03343nas a2200517 4500008004100000022001400041245015500055210006900210260001300279300001200292490000700304520187900311653000902190653001002199653001902209653003302228653002102261653001502282653001902297653001102316653001802327653001102345653001702356653001402373653002502387653000902412653002602421653001802447653001402465653002602479653001702505653001102522653001802533100001602551700002402567700002302591700002302614700002002637700002202657700002502679700002102704700002002725700002302745710002102768856003602789 2017 eng d a1941-722500aVisit-to-Visit Blood Pressure Variability and Mortality and Cardiovascular Outcomes Among Older Adults: The Health, Aging, and Body Composition Study.0 aVisittoVisit Blood Pressure Variability and Mortality and Cardio c2017 Feb a151-1580 v303 a

BACKGROUND: Level of blood pressure (BP) is strongly associated with cardiovascular (CV) events and mortality. However, it is questionable whether mean BP can fully capture BP-related vascular risk. Increasing attention has been given to the value of visit-to-visit BP variability.

METHODS: We examined the association of visit-to-visit BP variability with mortality, incident myocardial infarction (MI), and incident stroke among 1,877 well-functioning elders in the Health, Aging, and Body Composition Study. We defined visit-to-visit diastolic BP (DBP) and systolic BP (SBP) variability as the root-mean-square error of person-specific linear regression of BP as a function of time. Alternatively, we counted the number of considerable BP increases and decreases (separately; 10mm Hg for DBP and 20mm Hg for SBP) between consecutive visits for each individual.

RESULTS: Over an average follow-up of 8.5 years, 623 deaths (207 from CV disease), 153 MIs, and 156 strokes occurred. The median visit-to-visit DBP and SBP variability was 4.96 mmHg and 8.53 mmHg, respectively. After multivariable adjustment, visit-to-visit DBP variability was related to higher all-cause (hazard ratio (HR) = 1.18 per 1 SD, 95% confidence interval (CI) = 1.01-1.37) and CV mortality (HR = 1.35, 95% CI = 1.05-1.73). Additionally, individuals having more considerable decreases of DBP (≥10mm Hg between 2 consecutive visits) had higher risk of all-cause (HR = 1.13, 95% CI = 0.99-1.28) and CV mortality (HR = 1.30, 95% CI = 1.05-1.61); considerable increases of SBP (≥20mm Hg) were associated with higher risk of all-cause (HR = 1.18, 95% CI = 1.03-1.36) and CV mortality (HR = 1.37, 95% CI = 1.08-1.74).

CONCLUSIONS: Visit-to-visit DBP variability and considerable changes in DBP and SBP were risk factors for mortality in the elderly.

10aAged10aAging10aBlood Pressure10aBlood Pressure Determination10aBody Composition10aCalifornia10aCohort Studies10aFemale10aHealth Status10aHumans10aHypertension10aIncidence10aLongitudinal Studies10aMale10aMyocardial Infarction10aOffice Visits10aPrognosis10aRetrospective Studies10aRisk Factors10aStroke10aSurvival Rate1 aWu, Chenkai1 aShlipak, Michael, G1 aStawski, Robert, S1 aPeralta, Carmen, A1 aPsaty, Bruce, M1 aHarris, Tamara, B1 aSatterfield, Suzanne1 aShiroma, Eric, J1 aNewman, Anne, B1 aOdden, Michelle, C1 aHealth ABC Study uhttps://chs-nhlbi.org/node/857202432nas 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/767402020nas a2200181 4500008004100000022001400041245012900055210006900184260001600253520142300269100001601692700001801708700001701726700001601743700002001759700002301779856003601802 2018 eng d a1476-625600aDevelopment, Construct Validity, and Predictive Validity of a Continuous Frailty Scale: Results from Two Large U.S. Cohorts.0 aDevelopment Construct Validity and Predictive Validity of a Cont c2018 Apr 243 a

Frailty is an age-related clinical syndrome of decreased resilience to stressors. Among numerous assessments of frailty, the frailty phenotype (FP) scale, proposed by Fried and colleagues has been the most widely used one. We aimed to develop a continuous frailty scale that may overcome limitations facing the categorical FP scale and to evaluate its construct validity, predictive validity, and measurement properties. Data were from the Cardiovascular Health Study (N = 4243) and Health and Retirement Study (N = 7600). Frailty was conceptualized as a continuous construct, measured by five measures used in FP scale: gait speed, grip strength, exhaustion, physical activity, and weight loss. We used confirmatory factor analysis to investigate the relationship between five indicators and the latent frailty construct. We examined the association of the continuous frailty scale with mortality and disability. The unidimensional model fit the data satisfactorily; similar factor structure was observed across two cohorts. Gait speed and weight loss were the strongest and weakest indicators, respectively; grip strength, exhaustion, and physical activity had similar strength in measuring frailty. In each cohort, the continuous frailty scale was strongly associated with mortality and disability and persisted to be associated with outcomes among robust and prefrail persons classified by the FP scale.

1 aWu, Chenkai1 aGeldhof, John1 aXue, Qian-Li1 aKim, Dae, H1 aNewman, Anne, B1 aOdden, Michelle, C uhttps://chs-nhlbi.org/node/766202440nas a2200193 4500008004100000022001400041245013300055210006900188260001600257520178400273100002302057700002302080700002802103700001602131700002002147700002002167700002302187856003602210 2019 eng d a1473-559800aThe role of functional status on the relationship between blood pressure and cognitive decline: the Cardiovascular Health Study.0 arole of functional status on the relationship between blood pres c2019 May 013 a

OBJECTIVE: To examine whether self-reported functional status modified the association between blood pressure (BP) and cognitive decline among older adults.

METHODS: The study included 2097 US adults aged 75 years and older from the Cardiovascular Health Study, followed for up to 6 years. Functional status was ascertained by self-reported limitation in activities of daily living (ADL; none vs. any). Cognitive function was assessed by the Modified Mini Mental State Exam (3MSE). We used linear mixed models to examine whether the presence of at least one ADL limitation modified the association between BP and cognitive decline. Potential confounders included demographics, physiologic measures, antihypertensive medication use and apolipoprotein E ε4 allele. We conducted stratified analyses for significant interactions between BP and ADL.

RESULTS: The association between BP and change in 3MSE differed by baseline ADL limitation. Among participants without ADL limitation, elevated systolic BP (≥140 mmHg) was associated with a 0.15 decrease (95% CI -0.24 to -0.07); P value for interaction less than 0.001, whereas in those with an ADL limitation, elevated systolic BP was independently associated with a 0.30 increase in 3MSE scores per year (95% CI 0.06-0.55). Elevated diastolic BP (≥80 mmHg) was associated with an increase in cognitive function in both groups, although the increase was greater in those with ADL limitation (0.47 points per year vs. 0.18 points per year, P value for interaction = 0.01).

CONCLUSION: Elevated BP appears to be associated with a decrease in cognitive scores among functioning older adults, and modest improvements in cognitive function among poorly functioning elders.

1 aMiller, Lindsay, M1 aPeralta, Carmen, A1 aFitzpatrick, Annette, L1 aWu, Chenkai1 aPsaty, Bruce, M1 aNewman, Anne, B1 aOdden, Michelle, C uhttps://chs-nhlbi.org/node/804802307nas a2200241 4500008004100000022001400041245011000055210006900165260001600234520155400250100002401804700001901828700001801847700002001865700002001885700002401905700002101929700001601950700002201966700001801988700002302006856003602029 2020 eng d a1758-535X00aLevel and change in N-terminal pro B-type Natriuretic Peptide and kidney function and survival to age 90.0 aLevel and change in Nterminal pro Btype Natriuretic Peptide and  c2020 May 173 a

BACKGROUND: Many traditional cardiovascular risk factors do not predict survival to very old age. Studies have shown associations of estimated glomerular filtration rate (eGFR) and N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) with cardiovascular disease and mortality in older populations. This study aimed to evaluate the associations of the level and change in eGFR and NT-pro-BNP with longevity to age 90 years.

METHODS: The population included participants (n=3,645) in the Cardiovascular Health Study, aged between 67-75 at baseline. The main exposures were eGFR, calculated with the Berlin Initiative Study equation (BIS2), and NT-pro-BNP, and the main outcome was survival to age 90. Mixed models were used to estimate level and change of the main exposures.

RESULTS: There was an association between baseline level and change of both eGFR and NT-pro-BNP and survival to 90, and this association persisted after adjustment for covariates. Each 10 ml/min per 1.73 m2 higher eGFR level was associated with an adjusted odds ratio (OR) of 1.23 (95% CI: 1.13, 1.34) of survival to 90, and a 0.5 ml/min/ 1.73 m2 slower decline in eGFR was associated with an OR of 1.51 (95% CI: 1.31, 1.74). A 2-fold higher level of NT-pro-BNP level had an adjusted OR of 0.67 (95% CI: 0.61, 0.73), and a 1.05-fold increase per year in NT-pro-BNP had an OR of 0.53 (95% CI: 0.43, 0.65) for survival to age 90.

CONCLUSION: eGFR and NT-pro-BNP appear to be important risk factors for longevity to age 90.

1 aHäberle, Astrid, D1 aBiggs, Mary, L1 aCushman, Mary1 aPsaty, Bruce, M1 aNewman, Anne, B1 aShlipak, Michael, G1 aGottdiener, John1 aWu, Chenkai1 aGardin, Julius, M1 aBansal, Nisha1 aOdden, Michelle, C uhttps://chs-nhlbi.org/node/839502635nas a2200241 4500008004100000022001400041245006200055210006100117260001300178300001200191490000700203520196100210100002002171700002002191700002202211700002002233700001602253700002202269700002302291700002002314700002302334856003602357 2021 eng d a1942-008000aAssociation Between Myocardial Strain and Frailty in CHS.0 aAssociation Between Myocardial Strain and Frailty in CHS c2021 May ae0121160 v143 a

BACKGROUND: Myocardial strain, measured by speckle-tracking echocardiography, is a novel measure of subclinical cardiovascular disease and may reflect myocardial aging. We evaluated the association between myocardial strain and frailty-a clinical syndrome of lack of physiological reserve.

METHODS: Frailty was defined in participants of the CHS (Cardiovascular Health Study) as having ≥3 of the following clinical criteria: weakness, slowness, weight loss, exhaustion, and inactivity. Using speckle-tracking echocardiography data, we examined the cross-sectional (n=3206) and longitudinal (n=1431) associations with frailty among participants who had at least 1 measure of myocardial strain, left ventricular longitudinal strain (LVLS), left ventricular early diastolic strain rate and left atrial reservoir strain, and no history of cardiovascular disease or heart failure at the time of echocardiography.

RESULTS: In cross-sectional analyses, lower (worse) LVLS was associated with prevalent frailty; this association was robust to adjustment for left ventricular ejection fraction (adjusted odds ratio, 1.32 [95% CI, 1.07-1.61] per 1-SD lower strain; =0.007) and left ventricular stroke volume (adjusted OR, 1.32 [95% CI, 1.08-1.61] per 1-SD lower strain; =0.007). In longitudinal analyses, adjusted associations of LVLS and left ventricular early diastolic strain with incident frailty were 1.35 ([95% CI, 0.96-1.89] =0.086) and 1.58 ([95% CI, 1.11-2.27] =0.013, respectively). Participants who were frail and had the worst LVLS had a 2.2-fold increased risk of death (hazard ratio, 2.20 [95% CI, 1.81-2.66]; <0.0001).

CONCLUSIONS: In community-dwelling older adults without prevalent cardiovascular disease, worse LVLS by speckle-tracking echocardiography, reflective of subclinical myocardial dysfunction, was associated with frailty. Frailty and LVLS have an additive effect on mortality risk.

1 aTan, Annabel, X1 aShah, Sanjiv, J1 aSanders, Jason, L1 aPsaty, Bruce, M1 aWu, Chenkai1 aGardin, Julius, M1 aPeralta, Carmen, A1 aNewman, Anne, B1 aOdden, Michelle, C uhttps://chs-nhlbi.org/node/879002644nas a2200205 4500008004100000022001400041245016900055210006900224260001600293520193400309100001702243700002002260700002302280700002302303700002002326700002102346700001902367700001602386856003602402 2021 eng d a1758-535X00aAssociation of Retail Environment and Neighborhood Socioeconomic Status with Mortality among Community-dwelling Older Adults in the US: Cardiovascular Health Study.0 aAssociation of Retail Environment and Neighborhood Socioeconomic c2021 Oct 203 a

BACKGROUND: Few studies have examined the association of neighborhood environment and mortality among community-dwelling older populations. Geographic Information Systems (GIS)-based measures of neighborhood physical environment may provide new insights on the health effects of the social and built environment.

METHODS: We studied 4,379 community-dwelling older adults in the US aged ≥65 years from the Cardiovascular Health Study. Principal component analysis was used to identify neighborhood components from 48 variables assessing facilities and establishments, demographic composition, socio-economic status, and economic prosperity. We used a Cox model to evaluate the association of neighborhood components with five-year mortality. Age, sex, race, education, income, marital status, body mass index, smoking status, disability, coronary heart disease, and diabetes were included as covariates. We also examined the interactions between neighborhood components and sex and race (Black vs. white or other).

RESULTS: We identified five neighborhood components, representing facilities and resources, immigrant communities, community-level economic deprivation, resident-level socio-economic status and residents' age. Communities' economic deprivation and residents' socio-economic status were significantly associated with five-year mortality. We did not find interactions between sex or race and any of the five neighborhood components. The results were similar in a sensitivity analysis where we used ten-year mortality as the outcome.

CONCLUSIONS: We found that communities' economic status but not facilities in communities was associated with mortality among older adults. These findings revealed the importance and benefits living in a socio-economically advantaged neighborhood could have on health among older residents with different demographic backgrounds.

1 aZhang, Kehan1 aLovasi, Gina, S1 aOdden, Michelle, C1 aMichael, Yvonne, L1 aNewman, Anne, B1 aArnold, Alice, M1 aKim, Dae, Hyun1 aWu, Chenkai uhttps://chs-nhlbi.org/node/900802499nas a2200205 4500008004100000022001400041245008600055210006900141260001600210300001000226490000700236520189200243100002302135700001602158700002202174700002002196700001802216700002302234856003602257 2021 eng d a1873-258500aCardiovascular damage phenotypes and all-cause and CVD mortality in older adults.0 aCardiovascular damage phenotypes and allcause and CVD mortality  c2021 Jul 30 a35-400 v633 a

PURPOSE: The association between CVD risk factors and mortality is well established, however, current tools for addressing subgroups have focused on the overall burden of disease. The identification of risky combinations of characteristics may lead to a better understanding of physiologic pathways that underlie morbidity and mortality in older adults.

METHODS: Participants included 5067 older adults from the Cardiovascular Health Study, followed for up to 6 years. Using latent class analysis (LCA), we created CV damage phenotypes based on probabilities of abnormal brain infarctions, major echocardiogram abnormalities, N-terminal probrain natriuretic peptide, troponin T, interleukin-6, c reactive-protein, galectin-3, cystatin C. We assigned class descriptions based on the probability of having an abnormality among risk factors, such that a healthy phenotype would have low probabilities in all risk factors. Participants were assigned to phenotypes based on the maximum probability of membership. We used Cox-proportional hazards regression to evaluate the association between the categorical CV damage phenotype and all-cause and CVD-mortality.

RESULTS: The analysis yielded 5 CV damage phenotypes consistent with the following descriptions: healthy (59%), cardio-renal (11%), cardiac (15%), multisystem morbidity (6%), and inflammatory (9%). All four phenotypes were statistically associated with a greater risk of all-cause mortality when compared with the healthy phenotype. The multisystem morbidity phenotype had the greatest risk of all-cause death (HR: 4.02; 95% CI: 3.44, 4.70), and CVD-mortality (HR: 4.90, 95% CI: 3.95, 6.06).

CONCLUSIONS: Five CV damage phenotypes emerged from CVD risk factor measures. CV damage across multiple systems confers a greater mortality risk compared to damage in any single domain.

1 aMiller, Lindsay, M1 aWu, Chenkai1 aHirsch, Calvin, H1 aLopez, Oscar, L1 aCushman, Mary1 aOdden, Michelle, C uhttps://chs-nhlbi.org/node/883402778nas a2200385 4500008004100000022001400041245007500055210006900130260001300199300001100212490000700223520174600230653001001976653001101986653000901997653001802006653001102024653002302035653000902058653001502067653001802082100001802100700001902118700002302137700002702160700002002187700002202207700002002229700002202249700001602271700002202287700002402309700002302333856003602356 2022 eng d a1474-972600aPlasma proteomic signature of decline in gait speed and grip strength.0 aPlasma proteomic signature of decline in gait speed and grip str c2022 Dec ae137360 v213 a

The biological mechanisms underlying decline in physical function with age remain unclear. We examined the plasma proteomic profile associated with longitudinal changes in physical function measured by gait speed and grip strength in community-dwelling adults. We applied an aptamer-based platform to assay 1154 plasma proteins on 2854 participants (60% women, aged 76 years) in the Cardiovascular Health Study (CHS) in 1992-1993 and 1130 participants (55% women, aged 54 years) in the Framingham Offspring Study (FOS) in 1991-1995. Gait speed and grip strength were measured annually for 7 years in CHS and at cycles 7 (1998-2001) and 8 (2005-2008) in FOS. The associations of individual protein levels (log-transformed and standardized) with longitudinal changes in gait speed and grip strength in two populations were examined separately by linear mixed-effects models. Meta-analyses were implemented using random-effects models and corrected for multiple testing. We found that plasma levels of 14 and 18 proteins were associated with changes in gait speed and grip strength, respectively (corrected p < 0.05). The proteins most strongly associated with gait speed decline were GDF-15 (Meta-analytic p = 1.58 × 10 ), pleiotrophin (1.23 × 10 ), and TIMP-1 (5.97 × 10 ). For grip strength decline, the strongest associations were for carbonic anhydrase III (1.09 × 10 ), CDON (2.38 × 10 ), and SMOC1 (7.47 × 10 ). Several statistically significant proteins are involved in the inflammatory responses or antagonism of activin by follistatin pathway. These novel proteomic biomarkers and pathways should be further explored as future mechanisms and targets for age-related functional decline.

10aAdult10aFemale10aGait10aHand Strength10aHumans10aIndependent Living10aMale10aProteomics10aWalking Speed1 aLiu, Xiaojuan1 aPan, Stephanie1 aXanthakis, Vanessa1 aVasan, Ramachandran, S1 aPsaty, Bruce, M1 aAustin, Thomas, R1 aNewman, Anne, B1 aSanders, Jason, L1 aWu, Chenkai1 aTracy, Russell, P1 aGerszten, Robert, E1 aOdden, Michelle, C uhttps://chs-nhlbi.org/node/925502620nas a2200337 4500008004100000022001400041245005100055210005000106260001600156300001100172520166800183100001801851700002601869700002001895700002001915700002401935700001601959700002101975700001901996700002202015700002202037700002802059700002202087700002402109700002202133700002202155700002402177700002202201700002302223856003602246 2024 eng d a1474-972600aPlasma proteomic signature of human longevity.0 aPlasma proteomic signature of human longevity c2024 Mar 05 ae141363 a

The identification of protein targets that exhibit anti-aging clinical potential could inform interventions to lengthen the human health span. Most previous proteomics research has been focused on chronological age instead of longevity. We leveraged two large population-based prospective cohorts with long follow-ups to evaluate the proteomic signature of longevity defined by survival to 90 years of age. Plasma proteomics was measured using a SOMAscan assay in 3067 participants from the Cardiovascular Health Study (discovery cohort) and 4690 participants from the Age Gene/Environment Susceptibility-Reykjavik Study (replication cohort). Logistic regression identified 211 significant proteins in the CHS cohort using a Bonferroni-adjusted threshold, of which 168 were available in the replication cohort and 105 were replicated (corrected p value <0.05). The most significant proteins were GDF-15 and N-terminal pro-BNP in both cohorts. A parsimonious protein-based prediction model was built using 33 proteins selected by LASSO with 10-fold cross-validation and validated using 27 available proteins in the validation cohort. This protein model outperformed a basic model using traditional factors (demographics, height, weight, and smoking) by improving the AUC from 0.658 to 0.748 in the discovery cohort and from 0.755 to 0.802 in the validation cohort. We also found that the associations of 169 out of 211 proteins were partially mediated by physical and/or cognitive function. These findings could contribute to the identification of biomarkers and pathways of aging and potential therapeutic targets to delay aging and age-related diseases.

1 aLiu, Xiaojuan1 aAxelsson, Gisli, Thor1 aNewman, Anne, B1 aPsaty, Bruce, M1 aBoudreau, Robert, M1 aWu, Chenkai1 aArnold, Alice, M1 aAspelund, Thor1 aAustin, Thomas, R1 aGardin, Julius, M1 aSiggeirsdottir, Kristin1 aTracy, Russell, P1 aGerszten, Robert, E1 aLauner, Lenore, J1 aJennings, Lori, L1 aGudnason, Vilmundur1 aSanders, Jason, L1 aOdden, Michelle, C uhttps://chs-nhlbi.org/node/9640