Oxidative protein damage is associated with elevated serum interleukin-6 levels among older moderately to severely disabled women living in the community

BACKGROUND: Elevated interleukin (IL)-6 is associated with adverse outcomes. Our objective was to determine whether serum protein carbonyls, an indicator of oxidative protein damage and oxidative stress, were associated with IL-6. METHODS: Serum protein carbonyls and IL-6 were measured in 739 women, age > or =65 years, in the Women's Health and Aging Study I. RESULTS: Geometric mean of protein carbonyls was 0.082 nmol/mg. After adjusting for age and smoking status, log(e) serum protein carbonyls were associated with log(e) IL-6 (beta = 0.143, standard error [SE] = 0.048, p =.003) in linear regression analyses and with elevated IL-6 (> or =2.5 pg/mL) (odds ratio = 1.38, 95% confidence interval, 1.02-1.86, p =.037) in logistic regression analyses. CONCLUSION. Oxidative damage to proteins is independently associated with serum IL-6 among older women living in the community. Increased oxidative stress may be a factor involved in the pathogenesis of the proinflammatory state that occurs in older adults.     

Oxidative stress and severe walking disability among older women

Background

Oxidative stress has been implicated in sarcopenia and the loss of muscle strength with aging, but the relationship between oxidative stress and decrease in muscle strength and physical performance has not been well characterized. Serum protein carbonyls are markers of oxidative damage to proteins and are caused by oxidative stress.

Methods

Serum protein carbonyls were measured at baseline and compared with a decrease in walking speed and development of severe walking disability (inability to walk or walking speed <0.4 m/sec) over 36 months of follow-up in 545 moderately to severely disabled women, aged ≥65 years, living in the community in Baltimore, Maryland (the Women’s Health and Aging Study I).

Results

After adjusting for age, body mass index, smoking, and chronic diseases, log_e protein carbonyls (nmol/mg) were associated with a decrease in walking speed over 36 months (P = .002). During follow-up, 154 women (28.2%) developed severe walking disability. After adjusting for the same potential confounders, log_e protein carbonyls were associated with incident severe walking disability (hazards ratio 1.42, 95% confidence interval, 1.02-1.98, P = .037).

Conclusion

High oxidative stress, as indicated by oxidative damage to proteins, is an independent predictor of decrease in walking speed and progression to severe walking disability among older women living in the community.     

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.     

Low serum vitamin d does not predict new disability or loss of muscle strength in older women

OBJECTIVES: To determine whether serum levels of 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) predict accelerated decline in muscular strength or onset of new disability in mobility and upper extremity functioning over a 3-year follow-up. DESIGN: A community-based prospective cohort study. PARTICIPANTS: Six hundred twenty-eight moderately to severely disabled women aged 65 and older living in the community. MEASUREMENTS: Subjects were divided into three groups of baseline 25(OH)D serum levels (deficiency: <25 nmol/L; low normal: 25-52 nmol/L; high normal: > or =53 nmol/L) and into tertiles of PTH levels. Objective performance measures (hip flexor, knee extensor, and grip strengths; walking speed; and time for repeated chair stands) and disability in activities involving mobility and upper extremity function were assessed at baseline and every 6 months for 3 years. Decline in performance measures and onset of new disability were compared between 25(OH)D and PTH groups using random effects models and proportional hazards models, respectively, while adjusting for age, race, education, body mass index, baseline performance, and chronic conditions. RESULTS: The annual rate of decline over 3 years in muscular strength, walking speed, and time to perform repeated chair stands was similar across 25(OH)D groups. We observed a nonsignificantly faster decline in proximal muscle strength and walking speed with increasing PTH levels. There was no association for either measure between serum levels and the risk of incident disability in activities relating to mobility and upper extremity function. CONCLUSION: This study does not support the hypothesis that vitamin D deficiency is associated with loss in muscular strength and decline in mobility and upper extremity functioning over time in older women who were moderately to severely disabled at baseline.     

Types of anemia and mortality among older disabled women living in the community: the Women's Health and Aging Study I

AIMS: To classify the different types of anemia among moderately to severely disabled women living in the community and examine the relationship between types of anemia and mortality. METHODS: We studied anemia in 688 women, >or=65 years, in the Women's Health and Aging Study I, a population based study of moderately to severely disabled older women living in the community in Baltimore, Maryland. Anemia was defined by World Health Organization criteria. Causes of anemia were classified as due to nutritional deficiencies (iron, folate, and B12 deficiencies), anemia of chronic inflammation, anemia with renal disease, and unexplained anemia. RESULTS: 147 of 688 (21.4%) women were anemic (hemoglobin <12 g/dL). Of the 147 anemic women, 22 (15.0%) had anemia due to nutritional causes, 45 (30.6%) had anemia due to chronic inflammation, 29 (19.7%) had anemia and renal disease, and 51 (34.7%) had unexplained anemia. The proportions of those who died over five years among non-anemic women and women with anemia due to nutritional causes, chronic inflammation, renal disease, and unexplained anemia were 26.1%, 18.2%, 38.6%, 64.3%, and 33.3%, respectively (p<0.0001). Compared with non-anemic women, those with anemia and renal disease (HR 1.99, 95% CI 1.18-3.35, p=0.009) and anemia of chronic inflammation (HR 1.69, 95% CI 1.00-2.84, p=0.05) had higher risk of death. CONCLUSIONS: Anemia is common among moderately to severely disabled older women living in the community, and about one-third of the anemia is unexplained. Anemia with renal disease and anemia of chronic inflammation are associated with a higher mortality.     

Long-term prognostic importance of total cholesterol in elderly survivors of an acute myocardial infarction: the Cooperative Cardiovascular Pilot Project

OBJECTIVES: To determine the long-term prognostic importance of in-hospital total serum cholesterol in elderly survivors of acute myocardial infarction (AMI). DESIGN: Retrospective medical record review. SETTING: Acute care, nongovernmental hospitals in Alabama, Connecticut, Iowa, and Wisconsin. PARTICIPANTS: Four thousand nine hundred twenty-three Medicare beneficiaries from four states aged 65 and older discharged alive with a principal diagnosis of AMI between June 1, 1992, and February 28, 1993, who had a measurement of total serum cholesterol during hospitalization. MEASUREMENTS: Primary endpoint of all-cause mortality within 6 years of discharge. RESULTS: Of the 7,166 hospitalizations meeting study inclusion criteria, 4,923 (68.7%) had total cholesterol assessed, and 22% had a cholesterol level of 240 mg/dL or greater. Of AMI hospitalization survivors with cholesterol of 240 md/dL or greater, 17.2% died within 1 year and 47.9% died within 6 years, compared with 17.4% (P =.73) and 48.7% (P =.98) of those with a cholesterol level less than 240 mg/dL. The adjusted hazard ratio for elevated total serum cholesterol measured during hospitalization for all-cause mortality in the 6 years after discharge was 0.97 (95% confidence interval (CI) = 0.87-1.09). The unadjusted 1- and 6-year mortality rates for those with total cholesterol less than 160 mg/dL were 22.2% and 55.5%, respectively, not significantly different from mortality for patients with cholesterol of 160 mg/dL or greater, even after adjustment. CONCLUSION: Among elderly survivors of AMI, elevated total serum cholesterol measured postinfarction is not associated with an increased risk of all-cause mortality in the 6 years after discharge. Furthermore, this study found no evidence of an increased risk of all-cause mortality in patients with low total cholesterol. Further studies are needed to determine the relationship of postinfarction lipid subfractions and mortality in older patients with coronary artery disease (CAD).     

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.     

The protective effect of emotional vitality on adverse health outcomes in disabled older women

OBJECTIVE: Although the adverse physical health consequences of negative emotions have been studied extensively, much less is known about the potential impact of positive emotions. This study examines whether emotional vitality protects against progression of disability and mortality in disabled older women. DESIGN: A community-based study, The Women's Health and Aging Study. PARTICIPANTS: A total of 1002 moderately to severely disabled women aged 65 years and older living in the community. MEASUREMENTS: Emotional vitality was defined as having a high sense of personal mastery, being happy, and having low depressive symptomatology and anxiety. The onset of new disability was determined by semiannual assessments of disability in performing activities of daily living (ADLs), walking across a room, walking 1/4 mile, and lifting/carrying 10 pounds. Mortality status was determined by proxy interviews and linkage with death certificates. Survival analyses with time to onset of specific disabilities (among those not disabled at baseline) and time to mortality were performed and adjusted for age, baseline level of difficulty, physical performance, and chronic conditions. RESULTS: Three hundred fifty-one of the 1002 older disabled women studied were emotionally vital. Among women without the specific disability at baseline, emotional vitality was associated with a significantly decreased risk for incident disability performing ADLs (RR = 0.81, 95% CI = 0.66-0.99), for incident disability walking one-quarter mile (RR = 0.73, 95% CI = 0.59-0.92), and for incident disability lifting/carrying 10 pounds (RR = 0.77, 95% CI = 0.63-0.95). Emotional vitality was also associated with a lower risk of dying (RR = 0.56, 95% CI = 0.39-0.80). These results were not simply caused by the absence of depression since protective health effects remained when emotionally vital women were compared with 334 women who were not emotionally vital and not depressed. CONCLUSIONS: Emotional vitality in older disabled women reduces the risk for subsequent new disability and mortality. Our findings suggest that positive emotions can protect older persons against adverse health outcomes.     

Serum cholesterol concentrations and all-cause mortality in older people

OBJECTIVE: To study the impact of serum cholesterol concentrations on the total risk of mortality in older people. DESIGN: Retrospective cohort study with a follow-up of 8-10 years. SUBJECTS: A total of 989 subjects (367 men and 622 women) aged 65 and over, living in the Marshfield Epidemiologic Study Area at the time of their first complete serum lipid assessment. METHODS: We calculated sex-specific mean levels of serum total cholesterol, low-density lipoprotein, high-density lipoprotein and triglycerides, and the ratio of total cholesterol to high-density lipoprotein, for subjects who died of all causes and for those who survived to the end of follow-up, with adjustment for relevant covariates. We obtained estimates of the risk factor-adjusted sex-specific relative risk for all-cause mortality with approximate quartiles of serum cholesterol concentrations by proportional hazards regression models. We also evaluated the possible combined effects of age, sex and cholesterol on all-cause mortality. RESULTS: A high level of high-density lipoprotein was significantly associated with a low total risk of mortality in older men. Conversely, an elevated ratio of total cholesterol to high-density lipoprotein was directly related to an increased total risk of mortality in older men. Age and high-density lipoprotein level had a significant synergistic effect on all-cause mortality for the elderly men. We found little or no association in women between all-cause mortality and any of the lipid measures studied. CONCLUSIONS: An increased ratio of total cholesterol to high-density lipoprotein appears to be associated with an increase in risk for all-cause mortality in men aged 65 and over, while an elevated level of high-density lipoprotein, considered alone, seems to be protective against mortality from all causes in men aged 65-74 years, but this effect diminishes over the age of 75.     

C-reactive protein independently predicts HIV-related outcomes among women and children in a resource-poor setting

OBJECTIVE: To evaluate C-reactive protein (CRP) as a predictor of HIV-related outcomes among women and children in a resource-poor setting. DESIGN: We measured serum CRP concentration among 606 HIV-infected women, all of whom were not taking highly-active antiretroviral therapy, 3 to 11 months after they gave birth, and assessed relationships of CRP to HIV-related endpoints, including maternal disease progression, mother-to-child transmission of HIV, and maternal and child mortality. METHODS: We used Cox proportional hazards and regression models adjusted for age, sociodemographic characteristics, anthropometric measurements, hemoglobin, CD4 cell count, HIV viral load, and, for child outcomes, breastfeeding status. RESULTS: Ninety-four women had a high CRP concentration (> 10 mg/l). During the follow-up, 56 women progressed to WHO stage 4 and 188 died, and a high maternal CRP concentration was associated with a 2.26-fold [95% confidence interval (CI), 1.64-3.12] greater risk of progression to stage 4 or death. Among children, 174 acquired HIV and 116 died by age 2 years, and a high maternal CRP concentration was associated with a 3.03-fold (95% CI, 1.85-4.96) greater risk of child mortality. In multivariate analyses among adults, a high maternal CRP concentration was associated with a 1.55-fold (95% CI, 1.08-2.23) greater risk of progression to stage 4 or death. A maternal CRP concentration was not significantly associated with mother-to-child transmission of HIV. CONCLUSIONS: A high maternal CRP concentration independently predicts HIV disease progression, maternal mortality, and child mortality in a resource-poor setting. C-reactive protein may be an important and inexpensive prognostic indicator for HIV-infected women and their children.     

Functional Decline and Recovery of Activities of Daily Living in Hospitalized, Disabled Older Women: The Women's Health and Aging Study I

OBJECTIVES: To determine, in disabled, older, community-dwelling women who were hospitalized, the rates and predictors of functional decline, the probability and time course of subsequent functional recovery, and predictors of functional recovery.
DESIGN: Population-based observational cohort.
SETTING: Woman's Health and Aging Study.
PARTICIPANTS: A subset of the 1,002 moderately to severely disabled community-dwelling older women who were hospitalized over 3 years (N=457).
MEASUREMENTS: Functional decline and complete and partial recovery were defined using a 0 to 6 scale of dependencies in activities of daily living (ADLs) evaluated every 6 months over 3 years. Complete recovery was defined as returning to baseline function (function at visit immediately preceding hospitalization) after functional decline; partial recovery was defined as any improvement in the ADL scale after functional decline. Multiple logistic regression analysis was used to determine predictors of functional decline. Kaplan-Meier curves estimate the proportions recovering as a function of time since hospitalization. Discrete-time proportional hazards models regress the time-to-recovery hazards on the predictor variables.
RESULTS: Thirty-three percent of hospitalized women experienced functional decline at the first visit after hospitalization. Frailty, longer length of stay, and higher education were associated with functional decline. Fifty percent fully recovered over the subsequent 30 months, with 33% recovering within 6 months and an additional 14% over the following 6 months. Younger women were more likely to recover (aged 80 to 70, hazard ratio=0.39, 95% confidence interval=0.24–0.64).
CONCLUSION: Although most recovery of function occurs by 6 months after the first visit after a hospitalization, a substantial proportion of disabled community-dwelling women recover over the following 2 years.     

Relationship Between Higher Estradiol Levels and 9-Year Mortality in Older Women: The Invecchiare in Chianti Study

OBJECTIVES: To investigate the relationship between total estradiol (E2) levels and 9-year mortality in older postmenopausal women not taking hormone replacement therapy (HRT).
DESIGN: Population-based study of persons living in the Chianti geographic area (Tuscany, Italy).
SETTING: Community.
PARTICIPANTS: A representative sample of 509 women aged 65 and older with measures of total E2.
MEASUREMENTS: Serum total E2 was measured at the University of Parma using ultrasensitive radioimmunoassay (RIA).
RESULTS: Women who died (n=135) during 9 years of follow up were older; had higher total E2 levels; and were more likely to have evidence of stroke, hypertension, diabetes mellitus, and congestive heart failure at baseline than survivors. Higher E2 levels were associated with a greater likelihood of death (hazard ratio (HR)=1.03, 95% confidence interval (CI)=1.01–1.06), and the relationship was independent of age, waist:hip ratio, C-reactive protein, education, cognitive function, physical activity, caloric intake, smoking, and chronic disease (HR=1.08 pg/mL, 95% CI=1.03–1.13, P =.003). The excessive risk of death associated with higher total E2 was not attenuated after adjustment for total testosterone (HR=1.12, 95% CI=1.02–1.18, P <.001) and after further adjustment for insulin resistance evaluated using the homeostasis model assessment (HR=1.07, 95% CI=1.03–1.17, P <.001).
Total E2 was highly predictive of death after more than 5 years (HR=1.42: CI 1.01–1.91, P =.04) and not predictive of death for less than 5 years ( P =.78).
CONCLUSION: Higher total E2 concentration predicts mortality in older women not taking HRT.     

Heart failure survival among older adults in the United States: a poor prognosis for an emerging epidemic in the Medicare population

OBJECTIVE: To describe the 6-year probability of survival for older adults after their first hospitalization for heart failure. SETTING: National Medicare hospital claims records for 1984 through 1986 and Medicare enrollment records from 1986 through 1992. DESIGN: We identified a national cohort of 170 239 (9% black patients) Medicare patients, 67 years or older, with no evidence of heart failure in 1984 or 1985, who were hospitalized and discharged for the first time in 1986 with a principal diagnosis of heart failure. For groups defined by race, sex, age, Medicaid eligibility, and comorbid conditions, we compared the probability of survival with Cox proportional hazards regression. RESULTS: Only 19% of black men, 16% of white men, 25% of black women, and 23% of white women survived 6 years. One third died within the first year. Men had lower median survival and 38% greater risk of mortality than did women (P<.05). White men had 10% greater risk of mortality than did black men (P<.05). Medicaid eligibility (white adults only) and diabetes were associated with increased mortality (P<.05). CONCLUSIONS: The prognosis for older adults with heart failure underscores the importance of prevention strategies and early detection and treatment modalities that can prevent, improve, or reverse myocardial dysfunction, particularly for the growing number of adults who are at increased risk for developing heart failure because of hypertension, diabetes, or myocardial infarction.     

DHEAS levels and mortality in disabled older women: the Women's Health and Aging Study I

BACKGROUND: Dehydroepiandrosterone sulfate (DHEAS) is an endogenously produced sex steroid that has been hypothesized to have anti-aging effects. Low DHEAS levels are associated with mortality in older men, but the relationship between DHEAS levels and mortality in women is not clearly defined. METHODS: The relationship between serum DHEAS level and 5-year mortality was analyzed in a cohort of 539 disabled women aged 65-100 years enrolled in the Women's Health and Aging Study I (WHAS I). Using Cox proportional hazard models, we calculated multivariate-adjusted mortality risks by DHEAS quartiles and by DHEAS continuously, allowing for a nonlinear relationship. We also examined cause-specific mortality. RESULTS: We found a U-shaped relationship between DHEAS level and mortality. After adjusting for multiple covariates, women in the top and bottom DHEAS quartiles had a more than 2-fold higher 5-year mortality than did those in the middle quartiles (hazard ratio, 2.15; 95% confidence interval [CI], 1.17-3.98 for the top quartile and 2.05; 95% CI, 1.27-3.32 for the bottom quartile, each compared to the third quartile). Women with higher DHEAS levels tended to have greater cancer mortality, whereas those with lower DHEAS tended to have greater cardiovascular mortality. CONCLUSION: Disabled older women with either low or high levels of DHEAS are at greater risk for death than are those with intermediate levels. More research is needed to determine if targeted dehydroepiandrosterone supplementation would provide clinical benefit to disabled older women.     

Low serum testosterone and mortality in male veterans

BACKGROUND: Low serum testosterone is a common condition in aging associated with decreased muscle mass and insulin resistance. This study evaluated whether low testosterone levels are a risk factor for mortality in male veterans. METHODS: We used a clinical database to identify men older than 40 years with repeated testosterone levels obtained from October 1, 1994, to December 31, 1999, and without diagnosed prostate cancer. A low testosterone level was a total testosterone level of less than 250 ng/dL (<8.7 nmol/L) or a free testosterone level of less than 0.75 ng/dL (<0.03 nmol/L). Men were classified as having a low testosterone level (166 [19.3%]), an equivocal testosterone level (equal number of low and normal levels) (240 [28.0%]), or a normal testosterone level (452 [52.7%]). The risk for all-cause mortality was estimated using Cox proportional hazards regression models, adjusting for demographic and clinical covariates over a follow-up of up to 8 years. RESULTS: Mortality in men with normal testosterone levels was 20.1% (95% confidence interval [CI], 16.2%-24.1%) vs 24.6% (95% CI, 19.2%-30.0%) in men with equivocal testosterone levels and 34.9% (95% CI, 28.5%-41.4%) in men with low testosterone levels. After adjusting for age, medical morbidity, and other clinical covariates, low testosterone levels continued to be associated with increased mortality (hazard ratio, 1.88; 95% CI, 1.34-2.63; P<.001) while equivocal testosterone levels were not significantly different from normal testosterone levels (hazard ratio, 1.38; 95% CI, 0.99%-1.92%; P=.06). In a sensitivity analysis, men who died within the first year (50 [5.8%]) were excluded to minimize the effect of acute illness, and low testosterone levels continued to be associated with elevated mortality. CONCLUSIONS: Low testosterone levels were associated with increased mortality in male veterans. Further prospective studies are needed to examine the association between low testosterone levels and mortality.     

Aging, resting metabolic rate, and oxidative damage: results from the Louisiana Healthy Aging Study

BACKGROUND: The aging process occurs at variable rates both among and within species and may be related to the variability in oxygen consumption and free radical production impacting oxidative stress. The current study was designed to test whether nonagenarians have a relatively low metabolic rate and whether it is associated with low levels of oxidative stress relative to age. METHODS: Resting metabolic rate (RMR) and markers of oxidative stress to lipids, proteins, and DNA were measured in three groups of individuals aged 20-34 (n=47), 60-74 (n=49), and>or=90 years (n=74). RESULTS: RMR, adjusted for fat-free mass, fat mass, and sex, was lower in both older groups when compared to the young group (p相似文献   

Handgrip strength and cause-specific and total mortality in older disabled women: exploring the mechanism

OBJECTIVES: To examine the association between muscle strength and total and cause-specific mortality and the plausible contributing factors to this association, such as presence of diseases commonly underlying mortality, inflammation, nutritional deficiency, physical inactivity, smoking, and depression. DESIGN: Prospective population-based cohort study with mortality surveillance over 5 years. SETTING: Elderly women residing in the eastern half of Baltimore, Maryland, and part of Baltimore County. PARTICIPANTS: Nine hundred nineteen moderately to severely disabled women aged 65 to 101 who participated in handgrip strength testing at baseline as part of the Women's Health and Aging Study. MEASUREMENTS: Cardiovascular disease (CVD), cancer, respiratory disease, other measures (not CVD, respiratory, or cancer), total mortality, handgrip strength, and interleukin-6. RESULTS: Over the 5-year follow-up, 336 deaths occurred: 149 due to CVD, 59 due to cancer, 38 due to respiratory disease, and 90 due to other diseases. The unadjusted relative risk (RR) of CVD mortality was 3.21 (95% confidence interval (CI) = 2.00-5.14) in the lowest and 1.88 (95% CI = 1.11-3.21) in the middle compared with the highest tertile of handgrip strength. The unadjusted RR of respiratory mortality was 2.38 (95% CI = 1.09-5.20) and other mortality 2.59 (95% CI = 1.59-4.20) in the lowest versus the highest grip-strength tertile. Cancer mortality was not associated with grip strength. After adjusting for age, race, body height, and weight, the RR of CVD mortality decreased to 2.17 (95% CI = 1.26-3.73) in the lowest and 1.56 (95% CI = 0.89-2.71) in the middle, with the highest grip-strength tertile as the reference. Further adjustments for multiple diseases, physical inactivity, smoking, interleukin-6, C-reactive protein, serum albumin, unintentional weight loss, and depressive symptoms did not materially change the risk estimates. Similar results were observed for all-cause mortality. CONCLUSION: In older disabled women, handgrip strength was a powerful predictor of cause-specific and total mortality. Presence of chronic diseases commonly underlying death or the mechanisms behind decline in muscle strength in chronic disease, such as inflammation, poor nutritional status, disuse, and depression, all of which are independent predictors of mortality, did not explain the association. Handgrip strength, an indicator of overall muscle strength, may predict mortality through mechanisms other than those leading from disease to muscle impairment. Grip strength tests may help identify patients at increased risk of deterioration of health.     

Postprandial hypotension predicts all-cause mortality in older, low-level care residents

OBJECTIVES: To evaluate which indices of blood pressure (BP) homeostasis are the strongest predictors of mortality in older low-level-care residents in long-term health facilities. DESIGN: Prospective cohort study. SETTING: Eight long-term healthcare facilities in Canberra, Australia. PARTICIPANTS: A total of 179 randomly selected semi-independent residents aged 65 and older (mean age+/-standard deviation 83.2+/-7.0; 80% women). MEASUREMENTS: Baseline BP levels taken while lying, after standing for 1 and 3 minutes, and sitting before and 1 hour after meal intake were recorded, as well as demographic information, chronic medical conditions, medications, and all-cause mortality during follow-up. Postprandial hypotension (PPH) was defined as a fall in systolic BP (SBP) of 20 mmHg or more 1 hour postmeal while sitting. Orthostatic hypotension (OH) was defined as a fall in SBP of 20 mmHg or more or in diastolic BP (DBP) of 10 mmHg or more within 3 minutes of standing from a supine position. Hypertension was defined as BP greater than 160/90 mmHg at commencement of the study. Mean arterial pressure (MAP) and pulse pressure (PP) were calculated. RESULTS: At baseline, 47% of participants had hypertension, 38% PPH, and 23% OH; PP was 70 mmHg or greater in 54%, and DBP was 65 mmHg or lower in 6%. Over 4.7 years, 97 (54%) participants died. Those who died were significantly older and more likely to have PPH (47% vs 28%) and atrial fibrillation (35% vs 17%) and a significantly greater decrease in BP after meal intake. Mortality rates in those with and without PPH were 145.0 and 98.5 per 1,000 person-years, respectively. Using multivariate Cox proportional hazards models after adjustment for age, sex, presence of atrial fibrillation, Parkinson's disease, and use of diuretics, PPH was the only BP parameter that significantly and independently predicted 4.7-year all-cause mortality (relative risk (RR)=1.79; 95% confidence interval (CI)=1.19-2.68; P=.005). Further adjustment for the presence of OH, hypertension, low resting BP, coronary artery disease, cerebrovascular disease, congestive heart failure, history of syncope, cognitive impairment, cancer, diabetes mellitus, chronic obstructive pulmonary disease, and history of smoking did not reveal any new statistically significant associations. There was a dose-response relationship between postprandial fall in SBP and mortality rates. Absolute postprandial SBP of 120 mmHg or less was also significantly associated with total mortality (RR=1.69, 95% CI=1.04-2.78; P=.04). Low DBP was also associated with increased mortality (RR=1.10, 95% CI=1.01-1.13; P=.03), although this association became nonsignificant in multivariate analysis. CONCLUSION: In older low-level-care residents, PPH is an independent predictor of all-cause mortality with no added predictive value explained by other BP indices: OH, hypertension, PP, MAP.     

Predictors of health resource use by disabled older female Medicare beneficiaries living in the community

OBJECTIVES: To identify specific clinical factors that could best predict resource use by disabled older women. DESIGN: Cross-sectional. SETTING: Urban community in Baltimore, Maryland. PARTICIPANTS: One thousand two community-dwelling, moderately to severely disabled, female Medicare beneficiaries aged 65 and older, from the Women's Health and Aging Study I (WHAS). MEASUREMENTS: WHAS data were merged with participants' 1992-1994 Medicare claims data for the year after baseline evaluation, reflecting inpatient, outpatient, home-based, and skilled-nursing services. The independent contributions of factors hypothesized to predict health expenditures were assessed, using chi-square and regression analyses, with the logarithm of Medicare expenditures as the primary outcome. RESULTS: Demographic factors were not associated with Medicare expenditures. Factors associated with expenditures in bivariate analyses included heart disease (1.4x), chronic obstructive pulmonary disease (1.3x), diabetes mellitus (1.1x), smoking, comorbidity, and severity of disability, as well as low creatinine clearance, serum albumin, caloric expenditure, or skinfold thickness. Heart disease, diabetes mellitus, and low skinfold thickness remained significant after adjustment for other factors. CONCLUSION: Heart disease, diabetes mellitus, and low skinfold thickness are important independent predictors of 1-year Medicare expenditures by disabled older women. Many other variables that reflect disease, disability, nutrition, or personal habits have less predictive ability. Most demographic factors are not predictors of expenditures in this population. Focusing on the best predictors may facilitate more-effective risk adjustment and creation of related health policies.     

Risk of Dementia in Older Breast Cancer Survivors: A Population-Based Cohort Study of the Association with Adjuvant Chemotherapy

OBJECTIVES: To assess whether there is an association between delivery of adjuvant chemotherapy to older women with breast cancer and development of dementia over time.
DESIGN: Retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER) data linked to Medicare claims data.
SETTING: Women residing in geographic areas included in the SEER registry.
PARTICIPANTS: Women aged 66 to 80 diagnosed with non-metastatic invasive breast cancer from 1992 to 1999 were included. It was determined whether patients had undergone chemotherapy within 6 months of diagnosis.
MEASUREMENTS: Whether women developed dementia over time was determined using diagnostic codes. The effect of adjuvant chemotherapy on development of dementia was evaluated, adjusting for confounders using a proportional hazards model stratified for age.
RESULTS: Twenty-one thousand three hundred sixty-two women met selection criteria; 2,913 received chemotherapy, and 18,449 did not. Women who received chemotherapy were younger than those who did not (median aged 70 vs 73; P <.001). Median follow-up time was 59 months. After controlling for other factors, it was found that chemotherapy was not associated with a greater risk of development of dementia over time for any age group (hazard ratio for dementia in women receiving chemotherapy: aged 66–70=0.83, 95% confidence interval (CI)=0.48–1.45, P =.5; aged 71–75=0.74, 95% CI=0.46–1.18, P =.2; aged 76–80=0.49, 95% CI=0.28–0.88, P =.02).
CONCLUSION: Receipt of chemotherapy in older women with breast cancer was not associated with a greater risk of dementia diagnosis over time; very elderly women who undergo chemotherapy may be at lower baseline risk. The use of a claims-based definition of dementia limited the study.