risk factor for incident stroke in elderly persons.     

High serum uric acid level and low urine pH as predictors of metabolic syndrome: a retrospective cohort study in a Japanese urban population

The objective of this study was to evaluate whether hyperuricemia, acidic urine, or their combination predicts metabolic syndrome (MetS). In study 1, 69,094 subjects who received a general health checkup between 1985 and 2005 were included in a cross-sectional study of serum uric acid (SUA) and urine pH in relation to MetS. In study 2, the association of SUA and urine pH with MetS development over a 5-year period was evaluated in 5617 subjects with body mass index less than 25 kg/m(2) at the first examination. In study 1, higher SUA and lower urine pH were both positively correlated to MetS status (P < .001). The combination of high SUA and low urine pH was significantly associated with higher MetS prevalence compared with the combination of low SUA and high urine pH (odds ratio, 3.383; 95% confidence interval [CI], 3.034-3.784 in men; odds ratio, 4.000; 95% CI, 2.992-5.452 in women). In study 2, the top quartile of SUA levels was associated with higher MetS development compared with the bottom quartile during the 5-year period in men (hazard ratio [HR], 1.793; 95% CI, 1.084-2.966; P = .023). In women, the HR was 3.732 (95% CI, 0.391-35.62; P = .252) for the upper vs the lower half of SUA levels. For urine pH, the HR was 1.955 (95% CI, 1.089-3.509; P = .025) for the bottom vs the top quartile in men. A likelihood ratio test confirmed that high SUA and low urine pH act synergistically in the development of MetS. High SUA, low urine pH, and their combination are predictive risk factors for MetS development.     

Red blood cell distribution width,multimorbidity, and the risk of death in hospitalized older patients

We aimed to assess the association between red blood cell distribution width (RDW) and mortality in patients enrolled by a Geriatric Department. One hundred twenty-two patients were followed up during 5 years. The primary end point was all-cause mortality, and hazard ratios were estimated using a Cox proportional hazard model. Higher RDW values were strongly associated with an increased risk of death. Survival curves across RDW quartiles were statistically different according to the log-rank test (p = 0.017). The first quartile presented higher probability of survival compared to the last one. The gradient from lower to higher risk across quartiles was clear both in the 5-year mortality risk and in the mortality rate per 100 person-years, which ranged from 18.9 to 42.6. However, in the Cox regression model after adjusting for age, severity, and other factors, excess risk was only observed in the highest RDW quartile, with a hazard ratio of 2.24 (CI_95% 1.13–4.42) vs the first quartile. RDW is a good predictor of mortality in hospitalized older adults beyond those with cardiovascular risk factors, and it could serve as an integrative measure of multiple clinical and subclinical processes simultaneously occurring in complex patients.     

Associations of the −174 G/C Interleukin-6 Gene Promoter Polymorphism with Serum Interleukin 6 and Mortality in the Elderly

Serum interleukin-6 (sIL6) is an acknowledged predictor of all-cause mortality in older age. A common G/C polymorphism has been identified at position −174 of the IL6 gene promoter (IL6−174G>C), but its associations with sIL6 and mortality are still unclear. Data from a population-based elderly cohort (n = 824) were used to study the associations of baseline sIL6 with the IL6−174 C-allele (C+) carrier status and all-cause mortality at 4 years, in the presence and absence of preexisting major diseases (PMD). Analyses were adjusted for socio-demographic factors and body-mass-index. Three-hundred-eighty-eight participants (47.1%) had PMD. Compared to the bottom sIL6 quartile, mortality increased both in presence [Hazard Ratio (HR) = 3.04; 95% confidence interval (CI): 1.48–6.25] and absence of PMD [HR = 3.91; 95%CI: 1.42–10.72] for the third higher sIL6 quartile, but only in presence of PMD for the top sIL6 quartile [HR = 2.30; 95%CI: 1.09–4.83]. In absence of PMD, C+ carrier status did not affect both sIL6 and mortality. In presence of PMD, C+ carrier status was associated with increased baseline sIL6 [odds ratio 2.01; 95%CI: 1.25–3.22, for all sIL6 quartiles above the bottom] but not with increased mortality risk. A survival advantage was even found for C+ carriers with PMD and sIL6 in the top quartile [HR = 0.31, 95%CI: 0.13–0.76]. In conclusion, although associated with increased sIL6 levels in presence of major diseases, the IL6−174 C-allele does not seem to have direct detrimental effects on survival in older age.     

Diabetes, hyperglycaemia and mortality in disabled older women: The Women's Health and Ageing Study I.

AIMS: Diabetes is associated with increased mortality in older adults, but the specific contributions of diabetes-associated clinical conditions and of increasing hyperglycaemia to mortality risk are unknown. We evaluated whether cardiovascular disease, comorbidities, or degree of hyperglycaemia, particularly severe hyperglycaemia, affected diabetes-related mortality risk in older, disabled women. METHODS: Six-year mortality follow-up of a random sample of 576 disabled women (aged 65-101 years), recruited from the Medicare eligibility list in Baltimore (MD, USA). All-cause and cardiovascular mortality were evaluated by diabetes status: no diabetes; diabetes with mild, moderate, and severe hyperglycaemia [defined by tertiles of glycosylated haemoglobin (GHB) among women with diabetes]. RESULTS: Diabetes with mild, moderate, and severe hyperglycaemia was associated with an increased hazard rate (HR) for all-cause mortality, even after adjustment for demographics, risks for cardiovascular disease, cardiovascular and non-cardiovascular conditions, and other known mortality risks. A dose-response effect was suggested [mild hyperglycaemia, HR 1.81, 95% confidence interval (CI) 1.03, 3.17; moderate hyperglycaemia, HR 2.02, 95% CI 1.34, 3.57; severe hyperglycaemia, HR 2.22, 95% CI 1.17, 4.25]. Women with diabetes had a significantly increased HR for non-cardiovascular death, but not for cardiovascular death, compared with those without diabetes. CONCLUSIONS: Diabetes, whether characterized by mild, moderate or severe hyperglycaemia, appears to be an independent risk factor for excess mortality in older disabled women and this risk may increase with increasing hyperglycaemia. This mortality risk is not completely explained by vascular complications, and involves non-cardiovascular deaths. Risks and benefits of diabetes management, including glycaemic control and management of vascular and other comorbidities, should be studied in older people with complications and comorbidities.