03487nas a2200505 4500008004100000022001400041245012900055210006900184260001300253300001100266490000700277520205800284653000902342653002202351653001502373653002302388653001902411653001102430653001102441653001702452653004602469653001902515653001802534653001402552653000902566653004502575653001702620100001902637700001802656700001802674700002102692700001702713700001702730700002102747700002202768700001702790700001702807700002002824700001702844700002502861700001902886700002002905700002002925856003602945 2014 eng d a1758-535X00aSimple biologically informed inflammatory index of two serum cytokines predicts 10 year all-cause mortality in older adults.0 aSimple biologically informed inflammatory index of two serum cyt c2014 Feb a165-730 v693 a

BACKGROUND: Individual measurements of inflammation have been utilized to assess adverse outcomes risk in older adults with varying degrees of success. This study was designed to identify biologically informed, aggregate measures of inflammation for optimal risk assessment and to inform further biological study of inflammatory pathways.

METHODS: In total, 15 nuclear factor-kappa B-mediated pathway markers of inflammation were first measured in baseline serum samples of 1,155 older participants in the InCHIANTI population. Of these, C-reactive protein, interleukin-1-receptor antagonist, interleukin-6, interleukin-18, and soluble tumor necrosis factor-α receptor-1 were independent predictors of 5-year mortality. These five inflammatory markers were measured in baseline serum samples of 5,600 Cardiovascular Health Study participants. A weighted summary score, the first principal component summary score, and an inflammation index score were developed from these five log-transformed inflammatory markers, and their prediction of 10-year all-cause mortality was evaluated in Cardiovascular Health Study and then validated in InCHIANTI.

RESULTS: The inflammation index score that included interleukin-6 and soluble tumor necrosis factor-α receptor-1 was the best predictor of 10-year all-cause mortality in Cardiovascular Health Study, after adjusting for age, sex, education, race, smoking, and body mass index (hazards ratio = 1.62; 95% CI: 1.54, 1.70) compared with all other single and combined measures. The inflammation index score was also the best predictor of mortality in the InCHIANTI validation study (hazards ratio 1.33; 95% CI: 1.17-1.52). Stratification by sex and CVD status further strengthened the association of inflammation index score with mortality.

CONCLUSION: A simple additive index of serum interleukin-6 and soluble tumor necrosis factor-α receptor-1 best captures the effect of chronic inflammation on mortality in older adults among the 15 biomarkers measured.

10aAged10aAged, 80 and over10aBiomarkers10aC-Reactive Protein10aCohort Studies10aFemale10aHumans10aInflammation10aInterleukin 1 Receptor Antagonist Protein10aInterleukin-1810aInterleukin-610aLongevity10aMale10aReceptors, Tumor Necrosis Factor, Type I10aRisk Factors1 aVaradhan, Ravi1 aYao, Wenliang1 aMatteini, Amy1 aBeamer, Brock, A1 aXue, Qian-Li1 aYang, Huanle1 aManwani, Bhavish1 aReiner, Alexander1 aJenny, Nancy1 aParekh, Neel1 aFallin, Daniele1 aNewman, Anne1 aBandeen-Roche, Karen1 aTracy, Russell1 aFerrucci, Luigi1 aWalston, Jeremy uhttps://chs-nhlbi.org/node/660802878nas a2200181 4500008004100000022001400041245010200055210006900157260001600226520230000242100001902542700002102561700001102582700002302593700002502616700001902641856003602660 2017 eng d a1537-194800aDevelopment of a Claims-based Frailty Indicator Anchored to a Well-established Frailty Phenotype.0 aDevelopment of a Claimsbased Frailty Indicator Anchored to a Wel c2017 Apr 213 a

BACKGROUND: Fried and colleagues described a frailty phenotype measured in the Cardiovascular Health Study (CHS). This phenotype is manifest when ≥3 of the following are present: low grip strength, low energy, slowed waking speed, low physical activity, or unintentional weight loss. We sought to approximate frailty phenotype using only administrative claims data to enable frailty to be assessed without physical performance measures.

STUDY DESIGN: We used the CHS cohort data linked to participants Medicare claims. The reference standard was the frailty phenotype measured at visits 5 and 9. With penalized logistic regression, we developed a parsimonious index for predicting the frailty phenotype using a linear combination of diagnoses, operationalized with claims data. We assessed the predictive validity of frailty index by examining how well it predicted common aging-related outcomes including hospitalization, disability, and death.

RESULTS: There were 4454 CHS participants from 4 clinical sites. In total, 84% were white, 58% were women and their mean age was 72 years at enrollment. Approximately 11% of the cohort was frail. The model had an area under the receiver operating curve of 0.75 to concurrently predict a frailty phenotype. This Claims-based Frailty Indicator significantly predicted death (odds ratio, 1.84), time to death (hazards ratio, 1.71), number of hospital admissions (incidence rate ratio, 1.74), and nursing home admission (odds ratio, 1.47) in models adjusted for age and sex.

CONCLUSIONS: Claims data alone can be used to classify individuals as frail and nonfrail. The Claims-based Frailty Indicator might be used in research with large datasets for confounding adjustment or risk prediction. The indicator might also be used for emergency preparedness for identification of regions enriched with frail individuals.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.

1 aSegal, Jodi, B1 aChang, Hsien-Yen1 aDu, Yu1 aWalston, Jeremy, D1 aCarlson, Michelle, C1 aVaradhan, Ravi uhttps://chs-nhlbi.org/node/736002992nas a2200397 4500008004100000022001400041245008300055210006900138260001300207300001400220490000700234520188600241653003102127653000902158653002202167653001902189653001902208653001102227653002202238653001802260653001102278653000902289653002502298653001702323653001102340653001802351100003202369700002702401700002102428700001902449700002902468700001802497700002002515700002302535856003602558 2017 eng d a1524-462800aFactors Associated With Ischemic Stroke Survival and Recovery in Older Adults.0 aFactors Associated With Ischemic Stroke Survival and Recovery in c2017 Jul a1818-18260 v483 a

BACKGROUND AND PURPOSE: Little is known about factors that predispose older adults to poor recovery after a stroke. In this study, we sought to evaluate prestroke measures of frailty and related factors as markers of vulnerability to poor outcomes after ischemic stroke.

METHODS: In participants aged 65 to 99 years with incident ischemic strokes from the Cardiovascular Health Study, we evaluated the association of several risk factors (frailty, frailty components, C-reactive protein, interleukin-6, and cystatin C) assessed before stroke with stroke outcomes of survival, cognitive decline (≥5 points on Modified Mini-Mental State Examination), and activities of daily living decline (increase in limitations).

RESULTS: Among 717 participants with incident ischemic stroke with survival data, slow walking speed, low grip strength, and cystatin C were independently associated with shorter survival. Among participants <80 years of age, frailty and interleukin-6 were also associated with shorter survival. Among 509 participants with recovery data, slow walking speed, and low grip strength were associated with both cognitive and activities of daily living decline poststroke. C-reactive protein and interleukin-6 were associated with poststroke cognitive decline among men only. Frailty status was associated with activities of daily living decline among women only.

CONCLUSIONS: Markers of physical function-walking speed and grip strength-were consistently associated with survival and recovery after ischemic stroke. Inflammation, kidney function, and frailty also seemed to be determinants of survival and recovery after an ischemic stroke. These markers of vulnerability may identify targets for differing pre and poststroke medical management and rehabilitation among older adults at risk of poor stroke outcomes.

10aActivities of Daily Living10aAged10aAged, 80 and over10aBrain Ischemia10aCohort Studies10aFemale10aFollow-Up Studies10aFrail Elderly10aHumans10aMale10aRecovery of Function10aRisk Factors10aStroke10aSurvival Rate1 aWinovich, Divya, Thekkethal1 aLongstreth, William, T1 aArnold, Alice, M1 aVaradhan, Ravi1 aHazzouri, Adina, Zeki Al1 aCushman, Mary1 aNewman, Anne, B1 aOdden, Michelle, C uhttps://chs-nhlbi.org/node/749302432nas a2200181 4500008004100000022001400041245013300055210006900188260001600257520183000273100001602103700001602119700001702135700002002152700001902172700002302191856003602214 2018 eng d a1758-535X00aAssociation of Frailty with Recovery from Disability among Community-Dwelling Older Adults: Results from Two Large U.S. Cohorts.0 aAssociation of Frailty with Recovery from Disability among Commu c2018 Apr 103 a

Background: Disability in activities of daily living (ADLs) is a dynamic process and transitions among different disability states are common. However, little is known about factors affecting recovery from disability. We examined the association between frailty and recovery from disability among non-disabled community-dwelling elders.

Methods: We studied 1023 adults from the Cardiovascular Health Study (CHS) and 685 adults from the Health and Retirement Study (HRS), who were ≥65 years and had incident disability, defined as having difficulty in ≥1 ADL (dressing, eating, toileting, bathing, transferring, walking across a room). Disability recovery was defined as having no difficulty in any ADLs. Frailty was assessed by slowness, weakness, exhaustion, inactivity, and shrinking. Persons were classified as "non-frail" (0 criteria), "prefrail" (1-2 criteria), or "frail" (3-5 criteria).

Results: In total, 539 (52.7%) CHS participants recovered from disability within one year. Almost two-thirds of non-frail persons recovered, while less than two-fifths of the frail recovered. In the HRS, 234 (34.2%) participants recovered from disability within two years. Approximately half of the non-frail recovered, while less than one-fifth of the frail recovered. After adjustment, prefrail and frail CHS participants were 16% and 36% less likely to recover than the non-frail, respectively. In the HRS, frail persons had a 41% lower likelihood of recovery than the non-frail.

Conclusions: Frailty is an independent predictor of poor recovery from disability among non-disabled older adults. These findings validate frailty as a marker of decreased resilience and may offer opportunities for individualized interventions and geriatric care based on frailty assessment.

1 aWu, Chenkai1 aKim, Dae, H1 aXue, Qian-Li1 aLee, David, S H1 aVaradhan, Ravi1 aOdden, Michelle, C uhttps://chs-nhlbi.org/node/767402707nas a2200241 4500008004100000022001400041245011900055210006900174260001600243520193300259100002902192700002002221700002002241700002002261700002002281700002402301700001902325700001902344700002102363700001902384700002602403856003602429 2021 eng d a1758-535X00aStatins and cognitive decline in the Cardiovascular Health Study: A comparison of different analytical approaches.0 aStatins and cognitive decline in the Cardiovascular Health Study c2021 Jul 313 a

BACKGROUND: Despite their well-established benefits for the prevention of cardiovascular disease, robust evidence on the effects of statins on cognition is largely inconclusive. We apply various study designs and analytical approaches to mimic randomized controlled trial (RCT) effects from observational data.

METHODS: We used observational data from 5,580 participants enrolled in the Cardiovascular Health Study from 1989/90 to 1999/2000. We conceptualized the cohort as an overlapping sequence of non-randomized trials. We compared multiple selection (eligible population, prevalent users, new-users) and analytic approaches (multivariable adjustment, inverse probability treatment weights, propensity score matching) to evaluate the association between statin use and 5-year change in global cognitive function, assessed using the Modified Mini-Mental State (3MS) examination.

RESULTS: When comparing prevalent users to non-users (N=2,772), statin use was associated with slower cognitive decline over 5 years (adjusted annual change in 3MSE = 0.34 points/year; 95% CI:0.05;0.63). Compared to prevalent user design, estimates from new user designs (e.g. comparing eligible statin initiators to non-initiators) were attenuated showing either null or negative association, though not significant. For example, in a propensity score-matched sample of statin-eligible individuals (N=454), annual 3MS change comparing statin initiators to non-initiators was -0.21 points/year (95% CI:-0.81;0.39).

CONCLUSIONS: The association of statin use and cognitive decline is attenuated towards the null when using rigorous analytical approaches that more closely mimic RCTs. Point estimates, even within the same study, may vary depending on the analytical methods used. Further studies that leverage natural or quasi experiments around statin use are needed to replicate our findings.

1 aHazzouri, Adina, Zeki Al1 aJawadekar, Neal1 aGrasset, Leslie1 aKaiser, Paulina1 aKezios, Katrina1 aCalonico, Sebastian1 aGlymour, Maria1 aHirsch, Calvin1 aArnold, Alice, M1 aVaradhan, Ravi1 aOpoodden, Michelle, C uhttps://chs-nhlbi.org/node/8840