@article {1245, title = {Association of serial measures of cardiac troponin T using a sensitive assay with incident heart failure and cardiovascular mortality in older adults.}, journal = {JAMA}, volume = {304}, year = {2010}, month = {2010 Dec 08}, pages = {2494-502}, abstract = {

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

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

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

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

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

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

}, keywords = {Aged, Biomarkers, Cardiovascular Diseases, Cohort Studies, Female, Heart Failure, Humans, Incidence, Male, Predictive Value of Tests, Risk, Sensitivity and Specificity, Troponin T, United States}, issn = {1538-3598}, doi = {10.1001/jama.2010.1708}, author = {deFilippi, Christopher R and de Lemos, James A and Christenson, Robert H and Gottdiener, John S and Kop, Willem J and Zhan, Min and Seliger, Stephen L} } @article {1268, title = {Predictive value of depressive symptoms and B-type natriuretic peptide for new-onset heart failure and mortality.}, journal = {Am J Cardiol}, volume = {107}, year = {2011}, month = {2011 Mar 01}, pages = {723-9}, abstract = {

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.

}, keywords = {Aged, Depression, Disease Progression, Female, Follow-Up Studies, Heart Failure, Humans, Incidence, Male, Natriuretic Peptide, Brain, Prognosis, Retrospective Studies, Risk Factors, Survival Rate, United States}, issn = {1879-1913}, doi = {10.1016/j.amjcard.2010.10.055}, author = {van den Broek, Krista C and deFilippi, Christopher R and Christenson, Robert H and Seliger, Stephen L and Gottdiener, John S and Kop, Willem J} } @article {1559, title = {Relation of vitamin D and parathyroid hormone to cardiac biomarkers and to left ventricular mass (from the Cardiovascular Health Study).}, journal = {Am J Cardiol}, volume = {111}, year = {2013}, month = {2013 Feb 01}, pages = {418-24}, abstract = {

Vitamin D and parathyroid hormone (PTH) may affect cardiovascular health in patients with kidney disease and in the general population. The aim of this study was to investigate associations of serum 25-hydroxyvitamin D (25(OH)D) and PTH concentrations with a comprehensive set of biochemical, electrocardiographic, and echocardiographic measurements of cardiac structure and function in the Cardiovascular Health Study. A total of 2,312 subjects who were free of cardiovascular disease at baseline were studied. Serum 25(OH)D and intact PTH concentrations were measured using mass spectrometry and a 2-site immunoassay. Outcomes were N-terminal pro-B-type natriuretic peptide, cardiac troponin T, electrocardiographic measures of conduction, and echocardiographic measures of left ventricular mass and diastolic dysfunction. At baseline, subjects had a mean age of 73.9 {\textpm} 4.9 years, 69.7\% were women, and 21\% had chronic kidney disease (glomerular filtration rate <60 ml/min). Mean 25(OH)D was 25.2 {\textpm} 10.2 ng/ml, and median PTH was 51 pg/ml (range 39 to 65). After adjustment, 25(OH)D was not associated with any of the biochemical, conduction, or echocardiographic outcomes. Serum PTH levels >=65 pg/ml were associated with greater N-terminal pro-B-type natriuretic peptide, cardiac troponin T, and left ventricular mass in patients with chronic kidney disease. The regression coefficients were: 120 pg/ml (95\% confidence interval 36.1 to 204), 5.2 pg/ml (95\% confidence interval 3.0 to 7.4), and 17 g (95\% confidence interval 6.2 to 27.8) (p <0.001). In subjects with normal kidney function, PTH was not associated with the outcomes. In conclusion, in older adults with chronic kidney disease, PTH excess is associated with higher N-terminal pro-B-type natriuretic peptide, cardiac troponin T, and left ventricular mass. These findings suggest a role for PTH in cardiovascular health and the prevention of cardiac diseases.

}, keywords = {Adult, Aged, Biomarkers, Cardiovascular Diseases, Echocardiography, Electrocardiography, Female, Follow-Up Studies, Heart Ventricles, Humans, Incidence, Male, Mass Spectrometry, Middle Aged, Parathyroid Hormone, Prospective Studies, United States, Vitamin D}, issn = {1879-1913}, doi = {10.1016/j.amjcard.2012.10.021}, author = {van Ballegooijen, Adriana J and Visser, Marjolein and Kestenbaum, Bryan and Siscovick, David S and de Boer, Ian H and Gottdiener, John S and deFilippi, Christopher R and Brouwer, Ingeborg A} } @article {6137, title = {Relations of plasma total and high-molecular-weight adiponectin to new-onset heart failure in adults >=65 years of age (from the Cardiovascular Health study).}, journal = {Am J Cardiol}, volume = {113}, year = {2014}, month = {2014 Jan 15}, pages = {328-34}, abstract = {

Adiponectin exhibits cardioprotective properties in experimental studies, but elevated levels have been linked to increased mortality in older adults and patients with chronic heart failure (HF). The adipokine{\textquoteright}s association with new-onset HF remains less well defined. The aim of this study was to investigate the associations of total and high-molecular weight (HMW) adiponectin with incident HF (n = 780) and, in a subset, echocardiographic parameters in a community-based cohort of adults aged >=65 years. Total and HMW adiponectin were measured in 3,228 subjects without prevalent HF, atrial fibrillation or CVD. The relations of total and HMW adiponectin with HF were nonlinear, with significant associations observed only for concentrations greater than the median (12.4 and 6.2 mg/L, respectively). After adjustment for potential confounders, the hazard ratios per SD increment in total adiponectin were 0.93 (95\% confidence interval 0.72 to 1.21) for concentrations less than the median and 1.25 (95\% confidence interval 1.14 to 1.38) higher than the median. There was a suggestion of effect modification by body mass index, whereby the association appeared strongest in participants with lower body mass indexes. Consistent with the HF findings, higher adiponectin tended to be associated with left ventricular systolic dysfunction and left atrial enlargement. Results were similar for HMW adiponectin. In conclusion, total and HMW adiponectin showed comparable relations with incident HF in this older cohort, with a threshold effect of increasing risk occurring at their median concentrations. High levels of adiponectin may mark or mediate age-related processes that lead to HF in older adults.

}, keywords = {Adiponectin, Age of Onset, Aged, Biomarkers, Cross-Sectional Studies, Echocardiography, Doppler, Enzyme-Linked Immunosorbent Assay, Female, Follow-Up Studies, Heart Failure, Humans, Incidence, Male, Prognosis, Prospective Studies, Recurrence, Severity of Illness Index, United States, Ventricular Function, Left}, issn = {1879-1913}, doi = {10.1016/j.amjcard.2013.09.027}, author = {Karas, Maria G and Benkeser, David and Arnold, Alice M and Bartz, Traci M and Djouss{\'e}, Luc and Mukamal, Kenneth J and Ix, Joachim H and Zieman, Susan J and Siscovick, David S and Tracy, Russell P and Mantzoros, Christos S and Gottdiener, John S and deFilippi, Christopher R and Kizer, Jorge R} } @article {6235, title = {Troponin T, NT-proBNP, and venous thromboembolism: the Longitudinal Investigation of Thromboembolism Etiology (LITE).}, journal = {Vasc Med}, volume = {19}, year = {2014}, month = {2014 Feb}, pages = {33-41}, abstract = {

Increased levels of plasma troponins and natriuretic peptides are markers of cardiac dysfunction associated with increased risk of cardiovascular disease. Little information exists on cardiac dysfunction and occurrence of venous thromboembolism (VTE). In two prospective epidemiological cohorts, we tested the hypothesis that high-sensitivity troponin T (TnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP) are associated positively with VTE occurrence. The Atherosclerosis Risk in Communities (ARIC) study and the Cardiovascular Health Study (CHS) measured plasma TnT and NT-proBNP in 13,719 men or women with no history of venous thrombosis, coronary heart disease, or heart failure and followed them for approximately 10 years for VTE occurrence (n = 348 VTEs). In both ARIC and CHS, TnT was associated positively with incidence of total VTE and provoked VTE, but not with unprovoked VTE: age, race, and sex-adjusted hazard ratios for total VTE in the pooled analysis were 1.00, 0.85, 1.36, 1.51, and 1.98 (p-trend <0.0001) across five categories of TnT. In contrast, the association of NT-proBNP with VTE was positive in ARIC (hazard ratios approximately 2.5-fold for the highest versus lowest NT-proBNP quintiles), but non-existent in CHS.

}, keywords = {Aged, Aged, 80 and over, Atherosclerosis, Biomarkers, Female, Heart Failure, Humans, Incidence, Longitudinal Studies, Male, Middle Aged, Natriuretic Peptide, Brain, Peptide Fragments, Prospective Studies, Risk Factors, Troponin T, Venous Thromboembolism}, issn = {1477-0377}, doi = {10.1177/1358863X14520869}, author = {Folsom, Aaron R and Lutsey, Pamela L and Nambi, Vijay and deFilippi, Christopher R and Heckbert, Susan R and Cushman, Mary and Ballantyne, Christie M} }