02577nas a2200433 4500008004100000022001400041245014900055210006900204260001600273300001000289490000700299520121600306653003901522653001601561653000901577653002401586653001601610653002801626653002101654653002401675653004001699653002801739653001101767653001601778653002101794653001101815653000901826653002601835653002401861653001701885653002401902653003101926100002101957700002401978700002302002700002202025710006102047856003502108 2002 eng d a0002-914900aLeft atrial dimensions determined by M-mode echocardiography in black and white older (> or =65 years) adults (The Cardiovascular Health Study).0 aLeft atrial dimensions determined by Mmode echocardiography in b c2002 Nov 01 a983-70 v903 a

Stroke and atrial fibrillation are common and serious illnesses in the elderly, the risks of which are substantially increased by left atrial (LA) enlargement. Despite growing recognition of the importance of LA enlargement, the distribution and correlates of LA dimension in the elderly have not been well defined. A total of 3,882 women and men aged >65 years were studied. Increased LA dimension was independently associated with increased weight, mitral annular calcium, regional wall motion abnormalities, mitral early peak inflow velocity, and left ventricular (LV) fractional shortening. Increased LA dimension was negatively associated with aortic leaflet thickening. The relation with LV fractional shortening was curvilinear with a nadir at 35% to 40%. LA dimension in black men was approximately 1.9 mm less than in white men in multivariate analyses. Adjustment for spirometric lung volumes and chest dimensions appeared to diminish the race-LA dimension relation. Thus, LA dimension is strongly associated with weight and with several echocardiographic valvular abnormalities; its relation with LV fractional shortening is U-shaped with a nadir at the borderline of LV functional impairment.

10aAfrican Continental Ancestry Group10aAge Factors10aAged10aBlood Flow Velocity10aBody Weight10aCardiovascular Diseases10aEchocardiography10aElectrocardiography10aEuropean Continental Ancestry Group10aEvidence-Based Medicine10aFemale10aHeart Atria10aHeart Ventricles10aHumans10aMale10aMultivariate Analysis10aProspective Studies10aRisk Factors10aStatistics as Topic10aVentricular Function, Left1 aManolio, Teri, A1 aGottdiener, John, S1 aTsang, Teresa, S M1 aGardin, Julius, M1 aCardiovascular Health Study Collaborative Research Group uhttps://chs-nhlbi.org/node/70703533nas a2200457 4500008004100000022001400041245014200055210006900197260001600266300001000282490000800292520220800300653000902508653001902517653002102536653001102557653001802568653001102586653002502597653000902622653002602631653001502657653001402672653001702686653001102703653003502714653003102749100002402780700002502804700002102829700002002850700002102870700002302891700001802914700001802932700002202950700002202972700002502994700002103019856003503040 2002 eng d a1539-370400aOutcome of congestive heart failure in elderly persons: influence of left ventricular systolic function. The Cardiovascular Health Study.0 aOutcome of congestive heart failure in elderly persons influence c2002 Oct 15 a631-90 v1373 a

BACKGROUND: Most persons with congestive heart failure are elderly, and many elderly persons with congestive heart failure have normal left ventricular systolic function.

OBJECTIVE: To evaluate the relationship between left ventricular systolic function and outcome of congestive heart failure in elderly persons.

DESIGN: Population-based longitudinal study of coronary heart disease and stroke.

SETTING: Four U.S. sites: Forsyth County, North Carolina; Sacramento County, California; Allegheny County, Pennsylvania; and Washington County, Maryland.

PARTICIPANTS: 5888 persons who were at least 65 years of age and were recruited from the community.

MEASUREMENTS: Total mortality and cardiovascular morbidity and mortality.

RESULTS: Of 5532 participants, 269 (4.9%) had congestive heart failure. Among these, left ventricular function was normal in 63%, borderline decreased in 15%, and overtly impaired in 22%. The mortality rate was 25 deaths per 1000 person-years in the reference group (no congestive heart failure and normal left ventricular function at baseline); 154 deaths per 1000 person-years in participants with congestive heart failure and impaired left ventricular systolic function; 87 and 115 deaths per 1000 person-years in participants with congestive heart failure and normal or borderline systolic function, respectively; and 89 deaths per 1000 person-years in persons with impaired left ventricular function but no congestive heart failure. Although the risk for death from congestive heart failure was lower in persons with normal systolic function than in those with impaired function, more deaths were associated with normal systolic function because more persons with heart failure fall into this category.

CONCLUSIONS: Community-dwelling elderly persons, especially those with impaired left ventricular function, have a substantial risk for death from congestive heart failure. However, more deaths occur from heart failure in persons with normal systolic function because left ventricular function is more often normal than impaired in elderly persons with heart failure.

10aAged10aCause of Death10aEchocardiography10aFemale10aHeart Failure10aHumans10aLongitudinal Studies10aMale10aMyocardial Infarction10aPrevalence10aPrognosis10aRisk Factors10aStroke10aVentricular Dysfunction, Right10aVentricular Function, Left1 aGottdiener, John, S1 aMcClelland, Robyn, L1 aMarshall, Robert1 aShemanski, Lynn1 aFurberg, Curt, D1 aKitzman, Dalane, W1 aCushman, Mary1 aPolak, Joseph1 aGardin, Julius, M1 aGersh, Bernard, J1 aAurigemma, Gerard, P1 aManolio, Teri, A uhttps://chs-nhlbi.org/node/70503482nas a2200397 4500008004100000022001400041245016900055210006900224260001300293300001200306490000700318520230100325653000902626653001502635653002802650653001902678653001102697653001402708653001102722653000902733653001302742653001302755653001902768653001702787653003002804653001702834653001702851653002602868653003102894100002502925700002202950700002302972700002202995710003203017856003503049 2004 eng d a0277-953600aThe association of personal and neighborhood socioeconomic indicators with subclinical cardiovascular disease in an elderly cohort. The cardiovascular health study.0 aassociation of personal and neighborhood socioeconomic indicator c2004 Nov a2139-470 v593 a

There has been recent interest in determining whether neighborhood characteristics are related to the cardiovascular health of residents. However, there are no data regarding the relationship between neighborhood socioeconomic status (SES) and prevalence of subclinical cardiovascular disease (CVD) in the elderly. We related personal SES (education, income, and occupation type) and neighborhood socioeconomic characteristics (a block-group score summing six variables reflecting neighborhood income and wealth, education, and occupation) to the prevalence of subclinical CVD (asymptomatic peripheral vascular disease or carotid atherosclerosis, electrocardiogram or echocardiogram abnormalities, and/or positive responses to Rose Questionnaire claudication or angina pectoris) among 3545 persons aged 65 and over, without prevalent CVD, in the Cardiovascular Health Study. Sixty percent of participants had at least one indicator of subclinical disease. Compared to those without, those with subclinical disease had significantly lower education, income, and neighborhood scores and were more likely to have blue-collar jobs. After adjustment for age, gender, and race, those in the lowest SES groups had increased prevalence of subclinical disease compared with those in the highest SES groups (OR = 1.50; 95% CI 1.21, 1.86 for income; OR = 1.41; 95% CI 1.18, 1.69 for education; OR = 1.39; 95% CI 1.16, 1.67 for block-group score). Those reporting a blue-collar lifetime occupation had greater prevalence of subclinical disease relative to those reporting a white-collar occupation (OR = 1.29; 95% CI 1.02-1.59). After adjustment for behavioral and biomedical risk factors, all of these associations were reduced. Neighborhood score tended to remain inversely associated with subclinical disease after adjustment for personal socioeconomic indicators but associations were not statistically significant. Personal income and blue-collar occupation remained significantly associated with subclinical disease after simultaneous adjustment for neighborhood score and education. Personal and neighborhood socioeconomic indicators were associated with subclinical disease prevalence in this elderly cohort. These relationships were reduced after controlling for traditional CVD risk factors.

10aAged10aCalifornia10aCardiovascular Diseases10aCohort Studies10aFemale10aGeography10aHumans10aMale10aMaryland10aMedicare10aNorth Carolina10aPennsylvania10aResidence Characteristics10aRisk Factors10aSocial Class10aSocioeconomic Factors10aSurveys and Questionnaires1 aNordstrom, Cheryl, K1 aRoux, Ana, V Diez1 aJackson, Sharon, A1 aGardin, Julius, M1 aCardiovascular Health Study uhttps://chs-nhlbi.org/node/79903282nas a2200481 4500008004100000022001400041245017500055210006900230260001600299300001200315490000700327520181100334653000902145653002202154653002802176653001302204653002102217653002402238653001102262653002202273653002102295653001102316653003402327653002502361653000902386653002602395653002402421653001702445653003202462653002402494653001802518653003402536100002102570700001802591700002102609700002402630700002302654700002202677700002102699700002102720700002402741856003502765 2004 eng d a0735-109700aIncreased left ventricular mass is a risk factor for the development of a depressed left ventricular ejection fraction within five years: the Cardiovascular Health Study.0 aIncreased left ventricular mass is a risk factor for the develop c2004 Jun 16 a2207-150 v433 a

OBJECTIVES: Our aim in this study was to determine whether increased left ventricular mass (LVM) is a risk factor for the development of a reduced left ventricular ejection fraction (LVEF).

BACKGROUND: Prior studies have shown that increased LVM is a risk factor for heart failure but not whether it is a risk factor for a low LVEF.

METHODS: As part of the Cardiovascular Health Study, a prospective population-based longitudinal study, we performed echocardiograms upon participant enrollment and again at follow-up of 4.9 +/- 0.14 years. In the present analysis, we identified 3,042 participants who had at baseline a normal LVEF and an assessment of LVM (either by electrocardiogram or echocardiogram), and at follow-up a measurable LVEF. The frequency of the development of a qualitatively depressed LVEF on two-dimensional echocardiography, corresponding approximately to an LVEF <55%, was analyzed by quartiles of baseline LVM. Multivariable regression determined whether LVM was independently associated with the development of depressed LVEF.

RESULTS: Baseline quartile of echocardiographic LVM indexed to body surface area was associated with development of a depressed LVEF (4.8% in quartile 1, 4.4% in quartile 2, 7.5% in quartile 3, and 14.1% in quartile 4 [p < 0.001]). A similar relationship was seen in the subgroup of participants without myocardial infarction (p < 0.001). In multivariable regression that adjusted for confounders, both baseline echocardiographic (p < 0.001) and electrocardiographic (p < 0.001) LVM remained associated with development of depressed LVEF.

CONCLUSIONS: Increased LVM as assessed by electrocardiography or echocardiography is an independent risk factor for the development of depressed LVEF.

10aAged10aBody Surface Area10aCoronary Artery Disease10aDiastole10aEchocardiography10aElectrocardiography10aFemale10aFollow-Up Studies10aHeart Ventricles10aHumans10aHypertrophy, Left Ventricular10aLongitudinal Studies10aMale10aMultivariate Analysis10aProspective Studies10aRisk Factors10aSensitivity and Specificity10aStatistics as Topic10aStroke Volume10aVentricular Dysfunction, Left1 aDrazner, Mark, H1 aRame, Eduardo1 aMarino, Emily, K1 aGottdiener, John, S1 aKitzman, Dalane, W1 aGardin, Julius, M1 aManolio, Teri, A1 aDries, Daniel, L1 aSiscovick, David, S uhttps://chs-nhlbi.org/node/79003370nas 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/88602551nas a2200385 4500008004100000022001400041245013900055210006900194260001300263300001100276490000700287520145000294653000901744653002001753653001101773653003801784653001101822653001401833653000901847653002601856653001501882653001501897653002401912653001701936653001301953653001101966653001801977100001701995700002202012700001802034700002202052700001802074710003702092856003602129 2009 eng d a1873-258500aSibling history of myocardial infarction or stroke and risk of cardiovascular disease in the elderly: the Cardiovascular Health Study.0 aSibling history of myocardial infarction or stroke and risk of c c2009 Dec a858-660 v193 a

PURPOSE: To assess the relationship between sibling history of myocardial infarction (MI) or stroke with cardiovascular disease (CVD) and risk factors in older adults.

METHODS: Prospective cohort study of 5,888 older adults participating in the Cardiovascular Health Study (CHS). History of MI and stroke in siblings was obtained by self-report. Participants with positive sibling histories were compared to those with negative histories to determine if prevalent or incident disease (coronary heart disease [CHD], MI, stroke, angina), subclinical CVD (carotid wall thickness, left ventricular mass, hypertension, diabetes, ankle-brachial index), CVD risk factors differed between groups.

RESULTS: More than 91% (n = 5,383) of CHS participants reported at least one sibling. Sibling history of MI was associated with increased disease prevalence (CHD, MI, angina) and incidence (CHD, angina). Sibling history of stroke was associated with increased disease prevalence (CHD, angina). Sibling history of either MI or stroke was associated with increased disease prevalence and incidence for CHD, MI and angina, more subclinical disease, and a higher CVD risk profile.

CONCLUSIONS: Sibling history of MI and stroke were markers of higher CVD risk status even in older adults. Of clinical importance, participants with positive sibling history have numerous risk factors amenable to intervention.

10aAged10aAtherosclerosis10aFemale10aGenetic Predisposition to Disease10aHumans10aIncidence10aMale10aMyocardial Infarction10aOdds Ratio10aPrevalence10aProspective Studies10aRisk Factors10aSiblings10aStroke10aUnited States1 aYanez, David1 aBurke, Gregory, L1 aManolio, Teri1 aGardin, Julius, M1 aPolak, Joseph1 aCHS Collaborative Research Group uhttps://chs-nhlbi.org/node/114603070nas a2200445 4500008004100000022001400041245015700055210006900212260001300281300001100294490000800305520172400313653005102037653002202088653000902110653001502119653002302134653002802157653002102185653002102206653004002227653001102267653001102278653001402289653001702303653001802320653000902338653001602347653003202363653002402395653001702419100002202436700002202458700001702480700002202497700002702519700002202546700002002568856003602588 2013 eng d a1879-148400aImpact of inflammatory biomarkers on relation of high density lipoprotein-cholesterol with incident coronary heart disease: cardiovascular Health Study.0 aImpact of inflammatory biomarkers on relation of high density li c2013 Dec a246-510 v2313 a

BACKGROUND: Inflammatory factors and low HDL-C relate to CHD risk, but whether inflammation attenuates any protective association of high HDL-C is unknown.

OBJECTIVE: Investigate inflammatory markers' individual and collective impact on the association of HDL-C with incident coronary heart disease (CHD).

METHODS: In 3888 older adults without known cardiovascular disease (CVD), we examined if the inflammatory markers C-reactive protein (CRP), interleukin-6 (IL-6), and lipoprotein-associated phospholipase A2 (Lp-PLA₂) modify the relation of HDL-C with CHD. HDL-C, CRP, IL-6, and Lp-PLA₂ values were grouped as using gender-specific tertiles. Also, an inflammation index of z-score sums for CRP, IL-6, and Lp-PLA₂ was categorized into tertiles. We calculated CHD incidence for each HDL-C/inflammation group and performed Cox regression, adjusted for standard CVD risk factors and triglycerides to examine the relationship of combined HDL-C-inflammation groups with incident events.

RESULTS: CHD incidence (per 1000 person years) was higher for higher levels of CRP, IL-6, and the index, and lower for higher levels of HDL-C. Compared to high HDL-C/low-inflammation categories (referent), adjusted HRs for incident CHD were increased for those with high HDL-C and high CRP (HR = 1.50, p < 0.01) or highest IL-6 tertile (HR = 1.40, p < 0.05), but not with highest Lp-PLA₂ tertile. Higher CHD incidence was similarly seen for those with intermediate or low HDL-C accompanied by high CRP, high IL-6, or a high inflammatory index.

CONCLUSION: The protective relation of high HDL-C for incident CHD appears to be attenuated by greater inflammation.

10a1-Alkyl-2-acetylglycerophosphocholine Esterase10aAfrican Americans10aAged10aBiomarkers10aC-Reactive Protein10aCardiovascular Diseases10aCholesterol, HDL10aCoronary Disease10aEuropean Continental Ancestry Group10aFemale10aHumans10aIncidence10aInflammation10aInterleukin-610aMale10aMiddle Aged10aProportional Hazards Models10aProspective Studies10aRisk Factors1 aTehrani, David, M1 aGardin, Julius, M1 aYanez, David1 aHirsch, Calvin, H1 aLloyd-Jones, Donald, M1 aStein, Phyllis, K1 aWong, Nathan, D uhttps://chs-nhlbi.org/node/616703118nas a2200373 4500008004100000022001400041245016800055210006900223260001300292300001600305490000700321520198600328653000902314653002802323653003502351653002102386653001602407653001102423653001102434653001402445653002502459653000902484653003102493653001702524653003202541653001102573653001802584100002202602700002002624700002102644700002302665700002002688856003602708 2014 eng d a1097-679500aWhat do carotid intima-media thickness and plaque add to the prediction of stroke and cardiovascular disease risk in older adults? The cardiovascular health study.0 aWhat do carotid intimamedia thickness and plaque add to the pred c2014 Sep a998-1005.e20 v273 a

BACKGROUND: The aim of this study was to evaluate whether the addition of ultrasound carotid intima-media thickness (CIMT) measurements and risk categories of plaque help predict incident stroke and cardiovascular disease (CVD) in older adults.

METHODS: Carotid ultrasound studies were recorded in the multicenter Cardiovascular Health Study. CVD was defined as coronary heart disease plus heart failure plus stroke. Ten-year risk prediction Cox proportional-hazards models for stroke and CVD were calculated using Cardiovascular Health Study-specific coefficients for Framingham risk score factors. Categories of CIMT and CIMT plus plaque were added to Framingham risk score prediction models, and categorical net reclassification improvement (NRI) and Harrell's c-statistic were calculated.

RESULTS: In 4,384 Cardiovascular Health Study participants (61% women, 14% black; mean baseline age, 72 ± 5 years) without CVD at baseline, higher CIMT category and the presence of plaque were both associated with higher incidence rates for stroke and CVD. The addition of CIMT improved the ability of Framingham risk score-type risk models to discriminate cases from noncases of incident stroke and CVD (NRI = 0.062, P = .015, and NRI = 0.027, P < .001, respectively), with no further improvement by adding plaque. For both outcomes, NRI was driven by down-classifying those without incident disease. Although the addition of plaque to CIMT did not result in a significant NRI for either outcome, it was significant among those without incident disease.

CONCLUSIONS: In older adults, the addition of CIMT modestly improves 10-year risk prediction for stroke and CVD beyond a traditional risk factor model, mainly by down-classifying risk in those without stroke or CVD; the addition of plaque to CIMT adds no statistical benefit in the overall cohort, although there is evidence of down-classification in those without events.

10aAged10aCardiovascular Diseases10aCarotid Intima-Media Thickness10aCarotid Stenosis10aComorbidity10aFemale10aHumans10aIncidence10aLongitudinal Studies10aMale10aReproducibility of Results10aRisk Factors10aSensitivity and Specificity10aStroke10aSurvival Rate1 aGardin, Julius, M1 aBartz, Traci, M1 aPolak, Joseph, F1 aO'Leary, Daniel, H1 aWong, Nathan, D uhttps://chs-nhlbi.org/node/656403214nas a2200397 4500008004100000022001400041245014200055210006900197260001300266490000600279520204500285653000902330653002202339653002802361653001102389653001902400653001802419653002002437653001102457653002602468653001802494653000902512653001402521653002402535653003102559653002002590653001702610653001802627653001802645653003402663100001902697700002302716700002202739700001902761856003602780 2015 eng d a2047-998000aCardiovascular and Mortality Outcomes in the Elderly With Impaired Cardiac and Pulmonary Function: The Cardiovascular Health Study (CHS).0 aCardiovascular and Mortality Outcomes in the Elderly With Impair c2015 Dec0 v43 a

BACKGROUND: Impaired pulmonary function (IPF) and left ventricular systolic dysfunction (LVSD) are prevalent in the elderly and are associated with significant morbidity and mortality. The main objectives of this study were to examine the relative impact and joint association of IPF and LVSD with heart failure, cardiovascular mortality and all-cause mortality, and their impact on risk classification using a continuous net reclassification index.

METHODS AND RESULTS: We followed 2342 adults without prevalent cardiovascular disease (mean age, 76 years) from the Cardiovascular Health Study for a median of 12.6 years. LVSD was defined as LV ejection fraction <55%. IPF was defined as: forced expiratory volume in 1 second:forced vital capacity <70%, and predicted forced expiratory volume in 1 second <80%. Outcomes included heart failure hospitalization, cardiovascular mortality, all-cause mortality, and composite outcome. LVSD was detected in 128 subjects (6%), IPF in 441 (19%) and both in 38 (2%). Compared to those without LVSD or IPF, there was a significantly increased cardiovascular risk for groups of LVSD only, IPF only, and LVSD plus IPF, adjusted hazard ratio (95% CI) 2.1 (1.5-3.0), 1.7 (1.4-2.1), and 3.2 (2.0-5.1) for HF; 1.8 (1.2-2.6), 1.4 (1.1-1.8), and 2.8 (1.7-4.7) for cardiovascular mortality; 1.3 (1.0-1.8), 1.7 (1.4-1.9), and 2.1 (1.5-3.0) for all-cause mortality, and 1.6 (1.3-2.1), 1.7 (1.5-1.9), and 2.4 (1.7-3.3) for composite outcome, respectively. Risk classification improved significantly for all outcomes when IPF was added to the adjusted model with LVSD or LVSD to IPF.

CONCLUSIONS: While risk of cardiovascular outcomes was the highest among elderly with both LVSD and IPF, risk was comparable between subjects with IPF alone and those with LVSD alone. This observation, combined with improved risk classification by adding IPF to LVSD or LVSD to IPF, underscore the importance of comprehensive heart and lung evaluation in cardiovascular outcome assessment.

10aAged10aAged, 80 and over10aCardiovascular Diseases10aFemale10aHeart Diseases10aHeart Failure10aHospitalization10aHumans10aKaplan-Meier Estimate10aLung Diseases10aMale10aMortality10aProspective Studies10aRespiratory Function Tests10aRisk Assessment10aRisk Factors10aStroke Volume10aUnited States10aVentricular Dysfunction, Left1 aWaheed, Salman1 aChaves, Paulo, H M1 aGardin, Julius, M1 aCao, Jie, Jane uhttps://chs-nhlbi.org/node/693503413nas a2200445 4500008004100000022001400041245010800055210006900163260001300232300001200245490000600257520216400263653000902427653002202436653002802458653001602486653002202502653001102524653002102535653001102556653003402567653002002601653000902621653002502630653001402655653003202669653002402701653002002725653001702745653001702762653001802779100001702797700001702814700002202831700002402853700001702877700001702894700002002911856003602931 2015 eng d a1876-759100aLV Mass as a Predictor of CVD Events in Older Adults With and Without Metabolic Syndrome and Diabetes.0 aLV Mass as a Predictor of CVD Events in Older Adults With and Wi c2015 Sep a1007-150 v83 a

OBJECTIVES: The purpose of this study was to examine the prognostic significance of left ventricular (LV) mass for cardiovascular disease (CVD) events in older adults with and without metabolic syndrome (MetS) and diabetes mellitus (DM).

BACKGROUND: MetS and DM are associated with increased CVD risk, but it is unclear in these groups whether subclinical CVD as shown by increased LV mass improves risk prediction compared to standard risk factors in older individuals.

METHODS: We studied 3,724 adults (mean 72.4 ± 5.4 years of age, 61.0% female, 4.4% African-American) from the Cardiovascular Health Study who had MetS but not DM or had DM alone or had neither condition. Cox regression was used to examine the association of LV mass, (alone and indexed by height and body surface area [BSA]) as determined by echocardiography, with CVD events, including coronary heart disease (CHD), stroke, heart failure (HF), and CVD death, as well as total mortality. We also assessed the added prediction, discriminative value, and net reclassification improvement (NRI) for clinical utility of LV mass compared to standard risk factors.

RESULTS: Over a mean follow-up of 14.2 ± 6.3 years, 2,180 subjects experienced CVD events, including 986 CVD deaths. After adjustment for age, sex and standard risk factors, LV mass was positively associated with CVD events in those with MetS (hazard ratio [HR]: 1.4, p < 0.001) and without MetS (HR: 1.4, p < 0.001), but not DM (HR: 1.0, p = 0.62), with similar findings for LV mass indexed for height or BSA. Adding LV mass to standard risk factors moderately improved the prediction accuracy in the overall sample and MetS group from changes in C-statistics (p < 0.05). Categorical-free net reclassification improvement increased significantly by 17% to 19% in those with MetS. Findings were comparable for CHD, CVD mortality, and total mortality.

CONCLUSIONS: LV mass is associated with increased CVD risk and provides modest added prediction and clinical utility compared to standard risk factors in older persons with and without MetS but not with DM.

10aAged10aAged, 80 and over10aCardiovascular Diseases10aComorbidity10aDiabetes Mellitus10aFemale10aHeart Ventricles10aHumans10aHypertrophy, Left Ventricular10aLogistic Models10aMale10aMetabolic Syndrome X10aPrognosis10aProportional Hazards Models10aProspective Studies10aRisk Assessment10aRisk Factors10aTime Factors10aUnited States1 aHoang, Khiet1 aZhao, Yanglu1 aGardin, Julius, M1 aCarnethon, Mercedes1 aMukamal, Ken1 aYanez, David1 aWong, Nathan, D uhttps://chs-nhlbi.org/node/682603330nas a2200421 4500008004100000022001400041245012500055210006900180260001300249490000600262520208400268653003102352653000902383653001502392653002802407653003502435653002102470653001102491653001102502653002302513653000902536653003102545653002202576653001602598653002402614653001802638653001502656100002602671700001802697700002202715700002402737700002302761700002002784700002102804700002402825700002302849856003602872 2015 eng d a2047-998000aYears of able life in older persons--the role of cardiovascular imaging and biomarkers: the Cardiovascular Health Study.0 aYears of able life in older personsthe role of cardiovascular im c2015 Apr0 v43 a

BACKGROUND: As the U.S. population grows older, there is greater need to examine physical independence. Previous studies have assessed risk factors in relation to either disability or mortality, but an outcome that combines both is still needed.

METHODS AND RESULTS: The Cardiovascular Health Study is a population-based, prospective study where participants underwent baseline echocardiogram, measurement of carotid intima-media thickness (IMT), and various biomarkers, then followed for up to 18 years. Years of able life (YAL) constituted the number of years the participant was able to perform all activities of daily living. Linear regression was used to model the relationship between selected measures and outcomes, adjusted for confounding variables. Among 4902 participants, mean age was 72.6 ± 5.4 years, median YAL for males was 8.8 (interquartile range [IQR], 4.3 to 13.8) and 10.3 (IQR, 5.8 to 15.8) for females. Reductions in YAL in the fully adjusted model for females and males, respectively, were: -1.34 (95% confidence interval [CI], -2.18, -0.49) and -1.41 (95% CI, -2.03, -0.8) for abnormal left ventricular (LV) ejection fraction, -0.5 (95% CI, -0.78, -0.22) and -0.62 (95% CI, -0.87, -0.36) per SD increase in LV mass, -0.5 (95% CI, -0.7, -0.29) and -0.79 (95% CI, -0.99, -0.58) for IMT, -0.5 (95% CI, -0.64, -0.37) and -0.79 (95% CI, -0.94, -0.65) for N-terminal pro-brain natriuretic peptide, -1.08 (95% CI, -1.34, -0.83) and -0.73 (95% CI, -0.97, -0.5) for high-sensitivity troponin-T, and -0.26 (95% CI, -0.42, -0.09) and -0.23 (95% CI, -0.41, -0.05) for procollagen-III N-terminal propeptide. Most tested variables remained significant even after adjusting for incident cardiovascular (CV) disease.

CONCLUSIONS: In this population-based cohort, variables obtained by CV imaging and biomarkers of inflammation, coagulation, atherosclerosis, myocardial injury and stress, and cardiac collagen turnover were associated with YAL, an important outcome that integrates physical ability and longevity in older persons.

10aActivities of Daily Living10aAged10aBiomarkers10aCardiovascular Diseases10aCarotid Intima-Media Thickness10aEchocardiography10aFemale10aHumans10aIndependent Living10aMale10aNatriuretic Peptide, Brain10aPeptide Fragments10aProcollagen10aProspective Studies10aStroke Volume10aTroponin I1 aAlshawabkeh, Laith, I1 aYee, Laura, M1 aGardin, Julius, M1 aGottdiener, John, S1 aOdden, Michelle, C1 aBartz, Traci, M1 aArnold, Alice, M1 aMukamal, Kenneth, J1 aWallace, Robert, B uhttps://chs-nhlbi.org/node/670702367nas a2200217 4500008004100000022001400041245017300055210006900228260001300297300001100310490000700321520163400328100001701962700002301979700002102002700002202023700002202045700002602067700002002093856003602113 2016 eng d a1932-873700aCardiovascular Disease, Mortality Risk, and Healthcare Costs by Lipoprotein(a) Levels According to Low-density Lipoprotein Cholesterol Levels in Older High-risk Adults.0 aCardiovascular Disease Mortality Risk and Healthcare Costs by Li c2016 Jul a413-200 v393 a

BACKGROUND: The value of lipoprotein(a) (Lp[a]) for predicting cardiovascular disease (CVD) across low-density lipoprotein cholesterol (LDL-C) is uncertain.

HYPOTHESIS: In older high-risk adults, higher LDL and Lp(a) combined would be associated with higher CVD risk and more healthcare costs.

METHODS: We included 3251 high-risk subjects (prior CVD, diabetes, or 10-year Framingham CVD risk >20%) age ≥65 years from the Cardiovascular Health Study and examined the relation of Lp(a) tertiles with incident CVD, coronary heart disease (CHD), and all-cause mortality within LDL-C strata (spanning <70 mg/dL to ≥160 mg/dL). We also examined 1-year all-cause and CVD healthcare costs from Medicare claims.

RESULTS: Over a 22.5-year follow-up, higher Lp(a) levels predicted CVD and total mortality (both standardized hazard ratio [HR]: 1.06, P < 0.01), whereas higher LDL-C levels predicted higher CHD (standardized HR: 1.09, P < 0.01) but lower total mortality (standardized HR: 0.94, P < 0.001). Adjusted HRs in the highest (vs lowest) tertile of Lp(a) level were 1.95 (P = 0.06) for CVD events and 2.68 (P = 0.03) for CHD events when LDL-C was <70 mg/dL. One-year all-cause healthcare costs were increased for Lp(a) ($771 per SD of 56 µg/mL [P = 0.03], $1976 for Lp(a) 25-64 µg/mL vs <25 µg/mL [P = 0.02], and $1648 for Lp(a) ≥65 µg/mL vs <25 µg/mL [P = 0.054]) but not LDL-C.

CONCLUSIONS: In older high-risk adults, increased Lp(a) levels were associated with higher CVD risk, especially in those with LDL-C <70 mg/dL, and with higher healthcare costs.

1 aZhao, Yanglu1 aDelaney, Joseph, A1 aQuek, Ruben, G W1 aGardin, Julius, M1 aHirsch, Calvin, H1 aGandra, Shravanthi, R1 aWong, Nathan, D uhttps://chs-nhlbi.org/node/711703073nas a2200397 4500008004100000022001400041245013400055210006900189260001300258490000600271520187500277100002002152700002202172700002302194700002002217700002002237700002002257700002002277700003402297700002002331700001902351700001502370700002202385700002102407700001502428700001902443700001902462700002302481700002702504700002202531700001702553700002402570700002302594700002202617856003602639 2016 eng d a1941-329700aPredicting Heart Failure With Preserved and Reduced Ejection Fraction: The International Collaboration on Heart Failure Subtypes.0 aPredicting Heart Failure With Preserved and Reduced Ejection Fra c2016 Jun0 v93 a

BACKGROUND: Heart failure (HF) is a prevalent and deadly disease, and preventive strategies focused on at-risk individuals are needed. Current HF prediction models have not examined HF subtypes. We sought to develop and validate risk prediction models for HF with preserved and reduced ejection fraction (HFpEF, HFrEF).

METHODS AND RESULTS: Of 28,820 participants from 4 community-based cohorts, 982 developed incident HFpEF and 909 HFrEF during a median follow-up of 12 years. Three cohorts were combined, and a 2:1 random split was used for derivation and internal validation, with the fourth cohort as external validation. Models accounted for multiple competing risks (death, other HF subtype, and unclassified HF). The HFpEF-specific model included age, sex, systolic blood pressure, body mass index, antihypertensive treatment, and previous myocardial infarction; it had good discrimination in derivation (c-statistic 0.80; 95% confidence interval [CI], 0.78-0.82) and validation samples (internal: 0.79; 95% CI, 0.77-0.82 and external: 0.76; 95% CI: 0.71-0.80). The HFrEF-specific model additionally included smoking, left ventricular hypertrophy, left bundle branch block, and diabetes mellitus; it had good discrimination in derivation (c-statistic 0.82; 95% CI, 0.80-0.84) and validation samples (internal: 0.80; 95% CI, 0.78-0.83 and external: 0.76; 95% CI, 0.71-0.80). Age was more strongly associated with HFpEF, and male sex, left ventricular hypertrophy, bundle branch block, previous myocardial infarction, and smoking with HFrEF (P value for each comparison ≤0.02).

CONCLUSIONS: We describe and validate risk prediction models for HF subtypes and show good discrimination in a large sample. Some risk factors differed between HFpEF and HFrEF, supporting the notion of pathogenetic differences among HF subtypes.

1 aHo, Jennifer, E1 aEnserro, Danielle1 aBrouwers, Frank, P1 aKizer, Jorge, R1 aShah, Sanjiv, J1 aPsaty, Bruce, M1 aBartz, Traci, M1 aSanthanakrishnan, Rajalakshmi1 aLee, Douglas, S1 aChan, Cheeling1 aLiu, Kiang1 aBlaha, Michael, J1 aHillege, Hans, L1 aHarst, Pim1 aGilst, Wiek, H1 aKop, Willem, J1 aGansevoort, Ron, T1 aVasan, Ramachandran, S1 aGardin, Julius, M1 aLevy, Daniel1 aGottdiener, John, S1 ade Boer, Rudolf, A1 aLarson, Martin, G uhttps://chs-nhlbi.org/node/714002279nas a2200193 4500008004100000022001400041245018000055210006900235260001500304300001100319490000800330520159600338100002201934700002001956700002401976700002702000700002202027856003602049 2016 eng d a1879-191300aUsefulness of Left Ventricular Mass and Geometry for Determining 10-Year Prediction of Cardiovascular Disease in Adults Aged >65 Years (from the Cardiovascular Health Study).0 aUsefulness of Left Ventricular Mass and Geometry for Determining c2016 Sep 1 a684-900 v1183 a

Left ventricular (LV) mass and geometry are associated with risk of cardiovascular disease (CVD). We sought to determine whether LV mass and geometry contribute to risk prediction for CVD in adults aged ≥65 years of the Cardiovascular Health Study. We indexed LV mass to body size, denoted as LV mass index (echo-LVMI), and we defined LV geometry as normal, concentric remodeling, and eccentric or concentric LV hypertrophy. We added echo-LVMI and LV geometry to separate 10-year risk prediction models containing traditional risk factors and determined the net reclassification improvement (NRI) for incident coronary heart disease (CHD), CVD (CHD, heart failure [HF], and stroke), and HF alone. Over 10 years of follow-up in 2,577 participants (64% women, 15% black, mean age 72 years) for CHD and CVD, the adjusted hazards ratios for a 1-SD higher echo-LVMI were 1.25 (95% CI 1.14 to 1.37), 1.24 (1.15 to 1.33), and 1.51 (1.40 to 1.62), respectively. Addition of echo-LVMI to the standard model for CHD resulted in an event NRI of -0.011 (95% CI -0.037 to 0.028) and nonevent NRI of 0.034 (95% CI 0.008 to 0.076). Addition of echo-LVMI and LV geometry to the standard model for CVD resulted in an event NRI of 0.013 (95% CI -0.0335 to 0.0311) and a nonevent NRI of 0.043 (95% CI 0.011 to 0.09). The nonevent NRI was also significant with addition of echo-LVMI for HF risk prediction (0.10, 95% CI 0.057 to 0.16). In conclusion, in adults aged ≥65 years, echo-LVMI improved risk prediction for CHD, CVD, and HF, driven primarily by improved reclassification of nonevents.

1 aDesai, Chintan, S1 aBartz, Traci, M1 aGottdiener, John, S1 aLloyd-Jones, Donald, M1 aGardin, Julius, M uhttps://chs-nhlbi.org/node/712203411nas a2200541 4500008004100000022001400041245007900055210006900134260001600203520185300219100002202072700002002094700002102114700001502135700002102150700001902171700003102190700002202221700002202243700001802265700002002283700002302303700002102326700002102347700001902368700001502387700002702402700002002429700002002449700002302469700002102492700002002513700002402533700001902557700002102576700002202597700002202619700001702641700002502658700001902683700002202702700002202724700002302746700002402769700002002793700002002813856003602833 2017 eng d a1879-084400aPredictors and outcomes of heart failure with mid-range ejection fraction.0 aPredictors and outcomes of heart failure with midrange ejection  c2017 Dec 113 a

AIMS: While heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF) are well described, determinants and outcomes of heart failure with mid-range ejection fraction (HFmrEF) remain unclear. We sought to examine clinical and biochemical predictors of incident HFmrEF in the community.

METHODS AND RESULTS: We pooled data from four community-based longitudinal cohorts, with ascertainment of new heart failure (HF) classified into HFmrEF [ejection fraction (EF) 41-49%], HFpEF (EF ≥50%), and HFrEF (EF ≤40%). Predictors of incident HF subtypes were assessed using multivariable Cox models. Among 28 820 participants free of HF followed for a median of 12 years, there were 200 new HFmrEF cases, compared with 811 HFpEF and 1048 HFrEF. Clinical predictors of HFmrEF included age, male sex, systolic blood pressure, diabetes mellitus, and prior myocardial infarction (multivariable adjusted P ≤ 0.003 for all). Biomarkers that predicted HFmrEF included natriuretic peptides, cystatin-C, and high-sensitivity troponin (P ≤ 0.0004 for all). Natriuretic peptides were stronger predictors of HFrEF [hazard ratio (HR) 2.00 per 1 standard deviation increase, 95% confidence interval (CI) 1.81-2.20] than of HFmrEF (HR 1.51, 95% CI 1.20-1.90, P = 0.01 for difference), and did not differ in their association with incident HFmrEF and HFpEF (HR 1.56, 95% CI 1.41-1.73, P = 0.68 for difference). All-cause mortality following the onset of HFmrEF was worse than that of HFpEF (50 vs. 39 events per 1000 person-years, P = 0.02), but comparable to that of HFrEF (46 events per 1000 person-years, P = 0.78).

CONCLUSIONS: We found overlap in predictors of incident HFmrEF with other HF subtypes. In contrast, mortality risk after HFmrEF was worse than HFpEF, and similar to HFrEF.

1 aBhambhani, Vijeta1 aKizer, Jorge, R1 aLima, João, A C1 aHarst, Pim1 aBahrami, Hossein1 aNayor, Matthew1 ade Filippi, Christopher, R1 aEnserro, Danielle1 aBlaha, Michael, J1 aCushman, Mary1 aWang, Thomas, J1 aGansevoort, Ron, T1 aFox, Caroline, S1 aGaggin, Hanna, K1 aKop, Willem, J1 aLiu, Kiang1 aVasan, Ramachandran, S1 aPsaty, Bruce, M1 aLee, Douglas, S1 aBrouwers, Frank, P1 aHillege, Hans, L1 aBartz, Traci, M1 aBenjamin, Emelia, J1 aChan, Cheeling1 aAllison, Matthew1 aGardin, Julius, M1 aJanuzzi, James, L1 aLevy, Daniel1 aHerrington, David, M1 aGilst, Wiek, H1 aBertoni, Alain, G1 aLarson, Martin, G1 ade Boer, Rudolf, A1 aGottdiener, John, S1 aShah, Sanjiv, J1 aHo, Jennifer, E uhttps://chs-nhlbi.org/node/754902701nas a2200241 4500008004100000022001400041245022700055210006900282260001600351300001200367490000800379520184500387100002202232700002202254700002002276700002302296700001802319700002202337700002402359700002002383700002002403856003602423 2017 eng d a1879-191300aRelation of the Myocardial Contraction Fraction, as Calculated from M-Mode Echocardiography, With Incident Heart Failure, Atherosclerotic Cardiovascular Disease and Mortality (Results from the Cardiovascular Health Study).0 aRelation of the Myocardial Contraction Fraction as Calculated fr c2017 Mar 15 a923-9280 v1193 a

We evaluated the association between 2-dimensional (2D) echocardiography (echo)-determined myocardial contraction fraction (MCF) and adverse cardiovascular outcomes including incident heart failure (HF), atherosclerotic cardiovascular disease (ASCVD), and mortality. The MCF, the ratio of left ventricular (LV) stroke volume (SV) to myocardial volume (MV), is a volumetric measure of myocardial shortening that can distinguish pathologic from physiological hypertrophy. Using 2D echo-guided M-mode data from the Cardiovascular Health Study, we calculated MCF in subjects with LV ejection fraction (EF) ≥55% and used Cox models to evaluate its association with incident HF, ASCVD, and all-cause mortality after adjusting for clinical and echo parameters. We assessed whether log2(SV) and log2(MV) were consistent with the expected 1:-1 ratio used in the definition of MCF. Among 2,147 participants (age 72 ± 5 years), average MCF was 59 ± 13%. After controlling for clinical and echo variables, each 10% absolute increment in MCF was associated with lower risk of HF (hazard ratio [HR] 0.88; 95% confidence interval [CI] 0.82, 0.94), ASCVD (HR 0.90; 95% CI 0.85, 0.95), and death (HR 0.93; 95% CI 0.89, 0.97). Moreover, the MCF was still significantly associated with ASCVD and mortality, but not HF, after adjustment for percent-predicted LV mass. Significant departure from the 1:-1 ratio was not observed for ASCVD or death, but did occur for HF, driven by a stronger association for MV than SV. In conclusion, among older adults without CVD or low LV ejection fraction, 2D echo-guided M-mode-derived MCF was independently associated with lower risk of adverse cardiovascular outcomes, but this ratiometric index may not capture the full relation that is apparent when its components are modeled separately in the case of HF.

1 aMaurer, Mathew, S1 aKoh, William, J H1 aBartz, Traci, M1 aVullaganti, Sirish1 aBarasch, Eddy1 aGardin, Julius, M1 aGottdiener, John, S1 aPsaty, Bruce, M1 aKizer, Jorge, R uhttps://chs-nhlbi.org/node/735003140nas a2200289 4500008004100000022001400041245015000055210006900205260001300274300000700287490000700294520224800301100002102549700001302570700002002583700002202603700001902625700002102644700002002665700001802685700002202703700002402725700002102749700002402770700002002794856003602814 2017 eng d a1862-351400aRelationship of bone mineral density with valvular and annular calcification in community-dwelling older people: The Cardiovascular Health Study.0 aRelationship of bone mineral density with valvular and annular c c2017 Dec a520 v123 a

Associations between bone mineral density and aortic valvular, aortic annular, and mitral annular calcification were investigated in a cross-sectional analysis of a population-based cohort of 1497 older adults. Although there was no association between continuous bone mineral density and outcomes, a significant association between osteoporosis and aortic valvular calcification in men was found.

INTRODUCTION: The process of cardiac calcification bears a resemblance to skeletal bone metabolism and its regulation. Experimental studies suggest that bone mineral density (BMD) and valvular calcification may be reciprocally related, but epidemiologic data are sparse.

METHODS: We tested the hypothesis that BMD of the total hip and femoral neck measured by dual-energy X-ray absorptiometry (DXA) is inversely associated with prevalence of three echocardiographic measures of cardiac calcification in a cross-sectional analysis of 1497 older adults from the Cardiovascular Health Study. The adjusted association of BMD with aortic valve calcification (AVC), aortic annular calcification (AAC), and mitral annular calcification (MAC) was assessed with relative risk (RR) regression.

RESULTS: Mean (SD) age was 76.2 (4.8) years; 58% were women. Cardiac calcification was highly prevalent in women and men: AVC, 59.5 and 71.0%; AAC 45.1 and 46.7%; MAC 42.8 and 39.5%, respectively. After limited and full adjustment for potential confounders, no statistically significant associations were detected between continuous BMD at either site and the three measures of calcification. Assessment of WHO BMD categories revealed a significant association between osteoporosis at the total hip and AVC in men (adjusted RR compared with normal BMD = 1.24 (1.01-1.53)). In graded sensitivity analyses, there were apparent inverse associations between femoral neck BMD and AVC with stenosis in men, and femoral neck BMD and moderate/severe MAC in women, but these were not significant.

CONCLUSION: These findings support further investigation of the sex-specific relationships between low BMD and cardiac calcification, and whether processes linking the two could be targeted for therapeutic ends.

1 aMassera, Daniele1 aXu, Shuo1 aBartz, Traci, M1 aBortnick, Anna, E1 aIx, Joachim, H1 aChonchol, Michel1 aOwens, David, S1 aBarasch, Eddy1 aGardin, Julius, M1 aGottdiener, John, S1 aRobbins, John, R1 aSiscovick, David, S1 aKizer, Jorge, R uhttps://chs-nhlbi.org/node/748804686nas a2200541 4500008004100000022001400041245011900055210006900174260001600243520308900259100002303348700001903371700003003390700002203420700002203442700002003464700002203484700002303506700001803529700002103547700002103568700001503589700002003604700002303624700002103647700002103668700001903689700001503708700002703723700002003750700002003770700002103790700002003811700002403831700001903855700002103874700002203895700002203917700002003939700001703959700002503976700002204001700001904023700002404042700002204066700002004088856003604108 2018 eng d a2380-659100aAssociation of Cardiovascular Biomarkers With Incident Heart Failure With Preserved and Reduced Ejection Fraction.0 aAssociation of Cardiovascular Biomarkers With Incident Heart Fai c2018 Jan 103 a

Importance: Nearly half of all patients with heart failure have preserved ejection fraction (HFpEF) as opposed to reduced ejection fraction (HFrEF), yet associations of biomarkers with future heart failure subtype are incompletely understood.

Objective: To evaluate the associations of 12 cardiovascular biomarkers with incident HFpEF vs HFrEF among adults from the general population.

Design, Setting, and Participants: This study included 4 longitudinal community-based cohorts: the Cardiovascular Health Study (1989-1990; 1992-1993 for supplemental African-American cohort), the Framingham Heart Study (1995-1998), the Multi-Ethnic Study of Atherosclerosis (2000-2002), and the Prevention of Renal and Vascular End-stage Disease study (1997-1998). Each cohort had prospective ascertainment of incident HFpEF and HFrEF. Data analysis was performed from June 25, 2015, to November 9, 2017.

Exposures: The following biomarkers were examined: N-terminal pro B-type natriuretic peptide or brain natriuretic peptide, high-sensitivity troponin T or I, C-reactive protein (CRP), urinary albumin to creatinine ratio (UACR), renin to aldosterone ratio, D-dimer, fibrinogen, soluble suppressor of tumorigenicity, galectin-3, cystatin C, plasminogen activator inhibitor 1, and interleukin 6.

Main Outcomes and Measures: Development of incident HFpEF and incident HFrEF.

Results: Among the 22 756 participants in these 4 cohorts (12 087 women and 10 669 men; mean [SD] age, 60 [13] years) in the study, during a median follow-up of 12 years, 633 participants developed incident HFpEF, and 841 developed HFrEF. In models adjusted for clinical risk factors of heart failure, 2 biomarkers were significantly associated with incident HFpEF: UACR (hazard ratio [HR], 1.33; 95% CI, 1.20-1.48; P < .001) and natriuretic peptides (HR, 1.27; 95% CI, 1.16-1.40; P < .001), with suggestive associations for high-sensitivity troponin (HR, 1.11; 95% CI, 1.03-1.19; P = .008), plasminogen activator inhibitor 1 (HR, 1.22; 95% CI, 1.03-1.45; P = .02), and fibrinogen (HR, 1.12; 95% CI, 1.03-1.22; P = .01). By contrast, 6 biomarkers were associated with incident HFrEF: natriuretic peptides (HR, 1.54; 95% CI, 1.41-1.68; P < .001), UACR (HR, 1.21; 95% CI, 1.11-1.32; P < .001), high-sensitivity troponin (HR, 1.37; 95% CI, 1.29-1.46; P < .001), cystatin C (HR, 1.19; 95% CI, 1.11-1.27; P < .001), D-dimer (HR, 1.22; 95% CI, 1.11-1.35; P < .001), and CRP (HR, 1.19; 95% CI, 1.11-1.28; P < .001). When directly compared, natriuretic peptides, high-sensitivity troponin, and CRP were more strongly associated with HFrEF compared with HFpEF.

Conclusions and Relevance: Biomarkers of renal dysfunction, endothelial dysfunction, and inflammation were associated with incident HFrEF. By contrast, only natriuretic peptides and UACR were associated with HFpEF. These findings highlight the need for future studies focused on identifying novel biomarkers of the risk of HFpEF.

1 ade Boer, Rudolf, A1 aNayor, Matthew1 adeFilippi, Christopher, R1 aEnserro, Danielle1 aBhambhani, Vijeta1 aKizer, Jorge, R1 aBlaha, Michael, J1 aBrouwers, Frank, P1 aCushman, Mary1 aLima, João, A C1 aBahrami, Hossein1 aHarst, Pim1 aWang, Thomas, J1 aGansevoort, Ron, T1 aFox, Caroline, S1 aGaggin, Hanna, K1 aKop, Willem, J1 aLiu, Kiang1 aVasan, Ramachandran, S1 aPsaty, Bruce, M1 aLee, Douglas, S1 aHillege, Hans, L1 aBartz, Traci, M1 aBenjamin, Emelia, J1 aChan, Cheeling1 aAllison, Matthew1 aGardin, Julius, M1 aJanuzzi, James, L1 aShah, Sanjiv, J1 aLevy, Daniel1 aHerrington, David, M1 aLarson, Martin, G1 aGilst, Wiek, H1 aGottdiener, John, S1 aBertoni, Alain, G1 aHo, Jennifer, E uhttps://chs-nhlbi.org/node/760303200nas a2200493 4500008004100000022001400041245009000055210006900145260001300214300001200227490000600239520182400245100001702069700002302086700002002109700002202129700001802151700001902169700002002188700001502208700002202223700002302245700002202268700002102290700001202311700001902323700001802342700002002360700002102380700001902401700002002420700002302440700002702463700002202490700002002512700001502532700001702547700001902564700002002583700002302603700002402626700002002650856003602670 2018 eng d a2213-178700aThe Association of Obesity and Cardiometabolic Traits With Incident HFpEF and HFrEF.0 aAssociation of Obesity and Cardiometabolic Traits With Incident  c2018 Aug a701-7090 v63 a

OBJECTIVES: This study evaluated the associations of obesity and cardiometabolic traits with incident heart failure with preserved versus reduced ejection fraction (HFpEF vs. HFrEF). Given known sex differences in HF subtype, we examined men and women separately.

BACKGROUND: Recent studies suggest that obesity confers greater risk of HFpEF versus HFrEF. Contributions of associated metabolic traits to HFpEF are less clear.

METHODS: We studied 22,681 participants from 4 community-based cohorts followed for incident HFpEF versus HFrEF (ejection fraction ≥50% vs. <50%). We evaluated the association of body mass index (BMI) and cardiometabolic traits with incident HF subtype using Cox models.

RESULTS: The mean age was 60 ± 13 years, and 53% were women. Over a median follow-up of 12 years, 628 developed incident HFpEF and 835 HFrEF. Greater BMI portended higher risk of HFpEF compared with HFrEF (hazard ratio [HR]: 1.34 per 1-SD increase in BMI; 95% confidence interval [CI]: 1.24 to 1.45 vs. HR: 1.18; 95% CI: 1.10 to 1.27). Similarly, insulin resistance (homeostatic model assessment of insulin resistance) was associated with HFpEF (HR: 1.20 per 1-SD; 95% CI: 1.05 to 1.37), but not HFrEF (HR: 0.99; 95% CI: 0.88 to 1.11; p < 0.05 for difference HFpEF vs. HFrEF). We found that the differential association of BMI with HFpEF versus HFrEF was more pronounced among women (p for difference HFpEF vs. HFrEF = 0.01) when compared with men (p = 0.34).

CONCLUSIONS: Obesity and related cardiometabolic traits including insulin resistance are more strongly associated with risk of future HFpEF versus HFrEF. The differential risk of HFpEF with obesity seems particularly pronounced among women and may underlie sex differences in HF subtypes.

1 aSavji, Nazir1 aMeijers, Wouter, C1 aBartz, Traci, M1 aBhambhani, Vijeta1 aCushman, Mary1 aNayor, Matthew1 aKizer, Jorge, R1 aSarma, Amy1 aBlaha, Michael, J1 aGansevoort, Ron, T1 aGardin, Julius, M1 aHillege, Hans, L1 aJi, Fei1 aKop, Willem, J1 aLau, Emily, S1 aLee, Douglas, S1 aSadreyev, Ruslan1 aGilst, Wiek, H1 aWang, Thomas, J1 aZanni, Markella, V1 aVasan, Ramachandran, S1 aAllen, Norrina, B1 aPsaty, Bruce, M1 aHarst, Pim1 aLevy, Daniel1 aLarson, Martin1 aShah, Sanjiv, J1 ade Boer, Rudolf, A1 aGottdiener, John, S1 aHo, Jennifer, E uhttps://chs-nhlbi.org/node/781202788nas a2200325 4500008004100000022001400041245013300055210006900188260001300257300001200270490000700282520178400289100002402073700002302097700002402120700002002144700002002164700002302184700002002207700002102227700001902248700002402267700002202291700002402313700002202337700002602359700002002385700002102405856003602426 2018 eng d a1941-329700aLong-Term Cognitive Decline After Newly Diagnosed Heart Failure: Longitudinal Analysis in the CHS (Cardiovascular Health Study).0 aLongTerm Cognitive Decline After Newly Diagnosed Heart Failure L c2018 Mar ae0044760 v113 a

BACKGROUND: Heart failure (HF) is associated with cognitive impairment. However, we know little about the time course of cognitive change after HF diagnosis, the importance of comorbid atrial fibrillation, or the role of ejection fraction. We sought to determine the associations of incident HF with rates of cognitive decline and whether these differed by atrial fibrillation status or reduced versus preserved ejection fraction.

METHODS AND RESULTS: Participants were 4864 men and women aged ≥65 years without a history of HF and free of clinical stroke in the CHS (Cardiovascular Health Study)-a community-based prospective cohort study in the United States, with cognition assessed annually from 1989/1990 through 1998/1999. We identified 496 participants with incident HF by review of hospital discharge summaries and Medicare claims data, with adjudication according to standard criteria. Global cognitive ability was measured by the Modified Mini-Mental State Examination. In adjusted models, 5-year decline in model-predicted mean Modified Mini-Mental State Examination score was 10.2 points (95% confidence interval, 8.6-11.8) after incident HF diagnosed at 80 years of age, compared with a mean 5-year decline of 5.8 points (95% confidence interval, 5.3-6.2) from 80 to 85 years of age without HF. The association was stronger at older ages than at younger ages, did not vary significantly in the presence versus absence of atrial fibrillation (=0.084), and did not vary significantly by reduced versus preserved ejection fraction (=0.734).

CONCLUSIONS: Decline in global cognitive ability tends to be faster after HF diagnosis than without HF. Clinical and public health implications of this finding warrant further attention.

1 aHammond, Christa, A1 aBlades, Natalie, J1 aChaudhry, Sarwat, I1 aDodson, John, A1 aLongstreth, W T1 aHeckbert, Susan, R1 aPsaty, Bruce, M1 aArnold, Alice, M1 aDublin, Sascha1 aSitlani, Colleen, M1 aGardin, Julius, M1 aThielke, Stephen, M1 aNanna, Michael, G1 aGottesman, Rebecca, F1 aNewman, Anne, B1 aThacker, Evan, L uhttps://chs-nhlbi.org/node/768001835nas a2200229 4500008004100000022001400041245009100055210006900146260001700215300001200232490000700244520114300251100002101394700002001415700002301435700002201458700002001480700002001500700002501520700002401545856003601569 2020 eng d a1546-415600aBrachial Flow-mediated Dilation and Risk of Dementia: The Cardiovascular Health Study.0 aBrachial Flowmediated Dilation and Risk of Dementia The Cardiova c2020 Jul-Sep a272-2740 v343 a

INTRODUCTION: Brachial flow-mediated dilation (FMD) is a physiologic measure of endothelial function. We determined the prospective association of brachial FMD with incident dementia among older adults.

METHODS: We included 2777 Cardiovascular Health Study participants who underwent brachial FMD measurement. Incident dementia was ascertained by medication use, International Classification of Diseases-9 codes, requirement for a proxy, and death certificates and calibrated to gold-standard assessments performed in a subset of the cohort.

RESULTS: Mean participant age at time of brachial FMD measurement was 77.9 years. We identified 1650 incident dementia cases (median follow-up=10.5 y). After adjusting for age, race, sex, education, clinic site, and baseline arterial diameter, risk of dementia for participants in the highest quartile of percent brachial FMD did not differ from those in lowest quartile (hazard ratio=0.89, 95% confidence interval: 0.77, 1.03).

CONCLUSIONS: Brachial FMD, measured late in life, is not associated with an increased risk of incident dementia.

1 aGarg, Parveen, K1 aTan, Annabel, X1 aOdden, Michelle, C1 aGardin, Julius, M1 aLopez, Oscar, L1 aNewman, Anne, B1 aRawlings, Andreea, M1 aMukamal, Kenneth, J uhttps://chs-nhlbi.org/node/839202307nas 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/839502800nas a2200433 4500008004100000022001400041245012300055210006900178260001700247300002100264490000700285520159700292653001601889653000901905653002001914653002201934653001101956653001101967653001401978653000901992653002202001653001402023653002402037653002002061653001702081653001602098653001702114653001802131100002102149700001602170700002002186700001902206700002702225700002302252700001602275700001702291700002202308856003602330 2020 eng d a1752-898400aPre-diabetes, diabetes and predictors of incident angina among older women and men in the Cardiovascular Health Study.0 aPrediabetes diabetes and predictors of incident angina among old c2020 Jan-Feb a14791641198884760 v173 a

Diabetes mellitus and angina pectoris are important conditions in older persons. The utility of pre-diabetes mellitus, diabetes mellitus and other risk factors as predictors of incident angina pectoris among older adults has not been characterized. We examined incident angina pectoris rates by sex and diabetes mellitus status in 4511 adults aged ⩾65 years without coronary heart disease at baseline from the Cardiovascular Health Study. Cox regression examined predictors of incident angina pectoris, including pre-diabetes mellitus or diabetes mellitus adjusted for sociodemographic characteristics and other risk factors, over 12.2 ± 6.9 years of follow-up. Overall, 39.1% of participants had pre-diabetes mellitus, 14.0% had diabetes mellitus and 532 (11.8%) had incident angina pectoris. Incident angina pectoris rates per 1000 person-years in those with neither condition, pre-diabetes mellitus, and diabetes mellitus were 7.9, 9.0 and 12.3 in women and 10.3, 11.2 and 14.5 in men, respectively. Pre-diabetes mellitus and diabetes mellitus were not independently associated with incident AP; however, key predictors of AP were male sex, low-density lipoprotein-cholesterol, triglycerides, systolic blood pressure, antihypertensive medication and difficulty performing at least one instrumental activity of daily living (all  < 0.05 to  < 0.01). In our cohort of older adult participants, while the incidence of AP is greater in those with diabetes mellitus, neither diabetes mellitus nor pre-diabetes mellitus independently predicted incident angina pectoris.

10aAge Factors10aAged10aAngina Pectoris10aDiabetes Mellitus10aFemale10aHumans10aIncidence10aMale10aPrediabetic State10aPrognosis10aProspective Studies10aRisk Assessment10aRisk Factors10aSex Factors10aTime Factors10aUnited States1 aMathenge, Njambi1 aFan, Wenjun1 aWong, Nathan, D1 aHirsch, Calvin1 aDelaney, Chris, Joseph1 aAmsterdam, Ezra, A1 aKoch, Bruce1 aCalara, Rico1 aGardin, Julius, M uhttps://chs-nhlbi.org/node/849903481nas a2200493 4500008004100000022001400041245010600055210006900161260001600230300001400246490000700260520202600267100002002293700001802313700002202331700002602353700002202379700002002401700002402421700002402445700002002469700002202489700001702511700002202528700002502550700002102575700001802596700002002614700002002634700003002654700002502684700001902709700002702728700002202755700002002777700002202797700002202819700002302841700002002864700002402884700002002908700002302928856003602951 2020 eng d a1558-359700aSex-Specific Associations of Cardiovascular Risk Factors and Biomarkers With Incident Heart Failure.0 aSexSpecific Associations of Cardiovascular Risk Factors and Biom c2020 Sep 22 a1455-14650 v763 a

BACKGROUND: Whether cardiovascular (CV) disease risk factors and biomarkers associate differentially with heart failure (HF) risk in men and women is unclear.

OBJECTIVES: The purpose of this study was to evaluate sex-specific associations of CV risk factors and biomarkers with incident HF.

METHODS: The analysis was performed using data from 4 community-based cohorts with 12.5 years of follow-up. Participants (recruited between 1989 and 2002) were free of HF at baseline. Biomarker measurements included natriuretic peptides, cardiac troponins, plasminogen activator inhibitor-1, D-dimer, fibrinogen, C-reactive protein, sST2, galectin-3, cystatin-C, and urinary albumin-to-creatinine ratio.

RESULTS: Among 22,756 participants (mean age 60 ± 13 years, 53% women), HF occurred in 2,095 participants (47% women). Age, smoking, type 2 diabetes mellitus, hypertension, body mass index, atrial fibrillation, myocardial infarction, left ventricular hypertrophy, and left bundle branch block were strongly associated with HF in both sexes (p < 0.001), and the combined clinical model had good discrimination in men (C-statistic = 0.80) and in women (C-statistic = 0.83). The majority of biomarkers were strongly and similarly associated with HF in both sexes. The clinical model improved modestly after adding natriuretic peptides in men (ΔC-statistic = 0.006; likelihood ratio chi-square = 146; p < 0.001), and after adding cardiac troponins in women (ΔC-statistic = 0.003; likelihood ratio chi-square = 73; p < 0.001).

CONCLUSIONS: CV risk factors are strongly and similarly associated with incident HF in both sexes, highlighting the similar importance of risk factor control in reducing HF risk in the community. There are subtle sex-related differences in the predictive value of individual biomarkers, but the overall improvement in HF risk estimation when included in a clinical HF risk prediction model is limited in both sexes.

1 aSuthahar, Navin1 aLau, Emily, S1 aBlaha, Michael, J1 aPaniagua, Samantha, M1 aLarson, Martin, G1 aPsaty, Bruce, M1 aBenjamin, Emelia, J1 aAllison, Matthew, A1 aBartz, Traci, M1 aJanuzzi, James, L1 aLevy, Daniel1 aMeems, Laura, M G1 aBakker, Stephan, J L1 aLima, João, A C1 aCushman, Mary1 aLee, Douglas, S1 aWang, Thomas, J1 adeFilippi, Christopher, R1 aHerrington, David, M1 aNayor, Matthew1 aVasan, Ramachandran, S1 aGardin, Julius, M1 aKizer, Jorge, R1 aBertoni, Alain, G1 aAllen, Norrina, B1 aGansevoort, Ron, T1 aShah, Sanjiv, J1 aGottdiener, John, S1 aHo, Jennifer, E1 ade Boer, Rudolf, A uhttps://chs-nhlbi.org/node/848802635nas a2200241 4500008004100000022001400041245006200055210006100117260001300178300001200191490000700203520196100210100002002171700002002191700002202211700002002233700001602253700002202269700002302291700002002314700002302334856003602357 2021 eng d a1942-008000aAssociation Between Myocardial Strain and Frailty in CHS.0 aAssociation Between Myocardial Strain and Frailty in CHS c2021 May ae0121160 v143 a

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

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

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

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

1 aTan, Annabel, X1 aShah, Sanjiv, J1 aSanders, Jason, L1 aPsaty, Bruce, M1 aWu, Chenkai1 aGardin, Julius, M1 aPeralta, Carmen, A1 aNewman, Anne, B1 aOdden, Michelle, C uhttps://chs-nhlbi.org/node/879003815nas a2200229 4500008004100000022001400041245017500055210006900230260001600299300001000315490000800325520304400333100001703377700002503394700002003419700001903439700002003458700002503478700002203503700002403525856003603549 2021 eng d a1879-191300aIncidence, Determinants and Mortality of Heart Failure Associated With Medical-Surgical Procedures in Patients ≥ 65 Years of Age (from the Cardiovascular Health Study).0 aIncidence Determinants and Mortality of Heart Failure Associated c2021 Aug 15 a71-780 v1533 a

Heart failure (HF) and myocardial infarction are serious complications of major noncardiac surgery in older adults. Many factors can contribute to the development of HF during the postoperative period. The incidence of, and risk factors for, procedure-associated heart failure (PHF) occurring at the time of, or shortly after, medical procedures in a population-based sample ≥ 65 years of age have not been fully characterized, particularly in comparison with HF not proximate to medical procedures. This analysis comprises 5,121 men and women free of HF at baseline from the Cardiovascular Health Study who were followed up for 12.0 years (median). HF events were documented by self-report at semi-annual contacts and confirmed by a formal adjudication committee using a review of the participants' medical records and standardized criteria for HF. Incident HF events were additionally adjudicated as either being related or unrelated to a medical procedure (PHF and non-PHF, respectively). We estimated cause-specific hazards ratios for the association of covariates with PHF and non-PHF. There were 1,728 incident HF events in the primary analysis: 168 (10%) classified as PHF, 1,526 (88%) as non-PHF, and 34 unclassified (2%). For those 1,045 participants in whom LV ejection fraction was known at the time of the HF event, it was ≥45% in 89 of 118 participants (75%) with PHF, compared to 517 of 927 participants (55%) with non-PHF (p < 0.001). Increased age, male gender, diabetes, and angina at baseline were associated with both PHF and non-PHF (range of hazard ratios (HR): 1.04-2.05]. Being Black was inversely associated with PHF [HR: 0.46, 95% confidence interval: 0.25-0.86]. Participants with increased age, without baseline angina, and with baseline LVEF<55% were at a significantly lower risk for PHF compared to non-PHF. Among those with PHF, surgical procedures-including cardiac, orthopedic, gastrointestinal, vascular, and urologic-comprised 83.3%, while percutaneous procedures comprised 8.9% (including 6.5% represented by cardiac catheterizations and pacemaker placements). Another group composed of a variety of procedures commonly requiring large fluid volume administration comprised 7.7%. There was a lower all-cause 30-day mortality in the PHF versus the non-PHF group (2.2% vs 5.7%), with a nonsignificant odds ratio of 0.39 in a minimally adjusted model. When individuals with prior myocardial infarction (MI) were excluded in a sensitivity analysis, the proportion of incident HF with concurrent MI was greater for PHF (32.9%) than for non-PHF (19.8%). In conclusion, PHF in older adults is a common entity with relatively low 30-day mortality. Baseline angina, lower age, and LVEF ≥ 55% were associated with a higher risk of PHF compared to non-PHF. Being Black was associated with a lower risk of PHF and PHF as a proportion of HF was lower in Black than in non-Black participants. Compared to non-PHF, PHF more frequently presented with concurrent MI and with preserved LV ejection fraction.

1 aShah, Monali1 aRodriguez, Carlos, J1 aBartz, Traci, M1 aLyles, Mary, F1 aKizer, Jorge, R1 aAurigemma, Gerard, P1 aGardin, Julius, M1 aGottdiener, John, S uhttps://chs-nhlbi.org/node/883702689nas a2200217 4500008004100000022001400041245012200055210007100177260001600248520198600264100002402250700002102274700001902295700002702314700001702341700001802358700002002376700001702396700002202413856003602435 2022 eng d a1879-191300aRelation of Cigarette Smoking and Heart Failure in Adults ≥65 Years of Age (From the Cardiovascular Health Study).0 aRelation of Cigarette Smoking and Heart Failure in Adults ≥65 Ye c2022 Jan 163 a

Cigarette smoking is associated with adverse cardiac outcomes, including incident heart failure (HF). However, key components of potential pathways from smoking to HF have not been evaluated in older adults. In a community-based study, we studied cross-sectional associations of smoking with blood and imaging biomarkers reflecting mechanisms of cardiac disease. Serial nested, multivariable Cox models were used to determine associations of smoking with HF, and to assess the influence of biochemical and functional (cardiac strain) phenotypes on these associations. Compared with never smokers, smokers had higher levels of inflammation (C-reactive protein and interleukin-6), cardiomyocyte injury (cardiac troponin T [hscTnT]), myocardial "stress"/fibrosis (soluble suppression of tumorigenicity 2 [sST2], galectin 3), and worse left ventricle systolic and diastolic function. In models adjusting for age, gender, and race (DEMO) and for clinical factors potentially in the causal pathway (CLIN), smoking exposures were associated with C-reactive protein and interleukin-6, sST2, hscTnT, and with N-terminal pro-brain natriuretic protein (in Whites). In DEMO adjusted models, the cumulative burden of smoking was associated with worse left ventricle systolic strain. Current smoking and former smoking were associated with HF in DEMO models (hazard ratio 1.41, 95% confidence interval 1.22 to 1.64 and hazard ratio 1.14, 95% confidence interval 1.03 to 1.25, respectively), and with current smoking after CLIN adjustment. Adjustment for time-varying myocardial infarction, inflammation, cardiac strain, hscTnT, sST2, and galectin 3 did not materially alter the associations. Smoking was associated with HF with preserved and decreased ejection fraction. In conclusion, in older adults, smoking is associated with multiple blood and imaging biomarker measures of pathophysiology previously linked to HF, and to incident HF even after adjustment for clinical intermediates.

1 aGottdiener, John, S1 aBůzková, Petra1 aKahn, Peter, A1 aDeFilippi, Christopher1 aShah, Sanjiv1 aBarasch, Eddy1 aKizer, Jorge, R1 aPsaty, Bruce1 aGardin, Julius, M uhttps://chs-nhlbi.org/node/897402620nas a2200337 4500008004100000022001400041245005100055210005000106260001600156300001100172520166800183100001801851700002601869700002001895700002001915700002401935700001601959700002101975700001901996700002202015700002202037700002802059700002202087700002402109700002202133700002202155700002402177700002202201700002302223856003602246 2024 eng d a1474-972600aPlasma proteomic signature of human longevity.0 aPlasma proteomic signature of human longevity c2024 Mar 05 ae141363 a

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

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