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Biomedical subjects

L P Fried

Publications and source records attributed to L P Fried.

At least 19 recordsLinked to original sources

Soluble intracellular adhesion molecule-1 is associated with cardiovascular disease risk and mortality in older adults.

BACKGROUND: Intracellular adhesion molecule-1 (ICAM-1) regulates leukocyte-endothelial attachment, a process crucial to atherosclerosis. Circulating soluble ICAM-1 (sICAM-1) may serve as a marker of cardiovascular disease (CVD) progression. OBJECTIVES: We examined the association of sICAM-1 with measures of subclinical CVD and risk of incident CVD events and death in older men and women (age > or = 65 years) from the Cardiovascular Health Study. METHODS: Selected participants were free of clinical CVD at baseline. Non-exclusive incident case groups were angina (n = 534), myocardial infarction (n = 304), stroke (n = 327), and death (n = 842; CVD death = 310). A total 643 subjects were free of events during follow-up. RESULTS: sICAM-1 was positively associated with C-reactive protein, interleukin-6 and fibrinogen and measures of subclinical CVD in these older men and women. In Cox regression models adjusted for age, gender, and race, increasing levels of sICAM-1 were associated with increased risk of all cause mortality in men and women. Hazard ratios (95% confidence intervals) for a one standard deviation increase in sICAM-1 (89.7 ng mL(-1)) were 1.3 (1.1-1.4) in men and 1.2 (1.1-1.3) in women. sICAM-1 was associated with increased risk of CVD death in women (1.2; 1.0-1.5), but not men (1.1; 0.9-1.3). There were no associations of sICAM-1 with non-fatal CVD events. CONCLUSIONS: While sICAM-1 was associated with death in older men and women, there was a more marked association between sICAM-1 and CVD death in women.

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Serum antioxidants, inflammation, and total mortality in older women.

The inflammatory cytokine interleukin-6 (IL-6) has been linked to poor health outcomes in older adults. Oxidative stress triggers the production of IL-6, and antioxidant micronutrients play a critical role in decreasing this inflammatory response. The authors sought to identify the relations between serum levels of antioxidant nutrients and IL-6 and mortality in older women. Levels of alpha- and beta-carotene, lycopene, lutein/zeaxanthin, alpha-cryptoxanthin, total carotenoids, retinol, alpha-tocopherol, zinc, and selenium were measured at baseline in 619 participants in Women's Health and Aging Study I (Baltimore, Maryland, 1992-1998). IL-6 was measured at baseline and at follow-up 1 and 2 years later, and all-cause mortality was determined over a 5-year period. Participants with the highest serum levels of alpha-carotene, total carotenoids, and selenium were significantly less likely to be in the highest tertile of serum IL-6 at baseline (p < 0.0001). Those with the lowest levels of alpha- and beta-carotene, lutein/zeaxanthin, and total carotenoids were significantly more likely to have increasing IL-6 levels over a period of 2 years. Those with the lowest selenium levels had a significantly higher risk of total mortality over a period of 5 years (hazard ratio = 1.54, 95% confidence interval: 1.03, 2.32). These findings suggest that specific antioxidant nutrients may play an important role in suppressing IL-6 levels in disabled older women.

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Benefits of fatty fish on dementia risk are stronger for those without APOE epsilon4.

OBJECTIVE: To compare associations of lean fish vs fatty fish (tuna or other fish) intake with dementia, Alzheimer disease (AD), and vascular dementia (VaD) and in relation to APOE epsilon4 status in the Cardiovascular Health Cognition Study (CHCS). METHODS: Fish intake was assessed by food frequency questionnaires. Incident dementia, AD, and VaD were determined through a series of cognitive tests, physician's assessment, and committee consensus. We used Cox proportional hazards regression to calculate hazard ratios of dementia, AD, and VaD with lean fried fish, fatty fish, or total fish intake, which were then stratified by the presence of APOE epsilon4. RESULTS: Although consumption of lean fried fish had no protective effect, consumption of fatty fish more than twice per week was associated with a reduction in risk of dementia by 28% (95% CI: 0.51 to 1.02), and AD by 41% (95% CI: 0.36 to 0.95) in comparison to those who ate fish less than once per month. Stratification by APOE epsilon4 showed this effect to be selective to those without the epsilon4 allele. Adjustment by education and income attenuated the effect. CONCLUSION: In the Cardiovascular Health Cognition Study, consumption of fatty fish was associated with a reduced risk of dementia and Alzheimer disease for those without the APOE epsilon4 allele.

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IL-6 gene variation is not associated with increased serum levels of IL-6, muscle, weakness, or frailty in older women.

Elevated levels of the inflammatory cytokine IL-6 are associated with the development of disability, frailty, and mortality in older adults. These outcomes are likely mediated through inflammatory activity that alters hormones, skeletal muscle, and the immune system. Polymorphic variants in the IL-6 gene influence IL-6 expression. We hypothesized that IL-6 alleles associate with increased serum of IL-6, decreased muscle strength, and frailty, and tested this in the Women's Health and Aging cohorts. We genotyped 463 participants age 70-79, and identified three common IL-6 haplotype blocks for the Caucasian (n=363) and African American (n=100) subsets. Using linear and logistic regression, and adjusting for age, BMI, race, and osteoarthritis, we identified no significant or clinically meaningful relationship between any single IL-6 single nucleotide polymorphism (SNP) or any IL-6 haplotype and serum IL-6 level, grip, knee, or hip strength, or frailty. Given that the promoter SNP (rs1800795) has been reported to influence IL-6 levels and health outcomes, we performed a similar association study in the In Chianti population (n=266) and confirmed lack of association. These results suggest that IL-6 gene variation may not be an important factor in the determination of elevated IL-6 levels and related phenotypes found in older women.

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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.

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Preclinical Alzheimer disease: neuropsychological test performance 1.5 to 8 years prior to onset.

OBJECTIVE: To determine if individuals ultimately diagnosed with Alzheimer disease (AD) exhibited evidence of cognitive impairment on neuropsychological tests administered between 1.5 years and 8.1 years before dementia onset. METHODS: A total of 693 community-dwelling individuals, part of the Cardiovascular Health Study, completed a neuropsychological test battery in 1991/92. Subjects were followed annually over the next 8 years (median follow-up = 7.4 years). Seventy-two individuals were ultimately diagnosed with AD (median follow-up = 4.5 years): 24 with AD onset 1.5 to 3.4 years after baseline neuropsychological testing, 20 with AD onset 3.5 to 5.0 years after testing, and 28 with onset 5.1 to 8.1 years after testing. A total of 621 individuals remained nondemented throughout the 8 years of follow-up (median follow-up = 7.5 years). RESULTS: Subjects ultimately diagnosed with AD had poorer scores on baseline neuropsychological measures than subjects who remained nondemented. Although individuals closest to AD onset (i.e., 1.5 to 3.4 years) performed the most poorly, cognitive impairment was detected in individuals who did not develop AD until 5 to 8 years later. CONCLUSIONS: Cognitive changes can be detected well before onset of Alzheimer disease.

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Risk factors for falling in home-dwelling older women with stroke: the Women's Health and Aging Study.

BACKGROUND AND PURPOSE: Much of our knowledge of risk factors for falls comes from studies of the general population. The aim of this study was to estimate the risk of falling associated with commonly accepted and stroke-specific factors in a home-dwelling stroke population. METHODS: This study included an analysis of prospective fall reports in 124 women with confirmed stroke over 1 year. Variables relating to physical and mental health, history of falls, stroke symptoms, self-reported difficulties in activities of daily living, and physical performance tests were collected during home assessments. RESULTS: Risk factors for falling commonly reported in the general population, including performance tests of balance, incontinence, previous falls, and sedative/hypnotic medications, did not predict falls in multivariate analyses. Frequent balance problems while dressing were the strongest risk factor for falls (odds ratio, 7.0). Residual balance, dizziness, or spinning stroke symptoms were also a strong risk factor for falling (odds ratio, 5.2). Residual motor symptoms were not associated with an increased risk of falling. CONCLUSIONS: Interventions to reduce the frequency of balance problems during complex tasks may play a significant role in reducing falls in stroke. Clinicians should be aware of the increased risk of falling in women with residual balance, dizziness, or spinning stroke symptoms and recognize that risk assessments developed for use in the general population may not be appropriate for stroke patients.

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Serum thyroxine level and cognitive decline in euthyroid older women.

BACKGROUND: Clinical and subclinical hypothyroidism is associated with cognitive impairment. OBJECTIVE: This study investigated the association between thyroxine (T(4)) and thyroid-stimulating hormone (TSH) level and change over time in cognitive performance in a sample of older women with normal thyroid gland function. METHODS: T(4) and TSH were measured at baseline in 628 women (> or = 65 years) enrolled in the Women's Health and Aging Study, a community-based study of physically impaired women. Cognitive function was assessed at baseline and after 1, 2, and 3 years, using the Mini-Mental State Examination (MMSE). Incident cognitive decline was defined as a decrease of more than one point/year in MMSE score between baseline and the end of the follow-up. The analysis included 464 subjects with normal thyroid gland function with a baseline and at least one follow-up MMSE. RESULTS: At baseline there was no association between T(4) and TSH level and cognitive function. In longitudinal analysis, adjusting for age, race, level of education, and other covariates, compared with women in the highest T(4) tertile (8.1 to 12.5 microg/dL), those in the lowest tertile (4.5 to 6.5 microg/dL) had a greater decline in MMSE score (-0.25 point/year vs -0.12 point/year; p = 0.04). A total of 95 women (20.5%) had cognitive decline during the study period (mean MMSE decline, 5.5 points). Compared with women in the highest T(4) tertile, those in the lowest tertile had a twofold risk of cognitive decline (adjusted relative risk, 1.97; 95% CI, 1.10 to 3.50). The results were not modified by baseline cognitive and physical function. There was no association between baseline TSH level and change in cognitive function. CONCLUSIONS: In older women, low T(4) levels, within the normal range, were associated with a greater risk of cognitive decline over a 3-year period. Thyroid hormone levels may contribute to cognitive impairment in physically impaired women.

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Cardiovascular disease, interleukin-6, and risk of mortality in older women: the women's health and aging study.

BACKGROUND: Systemic chronic inflammation has been found to be related to all-cause mortality risk in older persons. We investigated whether specific chronic conditions, particularly cardiovascular disease (CVD), affect the association between high interleukin (IL)-6 level and mortality in a sample of disabled older women. METHODS AND RESULTS: IL-6 serum level was measured at baseline in 620 women >/=65 years old. The presence and severity of medical conditions was ascertained by standard criteria that used multiple sources of information. The sample was surveyed over the 3-year follow-up. After adjustment for potential confounders, compared with those in the lowest tertile, women in the highest IL-6 tertile were at higher risk of all-cause mortality. The presence of CVD, however, strongly affected the risk of mortality associated with high IL-6. Among women with prevalent CVD, those with high IL-6 levels had >4-fold risk of death (RR 4.6; 95% CI 2.0 to 10.5) compared with women in the lowest tertile, whereas the relative risk associated with high IL-6 among those without CVD was much lower and not significant (RR 1.8; 95% CI 0.7 to 4.2). Adjustment for all chronic diseases and disease severity measures, including ankle-brachial index, forced expiratory volume, and exercise tolerance, did not change the results. CONCLUSIONS: IL-6 level is helpful in identifying a subgroup of older CVD patients with high risk of death over a period of 3 years. Systemic inflammation, as measured by IL-6, may be related to the clinical evolution of older patients with CVD.

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Self-reported preclinical disability identifies older women with early declines in performance and early disease.

There appears to be a preclinical stage of physical disability which precedes onset of task difficulty (disability) in those who develop disability progressively as a result of chronic disease. Such a stage provides a basis for identifying older adults at risk of becoming disabled. This cross-sectional study evaluated whether a preclinical stage of physical function identified by self-report is associated with decrements in objective physical performance measures or increases in disease; that is, whether these measures, in those with preclinical disability, are intermediate between individuals who report no difficulty and no preclinical changes and those who report difficulty. The Women's Health and Aging Study II, an observational study of 436 women 70-80 years of age who were among the two-thirds least disabled living in the community. Participants were sampled from the HCFA Medicare eligibility lists and were determined eligible if they reported no difficulty, or difficulty in only one of four domains of physical function: mobility, upper extremity, IADL and ADL tasks. At the first follow-up (18 months after baseline), participants completed questionnaires on physical functioning for tasks in each of these domains, with possible answer options for each task: they had (1) difficulty (disabled); (2) no difficulty and no modification of task performance (High Function); or (3) no difficulty but reported modification and/or change in frequency of task performance (a self-report measure of preclinical disability predictive of incident difficulty). At the same visit, standardized, objective measures of function and disease were obtained, including measured walk; chair stands; strength: hip flexion, knee extension, ankle dorsiflexion, and grip; balance: function reach, single leg stand, tandem stand; joint exam: hip pain on passive motion and knee pain or tenderness; spirometry; ankle:arm blood pressure ratio; visual function: acuity, contrast sensitivity, stereopsis; and graded treadmill exercise test. Data were analyzed from the first follow-up examination. Physical performance decreased, and disease frequency increased, in association with decreasing self-reported mobility function (in walking one-half mile and climbing 10 steps), across three self-report categories: High Function, Preclinical Disability (Task Modification but No Difficulty) and Disability (Difficulty). These findings pertained for measures of walking speed, balance, strength, and knee and hip osteoarthritis. Self-reported level of function predicted differences in ranges as well as means for walking speed, balance and strength. These findings indicate a physiologic basis for self-reported function, including preclinical disability, specifically that different levels of disease severity, impairments and physical performance are concurrently associated with different categories of self-reported function. They also suggest new avenues for screening and intervention to prevent disability.

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Coimpairments as predictors of severe walking disability in older women.

OBJECTIVE: Severe disabilities are common among older people who have impairments in a range of physiologic systems. It is not known, however, whether the presence of multiple impairments, or coimpairments, is associated with increased risk of developing new disability. The aim of this study was to determine the combined effects of two impairments, decreased knee-extension strength and poor standing balance, on the risk of developing severe walking disability among older, moderately-to-severely disabled women who did not have severe walking disability at baseline. DESIGN: The Women's Health and Aging Study is a 3-year prospective study with 6 semi-annual follow-up data-collection rounds following the baseline. SETTING: At baseline, knee-extension strength and standing balance tests took place in the participants' homes. PARTICIPANTS: 758 women who were not severely walking disabled at baseline. MEASUREMENTS: Severe walking disability was defined as customary walking speed of < 0.4 meters/second and inability to walk one quarter of a mile, or being unable to walk. RESULTS: Over the course of the study, 173 women became severely disabled in walking. The cumulative incidence of severe walking disability from the first to the sixth follow-up was: 7.8%, 12.0%, 15.1% 19.5% 21.2%, and 22.8%. In Cox proportional hazards models, both strength and balance were significant predictors of new walking disability. In the best balance category, the rates of developing severe walking disability expressed per 100 person years were 3.1, 6.1, and 5.3 in the highest- to lowest-strength tertiles. In the middle balance category, the rates were 9.6, 13.2, and 14.7, and in the poorest balance category 21.6, 12.7, and 37.1, correspondingly. The relative risk (RR) of onset of severe walking disability adjusted for age, height, weight, and race was more than five times greater in the group with poorest balance and strength (RR 5.12, 95% confidence limit [95% CI] 2.68-9.80) compared with the group with best balance and strength (the reference group). Among those who had poorest balance and best strength, the RR of severe walking disability was 3.08 (95% CI 1.33-7.14). Among those with best balance and poorest strength, the RR was 0.97 (95% CI 0.49-1.93), as compared with the reference group. CONCLUSION: The presence of coimpairments is a powerful predictor of new, severe walking disability, an underlying cause of dependence in older people. Substantial reduction in the risk of walking disability could be achieved even if interventions were successful in correcting only one of the impairments because a deficit in only one physiologic system may be compensated for by good capacity in another system.

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Polymorphic variation in the human myostatin (GDF-8) gene and association with strength measures in the Women's Health and Aging Study II cohort.

OBJECTIVES: To determine whether polymorphic variation in the myostatin gene differentially influences the maintenance of muscle strength in older adults, and to find supportive evidence in a cohort of older women. DESIGN: Correlation study of polymorphic variation in a cohort of older women. SETTING: Representatively sampled older female population living in the eastern half of Baltimore, Maryland. PARTICIPANTS: Participants were 286 women, age 70 to 79. Of these, 81.1% were Caucasian, 18.8% were African American, and 0.2% were Asian or Hispanic. MEASUREMENTS: Overall strength was measured with a dynamometer and defined as the sum of the strongest measures of hip, knee, and grip strength on the dominant side. RESULTS: We identified or confirmed six myostatin polymorphic variants in the Women's Health and Aging Study II population. Of the polymorphisms, K153R is the most common, with an allele frequency of 0.19 in African Americans. Unadjusted mean strength by genotype suggested lower muscle strength in those African-American women with the R genotype compared with those with the K genotype (K/K: 72.50 +/- 13.9 kg (n = 39) vs K/R: 67.14 +/- 11.4 kg (n = 13) vs R/R: 63.1 +/- 11.3 kg (n = 3)). After adjustment for race in a linear regression model, the R genotype remained associated with lower strength levels (P = .04). Statistical significance decreased when body mass index and race were both added to the model (P = .09). CONCLUSIONS: Recognizing that small sample size in the study of genes of modest effect are unlikely to yield significant differences, these data suggest an association of the R153 allele with lower strength in high-functioning older women, which should be studied further in a larger cohort.

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Weight change in old age and its association with mortality.

OBJECTIVES: Previous studies of weight change and mortality in older adults have relied on self-reported weight loss, have not evaluated weight gain, or have had limited information on health status. Our objective was to determine whether 5% weight gain or loss in 3 years was predictive of mortality in a large sample of older adults. DESIGN: Longitudinal observational cohort study. SETTING: Four U.S. communities. PARTICIPANTS: Four thousand seven hundred fourteen community-dwelling older adults, age 65 and older. MEASUREMENTS: Weight gain or loss of 5% in a 3-year period was examined in relationship to baseline health status and interim health events. Risk for subsequent mortality was estimated in those with weight loss or weight gain compared with the group whose weight was stable. RESULTS: Weight changes occurred in 34.6% of women and 27.3% of men, with weight loss being more frequent than gain. Weight loss was associated with older age, black race, higher weight, lower waist circumference, current smoking, stroke, any hospitalization, death of a spouse, activities of daily living disability, lower grip strength, and slower gait speed. Weight loss but not weight gain of 5% or more was associated with an increased risk of mortality that persisted after multivariate adjustment (Hazard ratio (HR) = 1.67, 95% CI = 1.29-2.15) and was similar in those with no serious illness in the period of weight change. Those with weight loss and low baseline weight had the highest crude mortality rate, although the HR for weight loss was similar for all tertiles of baseline weight and for those with or without a special diet, compared with those whose weight was stable. CONCLUSIONS: This study confirms that even modest decline in body weight is an important and independent marker of risk of mortality in older adults.

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Factors associated with healthy aging: the cardiovascular health study.

OBJECTIVES: To identify factors associated with remaining healthy in older adults. DESIGN: Longitudinal cohort study. SETTING: Data were collected at the four Cardiovascular Health Study field centers. PARTICIPANTS: 5,888 participants age 65 years and older in the Cardiovascular Health Study. MEASUREMENTS: Presence of chronic disease was assessed at baseline and over a maximum 7-year follow-up period. Participants who were free of chronic disease (no cardiovascular disease (CVD), chronic obstructive pulmonary disease, or self-reported cancer, except nonmelanoma skin cancer) at the baseline examination were then monitored for the onset of incident cancer, cardiovascular disease, and fatal outcomes. RESULTS: A high proportion of these older adults was healthy at the initial examination and remained healthy over the follow-up period. Numerous behavioral factors were associated with continued health, including physical activity, refraining from cigarette smoking, wine consumption (women), higher educational status, and lower waist circumference. A number of CVD risk factors and subclinical disease measures were associated with continued health, including higher high-density lipoprotein (HDL) cholesterol, lack of diabetes, thinner common carotid intimal nmedial thickness, lower blood pressure, lower C-reactive protein, and higher ankle-arm blood pressure ratio. Among the behavioral factors, exercise, not smoking, and not taking aspirin remained significant predictors of health even after controlling for CVD risk factors and subclinical disease in older adults. CONCLUSIONS: These data suggest that a number of modifiable behavioral factors (physical activity, smoking, and obesity) and cardiovascular risk factors (diabetes, HDL cholesterol, and blood pressure) are associated with maintenance of good health in older adults.

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Walking difficulty, walking speed, and age as predictors of self-rated health: the women's health and aging study.

BACKGROUND: Older persons reporting disability are more likely to report poor self-rated health, but little work has been done to assess the independent relationships of reported walking difficulty and measured walking performance with self-rated health. This study examines the associations of walking difficulty, walking speed, and age with self-rated health in older women. METHODS: The data are from the baseline of the Women's Health and Aging Study. Difficulty walking one quarter mile was used as a measure of mobility in the representative population aged 65 and older screened for the study (n = 3841) and in the one third most disabled study group (n = 1002). Maximal walking speed was measured in the study sample. RESULTS: Increasing severity of walking difficulty (in the screened population and in the disabled study group), slower walking speed (in the study group), and younger age were all associated with fair or poor self-rated health, after simultaneous adjustment for these and other objective measures of physical performance and health. The associations of both measures of walking with self-rated health weakened with age. CONCLUSIONS: Both walking difficulty and walking speed are independent determinants of self-rated health. Adjusted for health and functioning, self-rated health tends to improve with age.

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Frailty in older adults: evidence for a phenotype.

BACKGROUND: Frailty is considered highly prevalent in old age and to confer high risk for falls, disability, hospitalization, and mortality. Frailty has been considered synonymous with disability, comorbidity, and other characteristics, but it is recognized that it may have a biologic basis and be a distinct clinical syndrome. A standardized definition has not yet been established. METHODS: To develop and operationalize a phenotype of frailty in older adults and assess concurrent and predictive validity, the study used data from the Cardiovascular Health Study. Participants were 5,317 men and women 65 years and older (4,735 from an original cohort recruited in 1989-90 and 582 from an African American cohort recruited in 1992-93). Both cohorts received almost identical baseline evaluations and 7 and 4 years of follow-up, respectively, with annual examinations and surveillance for outcomes including incident disease, hospitalization, falls, disability, and mortality. RESULTS: Frailty was defined as a clinical syndrome in which three or more of the following criteria were present: unintentional weight loss (10 lbs in past year), self-reported exhaustion, weakness (grip strength), slow walking speed, and low physical activity. The overall prevalence of frailty in this community-dwelling population was 6.9%; it increased with age and was greater in women than men. Four-year incidence was 7.2%. Frailty was associated with being African American, having lower education and income, poorer health, and having higher rates of comorbid chronic diseases and disability. There was overlap, but not concordance, in the cooccurrence of frailty, comorbidity, and disability. This frailty phenotype was independently predictive (over 3 years) of incident falls, worsening mobility or ADL disability, hospitalization, and death, with hazard ratios ranging from 1.82 to 4.46, unadjusted, and 1.29-2.24, adjusted for a number of health, disease, and social characteristics predictive of 5-year mortality. Intermediate frailty status, as indicated by the presence of one or two criteria, showed intermediate risk of these outcomes as well as increased risk of becoming frail over 3-4 years of follow-up (odds ratios for incident frailty = 4.51 unadjusted and 2.63 adjusted for covariates, compared to those with no frailty criteria at baseline). CONCLUSIONS: This study provides a potential standardized definition for frailty in community-dwelling older adults and offers concurrent and predictive validity for the definition. It also finds that there is an intermediate stage identifying those at high risk of frailty. Finally, it provides evidence that frailty is not synonymous with either comorbidity or disability, but comorbidity is an etiologic risk factor for, and disability is an outcome of, frailty. This provides a potential basis for clinical assessment for those who are frail or at risk, and for future research to develop interventions for frailty based on a standardized ascertainment of frailty.

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Associations of subclinical cardiovascular disease with frailty.

BACKGROUND: Frail health in old age has been conceptualized as a loss of physiologic reserve associated with loss of lean mass, neuroendocrine dysregulation, and immune dysfunction. Little work has been done to define frailty and describe the underlying pathophysiology. METHODS: Frailty status was defined in participants of the Cardiovascular Health Study (CHS), a cohort of 5,201 community-dwelling older adults, based on the presence of three out of five clinical criteria. The five criteria included self-reported weight loss, low grip strength, low energy, slow gait speed, and low physical activity. We examined the spectrum of clinical and subclinical cardiovascular disease in those who were frail (3/5 criteria) or of intermediate frailty status (1 or 2/5 criteria), compared to those who were not frail (0/5). We hypothesized that the severity of frailty would be related to a higher prevalence of reported cardiovascular disease (CVD), as well as to a greater extent of CVD, measured by noninvasive testing. RESULTS: Of 4,735 eligible participants, 2,289 (48%) were not frail, 299 (6%) were frail, and 2.147 (45%) were of intermediate frailty status. Those who were frail were older (77.2 yrs) compared to those who were not frail (71.5 yrs) or intermediate (73.4 yrs) (p < .001). Frailty status was associated with clinical CVD and most strongly with congestive heart failure (odds ratio [OR] = 7.51 (95% confidence interval [CI] = 4.66-12.12). In those without a history of a CVD event (n = 1.259), frailty was associated with many noninvasive measures of CVD. Those with carotid stenosis >75% (adjusted OR = 3.41), ankle-arm index <0.8 (adjusted OR = 3.17) or 0.8-0.9 (adjusted OR = 2.01), major electrocardiography (ECG) abnormalities (adjusted OR = 1.58), greater left ventricular (LV) mass by echocardiography (adjusted OR = 1.16), and higher degree of infarct-like lesions in the brain (adjusted OR = 1.71), were more likely to be frail compared to those who were not frail. The overall associations of each of these noninvasive measures of CVD with frailty level were significant (all p < .05). CONCLUSIONS: Cardiovascular disease was associated with an increased likelihood of frail health. In those with no history of CVD, the extent of underlying cardiovascular disease measured by carotid ultrasound and ankle-arm index, LV hypertrophy by ECG and echocardiography, was related to frailty. Infarct-like lesions in the brain on magnet resonance imaging were related to frailty as well.

Black or African American↗