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/70903011nas a2200421 4500008004100000022001400041245007000055210006600125260001600191300001200207490000800219520184900227653000902076653002202085653001002107653002302117653002802140653001102168653001802179653001102197653002502208653000902233653002002242653002402262653001702286100002002303700002102323700002402344700002002368700002202388700001802410700002102428700001902449700002002468700001902488710004702507856003502554 2003 eng d a0003-992600a"Successful aging": effect of subclinical cardiovascular disease.0 aSuccessful aging effect of subclinical cardiovascular disease c2003 Oct 27 a2315-220 v1633 a

BACKGROUND: Cardiovascular diseases are the primary cause of death in older adults. Among those without clinical disease, high levels of subclinical disease are associated with poor survival. The effect of the extent of subclinical cardiovascular disease on the quality of the remaining years has not been defined.

METHODS: In a longitudinal cohort study, 2932 men and women aged 65 years and older were followed up for 8 years to determine the likelihood of maintaining intact health and functioning. Successful aging was defined as remaining free of cardiovascular disease, cancer, and chronic obstructive pulmonary disease and with intact physical and cognitive functioning.

RESULTS: Younger age at study entry and a lower extent of subclinical cardiovascular disease were independently associated with the likelihood of maintaining successful aging. In age-stratified summaries, those with subclinical disease had a trajectory of decline similar to subjects 5 years older without subclinical vascular disease. Regression analyses showed that the decline associated with subclinical disease was equivalent to 6.5 (95% confidence interval, 6.4-6.6) years of aging for women and 5.6 (95% confidence interval, 5.4-5.8) years of aging for men. Individual measures of the extent of cardiovascular disease, diabetes mellitus, smoking, and higher C-reactive protein level were also independently predictive of fewer years of successful aging, but none of these factors substantially attenuated the effect of age itself.

CONCLUSIONS: There is a graded relationship between the extent of vascular disease measured noninvasively and the likelihood of maintaining intact health and function. Prevention of subclinical vascular disease may increase the quality and the quantity of years in late life.

10aAged10aAged, 80 and over10aAging10aC-Reactive Protein10aCardiovascular Diseases10aFemale10aHealth Status10aHumans10aLongitudinal Studies10aMale10aQuality of Life10aRegression Analysis10aRisk Factors1 aNewman, Anne, B1 aArnold, Alice, M1 aNaydeck, Barbara, L1 aFried, Linda, P1 aBurke, Gregory, L1 aEnright, Paul1 aGottdiener, John1 aHirsch, Calvin1 aO'Leary, Daniel1 aTracy, Russell1 aCardiovascular Health Study Research Group uhttps://chs-nhlbi.org/node/75703216nas a2200445 4500008004100000022001400041245012700055210006900182260001300251300001000264490000700274520189900281653000902180653002202189653001502211653002202226653001902248653003302267653002402300653001102324653001502335653001102350653000902361653002702370653002302397653004202420653001502462653003202477653003102509653002002540653001702560653003202577653001802609100002202627700002602649700001602675700002302691700002102714856003502735 2005 eng d a1045-387300aSometimes higher heart rate variability is not better heart rate variability: results of graphical and nonlinear analyses.0 aSometimes higher heart rate variability is not better heart rate c2005 Sep a954-90 v163 a

OBJECTIVE: To determine the prevalence and effect on traditional heart rate variability (HRV) indices of abnormal HRV patterns in the elderly.

METHODS: Hourly Poincaré plots and plots of spectral HRV from normal-to-normal interbeat intervals and hourly nonlinear HRV values were examined in a subset of 290 consecutive participants in the Cardiovascular Health Study. Only subjects in normal sinus rhythm with > or = 18 hours of usable data were included. Eligible subjects were 71 +/- 5 years. During 7 years of follow-up, 21.7% had died. Hours were scored as normal (0), borderline (0.5), or abnormal (1) from a combination of plot appearance and HRV. Summed scores were normalized to 100% to create an abnormality score (ABN). Short-term HRV versus each 5th percentile of ABN was plotted and a cutpoint for markedly increased HRV identified. The t-tests compared HRV for subjects above and below this cutpoint. Cox regression evaluated the association of ABN and mortality.

RESULTS: Of 5,815 eligible hourly plots, 64.4% were normal, 14.5% borderline, and 21.1% abnormal. HR, SDNN, SDNNIDX, ln VLF and LF power, and power law slope did not differ by the cutpoint for increased short-term HRV, while SDANN and ln ULF power were significantly lower for those above the cutpoint. However, many HRV indices including LF/HF ratio and normalized LF and HF power were significantly different between groups (P < 0.001). Increased ABN was significantly associated with mortality (P = 0.019). Despite similar values for many HRV indices, being in the group above the cutpoint was significantly associated with mortality (P = 0.04).

CONCLUSIONS: Abnormal HR patterns that elevate many HRV indices are prevalent among the elderly and associated with higher risk of mortality. Consideration of abnormal HRV may improve HRV-based risk stratification.

10aAged10aAged, 80 and over10aAlgorithms10aArrhythmia, Sinus10aCohort Studies10aDiagnosis, Computer-Assisted10aElectrocardiography10aFemale10aHeart Rate10aHumans10aMale10aModels, Cardiovascular10aNonlinear Dynamics10aNumerical Analysis, Computer-Assisted10aPrevalence10aProportional Hazards Models10aReproducibility of Results10aRisk Assessment10aRisk Factors10aSensitivity and Specificity10aUnited States1 aStein, Phyllis, K1 aDomitrovich, Peter, P1 aHui, Nelson1 aRautaharju, Pentti1 aGottdiener, John uhttps://chs-nhlbi.org/node/85902615nas a2200445 4500008004100000022001400041245007500055210006900130260001300199300001100212490000700223520139000230653002201620653000901642653001301651653002801664653001901692653002801711653004001739653001101779653001801790653001801808653001101826653000901837653001601846653001901862653001501881653001801896653001601914100001901930700002501949700001701974700001601991700002002007700002102027700001902048700002002067710004702087856003502134 2006 eng d a1047-279700aThe association of race with frailty: the cardiovascular health study.0 aassociation of race with frailty the cardiovascular health study c2006 Jul a545-530 v163 a

PURPOSE: Frailty, which has been conceptualized as a state of decreased physiologic reserve contributing to functional decline, has a prevalence among older African Americans that is twice that in older whites. This study assesses the independent contribution of race to frailty.

METHODS: We evaluated 786 African-American and 4491 white participants of the Cardiovascular Health Study (CHS). Frailty is defined as meeting three or more of five criteria derived from CHS measures: lowest quintile for grip strength, self-reported exhaustion, unintentional weight loss of 10 lbs or greater in 1 year, slowest quintile for gait speed, and lowest quintile for physical activity. Controlling for age, sex, comorbidity, socioeconomic factors, and race, multinomial logistic regression estimated the odds ratio (OR) of prefrail (one or two criteria) to not frail and frail to not frail.

RESULTS: Among African Americans, 8.7% of men and 15.0% of women were frail compared with 4.6% and 6.8% of white men and women, respectively. In adjusted models, nonobese African Americans had a fourfold greater odds of frailty compared with whites. The increased OR of frailty associated with African-American race was less pronounced among those who were obese or disabled.

CONCLUSION: African-American race is associated independently with frailty.

10aAfrican Americans10aAged10aAsthenia10aCardiovascular Diseases10aCohort Studies10aCross-Sectional Studies10aEuropean Continental Ancestry Group10aFemale10aFrail Elderly10aHealth Status10aHumans10aMale10aMiddle Aged10aMotor Activity10aOdds Ratio10aUnited States10aWeight Loss1 aHirsch, Calvin1 aAnderson, Melissa, L1 aNewman, Anne1 aKop, Willem1 aJackson, Sharon1 aGottdiener, John1 aTracy, Russell1 aFried, Linda, P1 aCardiovascular Health Study Research Group uhttps://chs-nhlbi.org/node/87703370nas a2200409 4500008004100000022001400041245022900055210006900284260001600353300001000369490000700379520208600386653001602472653000902488653002202497653001002519653002802529653003002557653001102587653001802598653001102616653003402627653000902661653003302670653002602703653003002729653001702759653001602776653001102792100002202803700002102825700001802846700002002864700002002884700002102904856003502925 2006 eng d a0002-914900aUsefulness of aortic root dimension in persons > or = 65 years of age in predicting heart failure, stroke, cardiovascular mortality, all-cause mortality and acute myocardial infarction (from the Cardiovascular Health Study).0 aUsefulness of aortic root dimension in persons or 65 years of ag c2006 Jan 15 a270-50 v973 a

Echocardiographic measures of left ventricular (LV) function and structure as well as left atrial size have been reported to predict adverse cardiovascular disease (CVD) outcomes. Although anatomic changes of the aortic root are likely to reflect effects of hypertension and atherosclerosis, few data are available on the predictive value of aortic root dimension (ARD) for outcome in free-living populations. The purpose of this investigation was to determine whether in a cohort of patients aged > or = 65 years ARD was associated with traditional coronary heart disease (CHD) risk factors and with 10-year incident CVD outcomes. In the National Heart, Lung, and Blood Institute-sponsored Cardiovascular Health Study, 3,933 free-living black and white men and women > or = 65 years of age without prevalent CVD had 2-dimensional directed M-mode echocardiographic measurements of ARD as part of a comprehensive evaluation. ARD was associated with age and gender (greater in men) but not race. ARD was also positively associated with diastolic blood pressure, LV hypertrophy, major electrocardiographic abnormalities, and other echocardiographic measures, including LV mass, ventricular septal and posterior wall thickness, and LV dimension. After adjustment for other known risk factors, high ARD was associated with an increased risk for incident congestive heart failure (CHF) in men (hazard ratio for upper compared with all other quintiles 1.47, p = 0.014), stroke in men and women (hazard ratio 1.39 per cm, p = 0.015), CVD mortality in men and women (hazard ratio 1.48 per cm, p = 0.007), and total mortality in men and women taking antihypertensive medications (hazard ratio 1.46 per cm, p = 0.007), but not with incident myocardial infarction (MI) (hazard ratio 0.89, p = 0.39). In conclusion, in a cohort of patients aged > or = 65 years without clinical CVD at baseline, ARD was associated with several CHD risk factors and measures of subclinical disease and was predictive of incident CHF, stroke, CVD mortality, and all-cause mortality, but not of incident MI.

10aAge Factors10aAged10aAged, 80 and over10aAorta10aCardiovascular Diseases10aEchocardiography, Doppler10aFemale10aHeart Failure10aHumans10aHypertrophy, Left Ventricular10aMale10aMulticenter Studies as Topic10aMyocardial Infarction10aPredictive Value of Tests10aRisk Factors10aSex Factors10aStroke1 aGardin, Julius, M1 aArnold, Alice, M1 aPolak, Joseph1 aJackson, Sharon1 aSmith, Vivienne1 aGottdiener, John uhttps://chs-nhlbi.org/node/88603277nas a2200469 4500008004100000022001400041245015200055210006900207260001600276300001100292490000700303520192500310653002102235653000902256653001402265653002502279653001902304653001602323653003402339653002102373653001102394653001802405653002102423653001102444653001702455653002502472653000902497653002602506653001502532653002402547653001702571653002102588653001802609653001802627100002202645700002102667700002002688700002102708700002002729700002302749856003502772 2007 eng d a1558-359700aVentricular structure and function in hypertensive participants with heart failure and a normal ejection fraction: the Cardiovascular Health Study.0 aVentricular structure and function in hypertensive participants  c2007 Mar 06 a972-810 v493 a

OBJECTIVES: The purpose of this study was to evaluate left ventricular (LV) size and structure in elderly subjects with hypertension (HTN) and heart failure who have a normal ejection fraction (HFNEF) in a large population-based sample.

BACKGROUND: The pathophysiology of HFNEF is incompletely understood but is generally attributed to LV diastolic dysfunction with normal or reduced LV diastolic chamber size despite greater than normal filling pressures.

METHODS: In the Cardiovascular Health Study (n = 5,888), demographic and clinical characteristics and ventricular structure and function were compared in healthy normal subjects (healthy; n = 499), subjects with HTN but not heart failure (HTN; n = 2,184), and subjects with HTN and HFNEF (HFNEF; n = 167).

RESULTS: Subjects with HFNEF were older, more obese, and more often African American than healthy and HTN subjects and had a higher prevalence of diabetes, coronary heart disease, and anemia than HTN subjects. Serum creatinine and cystatin-C were increased in HFNEF subjects. Average LV diastolic dimension was significantly increased in HFNEF subjects (5.2 +/- 0.8 cm) compared with healthy (4.8 +/- 0.6 cm) and HTN (4.9 +/- 0.6 cm) subjects. As a result, average calculated stroke volume (89 +/- 25 ml vs. 78 +/- 20 ml and 80 +/- 20 ml) and cardiac output (6.0 +/- 2.0 l/min vs. 4.8 +/- 1.3 l/min and 5.1 +/- 1.4 l/min) were increased in HFNEF compared with healthy and HTN subjects, respectively.

CONCLUSIONS: As a group, HFNEF subjects have increased LV diastolic diameter and increased calculated stroke volume. They also have increased prevalence of multiple comorbidities, including anemia, renal dysfunction, and obesity, that can cause volume overload. These data suggest that extracardiac factors, via volume overload, may contribute to the pathophysiology of HFNEF in the elderly.

10aAge Distribution10aAged10aBody Size10aCase-Control Studies10aCohort Studies10aComorbidity10aContinental Population Groups10aEchocardiography10aFemale10aHeart Failure10aHeart Ventricles10aHumans10aHypertension10aLongitudinal Studies10aMale10aMultivariate Analysis10aPrevalence10aRegression Analysis10aRisk Factors10aSex Distribution10aStroke Volume10aUnited States1 aMaurer, Mathew, S1 aBurkhoff, Daniel1 aFried, Linda, P1 aGottdiener, John1 aKing, Donald, L1 aKitzman, Dalane, W uhttps://chs-nhlbi.org/node/94602997nas a2200397 4500008004100000022001400041245017000055210006900225260001700294300001000311490000700321520176400328653001602092653002802108653002702136653003602163653001102199653001102210653000902221653001502230653001402245653003102259653002002290653001702310653003202327653002202359653001802381653001802399653003602417100002202453700002102475700002202496700002402518700002102542856003602563 2010 eng d a1532-843000aAssociation of Holter-based measures including T-wave alternans with risk of sudden cardiac death in the community-dwelling elderly: the Cardiovascular Health Study.0 aAssociation of Holterbased measures including Twave alternans wi c2010 May-Jun a251-90 v433 a

BACKGROUND: Sudden cardiac death (SCD) can be the first manifestation of cardiovascular disease. Development of screening methods for higher/lower risk is critical.

METHODS: The Cardiovascular Health Study is a population-based study of risk factors for coronary heart disease and stroke those 65 years or older. Forty-nine (of 1649) with usable Holters and in normal sinus rhythm had SCD during follow-up and were matched with 2 controls, alive at the time of death of the case and not experiencing SCD on follow-up. Univariate and multivariate conditional logistic regression determined the association of Holter-based information and SCD.

RESULTS: In univariate models, the upper half of ventricular premature contraction (VPC) counts, abnormal heart rate turbulence, decreased normalized low-frequency power, increased T-wave alternans (TWA), and decreased the short-term fractal scaling exponent (DFA(1)) were associated with SCD, but time domain heart rate variability was not. In multivariate models, the upper half of VPC counts (odds ratio [OR], 6.6) and having TWA of 37 muV or greater on channel 2 (OR, 4.8) were independently associated with SCD. Also, the upper half of VPC counts (OR, 6.9) and having a DFA(1) of less than 1.05 (OR, 5.0) were independently associated with SCD. When additive effects were explored, having both higher VPCs and higher TWA was associated with an OR of 8.2 for SCD compared with 2.6 for having either. Also, having both higher VPCs and lower DFA(1) was associated with an OR of 9.6 for SCD compared with 3.1 for having either.

CONCLUSIONS: Results support a potential role for 24-hour Holter recordings to identify older adults at increased or lower risk of SCD.

10aComorbidity10aCoronary Artery Disease10aDeath, Sudden, Cardiac10aElectrocardiography, Ambulatory10aFemale10aHumans10aMale10aPrevalence10aPrognosis10aReproducibility of Results10aRisk Assessment10aRisk Factors10aSensitivity and Specificity10aSurvival Analysis10aSurvival Rate10aUnited States10aVentricular Premature Complexes1 aStein, Phyllis, K1 aSanghavi, Devang1 aSotoodehnia, Nona1 aSiscovick, David, S1 aGottdiener, John uhttps://chs-nhlbi.org/node/116202980nas a2200409 4500008004100000022001400041245012500055210006900180260001300249300001000262490000800272520179200280653000902072653001102081653003002092653002102122653001102143653003402154653002502188653000902213653003302222653001702255653002002272100002102292700001902313700002102332700001602353700001602369700002202385700002002407700001702427700002402444700002402468700002102492700002102513856003602534 2013 eng d a1879-148400aFibroblast growth factor 23, left ventricular mass, and left ventricular hypertrophy in community-dwelling older adults.0 aFibroblast growth factor 23 left ventricular mass and left ventr c2013 Nov a114-90 v2313 a

OBJECTIVES: In chronic kidney disease (CKD), high FGF23 concentrations are associated with left ventricular hypertrophy (LVH), cardiovascular events, and death. The associations of FGF23 with left ventricular mass (LVM) and LVH in the general population and the influence of CKD remains uncertain.

METHODS: C-terminal plasma FGF23 concentrations were measured, and LVM and LVH evaluated by echocardiogram among 2255 individuals ≥65 years in the Cardiovascular Health Study. Linear regression analysis adjusting for demographics, cardiovascular, and kidney related risk factors examined the associations of FGF23 concentrations with LVM. Analyses were stratified by CKD status and adjusted linear and logistic regression analysis explored the associations of FGF23 with LVM and LVH.

RESULTS: Among the entire cohort, higher FGF23 concentrations were associated with greater LVM in adjusted analyses (β = 6.71 [95% CI 4.35-9.01] g per doubling of FGF23). 32% (n = 624) had CKD (eGFR <60 mL/min/1.73 m(2) and/or urine albumin-to-creatinine ratio >30 mg/g). Associations were stronger among participants with CKD (p interaction = 0.006): LVM β = 9.71 [95% CI 5.86-13.56] g per doubling of FGF23 compared to those without CKD (β = 3.44 [95% CI 0.77, 6.11] g per doubling of FGF23). While there was no significant interaction between FGF23 and CKD for LVH (p interaction = 0.25), the OR (1.46 95% CI [1.20-1.77]) in the CKD group was statistically significant and of larger magnitude than the OR for in the no CKD group (1.12 [95% CI 0.97-1.48]).

CONCLUSION: In a large cohort of older community-dwelling adults, higher FGF23 concentrations were associated with greater LVM and LVH with stronger relationships in participants with CKD.

10aAged10aFemale10aFibroblast Growth Factors10aHeart Ventricles10aHumans10aHypertrophy, Left Ventricular10aLongitudinal Studies10aMale10aRenal Insufficiency, Chronic10aRisk Factors10aUltrasonography1 aJovanovich, Anna1 aIx, Joachim, H1 aGottdiener, John1 aMcFann, Kim1 aKatz, Ronit1 aKestenbaum, Bryan1 ade Boer, Ian, H1 aSarnak, Mark1 aShlipak, Michael, G1 aMukamal, Kenneth, J1 aSiscovick, David1 aChonchol, Michel uhttps://chs-nhlbi.org/node/737903473nas a2200409 4500008004100000022001400041245025300055210006900308260001300377300001100390490000600401520217700407653000902584653001502593653002102608653001102629653001802640653001102658653003402669653000902703653003102712653002202743653001402765653002402779653001702803653001502820100002402835700002002859700002002879700002402899700002102923700002102944700001802965700001702983700002703000856003603027 2015 eng d a2213-178700aOlder Adults, "Malignant" Left Ventricular Hypertrophy, and Associated Cardiac-Specific Biomarker Phenotypes to Identify the Differential Risk of New-Onset Reduced Versus Preserved Ejection Fraction Heart Failure: CHS (Cardiovascular Health Study).0 aOlder Adults Malignant Left Ventricular Hypertrophy and Associat c2015 Jun a445-550 v33 a

OBJECTIVES: This study hypothesized that biomarkers of subclinical myocardial injury (high-sensitivity cardiac troponin T [hs-cTnT]) and hemodynamic stress (N-terminal pro-B-type natriuretic peptide [NT-proBNP]) would differentiate heart failure (HF) risk among older adults with left ventricular hypertrophy (LVH).

BACKGROUND: The natural history of LVH, an important risk factor for HF, is heterogeneous.

METHODS: NT-proBNP and hs-cTnT were measured at baseline and after 2 to 3 years in older adults without prior HF or myocardial infarction in the CHS (Cardiovascular Health Study). LVH and left ventricular ejection fraction were determined by echocardiography. HF events were adjudicated over a median of 13.1 years and classified as preserved or reduced left ventricular ejection fraction (heart failure with preserved ejection fraction or heart failure with reduced ejection fraction [HFrEF]). Adjusted risk of HF by LVH and biomarker tertiles, and by LVH and longitudinal increase in each biomarker was estimated using Cox regression.

RESULTS: Prevalence of LVH was 12.5% among 2,347 participants with complete measures. Adjusted risk of HF (N = 643 events) was approximately 3.8-fold higher among participants with LVH and in the highest biomarker tertile, compared with those with low biomarker levels without LVH (NT-proBNP, hazard ratio [HR]: 3.78; 95% confidence interval [CI]: 2.78 to 5.15 and hs-cTnT, HR: 3.86; 95% CI: 2.84 to 5.26). The adjusted risk of HFrEF was 7.8 times higher among those with the highest tertile of hs-cTnT and LVH (HR: 7.83; 95% CI: 4.43 to 13.83). Those with LVH and longitudinal increases in hs-cTnT or NT-proBNP were approximately 3-fold more likely to develop HF, primarily HFrEF, compared with those without LVH and with stable biomarkers.

CONCLUSIONS: The combination of LVH with greater hs-cTnT or NT-proBNP levels, and their longitudinal increase, identifies older adults at highest risk for symptomatic HF, especially HFrEF. These biomarkers may characterize sub-phenotypes in the transition from LVH to HF and suggest modifiable targets for prevention.

10aAged10aBiomarkers10aEchocardiography10aFemale10aHeart Failure10aHumans10aHypertrophy, Left Ventricular10aMale10aNatriuretic Peptide, Brain10aPeptide Fragments10aPhenotype10aProspective Studies10aRisk Factors10aTroponin T1 aSeliger, Stephen, L1 ade Lemos, James1 aNeeland, Ian, J1 aChristenson, Robert1 aGottdiener, John1 aDrazner, Mark, H1 aBerry, Jarett1 aSorkin, John1 aDeFilippi, Christopher uhttps://chs-nhlbi.org/node/673502705nas a2200265 4500008004100000022001400041245013700055210006900192260001300261490000600274520188900280100002002169700001902189700001902208700001802227700001902245700002102264700002202285700002102307700001802328700001702346700001902363700002102382856003602403 2016 eng d a1942-008000aEchocardiographic Predictors of Sudden Cardiac Death: The Atherosclerosis Risk in Communities Study and Cardiovascular Health Study.0 aEchocardiographic Predictors of Sudden Cardiac Death The Atheros c2016 Aug0 v93 a

BACKGROUND: This study assessed the echocardiographic predictors of sudden cardiac death (SCD) within 2 population-based cohorts.

METHODS AND RESULTS: Echocardiograms were obtained on 2383 participants (1993-1995) from the ARIC study (Atherosclerosis Risk in Communities; 100% black) and 5366 participants (1987-1989 and 1994-1995) from the CHS (Cardiovascular Health Study). The main outcome was physician-adjudicated SCD. We used Cox proportional-hazards models with incident coronary heart disease and heart failure as time-dependent covariates to assess the association between echocardiographic variables and SCD, adjusting for Framingham risk score variables, coronary heart disease, and renal function. Cohort-specific results were meta-analyzed. During a median follow-up of 7.3 and 13.1 years, 44 ARIC study participants and 275 CHS participants had SCD, respectively. In the meta-analyzed results, the adjusted hazard ratios (95% confidence intervals) for predictors of SCD were 3.07 (2.29-4.11) for reduced left ventricular ejection fraction; 1.85 (1.36-2.52) for mitral annular calcification; 1.64 (1.07-2.51) for mitral E/A >1.5, and 1.52 (1.14-2.02) for mitral E/A <0.7 (versus mitral E/A 0.7-1.5); 1.30 (1.15-1.48) per 1 SD increase in left ventricular mass; and 1.15 (1.02-1.30) per 1 SD increase in left atrial diameter. A receiver-operating characteristic model for prediction of SCD using Framingham risk score variables had a C statistic of 0.61 for ARIC study and 0.67 for CHS; the full multivariable model including all echocardiographic variables had a C statistic of 0.76 for ARIC study and 0.74 for CHS.

CONCLUSIONS: In addition to reduced left ventricular ejection fraction, we identified other echocardiographic-derived variables predictive for SCD that provided incremental value compared with clinical risk factors.

1 aKonety, Suma, H1 aKoene, Ryan, J1 aNorby, Faye, L1 aWilsdon, Tony1 aAlonso, Alvaro1 aSiscovick, David1 aSotoodehnia, Nona1 aGottdiener, John1 aFox, Ervin, R1 aChen, Lin, Y1 aAdabag, Selcuk1 aFolsom, Aaron, R uhttps://chs-nhlbi.org/node/712502427nas a2200193 4500008004100000022001400041245009200055210006900147260001600216520182200232100001702054700002002071700002102091700001802112700002102130700002002151700002602171856003602197 2018 eng d a1526-632X00aLeft atrial diameter and vascular brain injury on MRI: The Cardiovascular Health Study.0 aLeft atrial diameter and vascular brain injury on MRI The Cardio c2018 Aug 293 a

OBJECTIVE: To determine the association left atrial diameter (LAD) and vascular brain injury on brain MRI.

METHODS: We analyzed data from the Cardiovascular Health Study (CHS), a prospective cohort of community-dwelling adults ≥65 years old. LAD was measured from 2-dimensional transthoracic echocardiograms. Among CHS participants who underwent brain MRI, we examined associations of LAD with brain infarcts and leukoaraiosis. Primary outcomes (number for analysis) were prevalent infarcts (2,327) and degree of leukoaraiosis on initial MRI (2,315). Secondary outcomes were prevalent nonlacunar infarcts (2,327), incident infarcts (939), incident nonlacunar infarcts (1,185), and degree of leukoaraiosis on follow-up MRI adjusted for initial MRI (1,158). Relative risk (RR) and linear regression models were adjusted for demographics, vascular risk factors, and potential confounders.

RESULTS: Mean age of the 2,335 participants with initial brain MRI was 72.0 ± 4.8 years; 38.7% were men; and 29.0% participants had prevalent infarcts. In multivariable, fully adjusted models, LAD was associated with prevalent infarcts (RR 1.20, 95% confidence interval [CI] 1.08-1.34) and prevalent nonlacunar infarcts (RR 1.28, 95% CI 1.06-1.54) but not with leukoaraiosis (-0.08, 95% CI -0.17 to 0.07), incident infarcts (RR 1.00, 95% CI 0.78-1.29), nonlacunar infarcts (RR 0.98, 95% CI 0.67-1.42), or worsening leukoaraiosis (-0.04, 95% CI -0.10 to 0.02).

CONCLUSION: LAD is independently associated with prevalent brain infarcts, particularly nonlacunar infarcts, but not leukoaraiosis. Larger studies are needed to determine associations with incident infarct risk and whether this risk in patients with left atrial enlargement can be reduced with anticoagulant agents.

1 aYaghi, Shadi1 aBartz, Traci, M1 aKronmal, Richard1 aKamel, Hooman1 aGottdiener, John1 aLongstreth, W T1 aElkind, Mitchell, S V uhttps://chs-nhlbi.org/node/782003329nas a2200277 4500008004100000022001400041245012700055210006900182260001600251490000600267520248500273100001902758700002302777700001102800700001902811700002002830700002102850700002002871700002302891700002302914700001502937700002302952700002002975700002002995856003603015 2020 eng d a2379-370800aCharacterization of cardiac mechanics and incident atrial fibrillation in participants of the Cardiovascular Health Study.0 aCharacterization of cardiac mechanics and incident atrial fibril c2020 Oct 020 v53 a

BACKGROUND: Left atrial (LA) and left ventricular (LV) remodeling are associated with atrial fibrillation (AF). The prospective associations of impairment in cardiac mechanical function, as assessed by speckle-tracking echocardiography, with incident AF are less clear.

METHODS: In the Cardiovascular Health Study, a community-based cohort of older adults, participants free of AF with echocardiograms of adequate quality for speckle tracking were included. We evaluated the associations of indices of cardiac mechanics (LA reservoir strain, LV longitudinal strain, and LV early diastolic strain rate) with incident AF.

RESULTS: Of 4341 participants with strain imaging, participants with lower LA reservoir strain were older, had more cardiometabolic risk factors, and had lower renal function at baseline. Over a median follow-up of 10 years, 497 (11.4%) participants developed AF. Compared with the highest quartile of LA reservoir strain, the lowest quartile of LA reservoir strain was associated with higher risk of AF after covariate adjustment, including LA volume and LV longitudinal strain (heart rate [HR], 1.80; 95% CI, 1.31-2.45; P < 0.001). The association of LA reservoir strain and AF was stronger in subgroups with higher blood pressure, NT-proBNP, and LA volumes. There were no associations of LV longitudinal strain and LV early diastolic strain rate with incident AF after adjustment for LA reservoir strain.

CONCLUSION: Lower LA reservoir strain was associated with incident AF, independent of LV mechanics, and with stronger associations in high-risk subgroups. These findings suggest that LA mechanical dysfunction precedes the development of AF. Therapies targeting LA mechanical dysfunction may prevent progression to AF.

FUNDING: This research was supported by contracts HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086 and grants KL2TR001424, R01HL107577, U01HL080295, and U01HL130114 from the NIH's National Center for Advancing Translational Sciences, and National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by R01AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org.

1 aPatel, Ravi, B1 aDelaney, Joseph, A1 aHu, Mo1 aPatel, Harnish1 aCheng, Jeanette1 aGottdiener, John1 aKizer, Jorge, R1 aMarcus, Gregory, M1 aTurakhia, Mintu, P1 aDeo, Rajat1 aHeckbert, Susan, R1 aPsaty, Bruce, M1 aShah, Sanjiv, J uhttps://chs-nhlbi.org/node/848602307nas 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/839502672nas a2200289 4500008004100000022001400041245010200055210006900157260001600226520178900242100002702031700002302058700002202081700002102103700001702124700002002141700002402161700002002185700002202205700002002227700002202247700002102269700001302290700002002303700002302323856003602346 2021 eng d a1468-201X00aPremature ventricular complexes and development of heart failure in a community-based population.0 aPremature ventricular complexes and development of heart failure c2021 Sep 073 a

OBJECTIVE: A higher premature ventricular complex (PVC) frequency is associated with incident congestive heart failure (CHF) and death. While certain PVC characteristics may contribute to that risk, the current literature stems from patients in medical settings and is therefore prone to referral bias. This study aims to identify PVC characteristics associated with incident CHF in a community-based setting.

METHODS: The Cardiovascular Health Study is a cohort of community-dwelling individuals who underwent prospective evaluation and follow-up. We analysed 24-hour Holter data to assess PVC characteristics and used multivariable logistic and Cox proportional hazards models to identify predictors of a left ventricular ejection fraction (LVEF) decline and incident CHF, respectively.

RESULTS: Of 871 analysed participants, 316 participants exhibited at least 10 PVCs during the 24-hour recording. For participants with PVCs, the average age was 72±5 years, 41% were women and 93% were white. Over a median follow-up of 11 years, 34% developed CHF. After adjusting for demographics, cardiovascular comorbidities, antiarrhythmic drug use and PVC frequency, a greater heterogeneity of the PVC coupling interval was associated with an increased risk of LVEF decline and incident CHF. Of note, neither PVC duration nor coupling interval duration exhibited a statistically significant relationship with either outcome.

CONCLUSIONS: In this first community-based study to identify Holter-based features of PVCs that are associated with LVEF reduction and incident CHF, the fact that coupling interval heterogeneity was an independent risk factor suggests that the mechanism of PVC generation may influence the risk of heart failure.

1 aLimpitikul, Worawan, B1 aDewland, Thomas, A1 aVittinghoff, Eric1 aSoliman, Elsayed1 aNah, Gregory1 aFang, Christina1 aSiscovick, David, S1 aPsaty, Bruce, M1 aSotoodehnia, Nona1 aHeckbert, Susan1 aStein, Phyllis, K1 aGottdiener, John1 aHu, Xiao1 aHempfling, Ralf1 aMarcus, Gregory, M uhttps://chs-nhlbi.org/node/892302808nas a2200205 4500008004100000022001400041245011800055210007100173260001600244520214500260100001802405700002102423700002102444700001802465700001702483700002702500700001902527700002002546856003602566 2024 eng d a1945-719700aAssociation of thyroid dysfunction in individuals ≥ 65 years of age with subclinical cardiac abnormalities.0 aAssociation of thyroid dysfunction in individuals ≥ 65 years of  c2024 Jan 063 a

CONTEXT: The relationship between thyroid dysfunction and measures of myocardial disease in older individuals remains to be defined.

OBJECTIVE: To evaluate the impact of thyroid dysfunction on structure and function of the left-heart chambers and blood markers of cardiac disease.

DESIGN: Cross-sectional analysis.

SETTING: The Cardiovascular Health Study, a community-based cohort of older individuals recruited from four urban areas in the United States.

PATIENTS: Of 3163 participants studied, 2477 were euthyroid, 465 had subclinical hypothyroidism (SCH), 47 overt hypothyroidism (OH), 45 endogenous (endo) subclinical hyperthyroidism (endo-SCT), and 129 had exogenous (exo) SCT due to thyroid hormone supplementation.

INTERVENTIONS: Clinical evaluation, blood sampling and biomarker measurement, 2-dimensional and speckle-tracking echocardiography.

MAIN OUTCOME MEASURE(S): Left heart myocardial deformation, circulating biomarkers of diastolic overload (NT-proBNP), fibrosis (sST2, gal-3), and cardiomyocyte injury (hs-cTnT).

RESULTS: SCH was associated with higher NT-proBNP (beta = 0.17, p = 0.004), whereas OH was associated with higher hs-cTnT (beta = 0.29, p = 0.005). There were also suggestive associations of SCH with higher sST2, as well as endo-SCT with higher gal-3 and lower (worse) left atrial reservoir strain. Left ventricular longitudinal strain and end-diastolic strain rate did not differ significantly from euthyroid participants in SCH, OH, or exo-SCT.

CONCLUSIONS: In this free-living elderly cohort, subclinical and overt hypothyroidism were associated with abnormalities of blood biomarkers consistent with diastolic overload and myocardial necrosis respectively, whereas subclinical hyperthyroidism tended to be associated with myocardial fibrosis and decreased left atrial strain. Our findings could represent stage B heart failure and illuminate distinct aspects of the pathobiology of heart disease related to thyroid gland dysfunction with potential clinical implications.

1 aBarasch, Eddy1 aGottdiener, John1 aBůzková, Petra1 aCappola, Anne1 aShah, Sanjiv1 aDeFilippi, Christopher1 aGardin, Julius1 aKizer, Jorge, R uhttps://chs-nhlbi.org/node/9574