03157nas a2200385 4500008004100000022001400041245011800055210006900173260001600242300001000258490000800268520204900276653000902325653001502334653002402349653001102373653002202384653001802406653001102424653001402435653000902449653003102458653001402489653002602503653001702529653001802546653001802564100002902582700003002611700002702641700002402668700002402692700001902716856003602735 2011 eng d a1879-191300aPredictive value of depressive symptoms and B-type natriuretic peptide for new-onset heart failure and mortality.0 aPredictive value of depressive symptoms and Btype natriuretic pe c2011 Mar 01 a723-90 v1073 a

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

10aAged10aDepression10aDisease Progression10aFemale10aFollow-Up Studies10aHeart Failure10aHumans10aIncidence10aMale10aNatriuretic Peptide, Brain10aPrognosis10aRetrospective Studies10aRisk Factors10aSurvival Rate10aUnited States1 avan den Broek, Krista, C1 adeFilippi, Christopher, R1 aChristenson, Robert, H1 aSeliger, Stephen, L1 aGottdiener, John, S1 aKop, Willem, J uhttps://chs-nhlbi.org/node/126803025nas a2200361 4500008004100000022001400041245012800055210006900183260001600252300001200268490000700280520196000287653000902247653001502256653001102271653001802282653001102300653000902311653001902320653003102339653002202370653002002392653001302412100003002425700002302455700002302478700002702501700002702528700002402555700002402579700002402603856003602627 2012 eng d a1558-359700aPhysical activity, change in biomarkers of myocardial stress and injury, and subsequent heart failure risk in older adults.0 aPhysical activity change in biomarkers of myocardial stress and  c2012 Dec 18 a2539-470 v603 a

OBJECTIVES: The aim of this study was to evaluate the association between physical activity and changes in levels of highly sensitive troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), and the subsequent risk of the development of heart failure (HF) in community-dwelling older adults.

BACKGROUND: Higher baseline levels of cTnT and NT-proBNP and increases over time correlate with the risk of HF in older adults. Factors modifying these levels have not been identified.

METHODS: NT-proBNP and cTnT were measured at baseline and 2 to 3 years later in adults 65 years of age and older free of HF participating in the Cardiovascular Health Study. Self-reported physical activity and walking pace were combined into a composite score. An increase was prespecified for NT-proBNP as a >25% increment from baseline to ≥190 pg/ml and for cTnT as a >50% increment from baseline in participants with detectable levels (≥3 pg/ml).

RESULTS: A total of 2,933 participants free of HF had NT-proBNP and cTnT measured at both time points. The probability of an increase in biomarker concentrations between baseline and follow-up visits was inversely related to the physical activity score. Compared with participants with the lowest score, those with the highest score had an odds ratio of 0.50 (95% confidence interval: 0.33 to 0.77) for an increase in NT-proBNP and an odds ratio of 0.30 (95% confidence interval: 0.16 to 0.55) for an increase in cTnT, after adjusting for comorbidities and baseline levels. A higher activity score associated with a lower long-term incidence of HF. Moreover, at each level of activity, an increase in either biomarker still identified those at higher risk.

CONCLUSIONS: These findings suggest that moderate physical activity has protective effects on early heart failure phenotypes, preventing cardiac injury and neurohormonal activation.

10aAged10aBiomarkers10aFemale10aHeart Failure10aHumans10aMale10aMotor Activity10aNatriuretic Peptide, Brain10aPeptide Fragments10aRisk Assessment10aTroponin1 adeFilippi, Christopher, R1 ade Lemos, James, A1 aTkaczuk, Andrew, T1 aChristenson, Robert, H1 aCarnethon, Mercedes, R1 aSiscovick, David, S1 aGottdiener, John, S1 aSeliger, Stephen, L uhttps://chs-nhlbi.org/node/154703186nas a2200481 4500008004100000022001400041245017800055210006900233260001300302300001200315490000700327520177800334653000902112653002002121653001502141653002802156653001102184653001802195653001102213653002302224653002302247653002502270653000902295653001602304653002602320653001402346653002002360653001702380653001602397653001502413100002002428700002402448700002002472700001702492700002402509700001702533700001802550700002402568700002102592700002502613700003002638856003602668 2015 eng d a1530-856100aPrognostic Significance of High-Sensitivity Cardiac Troponin T Concentrations between the Limit of Blank and Limit of Detection in Community-Dwelling Adults: A Metaanalysis.0 aPrognostic Significance of HighSensitivity Cardiac Troponin T Co c2015 Dec a1524-310 v613 a

BACKGROUND: There is controversy regarding whether to report concentrations of high-sensitivity cardiac troponin T (hs-cTnT) to the limit of blank (LOB) (3 ng/L) or the limit of detection (LOD) (5 ng/L) of the assay in community-based cohorts. We hypothesized that hs-cTnT concentrations between the LOB and LOD would be associated with poorer cardiovascular outcomes compared to concentrations below the LOB.

METHODS: hs-cTnT was analyzed in a total of 10 723 participants from the Cardiovascular Health Study (CHS), Atherosclerosis Risk in Communities (ARIC) study, and Dallas Heart Study (DHS). Participants were divided into 2 groups, those with hs-cTnT concentrations below the limit of blank (LOB) (<3 ng/L) and those with hs-cTnT between the LOB and limit of detection (LOD) (3-4.99 ng/L). Cross-sectional associations with traditional cardiovascular risk factors and cardiac structural measurements, and longitudinal associations with long-term cardiovascular outcomes of incident heart failure and cardiovascular death, were determined.

RESULTS: Participants with hs-cTnT between the LOB and LOD for all 3 cohorts were older, more likely to be male, and have a higher burden of cardiovascular risk factors and structural pathology. A metaanalysis of the 3 cohorts showed participants with hs-cTnT between the LOB and LOD were at increased risk of new-onset heart failure (hazard ratio, 1.18; 95% CI, 1.02-1.38) and cardiovascular mortality (hazard ratio, 1.29; 95% CI, 1.06-1.57).

CONCLUSIONS: hs-cTnT concentrations between the LOB and LOD (3-4.99 ng/L) are associated with a higher prevalence of traditional risk factors, more cardiac pathology, and worse outcomes than concentrations below the LOB (<3 ng/L).

10aAged10aAtherosclerosis10aBiomarkers10aCross-Sectional Studies10aFemale10aHeart Failure10aHumans10aIndependent Living10aLimit of Detection10aLongitudinal Studies10aMale10aMiddle Aged10aMyocardial Infarction10aPrognosis10aRisk Assessment10aRisk Factors10aSex Factors10aTroponin T1 aParikh, Ravi, H1 aSeliger, Stephen, L1 ade Lemos, James1 aNambi, Vijay1 aChristenson, Robert1 aAyers, Colby1 aSun, Wensheng1 aGottdiener, John, S1 aKuller, Lewis, H1 aBallantyne, Christie1 adeFilippi, Christopher, R uhttps://chs-nhlbi.org/node/687805208nas a2200541 4500008004100000022001400041245012300055210006900178260001500247300001300262490000600275520365800281653001003939653000903949653002003958653002803978653001904006653002404025653001104049653001104060653002504071653000904096653001604105653003204121653002404153653002004177653001704197100001704214700002104231700002004252700002704272700002204299700002304321700001704344700002404361700002304385700002304408700001804431700002304449700002704472700002104499700001904520700002704539700002104566700002304587700002004610856003604630 2020 eng d a2574-380500aPerformance of the Pooled Cohort Equations to Estimate Atherosclerotic Cardiovascular Disease Risk by Body Mass Index.0 aPerformance of the Pooled Cohort Equations to Estimate Atheroscl c2020 10 01 ae20232420 v33 a

Importance: Obesity is a global health challenge and a risk factor for atherosclerotic cardiovascular disease (ASVCD). Performance of the pooled cohort equations (PCE) for ASCVD risk by body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is unknown.

Objective: To assess performance of the PCE across clinical BMI categories.

Design, Setting, and Participants: This cohort study used pooled individual-level data from 8 community-based, prospective, longitudinal cohort studies with 10-year ASCVD event follow-up from 1996 to 2016. We included all adults ages 40 to 79 years without baseline ASCVD or statin use, resulting in a sample size of 37 311 participants. Data were analyzed from August 2017 to July 2020.

Exposures: Participant BMI category: underweight (<18.5), normal weight (18.5 to <25), overweight (25 to <30), mild obesity (30 to <35), and moderate to severe obesity (≥35).

Main Outcomes and Measures: Discrimination (Harrell C statistic) and calibration (Nam-D'Agostino χ2 goodness-of-fit test) of the PCE across BMI categories. Improvement in discrimination and net reclassification with addition of BMI, waist circumference, and high-sensitivity C-reactive protein (hsCRP) to the PCE.

Results: Among 37 311 participants (mean [SD] age, 58.6 [11.8] years; 21 897 [58.7%] women), 380 604 person-years of follow-up were conducted. Mean (SD) baseline BMI was 29.0 (6.2), and 360 individuals (1.0%) were in the underweight category, 9937 individuals (26.6%) were in the normal weight category, 13 601 individuals (36.4%) were in the overweight category, 7783 individuals (20.9%) were in the mild obesity category, and 5630 individuals (15.1%) were in the moderate to severe obesity category. Median (interquartile range [IQR]) 10-year estimated ASCVD risk was 7.1% (2.5%-15.4%), and 3709 individuals (9.9%) developed ASCVD over a median (IQR) 10.8 [8.5-12.6] years. The PCE overestimated ASCVD risk in the overall cohort (estimated/observed [E/O] risk ratio, 1.22; 95% CI, 1.18-1.26) and across all BMI categories except the underweight category. Calibration was better near the clinical decision threshold in all BMI groups but worse among individuals with moderate or severe obesity (E/O risk ratio, 1.36; 95% CI, 1.25-1.47) and among those with the highest estimated ASCVD risk ≥20%. The PCE C statistic overall was 0.760 (95% CI, 0.753-0.767), with lower discrimination in the moderate or severe obesity group (C statistic, 0.742; 95% CI, 0.721-0.763) compared with the normal-range BMI group (C statistic, 0.785; 95% CI, 0.772-0.798). Waist circumference (hazard ratio, 1.07 per 1-SD increase; 95% CI, 1.03-1.11) and hsCRP (hazard ratio, 1.07 per 1-SD increase; 95% CI, 1.05-1.09), but not BMI, were associated with increased ASCVD risk when added to the PCE. However, these factors did not improve model performance (C statistic, 0.760; 95% CI, 0.753-0.767) with or without added metrics.

Conclusions and Relevance: These findings suggest that the PCE had acceptable model discrimination and were well calibrated at clinical decision thresholds but overestimated risk of ASCVD for individuals in overweight and obese categories, particularly individuals with high estimated risk. Incorporation of the usual clinical measures of obesity did not improve risk estimation of the PCE. Future research is needed to determine whether incorporation of alternative high-risk obesity markers (eg, weight trajectory or measures of visceral or ectopic fat) into the PCE may improve risk prediction.

10aAdult10aAged10aBody Mass Index10aCardiovascular Diseases10aCohort Studies10aCorrelation of Data10aFemale10aHumans10aLongitudinal Studies10aMale10aMiddle Aged10aProportional Hazards Models10aProspective Studies10aRisk Assessment10aRisk Factors1 aKhera, Rohan1 aPandey, Ambarish1 aAyers, Colby, R1 aCarnethon, Mercedes, R1 aGreenland, Philip1 aNdumele, Chiadi, E1 aNambi, Vijay1 aSeliger, Stephen, L1 aChaves, Paulo, H M1 aSafford, Monika, M1 aCushman, Mary1 aXanthakis, Vanessa1 aVasan, Ramachandran, S1 aMentz, Robert, J1 aCorrea, Adolfo1 aLloyd-Jones, Donald, M1 aBerry, Jarett, D1 ade Lemos, James, A1 aNeeland, Ian, J uhttps://chs-nhlbi.org/node/8626