Cystatin C and frailty in older men.
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ABSTRACT:
SUBMITTER: Hart A
PROVIDER: S-EPMC3773269 | biostudies-literature | 2013 Sep
REPOSITORIES: biostudies-literature
Publications
Cystatin C and frailty in older men.
Hart Allyson A Paudel Misti L ML Taylor Brent C BC Ishani Areef A Orwoll Eric S ES Cawthon Peggy M PM Ensrud Kristine E KE
Journal of the American Geriatrics Society 20130903 9
<h4>Objectives</h4>To determine whether higher cystatin C would be associated with greater frailty in men aged 65 and older.<h4>Design</h4>Cross-sectional cohort study.<h4>Setting</h4>Six U.S. sites.<h4>Participants</h4>A random sample of community-dwelling men aged 65 and older enrolled in the Osteoporotic Fractures in Men (MrOS) Study (mean age 73.8; 9.8% frail and 47.2% intermediate frailty; N = 1,602).<h4>Measurements</h4>Serum cystatin C, creatinine, and frailty were measured. Frailty was a ...[more]
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Project description:BackgroundThis study examines the association between cystatin C (cysC) levels and risks of progression of frailty status or death in older men.MethodsProspective study of 2,613 men without overt frailty aged 67 years and older enrolled in the MrOS ancillary sleep study. Baseline measurements included serum cysC, serum creatinine, and frailty status. Repeat frailty status, performed an average of 3.4 years later, was assessed as an ordinal outcome of robust, intermediate stage (prefrail), frail or dead.ResultsMean age was 75.7 years. Men with higher cysC were older and had a higher comorbidity burden. After adjusting for age, clinical site, and race, higher cysC was associated with nearly twofold greater odds of being classified as intermediate stage versus robust (OR quartile 4 vs 1; 1.82, 95% confidence interval [CI] 1.35-2.45), a threefold greater odds of frailty versus robust (OR quartile 4 vs 1; 3.13, 95% CI 2.03-4.82), and a more than fivefold greater odds of death versus robust (OR quartile 4 vs 1; 5.48, 95% CI 2.98-10.08). Results were similar for cysC-based estimated glomerular filtration rate (eGFR). This relationship was attenuated but persisted after adjusting for additional potential confounders including baseline frailty status, body mass index, smoking status, comorbidity burden, self-reported disability, and serum albumin. In contrast, neither serum creatinine nor creatinine-based eGFR was associated in a graded manner with higher risks of development of frailty or death.ConclusionsIn this cohort of older men without overt frailty, higher cysC and cysC-based eGFR, but not creatinine or creatinine-based estimates of GFR, were associated with increased risks of frailty or death. These findings suggest that higher cysC level may be a promising biomarker for unsuccessful aging as manifested by increased risks of frailty and death.
| S-EPMC5458398 | biostudies-literature
Project description:ObjectivesTo determine the association of the frailty phenotype with subsequent healthcare costs and utilization.DesignProspective cohort study (Osteoporotic Fracture in Men [MrOS]).SettingSix US sites.ParticipantsA total of 1,514 community-dwelling men (mean age = 79.3 years) participating in the MrOS Year 7 (Y7) examination linked with their Medicare claims data.MeasurementsAt Y7, the frailty phenotype was operationalized using five components and categorized as robust, pre-frail, or frail. Multimorbidity and a frailty indicator (approximating the deficit accumulation index) were derived from claims data. Functional limitations were assessed by asking about difficulty performing instrumental activities of daily living. Total direct healthcare costs and utilization were ascertained during 36 months following Y7.ResultsMean of total annualized costs (2018 dollars) was $5,707 (standard deviation [SD] = 8,800) among robust, $8,964 (SD = 18,156) among pre-frail, and $20,027 (SD = 27,419) among frail men. Compared with robust men, frail men (cost ratio [CR] = 2.35; 95% confidence interval [CI] = 1.88-2.93) and pre-frail men (CR = 1.28; 95% CI = 1.11-1.48) incurred greater total costs after adjustment for demographics, multimorbidity, and cognitive function. Associations of phenotypic pre-frailty and frailty with higher total costs were somewhat attenuated but persisted after further consideration of functional limitations and a claims-based frailty indicator. Each individual frailty component was also associated with higher total costs. Frail vs robust men had higher odds of hospitalization (odds ratio [OR] = 2.62; 95% CI = 1.75-3.91) and skilled nursing facility (SNF) stay (OR = 3.36; 95% CI = 1.83-6.20). A smaller but significant effect of the pre-frail category on SNF stay was present.ConclusionPhenotypic pre-frailty and frailty were associated with higher subsequent total healthcare costs in older community-dwelling men after accounting for a claims-based frailty indicator, functional limitations, multimorbidity, cognitive impairment, and demographics. Assessment of the frailty phenotype or individual components such as slowness may improve identification of older community-dwelling adults at risk for costly extensive care.
| S-EPMC7666024 | biostudies-literature
Project description:ContextAs men age, the prevalence of frailty increases whereas levels of androgens decline. Little is known about the relation between these factors.ObjectiveThe aim of this study was to assess cross-sectional and longitudinal associations of estradiol, bioavailable estradiol, testosterone, bioavailable testosterone (bioT), and SHBG with frailty status.Design and settingThe Osteoporotic Fractures in Men (MrOS) study was conducted at six U.S. clinical centers.ParticipantsA total of 1469 community-dwelling men at least 65 yr old with baseline data participated; 1245 men had frailty status reassessed 4.1 yr later.Main outcome measureProportional odds models estimated the likelihood of greater frailty status. Frail men had at least three of the following: weakness, slowness, low activity, exhaustion, and shrinking/sarcopenia; intermediate men had one or two criteria; and robust men had none. At follow-up, death was included as an additional ordinal outcome. Sex hormones were assayed by spectrometry/chromatographic methods.ResultsIn cross-sectional analyses, men in the lowest quartile of bioT had 1.39-fold (95% confidence interval, 1.02, 1.91) increased odds of greater frailty status compared to men in the highest quartile after adjustment for covariates including age, body size, health status, and medical conditions. In age-adjusted longitudinal analyses, men in the lowest quartile of bioT had 1.51-fold (95% confidence interval, 1.10, 2.07) increased odds of greater frailty status 4.1 yr later. This association was largely attenuated by adjustment for covariates. No other hormones were associated in a cross-sectional or longitudinal manner with frailty status after adjustment.ConclusionsLow levels of bioT were independently associated with worse baseline frailty status. Frailty status should be considered as an outcome in trials of testosterone supplementation.
| S-EPMC2758722 | biostudies-literature
Project description:ObjectivesTo describe the natural history of frailty transitions in a large cohort of community-dwelling older men and identify predictors associated with progression to or improvement from states of greater frailty.DesignProspective cohort study.SettingSix U.S. sites.ParticipantsCommunity-dwelling men aged 65 and older (N = 5,086).MeasurementsFrailty was measured at baseline and an average of 4.6 years later. Frailty was defined as having three or more of the following components (low lean mass, weakness, self-reported exhaustion, low activity level, and slow walking speed); prefrailty was defined as having one or two components. Separate multivariable logistic regression models were analyzed for progression and improvement in frailty status.ResultsOf the 5,086 men, 8% were frail, 46% were prefrail, and 46% were robust at baseline. Between baseline and follow-up, 35% progressed in frailty status or died, 56% had no change in frailty status, and 15% of prefrail or frail participants improved, although only 0.5% improved across two levels, from frail to robust. In multivariable models, factors associated with improvement in frailty status included greater leg power, being married, and good or excellent self-reported health, whereas presence of any instrumental activity of daily living (IADL) limitations, low albumin levels, high interleukin-6 levels, and presence of chronic obstructive pulmonary disease or diabetes mellitus were associated with lower likelihood of improvement in frailty status.ConclusionImprovement in frailty status was possible in this cohort of community-dwelling older men, but improvement from frail to robust was rare. Several predictors were identified as possible targets for intervention, including prevention and management of comorbid medical conditions, prevention of IADL disability, physical exercise, and nutritional and social support.
| S-EPMC5681371 | biostudies-literature
Project description:ObjectiveTo test the hypothesis that non-frail older men with poorer sleep at baseline are at increased risk of frailty and death at follow-up.MethodsIn this prospective cohort study, subjective (questionnaires) and objective sleep parameters (actigraphy, in-home overnight polysomnography) were measured at baseline in 2505 non-frail men aged ≥67years. Repeat frailty status assessment performed an average of 3.4 years later; vital status assessed every four months. Sleep parameters expressed as dichotomized predictors using clinical cut-points. Status at follow-up exam classified as robust, intermediate (pre-frail) stage, frail, or died in interim.ResultsNone of the sleep disturbances were associated with the odds of being intermediate/frail/dead (vs. robust) at follow-up. Poor subjective sleep quality (multivariable odds ratio [MOR] 1.26, 95% CI 1.01-1.58), greater nighttime wakefulness (MOR 1.31, 95% CI 1.04-1.66), and greater nocturnal hypoxemia (MOR 1.47, 95% CI 1.02-2.10) were associated with a higher odds of frailty/death at follow-up (vs. robust/intermediate). Excessive daytime sleepiness (MOR 1.60, 95% CI 1.03-2.47), greater nighttime wakefulness (MOR 1.57, 95% CI 1.12-2.20), severe sleep apnea (MOR 1.74, 95% CI 1.04-2.89), and nocturnal hypoxemia (MOR 2.28, 95% CI 1.45-3.58) were associated with higher odds of death (vs. robust/intermediate/frail at follow-up). The association between poor sleep efficiency and mortality nearly reached significance (MOR 1.48, 95% CI 0.99-2.22). Short sleep duration and prolonged sleep latency were not associated with frailty/death or death at follow-up.ConclusionsAmong non-frail older men, poor subjective sleep quality, greater nighttime wakefulness, and greater nocturnal hypoxemia were independently associated with higher odds of frailty or death at follow-up, while excessive daytime sleepiness, greater nighttime wakefulness, severe sleep apnea and greater nocturnal hypoxemia were independently associated with an increased risk of mortality.
| S-EPMC3449012 | biostudies-literature
Project description:OBJECTIVES:To determine the cross-sectional and longitudinal associations between 25-hydroxyvitamin D (25(OH)D) levels and frailty status in older men. DESIGN:Prospective cohort study. SETTING:Six U.S. community-based centers. PARTICIPANTS:One thousand six hundred six men aged 65 and older. MEASUREMENTS:25(OH)D (liquid chromatography tandem mass spectroscopy) and frailty status (criteria similar to those used in the Cardiovascular Health Study) measured at baseline; frailty status assessment repeated an average of 4.6 years later. Frailty status was classified as robust, intermediate, or frail at baseline and robust, intermediate, frail, or dead at follow-up. RESULTS:After adjusting for multiple potential confounders, men with 25(OH)D levels less than 20.0 ng/mL had 1.5 times higher odds (multivariate odds ratio (MOR)=1.47, 95% confidence interval (CI)=1.07-2.02) of greater frailty status at baseline than men with 25(OH)D levels of 30.0 ng/mL or greater (referent group), whereas frailty status was similar in men with 25(OH)D levels from 20.0 to 29.9 ng/mL and those with levels of 30.0 ng/mL or greater (MOR=1.02, 95% CI=0.78-1.32). However, in 1,267 men not classified as frail at baseline, there was no association between lower baseline 25(OH)D level and odds of greater frailty status at the 4.6-year follow-up. Findings were the same when 25(OH)D was expressed in quartiles or as a continuous variable. CONCLUSION:Lower levels of 25(OH)D (<20.0 ng/mL) in community-dwelling older men were independently associated with greater evidence of frailty at baseline but did not predict greater risk of greater frailty status at 4.6 years.
| S-EPMC3343694 | biostudies-literature
Project description:Black versus white older Americans are more likely to experience frailty, a condition associated with adverse health outcomes. To reduce racial disparities in health, a complete understanding of the pathophysiology of frailty is needed. Metabolomics may further our understanding by characterizing differences in the body during a vigorous versus frail state. We sought to identify metabolites and biological pathways associated with vigor to frailty among 287 black men ages 70-81 from the Health, Aging, and Body Composition study. Using liquid chromatography-mass spectrometry, 350 metabolites were measured in overnight-fasting plasma. The Scale of Aging Vigor in Epidemiology (SAVE) measured vigor to frailty based on weight change, strength, energy, gait speed, and physical activity. Thirty-seven metabolites correlated with SAVE scores (p < 0.05), while adjusting for age and site. Fourteen metabolites remained significant after multiple comparisons adjustment (false discovery rate < 0.30). Lower values of tryptophan, methionine, tyrosine, asparagine, C14:0 sphingomyelin, and 1-methylnicotinamide, and higher values of glucoronate, N-carbamoyl-beta-alanine, isocitrate, creatinine, C4-OH carnitine, cystathionine, hydroxyphenylacetate, and putrescine were associated with frailer SAVE scores. Pathway analyses identified nitrogen metabolism, aminoacyl-tRNA biosynthesis, and the citric acid cycle. Future studies need to confirm these SAVE-associated metabolites and pathways that may indicate novel mechanisms involved in the frailty syndrome.
| S-EPMC6572139 | biostudies-literature
Project description:Backgroundincreasing numbers of older adults are living with frailty and its adverse consequences. We investigated relationships between diet quality or patterns and incident physical frailty in older British men and whether any associations were influenced by inflammation.Methodsprospective study of 945 men from the British Regional Heart Study aged 70-92 years with no prevalent frailty. Incident frailty was assessed by questionnaire after 3 years of follow-up. Frailty was defined as having at least three of: low grip strength, low physical activity, slow walking speed, unintentional weight loss and feeling of low energy, all based on self-report. The Healthy Diet Indicator (HDI) based on WHO dietary guidelines and the Elderly Dietary Index (EDI) based on a Mediterranean-style dietary intake were computed from questionnaire data and three dietary patterns were identified using principal components analysis: prudent, high fat/low fibre and high sugar.Resultsmen in the highest EDI category and those who followed a prudent diet were less likely to become frail [top vs bottom category odds ratio (OR) (95% CI) 0.49 (0.30, 0.82) and 0.53 (0.30, 0.92) respectively] after adjustment for potential confounders including BMI and prevalent cardiovascular disease. No significant association was seen for the HDI. By contrast those who had a high fat low fibre diet pattern were more likely to become frail [OR (95% CI) 2.54 (1.46, 4.40)]. These associations were not mediated by C-reactive protein (marker of inflammation).Conclusionsthe findings suggest adherence to a Mediterranean-style diet is associated with reduced risk of developing frailty in older people.
| S-EPMC6503938 | biostudies-literature
Project description:Background/objectivesTo estimate associations between lower urinary tract symptoms (LUTS) and phenotypic frailty in older men.DesignCross-sectional study.SettingCommunity-dwelling men recruited from 2000 to 2002 from six U.S. academic centers for the Osteoporotic Fractures in Men Study.ParticipantsA total of 5,979 men aged 65 and older.MeasurementsThe independent variable was LUTS severity (none/mild, moderate, or severe) assessed with the American Urologic Association Symptom Index. Participants were categorized as frail, intermediate stage, or robust using an adapted Cardiovascular Health Study index (components: low lean mass, weakness, exhaustion, slowness, and low physical activity). Associations were estimated with odds ratios and 95% confidence intervals (CIs) from multivariable multinomial logistic regression models adjusted for potential confounders of age, other demographics, health-related behaviors, and comorbidities.ResultsThe prevalence of frailty was 7%, 11%, and 18% among men with none/mild, moderate, and severe LUTS, respectively. Moderate and severe LUTS, overall and by storage and voiding subscores, were associated with higher odds of both intermediate stage and frailty in all models. After adjustment for confounders, the odds of frailty was 1.41 times higher among men with moderate LUTS (95% CI = 1.14-1.74) and 2.51 times higher among men with severe LUTS (95% CI = 1.76-3.55), compared with none/mild LUTS. Severe LUTS was associated with a greater odds of individual frailty components exhaustion and low physical activity.ConclusionThe prevalence of phenotypic frailty is higher among older community-dwelling men with moderate or severe LUTS compared with those with mild or no LUTS. The positive association between LUTS severity and frailty among older men appears independent of age and known frailty risk factors. Although the temporal direction of this association and the utility of LUTS or frailty interventions in this population remain unclear, the high co-occurrence of these conditions could lead to earlier identification of frailty when clinically appropriate.
| S-EPMC7744321 | biostudies-literature
Project description:BackgroundHigher serum cystatin C level is associated with an increased risk of hip fracture in postmenopausal white women, but there is a paucity of data for men. Whether estimated glomerular filtration rate (eGFR) based on cystatin C (eGFRcys) is superior in predicting hip fracture risk to eGFR based on creatinine (eGFRcr) or the combination (eGFR(cr-cys)) also is uncertain.Study designNested case-cohort.Setting & participantsParticipants enrolled in the Osteoporotic Fractures in Men (MrOS) Study (5,994 men aged ≥ 65 years from 6 US centers) including a random subcohort of 1,602 men and 168 men with incident hip fractures (51 of whom were in the subcohort).PredictoreGFR(cys), eGFR(cr), and eGFR(cr-cys) computed using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations and expressed in categories of <60, 60-74, and ≥ 75 mL/min/1.73 m(2) (referent group).OutcomeIncident hip fracture ascertained by participant contacts every 4 months and confirmed with radiographic reports.ResultsMedian eGFR(cys) was 72.9 (IQR, 60.5-85.7) mL/min/1.73 m(2). In unadjusted models, all measures of eGFR were associated with increased hip fracture risk. However, after adjustment for age, race, site, and body mass index, the association of lower eGFR(cys) (but not lower eGFR(cr) or lower eGFR(cr-cys)) with higher hip fracture risk remained: for <60 versus ≥ 75 mL/min/1.73 m(2), HRs were 1.96 [95% CI, 1.25-3.09], 0.84 [95% CI, 0.52-1.37], and 1.08 [95% CI, 0.66-1.77] for eGFR(cys), eGFR(cr), and eGFR(cr-cys), respectively. Similarly, after adjustment for age, race, site, and body mass index, eGFR < 60 mL/min/1.73 m(2) defined by eGFR(cys), but not eGFR(cr) or eGFR(cr-cys), was associated with higher hip fracture risk. The association between eGFR(cys) and hip fracture was not explained by levels of calciotropic hormones or inflammatory markers, but the relationship was attenuated and no longer reached significance (for <60 vs ≥ 75 mL/min/1.73 m(2): HR, 1.43; 95% CI, 0.88-2.34) after consideration of additional clinical risk factors and bone mineral density.LimitationsFindings not generalizable to other populations; residual confounding may exist.ConclusionsOlder community-dwelling men with lower eGFR(cys) have an increased risk of hip fracture that is explained in large part by greater burden of risk factors among men with lower eGFR(cys). In contrast, lower eGFR(cr) or lower eGFR(cr-cys) was not associated with a higher age-adjusted hip fracture risk.
| S-EPMC3833961 | biostudies-literature