03092nas a2200409 4500008004100000022001400041245015800055210006900213260001600282300001200298490000800310520185700318653000902175653002202184653003202206653002802238653001902266653002702285653002202312653001102334653001802345653002502363653001102388653001702399653002502416653000902441100002002450700002402470700001702494700002202511700001902533700002202552700002102574700002002595710003202615856003502647 2002 eng d a0003-992600aFrailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: results from the Cardiovascular Health Study.0 aFrailty and activation of the inflammation and coagulation syste c2002 Nov 11 a2333-410 v1623 a

BACKGROUND: The biological basis of frailty has been difficult to establish owing to the lack of a standard definition, its complexity, and its frequent coexistence with illness.

OBJECTIVE: To establish the biological correlates of frailty in the presence and absence of concurrent cardiovascular disease and diabetes mellitus.

METHODS: Participants were 4735 community-dwelling adults 65 years and older. Frail, intermediate, and nonfrail subjects were identified by a validated screening tool and exclusion criteria. Bivariate relationships between frailty level and physiological measures were evaluated by Pearson chi2 tests for categorical variables and analysis of variance F tests for continuous variables. Multinomial logistic regression was performed to evaluate multivariable relationships between frailty status and physiological measures.

RESULTS: Of 4735 Cardiovascular Health Study participants, 299 (6.3%) were identified as frail, 2147 (45.3%) as intermediate, and 2289 (48.3%) as not frail. Frail vs nonfrail participants had increased mean +/- SD levels of C-reactive protein (5.5 +/- 9.8 vs 2.7 +/- 4.0 mg/L), factor VIII (13 790 +/- 4480 vs 11 860 +/- 3460 mg/dL), and, in a smaller subset, D dimer (647 +/- 1033 vs 224 +/- 258 ng/mL) (P< or =.001 for all, chi2 test for trend). These differences persisted when individuals with cardiovascular disease and diabetes were excluded and after adjustment for age, sex, and race.

CONCLUSIONS: These findings support the hypothesis that there is a specific physiological basis to the geriatric syndrome of frailty that is characterized in part by increased inflammation and elevated markers of blood clotting and that these physiological differences persist when those with diabetes and cardiovascular disease are excluded.

10aAged10aAged, 80 and over10aBlood Coagulation Disorders10aCardiovascular Diseases10aCohort Studies10aDiabetes Complications10aDiabetes Mellitus10aFemale10aFrail Elderly10aGeriatric Assessment10aHumans10aInflammation10aLongitudinal Studies10aMale1 aWalston, Jeremy1 aMcBurnie, Mary, Ann1 aNewman, Anne1 aTracy, Russell, P1 aKop, Willem, J1 aHirsch, Calvin, H1 aGottdiener, John1 aFried, Linda, P1 aCardiovascular Health Study uhttps://chs-nhlbi.org/node/70902839nas a2200361 4500008004100000022001400041245014300055210006900198260001600267300001100283490000700294520177600301653000902077653002802086653003002114653002802144653001502172653001102187653001102198653001702209653000902226653001702235100001902252700002402271700002502295700002002320700002402340700002002364700001702384700001902401700002202420856003502442 2002 eng d a0002-914900aInflammation and coagulation factors in persons > 65 years of age with symptoms of depression but without evidence of myocardial ischemia.0 aInflammation and coagulation factors in persons 65 years of age  c2002 Feb 15 a419-240 v893 a

Depression is associated with increased cardiovascular disease, but the underlying mechanisms are not well understood. This study examines associations of depressive symptoms with inflammation and coagulation factors in persons aged > 65 years. Blood samples were obtained from 4,268 subjects free of cardiovascular disease (age 72.4 +/- 5.5 years, 2,623 women). Inflammation markers were C-reactive protein (CRP), white blood cell (WBC) count, total platelet count, and albumin; coagulation factors included factors VIIc and VIIIc and fibrinogen. Depression was assessed with the Center for Epidemiologic Studies Depression scale, and states of energy depletion with a validated exhaustion index. Statistical adjustments were made for risk factors (age, sex, race, systolic blood pressure, smoking status, diabetes mellitus) and physical measures of frailty (isometric handgrip, timed 15-feet walk test, activity level). Depression was associated with elevated CRP (3.31 +/- 0.10 vs 3.51 +/- 0.21 mg/L), WBC (6.14 +/- 0.03 vs 6.43 +/- 0.11 10(6)/L), fibrinogen (319 +/- 1 vs 326 +/- 3 mg/dl), and factor VIIc (124.6 +/- 0.6% vs 127.2 +/- 1.3%; all p <0.05). Exhaustion also was related to elevated inflammation and coagulation markers (p < 0.05). Exhausted men had markedly elevated CRP levels (6.82 +/- 2.10 mg/L) versus nonexhausted men (3.05 +/- 0.16: p = 0.007). After adjustment for control variables, exhaustion remained associated with albumin (p = 0.033), fibrinogen (p = 0.017), CRP (p = 0.066), and WBC (p = 0.060), whereas associations of depressive symptoms with biochemistry measures lost statistical significance. Thus, depression and exhaustion are associated with low-grade inflammation and elevated coagulation factors in persons aged > 65 years.

10aAged10aBlood Chemical Analysis10aBlood Coagulation Factors10aCardiovascular Diseases10aDepression10aFemale10aHumans10aInflammation10aMale10aRisk Factors1 aKop, Willem, J1 aGottdiener, John, S1 aTangen, Catherine, M1 aFried, Linda, P1 aMcBurnie, Mary, Ann1 aWalston, Jeremy1 aNewman, Anne1 aHirsch, Calvin1 aTracy, Russell, P uhttps://chs-nhlbi.org/node/67803506nas a2200373 4500008004100000022001400041245016100055210006900216260001300285300001100298490000700309520239700316653003102713653000902744653002502753653002402778653002102802653001102823653001102834653002502845653000902870653002602879653000902905653001802914100001902932700002002951700002102971700002002992700001803012700001903030700002303049700002503072856003503097 2005 eng d a0002-861400aThe course of functional decline in older people with persistently elevated depressive symptoms: longitudinal findings from the Cardiovascular Health Study.0 acourse of functional decline in older people with persistently e c2005 Apr a569-750 v533 a

OBJECTIVES: To examine the relationship between persistently high depressive symptoms and long-term changes in functional disability in elderly persons.

DESIGN: A community-based, prospective, observational study.

SETTING: Participant data from the Cardiovascular Health Study.

PARTICIPANTS: From the overall sample of 5,888 subjects, three types of participants were identified for this study: (1) persistently depressed individuals, who experienced an onset of depressive symptoms that persisted over 4 years (n=119); (2) temporarily depressed individuals, who experienced an onset of depressive symptoms that resolved over time (n=259); and (3) nondepressed individuals, with persistently low depressive symptoms throughout the follow-up period who were matched on baseline activity of daily living (ADL) scores, sex, and age to the previous two groups combined (n=378).

MEASUREMENTS: Four consecutive years of data were assessed: validated measures of depression (10-item CES-D), functional disability (10-item ADL/instrumental ADL measure), physical performance, medical illness, and cognition.

RESULTS: The persistently depressed group showed a greater linear increase in functional disability ratings than the temporarily depressed and nondepressed groups. This association between persistent depression and functional disability was robust even when controlling for baseline demographic and clinical/performance measures, including cognition. The persistently depressed group had an adjusted odds ratio (OR) of 5.27 (95% confidence interval (CI) 3.03-9.16) for increased functional disability compared with the nondepressed group over 3 years of follow-up, whereas the temporarily depressed group had an adjusted OR of 2.39 (95% CI=1.55-3.69) compared with the nondepressed group.

CONCLUSION: Persistently elevated depressive symptoms in elderly persons are associated with a steep trajectory of worsening functional disability, generating the hypothesis that treatments for late-life depression need to be assessed on their efficacy in maintaining long-term functional status as well as remission of depressive symptoms. These results also demonstrate the need for studies to differentiate between persistent and temporary depressive symptoms when examining their relationship to disability.

10aActivities of Daily Living10aAged10aCase-Control Studies10aDepressive Disorder10aDisabled Persons10aFemale10aHumans10aLongitudinal Studies10aMale10aMultivariate Analysis10aRisk10aUnited States1 aLenze, Eric, J1 aSchulz, Richard1 aMartire, Lynn, M1 aZdaniuk, Bozena1 aGlass, Thomas1 aKop, Willem, J1 aJackson, Sharon, A1 aReynolds, Charles, F uhttps://chs-nhlbi.org/node/82803286nas a2200325 4500008004100000022001400041245011700055210006900172260001300241300001100254490000600265520238300271653000902654653002202663653001102685653001302696653001802709653001102727653000902738653001502747653002002762100001802782700002402800700002202824700002302846700001402869700001902883700002202902856003602924 2009 eng d a1941-329700aAssociation between elevated fibrosis markers and heart failure in the elderly: the cardiovascular health study.0 aAssociation between elevated fibrosis markers and heart failure  c2009 Jul a303-100 v23 a

BACKGROUND: Myocardial fibrosis reflects excess collagen deposition in the extracellular left ventricular matrix, which has been associated with heart failure (HF). No studies have addressed the relation between fibrosis biomarkers and HF in the elderly.

METHODS AND RESULTS: Serum fibrosis markers were measured in 880 participants of the Cardiovascular Health Study (mean age 77+/-6 years, 48% women). Participants with systolic HF (n=131, left ventricular ejection fraction <55%) and those with diastolic HF (n=179, left ventricular ejection fraction > or =55%) were compared with controls (280 with cardiovascular risk factors, and 279 healthy individuals) using a nested case-control design. Fibrosis markers included carboxyl-terminal peptide of procollagen type I, carboxyl-terminal telopeptide of collagen type I, and amino-terminal peptide of procollagen type III. Echocardiography was used to document systolic and diastolic function parameters. Analysis of variance and logistic regression analysis (per tertile odds ratios [OR]), adjusted by age, gender, race, hypertension, atrial fibrillation, coronary heart disease, baseline serum glucose, serum cystatin C, serum creatinine, C-reactive protein, any angiotensin-converting enzyme inhibitor, spironolactone or any diuretic, NT-proBNP, and total bone mineral density were performed. Systolic HF was associated with significantly elevated carboxyl-terminal telopeptide of collagen type I (OR=2.6; 95% CI=1.2 to 5.7) and amino-terminal peptide of procollagen type III (OR=3.3; 95% CI=1.6 to 5.8), when adjusting for covariates. Associations of diastolic HF were significant for carboxyl-terminal telopeptide of collagen type I (OR=3.9; 95% CI=1.9 to 8.3) and amino-terminal peptide of procollagen type III (OR=2.7; 95% CI=1.4 to 5.4). HF was not associated with elevated carboxyl-terminal peptide of procollagen type I (P>0.10), and fibrosis markers did not significantly differ between HF with diastolic versus those with systolic dysfunction (P>0.10) whereas NT-proBNP mean values were higher in systolic heart failure than in diastolic heart failure (P<0.0001).

CONCLUSIONS: Fibrosis markers are significantly elevated in elderly individuals with diastolic or systolic HF. These associations remained significant when adjusting for covariates relevant to the aging process.

10aAged10aAged, 80 and over10aFemale10aFibrosis10aHeart Failure10aHumans10aMale10aMyocardium10aUltrasonography1 aBarasch, Eddy1 aGottdiener, John, S1 aAurigemma, Gerard1 aKitzman, Dalane, W1 aHan, Jing1 aKop, Willem, J1 aTracy, Russell, P uhttps://chs-nhlbi.org/node/113403367nas a2200481 4500008004100000022001400041245009900055210006900154260001300223300001100236490000700247520202200254653000902276653002202285653001502307653002302322653002802345653002002373653001502393653002402408653002802432653001202460653001102472653001302483653001902496653001802515653001102533653002702544653000902571653002602580653002202606653001602628653003702644653001702681653002602698100001902724700001902743700001802762700002002780700002502800700002402825856003602849 2010 eng d a1090-213900aAssociation between depressive symptoms and fibrosis markers: the Cardiovascular Health Study.0 aAssociation between depressive symptoms and fibrosis markers the c2010 Feb a229-350 v243 a

OBJECTIVE: Fibrosis plays an important role in heart failure (HF) and other diseases that occur more frequently with increasing age. Depression is associated with an increased risk of heart failure and other age-related diseases. This study examined the association between depressive symptoms and fibrosis markers in adults aged 65 years and above.

METHODS: Fibrosis markers and depressive symptoms were assessed in 870 participants (age=80.9+/-5.9 yrs, 49% women) using a case-control design based on heart failure status (307 HF patients and 563 age- and sex-matched controls, of whom 284 with CVD risk factors (hypertension, diabetes mellitus, or hypercholesterolemia) and 279 controls without these CVD risk factors). Fibrosis markers were procollagen type I (PIP), type I collagen (CITP), and procollagen type III (PIIINP). Inflammation markers included C-reactive protein, white blood cell counts and fibrinogen. Depression was assessed using the Center for Epidemiological Studies-Depression (CES-D) scale using a previously validated cut-off point for depression (CES-D > or = 8). Covariates included demographic and clinical variables.

RESULTS: Depression was associated with higher levels of PIP (median=411.0, inter-quartile range (IQR)=324.4-472.7 ng/mL vs. 387.6, IQR=342.0-512.5 ng/mL, p=0.006) and CITP (4.99, IQR=3.53-6.85 vs. 4.53, IQR=3.26-6.22 microg/L, p=0.024), but not PIIIINP (4.07, IQR=2.75-5.54 microg/L vs. 3.58, IQR=2.71-5.01 microg/L, p=0.29) compared to individuals without depression. Inflammation markers were also elevated in depressed participants (CRP, p=0.014; WBC, p=0.075; fibrinogen, p=0.074), but these inflammation markers did not account for the relationship between depression and fibrosis markers.

CONCLUSIONS: Depression is associated with elevated fibrosis markers and may therefore adversely affect heart failure and other age-related diseases in which extra-cellular matrix formation plays a pathophysiological role.

10aAged10aAged, 80 and over10aBiomarkers10aC-Reactive Protein10aCardiovascular Diseases10aCollagen Type I10aDepression10aElectrocardiography10aEndomyocardial Fibrosis10aFatigue10aFemale10aFibrosis10aHealth Surveys10aHeart Failure10aHumans10aInflammation Mediators10aMale10aMultivariate Analysis10aPeptide Fragments10aProcollagen10aPsychiatric Status Rating Scales10aRisk Factors10aSocioeconomic Factors1 aKop, Willem, J1 aKuhl, Emily, A1 aBarasch, Eddy1 aJenny, Nancy, S1 aGottlieb, Stephen, S1 aGottdiener, John, S uhttps://chs-nhlbi.org/node/113203876nas a2200385 4500008004100000022001400041245015500055210006900210260001600279300001300295490000800308520273900316653000903055653001503064653002803079653001903107653001103126653001803137653001103155653001403166653000903180653003003189653000903219653003203228653001503260653001803275100003003293700002303323700002703346700002403373700001903397700001403416700002403430856003603454 2010 eng d a1538-359800aAssociation of serial measures of cardiac troponin T using a sensitive assay with incident heart failure and cardiovascular mortality in older adults.0 aAssociation of serial measures of cardiac troponin T using a sen c2010 Dec 08 a2494-5020 v3043 a

CONTEXT: Older adults comprise the majority of new-onset heart failure (HF) diagnoses, but traditional risk-factor prediction models have limited accuracy in this population to identify those at highest risk for hospitalization or death.

OBJECTIVES: To determine if cardiac troponin T (cTnT) measured by a highly sensitive assay would be detectable in the majority of community-dwelling older adults, and if serial measures were associated with risk of HF hospitalization and cardiovascular death.

DESIGN, SETTING, AND PARTICIPANTS: A longitudinal nationwide cohort study (Cardiovascular Health Study) of 4221 community-dwelling adults aged 65 years or older without prior HF who had cTnT measured using a highly sensitive assay at baseline (1989-1990) and repeated after 2 to 3 years (n = 2918).

MAIN OUTCOME MEASURES: New-onset HF and cardiovascular death were examined through June 2008 with respect to cTnT concentrations, accounting for clinical risk predictors.

RESULTS: Cardiac troponin T was detectable (≥3.00 pg/mL) in 2794 participants (66.2%). During a median follow-up of 11.8 years, 1279 participants experienced new-onset HF and 1103 cardiovascular deaths occurred, with a greater risk of both end points associated with higher cTnT concentrations. Among those participants with the highest cTnT concentrations (>12.94 pg/mL), there was an incidence rate per 100 person-years of 6.4 (95% confidence interval [CI], 5.8-7.2; adjusted hazard ratio [aHR], 2.48; 95% CI, 2.04-3.00) for HF and an incidence rate of 4.8 (95% CI, 4.3-5.4; aHR, 2.91; 95% CI, 2.37-3.58) for cardiovascular death compared with participants with undetectable cTnT levels (incidence rate, 1.6; 95% CI, 1.4-1.8 and 1.1; 95% CI, 0.9-1.2 for HF and cardiovascular death, respectively). Among individuals with initially detectable cTnT, a subsequent increase of more than 50% (n = 393, 22%) was associated with a greater risk for HF (aHR, 1.61; 95% CI, 1.32-1.97) and cardiovascular death (aHR, 1.65; 95% CI, 1.35-2.03) and a decrease of more than 50% (n = 247, 14%) was associated with a lower risk for HF (aHR, 0.73; 95% CI, 0.54-0.97) and cardiovascular death (aHR, 0.71; 95% CI, 0.52-0.97) compared with participants with 50% or less change. Addition of baseline cTnT measurements to clinical risk factors was associated with only modest improvement in discrimination, with change in C statistic of 0.015 for HF and 0.013 for cardiovascular death.

CONCLUSION: In this cohort of older adults without known HF, baseline cTnT levels and changes in cTnT levels measured with a highly sensitive assay were significantly associated with incident HF and cardiovascular death.

10aAged10aBiomarkers10aCardiovascular Diseases10aCohort Studies10aFemale10aHeart Failure10aHumans10aIncidence10aMale10aPredictive Value of Tests10aRisk10aSensitivity and Specificity10aTroponin T10aUnited States1 adeFilippi, Christopher, R1 ade Lemos, James, A1 aChristenson, Robert, H1 aGottdiener, John, S1 aKop, Willem, J1 aZhan, Min1 aSeliger, Stephen, L uhttps://chs-nhlbi.org/node/124503245nas a2200433 4500008004100000022001400041245014400055210006900199260001300268300001100281490000700292520199000299653000902289653003802298653001502336653002302351653002802374653001902402653001902421653001602440653002402456653002402480653001102504653002202515653001502537653001102552653001702563653001802580653002002598653000902618653001702627100001902644700002202663700002202685700002402707700002002731700002402751856003602775 2010 eng d a1534-779600aAutonomic nervous system dysfunction and inflammation contribute to the increased cardiovascular mortality risk associated with depression.0 aAutonomic nervous system dysfunction and inflammation contribute c2010 Sep a626-350 v723 a

OBJECTIVE: To investigate prospectively whether autonomic nervous system (ANS) dysfunction and inflammation play a role in the increased cardiovascular disease (CVD)-related mortality risk associated with depression.

METHODS: Participants in the Cardiovascular Health Study (n = 907; mean age, 71.3 ± 4.6 years; 59.1% women) were evaluated for ANS indices derived from heart rate variability (HRV) analysis (frequency and time domain HRV, and nonlinear indices, including detrended fluctuation analysis (DFA(1)) and heart rate turbulence). Inflammation markers included C-reactive protein, interleukin-6, fibrinogen, and white blood cell count). Depressive symptoms were assessed, using the 10-item Centers for Epidemiological Studies Depression scale. Cox proportional hazards models were used to investigate the mortality risk associated with depression, ANS, and inflammation markers, adjusting for demographic and clinical covariates.

RESULTS: Depression was associated with ANS dysfunction (DFA(1), p = .018), and increased inflammation markers (white blood cell count, p = .012, fibrinogen p = .043) adjusting for covariates. CVD-related mortality occurred in 121 participants during a median follow-up of 13.3 years. Depression was associated with an increased CVD mortality risk (hazard ratio, 1.88; 95% confidence interval, 1.23-2.86). Multivariable analyses showed that depression was an independent predictor of CVD mortality (hazard ratio, 1.72; 95% confidence interval, 1.05-2.83) when adjusting for independent HRV and inflammation predictors (DFA(1), heart rate turbulence, interleukin-6), attenuating the depression-CVD mortality association by 12.7% (p < .001).

CONCLUSION: Autonomic dysfunction and inflammation contribute to the increased cardiovascular mortality risk associated with depression, but a large portion of the predictive value of depression remains unexplained by these neuroimmunological measures.

10aAged10aAutonomic Nervous System Diseases10aBiomarkers10aC-Reactive Protein10aCardiovascular Diseases10aCause of Death10aCohort Studies10aComorbidity10aDepressive Disorder10aElectrocardiography10aFemale10aFollow-Up Studies10aHeart Rate10aHumans10aInflammation10aInterleukin-610aLeukocyte Count10aMale10aRisk Factors1 aKop, Willem, J1 aStein, Phyllis, K1 aTracy, Russell, P1 aBarzilay, Joshua, I1 aSchulz, Richard1 aGottdiener, John, S uhttps://chs-nhlbi.org/node/121603168nas a2200349 4500008004100000022001400041245013400055210006900189260001600258300001100274490000700285520214700292653000902439653001502448653001102463653001802474653001102492653000902503653003102512653002202543653001402565653002402579653002002603653001702623653001802640100003002658700002702688700002402715700001902739700002402758856003602782 2010 eng d a1558-359700aDynamic cardiovascular risk assessment in elderly people. The role of repeated N-terminal pro-B-type natriuretic peptide testing.0 aDynamic cardiovascular risk assessment in elderly people The rol c2010 Feb 02 a441-500 v553 a

OBJECTIVES: This study sought to determine whether serial measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in community-dwelling elderly people would provide additional prognostic information to that from traditional risk factors.

BACKGROUND: Accurate cardiovascular risk stratification is challenging in elderly people.

METHODS: NT-proBNP was measured at baseline and 2 to 3 years later in 2,975 community-dwelling older adults free of heart failure in the longitudinal CHS (Cardiovascular Health Study). This investigation examined the risk of new-onset heart failure (HF) and death from cardiovascular causes associated with baseline NT-proBNP and changes in NT-proBNP levels, adjusting for potential confounders.

RESULTS: NT-proBNP levels in the highest quintile (>267.7 pg/ml) were independently associated with greater risks of HF (hazard ratio [HR]: 3.05; 95% confidence interval [CI]: 2.46 to 3.78) and cardiovascular death (HR: 3.02; 95% CI: 2.36 to 3.86) compared with the lowest quintile (<47.5 pg/ml). The inflection point for elevated risk occurred at NT-proBNP 190 pg/ml. Among participants with initially low NT-proBNP (<190 pg/ml), those who developed a >25% increase on follow-up to >190 pg/ml (21%) were at greater adjusted risk of HF (HR: 2.13; 95% CI: 1.68 to 2.71) and cardiovascular death (HR: 1.91; 95% CI: 1.43 to 2.53) compared with those with sustained low levels. Among participants with initially high NT-proBNP, those who developed a >25% increase (40%) were at higher risk of HF (HR: 2.06; 95% CI: 1.56 to 2.72) and cardiovascular death (HR: 1.88; 95% CI: 1.37 to 2.57), whereas those who developed a >25% decrease to

CONCLUSIONS: NT-proBNP levels independently predict heart failure and cardiovascular death in older adults. NT-proBNP levels frequently change over time, and these fluctuations reflect dynamic changes in cardiovascular risk.

10aAged10aBiomarkers10aFemale10aHeart Failure10aHumans10aMale10aNatriuretic Peptide, Brain10aPeptide Fragments10aPrognosis10aProspective Studies10aRisk Assessment10aRisk Factors10aUnited States1 adeFilippi, Christopher, R1 aChristenson, Robert, H1 aGottdiener, John, S1 aKop, Willem, J1 aSeliger, Stephen, L uhttps://chs-nhlbi.org/node/116403282nas a2200301 4500008004100000022001400041245018500055210006900240260001600309300001200325490000800337520234400345653000902689653001102698653002802709653001102737653000902748653001502757653001702772653002002789653003402809100001602843700002402859700002002883700001902903700002202922856003602944 2011 eng d a1879-191300aComparison of characteristics and outcomes of asymptomatic versus symptomatic left ventricular dysfunction in subjects 65 years old or older (from the Cardiovascular Health Study).0 aComparison of characteristics and outcomes of asymptomatic versu c2011 Jun 01 a1667-740 v1073 a

Although asymptomatic left ventricular (LV) systolic dysfunction (ALVSD) is common, its phenotype and prognosis for incident heart failure (HF) and mortality are insufficiently understood. Echocardiography was done in 5,649 participants in the Cardiovascular Health Study (age 73.0 ± 5.6 years, 57.6% women). The clinical characteristics and cardiovascular risk factors of the participants with ALVSD were compared to those with normal LV function (ejection fraction ≥55%) and with symptomatic LV systolic dysfunction (SLVSD; ejection fraction <55% and a history of HF). Cox proportional hazards models were used to estimate the risk of incident HF and mortality in those with ALVSD. Also, comparisons were made among the LV ejection fraction subgroups using previously validated cutoff values (<45% and 45% to 55%), adjusting for the demographic and cardiovascular disease risk factors. Those with ALVSD (7.3%) were more likely to have cardiovascular risk factors than those in the reference group (without LV dysfunction or symptomatic HF) but less likely than those with SLVSD. The HF rate was 24 occurrences per 1,000 person-years in the reference group and 57 occurrences per 1,000 person-years in those with ALVSD. The HF rate was 45 occurrences per 1,000 person-years for those with ALVSD and mildly impaired LV dysfunction and 93 occurrences per 1,000 person-years for those with ALVSD and moderate to severe LV dysfunction. The mortality rate was 51 deaths per 1,000 person-years in the reference group, 90 deaths per 1,000 person-years in the ALVSD group, and 156 deaths per 1,000 person-years in the SLVSD group. Adjusting for covariates, compared to the reference group, ALVSD was associated with an increased risk of incident HF (hazard ratio 1.60, 95% confidence interval 1.35 to 1.91), cardiovascular mortality (hazard ratio 2.13, 95% confidence interval 1.81 to 2.51), and all-cause mortality (hazard ratio 1.46, 95% confidence interval 1.29 to 1.64). In conclusion, subjects with ALVSD are characterized by a greater prevalence of cardiovascular risk factors and co-morbidities than those with normal LV function and without HF. However, the prevalence is lower than in those with SLVSD. Patients with ALVSD are at an increased risk of HF and mortality, particularly those with greater severity of LV impairment.

10aAged10aFemale10aHeart Failure, Systolic10aHumans10aMale10aPrevalence10aRisk Factors10aUltrasonography10aVentricular Dysfunction, Left1 aPandhi, Jay1 aGottdiener, John, S1 aBartz, Traci, M1 aKop, Willem, J1 aMehra, Mandeep, R uhttps://chs-nhlbi.org/node/129003004nas a2200337 4500008004100000022001400041245013200055210006900187260001300256300001000269490000700279520201500286653000902301653002202310653002802332653001502360653002602375653001102401653001102412653000902423653001902432653003702451653001802488100001502506700001802521700002402539700002402563700001902587700002402606856003602630 2011 eng d a1468-201X00aDepressive symptoms, physical inactivity and risk of cardiovascular mortality in older adults: the Cardiovascular Health Study.0 aDepressive symptoms physical inactivity and risk of cardiovascul c2011 Mar a500-50 v973 a

BACKGROUND: Depressed older individuals have a higher mortality than older persons without depression. Depression is associated with physical inactivity, and low levels of physical activity have been shown in some cohorts to be a partial mediator of the relationship between depression and cardiovascular events and mortality.

METHODS: A cohort of 5888 individuals (mean 72.8 ± 5.6 years, 58% female, 16% African-American) from four US communities was followed for an average of 10.3 years. Self-reported depressive symptoms (10-item Center for Epidemiological Studies Depression Scale) were assessed annually and self-reported physical activity was assessed at baseline and at 3 and 7 years. To estimate how much of the increased risk of cardiovascular mortality associated with depressive symptoms was due to physical inactivity, Cox regression with time-varying covariates was used to determine the percentage change in the log HR of depressive symptoms for cardiovascular mortality after adding physical activity variables.

RESULTS: At baseline, 20% of participants scored above the cut-off for depressive symptoms. There were 2915 deaths (49.8%), of which 1176 (20.1%) were from cardiovascular causes. Depressive symptoms and physical inactivity each independently increased the risk of cardiovascular mortality and were strongly associated with each other (all p < 0.001). Individuals with both depressive symptoms and physical inactivity had greater cardiovascular mortality than those with either individually (p < 0.001, log rank test). Physical inactivity reduced the log HR of depressive symptoms for cardiovascular mortality by 26% after adjustment. This was similar for persons with (25%) and without (23%) established coronary heart disease.

CONCLUSIONS: Physical inactivity accounted for a significant proportion of the risk of cardiovascular mortality due to depressive symptoms in older adults, regardless of coronary heart disease status.

10aAged10aAged, 80 and over10aCardiovascular Diseases10aDepression10aEpidemiologic Methods10aFemale10aHumans10aMale10aMotor Activity10aPsychiatric Status Rating Scales10aUnited States1 aWin, Sithu1 aParakh, Kapil1 aEze-Nliam, Chete, M1 aGottdiener, John, S1 aKop, Willem, J1 aZiegelstein, Roy, C uhttps://chs-nhlbi.org/node/127003385nas a2200421 4500008004100000022001400041245017900055210006900234260001600303300001300319490000700332520212700339653001602466653000902482653002202491653001502513653001902528653001002547653001102557653002202568653001802590653001102608653000902619653003102628653002202659653002402681653001702705653001802722653001802740653003102758100003002789700002702819700001902846700002402865700001402889700002402903856003602927 2011 eng d a1558-359700aLeft ventricular ejection fraction assessment in older adults: an adjunct to natriuretic peptide testing to identify risk of new-onset heart failure and cardiovascular death?0 aLeft ventricular ejection fraction assessment in older adults an c2011 Sep 27 a1497-5060 v583 a

OBJECTIVES: The goal of this paper was to determine whether assessment of left ventricular ejection fraction (LVEF) enhances prediction of new-onset heart failure (HF) and cardiovascular mortality over and above N-terminal pro-B-type natriuretic peptide (NT-proBNP) level in older adults.

BACKGROUND: Elevated NT-proBNP levels are common in older adults and are associated with increased risk of HF.

METHODS: NT-proBNP and LVEF were measured in 4,137 older adults free of HF. Repeat measures of NT-proBNP were performed 2 to 3 years later and echocardiography was repeated 5 years later (n = 2,375), with a median follow-up of 10.7 years. The addition of an abnormal (<55%) LVEF (n = 317 [7.7%]) to initially elevated or rising NT-proBNP levels was evaluated to determine risk of HF or cardiovascular mortality. Changes in NT-proBNP levels were also assessed for estimating the risk of conversion from a normal to abnormal LVEF.

RESULTS: For participants with a low baseline NT-proBNP level (<190 pg/ml; n = 2,918), addition of an abnormal LVEF did not improve the estimation of risk of HF and identified a moderate increase in adjusted risk for cardiovascular mortality (hazard ratio: 1.69 [95% confidence interval: 1.22 to 2.31]). Among those whose NT-proBNP subsequently increased ≥25% to ≥190 pg/ml, an abnormal LVEF was likewise associated with an increased risk of cardiovascular mortality but not HF. Participants with an initially high NT-proBNP level (≥190 pg/ml) were at greater risk overall for both outcomes, and those with an abnormal LVEF were at the highest risk. However, an abnormal LVEF did not improve model classification or risk stratification for either endpoint when added to demographic factors and change in NT-proBNP. An initially elevated NT-proBNP or rising level was associated with an increased risk of developing an abnormal LVEF.

CONCLUSIONS: Assessment of LVEF in HF-free older adults based on NT-proBNP levels should be considered on an individual basis, as such assessments do not routinely improve prognostication.

10aAge Factors10aAged10aAged, 80 and over10aBiomarkers10aCohort Studies10aDeath10aFemale10aFollow-Up Studies10aHeart Failure10aHumans10aMale10aNatriuretic Peptide, Brain10aPeptide Fragments10aProspective Studies10aRisk Factors10aStroke Volume10aSurvival Rate10aVentricular Function, Left1 adeFilippi, Christopher, R1 aChristenson, Robert, H1 aKop, Willem, J1 aGottdiener, John, S1 aZhan, Min1 aSeliger, Stephen, L uhttps://chs-nhlbi.org/node/133002897nas a2200397 4500008004100000022001400041245013200055210006900187260001300256300001100269490000600280520175800286653002402044653000902068653002002077653001902097653001602116653001502132653001102147653002202158653003102180653001102211653002002222653002502242653000902267100001902276700002402295700002102319700001602340700002302356700002002379700002002399700002002419700002402439856003602463 2011 eng d a1555-905X00aLongitudinal association of depressive symptoms with rapid kidney function decline and adverse clinical renal disease outcomes.0 aLongitudinal association of depressive symptoms with rapid kidne c2011 Apr a834-440 v63 a

BACKGROUND AND OBJECTIVES: Depression is a risk indicator for adverse outcomes in dialysis patients, but its prognostic impact in individuals who are not yet on dialysis is unknown. This study examines whether depressive symptoms are longitudinally associated with renal function decline, new-onset chronic kidney disease (CKD), ESRD, or hospitalization with acute kidney injury (AKI).

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Depressive symptoms were measured in a longitudinal cohort study with the 10-item Centers for Epidemiologic Studies Depression scale using a previously validated cut-off value (≥8). CKD at study entry and during follow-up was defined as an estimated GFR (eGFR) < 60 ml/min per m(2). Outcomes were rapid decline in eGFR (>3 ml/min per m(2) per year), new-onset CKD, ESRD (U.S. Renal Data System-based), and AKI (based on adjudicated medical record review). The median follow-up duration was 10.5 years.

RESULTS: Depressed participants (21.2%) showed a higher prevalence of CKD at baseline compared with nondepressed participants in multivariable analysis. Depression was associated with a subsequent risk of rapid decline in eGFR, incident ESRD, and AKI, but not incident CKD in unadjusted models. In multivariable analyses, only associations of depressive symptoms with AKI remained significant.

CONCLUSIONS: Elevated depressive symptoms are associated with subsequent adverse renal disease outcomes. The depression-related elevated risk of AKI was independent of traditional renal disease risk factors and may in part be explained by the predictive value of depression for acute coronary syndromes and heart failure hospitalizations that can be complicated by AKI.

10aAcute Kidney Injury10aAged10aChronic Disease10aCohort Studies10aComorbidity10aDepression10aFemale10aFollow-Up Studies10aGlomerular Filtration Rate10aHumans10aKidney Diseases10aLongitudinal Studies10aMale1 aKop, Willem, J1 aSeliger, Stephen, L1 aFink, Jeffrey, C1 aKatz, Ronit1 aOdden, Michelle, C1 aFried, Linda, F1 aRifkin, Dena, E1 aSarnak, Mark, J1 aGottdiener, John, S uhttps://chs-nhlbi.org/node/127703157nas a2200385 4500008004100000022001400041245011800055210006900173260001600242300001000258490000800268520204900276653000902325653001502334653002402349653001102373653002202384653001802406653001102424653001402435653000902449653003102458653001402489653002602503653001702529653001802546653001802564100002902582700003002611700002702641700002402668700002402692700001902716856003602735 2011 eng d a1879-191300aPredictive value of depressive symptoms and B-type natriuretic peptide for new-onset heart failure and mortality.0 aPredictive value of depressive symptoms and Btype natriuretic pe c2011 Mar 01 a723-90 v1073 a

Depression and natriuretic peptides predict heart failure (HF) progression, but the unique contributions of depression and biomarkers associated with HF outcomes are not known. The present study determined the additive predictive value of depression and aminoterminal pro-B-type natriuretic peptide (NT-proBNP) for new-onset HF in HF-free subjects and mortality in patients with HF. The participants in the Cardiovascular Health Study were assessed for depressive symptoms using the Center for Epidemiologic Studies Depression Scale and NT-proBNP using an electrochemiluminescence immunoassay. The validated cutoff values for depression (Center for Epidemiologic Studies Depression Scale ≥8) and NT-proBNP (≥190 pg/ml) were used. The risks of incident HF and mortality (cardiovascular disease-related and all-cause) were examined during a median follow-up of 11 years, adjusting for demographics, clinical factors, and health behaviors. In patients with HF (n = 208), depression was associated with an elevated risk of cardiovascular disease mortality (hazard ratios [HR] 2.07, 95% confidence interval [CI] 1.31 to 3.27) and all-cause mortality (HR 1.49, 95% CI 1.05 to 2.11), independent of the NT-proBNP level and covariates. The combined presence of depression and elevated NT-proBNP was associated with substantially elevated covariate-adjusted risks of cardiovascular disease mortality (HR 5.42, 95% CI 2.38 to 12.36) and all-cause mortality (HR 3.72, 95% CI 2.20 to 6.37). In the 4,114 HF-free subjects, new-onset HF was independently predicted by an elevated NT-proBNP level (HR 2.27, 95% CI 1.97 to 2.62) but not depression (HR 1.08, 95% CI 0.92 to 1.26) in covariate-adjusted analysis. In conclusion, depression and NT-proBNP displayed additive predictive value for mortality in patients with HF. These associations can be explained by complementary pathophysiologic mechanisms. The presence of both elevated depression and NT-proBNP levels might improve the identification of patients with HF with a high risk of mortality.

10aAged10aDepression10aDisease Progression10aFemale10aFollow-Up Studies10aHeart Failure10aHumans10aIncidence10aMale10aNatriuretic Peptide, Brain10aPrognosis10aRetrospective Studies10aRisk Factors10aSurvival Rate10aUnited States1 avan den Broek, Krista, C1 adeFilippi, Christopher, R1 aChristenson, Robert, H1 aSeliger, Stephen, L1 aGottdiener, John, S1 aKop, Willem, J uhttps://chs-nhlbi.org/node/126803482nas a2200481 4500008004100000022001400041245014000055210006900195260001300264300001000277490000600287520214200293653000902435653002202444653001002466653001502476653002802491653002502519653001902544653001302563653002002576653001102596653002202607653001802629653001102647653001402658653000902672653002202681653001302703653003002716653001602746653002402762653001802786653001802804100001802822700002402840700002202864700002302886700001402909700001902923700002202942856003602964 2011 eng d a1941-329700aThe relationship between serum markers of collagen turnover and cardiovascular outcome in the elderly: the Cardiovascular Health Study.0 arelationship between serum markers of collagen turnover and card c2011 Nov a733-90 v43 a

BACKGROUND: The deposition of collagen fibrils in the myocardial extracellular matrix increases with age and plays a key role in the pathophysiology of heart failure (HF). We sought to determine the predictive value of serum markers of collagen turnover for incident HF and cardiovascular (CV) morbidity, mortality, and all-cause mortality in elderly individuals.

METHODS AND RESULTS: In 880 participants in the Cardiovascular Health Study (mean age, 77±6 years; 48% women), serum levels of carboxyl-terminal peptide of procollagen type I (PIP), carboxyl-terminal telopeptide of collagen type I (CITP), and amino-terminal peptide of procollagen type III (PIIINP) were measured in 4 groups: HF with reduced ejection fraction (HFREF; n=146, EF <55%); HF with preserved EF (HFPEF; n=175, EF ≥55%), control subjects with CV risk factors but not HF (CVD; n=280), and healthy control subjects free of CV disease (n=279). Relationships between these serum markers and outcome at follow-up of 12±4 years (range, 3-17 years) was determined in six models including those adjusted for conventional risk factors, renal function, NT-proBNP and agents which interfere with collagen synthesis. For the entire cohort, in unadjusted and adjusted models, both PIIINP and CITP were associated with myocardial infarction, incident HF, hospitalization for HF, cardiovascular and all-cause mortality. In healthy control subjects, CITP and PIIINP were associated with all-cause death. In control subjects with risk factors, CITP was associated with incident HF, and in participants with HFPEF, CITP was associated with hospitalization for HF. No collagen biomarker was associated with outcome in participants with HFREF, and PIP was not associated with outcome in the cohort or its subgroups.

CONCLUSIONS: In both healthy and elderly individuals with CV disease at risk of developing HF, CITP and PIIINP are significantly associated with multiple adverse cardiac outcomes including myocardial infarction, HF, and death. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005133.

10aAged10aAged, 80 and over10aAging10aBiomarkers10aCardiovascular Diseases10aCase-Control Studies10aCohort Studies10aCollagen10aCollagen Type I10aFemale10aFollow-Up Studies10aHeart Failure10aHumans10aIncidence10aMale10aPeptide Fragments10aPeptides10aPredictive Value of Tests10aProcollagen10aProspective Studies10aStroke Volume10aSurvival Rate1 aBarasch, Eddy1 aGottdiener, John, S1 aAurigemma, Gerard1 aKitzman, Dalane, W1 aHan, Jing1 aKop, Willem, J1 aTracy, Russell, P uhttps://chs-nhlbi.org/node/132103296nas a2200541 4500008004100000022001400041245012200055210006900177260001600246300001100262490000600273520179100279653001602070653000902086653002202095653001502117653002502132653002802157653001302185653002002198653001102218653001302229653001802242653001102260653001802271653002502289653000902314653002602323653001502349653002202364653001302386653003002399653001602429653002402445653002002469653001702489653001702506653001502523653001802538100001902556700002402575700003002599700001802629700002402647700002002671700002702691856003602718 2012 eng d a1941-329700aCardiac microinjury measured by troponin T predicts collagen metabolism in adults aged >=65 years with heart failure.0 aCardiac microinjury measured by troponin T predicts collagen met c2012 Jul 01 a406-130 v53 a

BACKGROUND: Repeated myocardial microinjuries lead to collagen deposition and fibrosis, thereby increasing the risk of clinical heart failure. Little is known about the longitudinal association between increases in myocardial injury and the biology of collagen synthesis and deposition.

METHODS AND RESULTS: Repeated measures of highly sensitive cardiac troponin T (cTnT) were obtained in participants of the Cardiovascular Health Study (N=353; mean age, 74±6 years; 52% women) at baseline and at 3 years follow-up. Biomarkers of collagen metabolism were obtained at follow-up and included carboxyterminal propeptide of procollagen type I, carboxyterminal telopeptide of type I collagen, and aminoterminal propeptide of procollagen III. Multivariable linear regression analyses were used to examine the association between baseline cTnT and changes in cTnT with collagen metabolism markers at follow-up adjusting for demographics, heart failure status, and cardiovascular risk factors. Results indicated that cTnT increases over 3-years were significantly associated with higher levels of carboxyterminal telopeptide of type I collagen (β=0.22, P<0.001) and aminoterminal propeptide of procollagen III (β=0.12, P=0.035) at follow-up when adjusting for demographic, clinical, and biochemical covariates including baseline cTnT. These associations were stronger in patients with heart failure than in control subjects. Conclusions- Increases in myocardial microinjury measured by changes in cTnT adversely affect markers of collagen metabolism. These findings are important to the biology of myocardial fibrosis and tissue repair. Serial evaluation of cTnT combined with collagen metabolism markers may further elucidate the pathophysiology of heart failure.

10aAge Factors10aAged10aAged, 80 and over10aBiomarkers10aCase-Control Studies10aChi-Square Distribution10aCollagen10aCollagen Type I10aFemale10aFibrosis10aHeart Failure10aHumans10aLinear Models10aLongitudinal Studies10aMale10aMultivariate Analysis10aMyocardium10aPeptide Fragments10aPeptides10aPredictive Value of Tests10aProcollagen10aProspective Studies10aRisk Assessment10aRisk Factors10aTime Factors10aTroponin T10aUp-Regulation1 aKop, Willem, J1 aGottdiener, John, S1 adeFilippi, Christopher, R1 aBarasch, Eddy1 aSeliger, Stephen, L1 aJenny, Nancy, S1 aChristenson, Robert, H uhttps://chs-nhlbi.org/node/138902489nas a2200373 4500008004100000022001400041245011800055210006900173260000900242300001000251490000800261520146000269653000901729653001901738653002101757653001801778653001101796653001501807653001101822653000901833653002201842653001401864653002401878653001701902653001701919653001201936100001901948700002301967700001901990700002202009700002402031700002402055856003602079 2012 eng d a1421-975100aHeart rate response to a timed walk and cardiovascular outcomes in older adults: the cardiovascular health study.0 aHeart rate response to a timed walk and cardiovascular outcomes  c2012 a69-750 v1223 a

OBJECTIVES: To determine the relationship between heart rate response during low-grade physical exertion (6-min walk) with mortality and adverse cardiovascular outcomes in the elderly.

METHODS: Participants in the Cardiovascular Health Study who completed a 6-min walk test were included. We used delta heart rate (difference between postwalk heart rate and resting heart rate) as a measure of chronotropic response and examined its association with (1) all-cause mortality and (2) incident coronary heart disease event, using multivariable Cox regression models.

RESULTS: We included 2,224 participants (mean age 77 ± 4 years; 60% women; 85% white). The average delta heart rate was 26 beats/min. Participants in the lowest tertile of delta heart rate (<20 beats/min) had higher risk-adjusted mortality [hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.00-1.40] and incident coronary heart disease (HR 1.37, 95% CI 1.05-1.78) compared to subjects in the highest tertile (≥30 beats/min), with a significant linear trend across tertiles (p for trend <0.05 for both outcomes). This relationship was not significant after adjustment for distance walked.

CONCLUSION: Impaired chronotropic response during a 6-min walk test was associated with an increased risk of mortality and incident coronary heart disease among the elderly. This association was attenuated after adjusting for distance walked.

10aAged10aCause of Death10aCoronary Disease10aExercise Test10aFemale10aHeart Rate10aHumans10aMale10aPhysical Exertion10aPrognosis10aProspective Studies10aRisk Factors10aTime Factors10aWalking1 aGirotra, Saket1 aKitzman, Dalane, W1 aKop, Willem, J1 aStein, Phyllis, K1 aGottdiener, John, S1 aMukamal, Kenneth, J uhttps://chs-nhlbi.org/node/139302615nas a2200385 4500008004100000022001400041245012400055210006900179260000900248300001100257490000900268520150100277653000901778653002801787653002301815653001101838653001101849653001401860653002301874653002001897653002501917653000901942653002401951653003001975653001802005100002002023700002402043700002502067700001902092700001502111700002102126700002202147700002402169856003602193 2014 eng d a1687-981300aResidential relocation by older adults in response to incident cardiovascular health events: a case-crossover analysis.0 aResidential relocation by older adults in response to incident c c2014 a9519710 v20143 a

OBJECTIVE: We use a case-crossover analysis to explore the association between incident cardiovascular events and residential relocation to a new home address.

METHODS: We conducted an ambidirectional case-crossover analysis to explore the association between incident cardiovascular events and residential relocation to a new address using data from the Cardiovascular Health Study (CHS), a community-based prospective cohort study of 5,888 older adults from four U.S. sites beginning in 1989. Relocation was assessed twice a year during follow-up. Event occurrences were classified as present or absent for the period preceding the first reported move, as compared with an equal length of time immediately prior to and following this period.

RESULTS: Older adults (65+) that experience incident cardiovascular disease had an increased probability of reporting a change of residence during the following year (OR 1.6, 95% confidence interval (CI) = 1.2-2.1). Clinical conditions associated with relocation included stroke (OR: 2.0, 95% CI: 1.2-3.3), angina (OR: 1.6, 95% CI: 1.0-2.6), and congestive heart failure (OR: 1.5, 95% CI: 1.0-2.1).

CONCLUSIONS: Major incident cardiovascular disease may increase the probability of residential relocation in older adults. Case-crossover analyses represent an opportunity to investigate triggering events, but finer temporal resolution would be crucial for future research on residential relocations.

10aAged10aCardiovascular Diseases10aCross-Over Studies10aFemale10aHumans10aIncidence10aLife Change Events10aLogistic Models10aLongitudinal Studies10aMale10aProspective Studies10aResidence Characteristics10aUnited States1 aLovasi, Gina, S1 aRichardson, John, M1 aRodriguez, Carlos, J1 aKop, Willem, J1 aAhmed, Ali1 aBrown, Arleen, F1 aGreenlee, Heather1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/6335