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Background: Higher circulating concentrations of NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI) are associated with left ventricular remodeling and with incident heart failure. The associations of these cardiac biomarkers with changes in cardiac structure and function over time are uncharacterized., Methods: Among 2006 participants in the ARIC prospective cohort study (Atherosclerosis Risk in Communities) who were free of overt cardiovascular disease and underwent echocardiography at study visits 5 (2011- 2013) and 7 (2018-2019), we assessed the associations of NT-proBNP, hs-cTnT, and hs-cTnI concentrations at visit 5 with changes in left ventricular structure and function between visits 5 and 7 (≈7-year change) using multivariable linear regression with the biomarkers modeled as restricted cubic splines. Models were adjusted for age, sex, race, body mass index, smoking, diabetes, hypertension, and renal function at visit 5; blood pressure and heart rate at both visits; and the baseline value of the echocardiographic parameter of interest., Results: Mean±SD age was 74±4 years at visit 5; 61% were women; and 23% were Black adults. Median (25th-75th percentile) concentrations at visit 5 of NT-proBNP, hs-cTnT, and hs-cTnI were 87 ng/L (50-157 ng/L), 9 ng/L (6-12 ng/L), and 2.6 ng/L (1.9-3.9 ng/L). In adjusted models, elevated baseline concentrations of NT-proBNP and hs-cTnI were significantly associated with 7-year decline in left ventricular systolic function (ejection fraction, longitudinal and circumferential strain) and worsening diastolic indices. In contrast, elevated baseline concentrations of hs-cTnT were not significantly associated with 7-year changes in cardiac structure, systolic function, or diastolic function (all P >0.05)., Conclusions: Higher concentrations of NT-proBNP and hs-cTnI, but not hs-cTnT, were associated with greater declines in left ventricular function over ≈7 years in late life independently of traditional cardiovascular risk factors., Competing Interests: Dr Myhre has consulted for Amarin, AmGen, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Novartis, Novo Nordisk, Pharmacosmos, Roche Diagnostics, Sanofi, Us2.ai, and Vifor. Dr Ballantyne has been a consultant for Abbott Diagnostics and Roche Diagnostics. Dr Shah has received research support from Novartis and consulting fees from Philips Ultrasound and Janssen. The other authors report no conflicts.

Background: Elevated cardiac troponin levels in blood are associated with increased risk of cardiovascular diseases and mortality. Cardiac troponin levels are heritable, but their genetic architecture remains elusive., Methods: We conducted a transethnic genome-wide association analysis on high-sensitivity cTnT (cardiac troponin T; hs-cTnT) and high-sensitivity cTnI (cardiac troponin I; hs-cTnI) levels in 24 617 and 14 336 participants free of coronary heart disease and heart failure from 6 population-based cohorts, followed by a series of bioinformatic analyses to decipher the genetic architecture of hs-cTnT and hs-cTnI., Results: We identified 4 genome-wide significant loci for hs-cTnT including a novel locus rs3737882 in PPFIA4 and 3 previously reported loci at NCOA2 , TRAM1 , and BCL2 . One known locus at VCL was replicated for hs-cTnI. One copy of C allele for rs3737882 was associated with a 6% increase in hs-cTnT levels (minor allele frequency, 0.18; P =2.80×10 -9 ). We observed pleiotropic loci located at BAG3 and ANO5 . The proportions of variances explained by single-nucleotide polymorphisms were 10.15% and 7.74% for hs-cTnT and hs-cTnI, respectively. Single-nucleotide polymorphisms were colocalized with BCL2 expression in heart tissues and hs-cTnT and with ANO5 expression in artery, heart tissues, and whole blood and both troponins. Mendelian randomization analyses showed that genetically increased hs-cTnT and hs-cTnI levels were associated with higher odds of atrial fibrillation (odds ratio, 1.38 [95% CI, 1.25-1.54] for hs-cTnT and 1.21 [95% CI, 1.06-1.37] for hs-cTnI)., Conclusions: We identified a novel genetic locus associated with hs-cTnT in a multiethnic population and found that genetically regulated troponin levels were associated with atrial fibrillation.

Background: Circulating high sensitivity cardiac troponin T (hs-cTnT) is associated with incidence of atrial fibrillation (AF), but the association of changes in hs-cTnT over time on incident AF has not been explored., Hypothesis: Six-year increase in circulating hs-cTnT will be associated with increased risk of AF and will contribute to improved prediction of incident AF., Methods: We conducted a prospective cohort analysis of 8431 participants from the Atherosclerosis Risk in Communities (ARIC) study. hs-cTnT change was categorized at visit 2 and 4 as undetectable (<5 ng/L), detectable (≥5 ng/L, <14 ng/L), or elevated (≥14 ng/L). We used Cox regression to examine the association between the combination of hs-cTnT categories at two visits and incident AF. We also assessed the impact of adding absolute hs-cTnT change on risk discrimination for AF by C-statistics and net reclassification improvement (NRI)., Results: Over a mean follow-up of 16.5 years, 1629 incident AF cases were diagnosed. Among participants with undetectable hs-cTnT at visit 2, the multivariable HR of AF was 1.28 (95% CI 1.12-1.48) among those with detectable or elevated hs-cTnT at visit 4 compared to those in which hs-cTnT remained undetectable. Among those with detectable hs-cTnT at visit 2, compared to those who remained in the detectable hs-cTnT group, reduction to undetectable at visit 4 was associated with lower risk of AF (HR 0.74, 95% CI 0.59-0.94), while increment to elevated was associated with higher AF risk (HR 1.30, 95% CI 1.01-1.68). Adding hs-cTnT change to our main model with baseline hs-cTnT did not result in significant improvement in the C-statistic or substantial NRI., Conclusion: Six-year increase in circulating hs-cTnT was associated with elevated risk of incident AF., (© 2021 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Background/objectives: Traditional cardiovascular risk factors are less predictive in older age. High-sensitivity cardiac troponin I (hs-cTnI) is a marker of subclinical cardiomyocyte damage associated with cardiovascular risk in middle-aged adults. We hypothesized hs-cTnI would be indicative of mortality and cardiovascular risk beyond traditional cardiovascular risk factors in older adults and may be more discriminatory compared to hs-troponin T (hs-cTnT)., Design: Prospective cohort study., Setting: Population-based Atherosclerosis Risk in Communities (ARIC) Study., Participants: We included 5,876 ARIC participants at Visit 5 (2011-2013)., Outcomes and Measures: We used Cox regression for the association of hs-cTnI categories (women: <4, 4-<10, ≥10 ng/ml; men: <6, 6-<12, ≥12 ng/ml, prevalent cardiovascular disease (CVD)) with mortality and incident CVD (atherosclerotic CVD [ASCVD]: coronary heart disease or stroke, or heart failure)., Results: Participants were ages 66 to 90, 23% black, 42% male, and 24% had prevalent CVD. There were 1,053 (321 CVD) deaths (median follow-up 6.3 years). Participants with elevated hs-cTnI and no CVD (7% of participants) had mortality risk similar to those with a history of CVD (55.6 vs 55.7 deaths/1,000 person-years, P = .99). After adjustment, elevated hs-cTnI and no CVD (hazard ratio (HR) = 2.38, 95% confidence interval (CI) = 1.85-3.06) and prevalent CVD (HR = 2.21, 95% CI = 1.90-2.57) remained associated with mortality, compared to low hs-cTnI and no CVD. Elevated hs-cTnI was independently associated with incident CVD (HR = 3.41, 95% CI = 2.58-4.51), ASCVD (HR = 2.02, 95% CI = 1.36-2.98), and heart failure (HR = 6.16, 95% CI = 4.24-8.95). The addition of hs-cTnI significantly improved C-statistics for all outcomes and added greater discrimination than hs-cTnT for cardiovascular mortality and incident heart failure., Conclusions: Hs-cTnI improves mortality and CVD risk stratification in older adults beyond traditional risk factors and improved model discrimination more than hs-cTnT for certain outcomes. Elevated hs-cTnI without CVD identifies a high-risk group with comparable mortality risk as those with a history of clinical CVD., (© 2020 The American Geriatrics Society.)

Background: Cardiac markers such as high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B natriuretic peptide (NTproBNP) are predictors of developing acute kidney injury (AKI) during hospitalization for surgery or revascularization. However, their associations with the long-term risk of AKI in the general population are uncharacterized., Methods: We conducted a prospective cohort study in 10 669 participants of the Atherosclerosis Risk in Communities Study (visit 4, 1996-1998, mean age, 63 years, 56% female, 22% black race) to examine the association of plasma concentrations of hs-cTnT and NTproBNP with the incident hospitalization with AKI. We used multivariable Cox regression analysis to estimate hazard ratios (HRs)., Results: During follow-up, 1907 participants had an incident hospitalization with AKI. Participants with higher concentrations of hs-cTnT had a higher risk of hospitalization with AKI in a graded fashion (adjusted HR, 1.88 [95%CI , 1.59-2.21] for ≥14 ng/L, 1.36 [1.18-1.57] for 9-13 ng/L, and 1.16 [1.03-1.30] for 5-8 ng/L compared to <5 ng/L). The graded association was also observed for NTproBNP (HR, 2.27 [1.93-2.68] for ≥272.7 pg/mL, 1.67 [1.45-1.93] for 142.4-272.6 pg/mL, and 1.31 [1.17-1.47] for 64.0-142.3 pg/mL compared to <64.0 pg/mL). The addition of hs-cTnT and NTproBNP to a model with established predictors significantly improved 10-year risk prediction for hospitalization with AKI (Δc-statistic, 0.015 [95%CI, 0.006-0.024])., Conclusions: In middle-aged to older black and white adults in the community, higher concentrations of hs-cTnT and NTproBNP were robustly associated with an increased risk of hospitalization with AKI. These results suggest the usefulness of hs-cTnT and NT-proBNP to identify people at risk of AKI in the general population., (© American Association for Clinical Chemistry 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background hs-cTnT (high-sensitivity cardiac troponin T), but not NT-proBNP (N-terminal pro-B natriuretic peptide), has been shown to predict bleeding in patients with atrial fibrillation. Whether these biomarkers are independently associated with bleeding in the general population is unknown. Methods and Results We used Cox proportional hazards models to examine the association of hs-cTnT and NT-proBNP with incident bleeding (defined by International Classification of Diseases, Ninth Revision [ ICD-9 ] codes) among 9550 middle-aged men and women without a history of cardiovascular disease or bleeding. There were 847 hospitalizations with bleeding (92% from gastrointestinal bleeding) during a median follow-up of 9.0 years. Serum levels of hs-cTnT were associated with bleeding in a graded fashion, with a hazard ratio of 1.28 (95% CI, 1.06-1.59) for 6 to <9 ng/L, 1.52 (1.21-1.91) for 9 to <14, and 2.05 (1.56-2.69) for ≥14 versus <3 ng/L. For NT-proBNP, the highest category (≥264 versus <42 pg/mL) showed a hazard ratio of 2.00 (1.59-2.61), and the remaining 3 categories had hazard ratios ranging from 1.2 to 1.3. Individuals in the highest category of both hs-cTnT and NT-proBNP had a hazard ratio of 3.03 (1.97-4.68) compared with those in the lowest categories. Conclusions In a community-based population, elevated hs-cTnT and NT-proBNP were associated with bleeding-related hospitalizations. These biomarkers may have a high utility in identifying people at high risk for bleeding. There is a need for research on the underlying mechanisms linking subclinical cardiac abnormalities and bleeding.

Cancer survivors might have an excess risk of cardiovascular disease (CVD) resulting from toxicities of cancer therapies and a high burden of CVD risk factors. We sought to evaluate the association of cancer survivorship with subclinical myocardial damage, as assessed by elevated high-sensitivity cardiac troponin T (hs-cTnT) test results. We included 3,512 participants of the Atherosclerosis Risk in Communities Study who attended visit 5 (2011-2013) and were free of CVD (coronary heart disease, heart failure, or stroke). We used multivariate logistic regression to evaluate the cross-sectional associations of survivorship from any, non-sex-related, and sex-related cancers (e.g., breast, prostate) with elevated hs-cTnT (≥14 ng/L). Of 3,512 participants (mean age, 76 years; 62% women; 21% black), 19% were cancer survivors. Cancer survivors had significantly higher odds of elevated hs-cTnT (OR = 1.26, 95% CI: 1.03, 1.53). Results were similar for survivors of non-sex-related and colorectal cancers, but there was no association between survivorship from breast and prostate cancers and elevated hs-cTnT. Results were similar after additional adjustments for CVD risk factors. Survivors of some cancers might be more likely to have elevated hs-cTnT than persons without prior cancer. The excess burden of subclinical myocardial damage in this population might not be fully explained by traditional CVD risk factors., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Whether persons without prevalent cardiovascular disease (CVD) but elevated levels of high-sensitivity cardiac troponin T (hs-cTnT) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) are at high risk of infection is unknown. Using 1996-2013 data from the Atherosclerosis Risk in Communities Study, we estimated hazard ratios for incident hospitalization with infection in relation to plasma hs-cTnT and NT-proBNP concentrations among participants without prevalent CVD and contrasted them with hazard ratios for persons with prevalent CVD (coronary heart disease, heart failure, or stroke). In a multivariable Cox model, prevalent CVD was significantly associated with risk of hospitalization with infection (hazard ratio (HR) = 1.31, 95% confidence interval (CI): 1.19, 1.45). Among participants without prevalent CVD, hs-cTnT and NT-proBNP were independently associated with infection risk in a graded fashion (e.g., HR = 1.44 (95% CI: 1.24, 1.69) for hs-cTnT ≥14 ng/L and HR = 1.28 (95% CI: 1.14, 1.44) for hs-cTnT 9-13 ng/L vs. <3 ng/L; HR = 1.57 (95% CI: 1.35, 1.81) for NT-proBNP ≥248.1 pg/mL and HR = 1.19 (95% CI: 1.06, 1.34) for NT-proBNP 137.2-248.0 pg/mL vs. <48.1 pg/mL). The 15-year cumulative incidences of hospitalization with infection were similar for participants with prevalent CVD and participants who did not have prevalent CVD but had hs-cTnT ≥14 ng/L or NT-proBNP ≥248.1 pg/mL. Thus, hs-cTnT and NT-proBNP were independently associated with infection risk. Persons without CVD but with elevated hs-cTnT or NT-proBNP levels should be recognized to have similar infection risks as persons with prevalent CVD., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Measures of serum cardiac troponins and natriuretic peptides have become established as prognostic heart failure risk markers. In addition to detecting myocardial fibrosis through late gadolinium enhancement (LGE), extracellular volume fraction (ECV) measures by cardiac magnetic resonance (CMR) have emerged as a phenotypic imaging risk marker for incident heart failure outcomes. We sought to examine the relationship between cardiac troponins, natriuretic peptides, ECV and their associations with incident heart failure events in a CMR referral base. Mid short axis T1 maps were divided into 6 cardiac segments, each classified as LGE absent or present. Global ECV was derived from T1 maps using the area-weighted average of only LGE-absent segments. ECV was considered elevated if measured >30%, the upper 95% bounds of a reference healthy group without known cardiac disease (n = 28). Patients were dichotomized by presence of elevated ECV. High-sensitivity cardiac troponin T (hs-cTnT) and N-terminal B-type natriuretic peptide (NT-proBNP) were measured using serum samples acquired and stored at time of CMR scan, and patients were categorized into 3 groups for each blood marker based on recommended cutoff values. Subsequent heart failure admission and any death were ascertained. Relationships with ECV, hs-cTnT, and NT-proBNP were examined separately and as a composite with Cox proportional hazard models. Of 1,604 serial patients referred for a clinical CMR with myocardial T1 maps, 331 were eligible after exclusions and had blood available and were followed over a median 25.0 [interquartile range 21.8, 31.7] months. After adjustments for age (mean 57.3 [standard deviation (SD) 15.1 years), gender (61% male), and ethnicity (12.7% black), elevated ECV remained a predictor of a first composite heart failure outcome for patients with high levels of hs-cTnT (≥14 ng/L; hazard ratio [HR] 2.42 [95% confidence interval (CI) 1.17, 5.03]; p = 0.02) and NT-proBNP (≥300 pg/mL; HR 2.28 [95% CI 1.24, 4.29]; p = 0.01). Similar trends were seen for lower category levels of blood markers, but did not persist with minimal covariate adjustments. Elevated measures of ECV by CMR are associated with incident heart failure outcomes in patients with high hs-cTnT and NT-proBNP levels. This imaging marker may have a role for additional heart failure risk stratification.

Objectives: Cardiac troponin T, measured using a high-sensitive assay (hs-cTnT), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are associated with increased stroke risk and perhaps with cognitive decline. However, few well-designed prospective studies with extended follow-up have been conducted. We aimed to estimate the association of hs-cTnT and NT-proBNP with 15-year cognitive change in the Atherosclerosis Risk in Communities (ARIC) study., Design: Prospective cohort study., Setting: Four US communities., Participants: A total of 9114 and 9108 participants from the Atherosclerosis Risk in Communities study for analyses of hs-cTnT and NT-proBNP, respectively., Measurements: We examined association of hs-cTnT and NT-proBNP with 15-year change (1996-1998 to 2011-2013) in three cognitive tests of executive function (Digit Symbol Substitution Test), verbal learning memory (Delayed Word Recall Test), and semantic fluency (Word Fluency Test), and an overall score combining the three tests using multivariable linear mixed effect models. We conducted several sensitivity analyses including multiple imputations to address bias due to missing data and attrition, and we compared associations within groups combining hs-cTnT and NT-proBNP into a three-level categorical variable., Results: At baseline (1996-1998), mean age was 63.4 (standard deviation [SD] = 5.7) years; 56.4% were women, and 17.5% were black. The hs-cTnT at baseline was not associated with cognitive change in any measure. Some evidence indicated accelerated decline in verbal learning and memory when comparing those in the highest with the lowest NT-proBNP quintiles; however, this association was not replicated when considering clinically relevant cutoffs or deciles of exposure in survivors. Sensitivity analyses were consistent with our primary analyses. There was little evidence to support effect modification by any considered factors. People with highest levels of both biomarkers had excessive decline in global z scores vs people with lowest levels (-.34; 95% confidence interval = -.63 to -.04)., Conclusion: Markers of myocardial injury and stretch were not associated with cognitive decline following 15 years among survivors, but when combined together they were suggestive in post hoc analysis. Whether this represents targets of intervention should be examined in the future. J Am Geriatr Soc 67:2353-2361, 2019., (© 2019 The American Geriatrics Society.)

High-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) at the time of myocardial infarction (MI) are strong predictors of prognosis. However, whether their premorbid (before MI occurrence) levels are associated with prognosis after incident MI is unknown., Methods: In 1,054 participants from the Atherosclerosis Risk in Communities Study with incident MI, we evaluated premorbid levels of hs-cTnT and NT-proBNP measured on median 5.8 (interquartile interval 3.0-11.5 [mean 5.5]) years prior to incident MI and their associations with subsequent composite and individual outcomes of all-cause mortality, cardiovascular mortality, recurrent MI, heart failure, and stroke., Results: During a median follow-up of 3.0 years after MI, 801 participants developed the composite outcome. Both hs-cTnT and NT-proBNP were independently associated with the composite outcome after incident MI. Among individual outcomes, all-cause mortality, cardiovascular mortality, and heart failure showed significant associations with both cardiac markers. Overall, NT-proBNP demonstrated a more evident relationship than hs-cTnT. Indeed, the addition of premorbid NT-proBNP alone, but not hs-cTnT alone, to conventional predictors at incident MI significantly improved risk prediction of the composite outcome after incident MI (Δc-statistic 0.013 [95% CI 0.005-0.022] from 0.691 with conventional predictors)., Conclusions: Premorbid levels of hs-cTnT and NT-proBNP assessed on average 6 years prior to incident MI were associated with adverse outcomes after incident MI. These results further highlight the importance of cardiac health at an earlier stage of life., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Isolated systolic hypertension (ISH) and elevated pulse pressure (PP) are common blood pressure (BP) abnormalities in older adults, reflect poor vascular compliance, and can signify risk for cardiovascular outcomes. We sought to characterize the associations of ISH and widened PP with high-sensitivity Troponin-T (hs-cTnT; a marker of myocardial damage) and N-terminal pro-B-type natriuretic peptide (NT-proBNP; a marker of hemodynamic stress) levels in older adults. We performed a cross-sectional analysis of 5,251 Atherosclerosis Risk in Communities (ARIC) study participants without heart failure who attended visit 5 (2011 to 2013). We used logistic regression to evaluate the association of ISH (systolic BP ≥140 mm Hg and diastolic BP < 90 mm Hg) and quartiles of PP with detectable (≥5 ng/L) and elevated hs-cTnT (≥14 ng/L); as well as elevated NT-proBNP (≥100 pg/mL). The mean age was 75 years, 58% were women, and 78% were white. ISH was present in 24.7% and PP ≥ 70 mm Hg in 30.3% of this cohort. Compared to participants with nonhypertensive BP (<140/90 mm Hg), ISH was independently associated with hs-cTnT and NT-proBNP; adjusted odds ratio of 1.5 (95% confidence interval: 1.1 to 1.9) for detectable hs-cTnT; 1.3 (1.1 to 1.5) for elevated hs-cTnT; and 1.8 (1.6 to 2.1) for elevated NT-proBNP. Increasing quartiles of PP were also significantly associated with both elevated hs-cTnT (p-for-trend <0.0001) and NT-proBNP (p-for-trend <0.0001). These associations were not modified by BP treatment status. In conclusion, ISH and wide PP are relatively common in older adults despite contemporary BP treatment and are associated with abnormalities in hs-cTnT and NT-pro BNP, findings that could guide personalized treatment of older patients with these BP aberrations., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Arterial stiffness independently predicts cardiovascular disease. However, few studies have evaluated the associations of central and peripheral pulse wave velocity (PWV) with biomarkers of both myocardial stress (natriuretic peptide [NT-proBNP]) and damage (high-sensitivity cardiac troponin-T [hs-cTnT]) among persons without cardiac disease., Methods: We examined 3,348 participants (67-90 years) without prevalent cardiac disease in the Atherosclerosis Risk in Communities (ARIC) Study (2011-13). The cross-sectional associations of PWV quartiles for central arterial segments (carotid-femoral, heart-carotid, heart-femoral) and peripheral artery (femoral-ankle) with NT-proBNP and hs-cTnT were evaluated accounting for potential confounders., Results: Most PWV measures demonstrated J- or U-shaped associations with the two cardiac biomarkers. The highest (Q4) vs. second lowest (Q2) quartile of central PWV measures (carotid-femoral, heart-carotid, heart-femoral PWV) were associated with higher levels of NT-proBNP independently of demographic characteristics. The associations were less evident for hs-cTnT. These associations were attenuated after adjusting for traditional cardiovascular risk factors, but the heart-carotid PWV-NT-proBNP relationship remained borderline significant (difference in log-NT-proBNP = 0.08 [-0.01, 0.17] in Q4 vs. Q2, p = 0.07). Peripheral PWV demonstrated inverse associations. Higher values of NT-proBNP were seen in the lowest vs. second lowest quartile of all PWV measures., Conclusions: Central stiffness measures showed stronger associations with cardiac biomarkers (particularly NT-proBNP) than peripheral measures among older adults without cardiac disease. Our findings are consistent with the concept of ventricular-vascular coupling and suggest that central rather than peripheral arterial hemodynamics are more closely related to myocardial stress rather than damage., Competing Interests: The authors have declared that no competing interests exist.

Aims: Cardiac troponin T (cTnT) is suggested as a predictor of amputation in patients with peripheral artery disease (PAD). However, cTnT-PAD association has not been systematically studied in a large study. This study evaluated the association of high-sensitivity cTnT (hs-cTnT) with PAD incidence and also explored whether natriuretic peptide (NT-proBNP), another representative cardiac marker, predicts PAD risk., Methods and Results: Among 12 288 middle-aged adults, the associations of hs-cTnT and NT-proBNP with incident PAD (hospitalizations with PAD diagnosis or leg revascularization [cases with rest pain or tissue loss considered as critical limb ischaemia (CLI)]) were quantified with multivariable Cox regression models. The risk discrimination was assessed by c-statistic. During a follow-up over 22 years, 454 participants developed PAD (164 CLI cases). In demographically adjusted models, the highest category of hs-cTnT (≥14 vs. <3 ng/L) and NT-proBNP (≥258.3 vs. <51.5 pg/mL) showed ∼8- and 10-20-fold higher risk of PAD and CLI, respectively. Even after adjusting for potential confounders and each other, hazard ratios were greater for CLI than for PAD (7.74 95% confidence interval [95% CI 4.43-13.55] vs. 2.84 [2.02-4.00] for the highest vs. reference hs-cTnT category and 4.63 [2.61-8.23] vs. 3.16 [2.23-4.49] for the highest vs. reference NT-proBNP category). The addition of these cardiac markers improved c-statistics for CLI., Conclusion: High-sensitivity cTnT and NT-proBNP were independently associated with incident PAD, particularly its severe form, CLI. Although future studies are warranted to investigate pathophysiological mechanisms behind these associations, our study suggests the usefulness of cardiac markers to identify individuals at high risk of CLI.

The impact of lifestyle-related factors on temporal decreases in high-sensitivity cardiac troponin T (hs-cTnT), possibly reflecting reversal of subclinical myocardial damage, has not been evaluated in a community-based setting. We measured hs-cTnT twice, 6 years apart, in 9,256 participants from the Atherosclerosis Risk in Communities (ARIC) Study who were free from baseline cardiovascular disease. We used Poisson and multinomial regression to evaluate the associations of cigarette smoking, alcohol consumption, body mass index, healthy diet score, physical activity, and Life's Simple 7 (LS7) score (a composite measure of lifestyle-related health factors) with 6-year decreases in hs-cTnT. Of the 3,017 patients with detectable baseline hs-cTnT (≥5 ng/L), 2,418 (80%) remained detectable, whereas 599 (20%) had undetectable levels (<5 ng/L) at the 6-year follow-up visit. Patients with a body mass index of <30 kg/m 2 , adherence to American Heart Association's physical activity guidelines, and average or optimal LS7 scores were more likely to improve from a detectable to an undetectable hs-cTnT level during follow-up. There was a robust association between optimal LS7 score and temporal hs-cTnT reduction (relative risk 1.64, 95% confidence interval 1.11 to 2.42, for baseline ≥5 ng/L and for follow-up <5 ng/L). A greater duration of exposure to average or optimal LS7 score was also associated with increased likelihood of temporal hs-cTnT reduction (p-trend <0.001). In conclusion, we found that lifestyle factors and the LS7 score were associated with reversal of subclinical myocardial damage. In conclusion, our results support the growing evidence that hs-cTnT levels change in response to lifestyle modifications and hs-cTnT may serve as a useful dynamic surrogate for monitoring cardiovascular risk., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background Metabolic syndrome (MetS) is associated with increased risk for cardiovascular disease, but there is heterogeneity in this risk. We evaluated whether high-sensitivity troponin T (hs-cTnT), a marker associated with cardiovascular disease, can stratify risk in MetS. Methods We evaluated associations between MetS (and groups with similar number of MetS components) and incident heart failure hospitalization, coronary heart disease, stroke and death using hs-cTnT categories after adjusting for risk factors/markers between 1996 and 2011 in 8204 individuals in the Atherosclerosis Risk In Communities study. Results The mean age of the population was 63 years (56% women, 19% Blacks). hs-cTnT levels were higher with MetS and with increasing MetS components. In individuals with MetS, higher hs-cTnT levels were associated with increased hazard ratios for heart failure, coronary heart disease and death. Within each number of MetS components, higher hs-cTnT was associated with progressively higher heart failure, coronary heart disease and death hazards. The association was particularly strong for heart failure. With increasing hs-cTnT categories, the hazard ratios (95% confidence interval) for heart failure in individuals with MetS increased gradually from 1.68 (1.31-2.16) to 3.76 (2.69-5.26) ( p-trend < 0.001) compared with those with MetS and hs-cTnT < 5 ng/l; and respective hazard ratios with increasing hs-cTnT categories in those with all five MetS components ranged from 2.22 (1.17-4.21) to 4.23 (1.89-9.50) ( p-trend 0.004) compared with those with all five MetS components and hs-cTnT < 5 ng/l. However, mostly there were no significant interactions of hs-cTnT with MetS or its components. Conclusion hs-cTnT is useful for identifying MetS patients with increased hazards for coronary heart disease, death and particularly heart failure.

Background: The optimal systolic blood pressure (SBP) treatment goal is in question, with SPRINT (Systolic Blood Pressure Intervention Trial) suggesting benefit for 120 mm Hg. However, achieving an SBP this low may reduce diastolic blood pressure (DBP) to levels that could compromise myocardial perfusion., Objectives: This study sought to examine the independent association of DBP with myocardial damage (using high-sensitivity cardiac troponin-T [hs-cTnT]) and with coronary heart disease (CHD), stroke, or death over 21 years., Methods: The authors studied 11,565 adults from the ARIC (Atherosclerosis Risk In Communities) cohort, analyzing DBP and hs-cTnT associations as well as prospective associations between DBP and events., Results: Mean baseline age was 57 years, 57% of patients were female, and 25% were black. Compared with persons who had DBP between 80 to 89 mm Hg at baseline (ARIC visit 2), the adjusted odds ratio of having hs-cTnT ≥14 ng/l at that visit was 2.2 and 1.5 in those with DBP <60 mm Hg and 60 to 69 mm Hg, respectively. Low DBP at baseline was also independently associated with progressive myocardial damage on the basis of estimated annual change in hs-cTnT over the 6 years between ARIC visits 2 and 4. In addition, compared with a DBP of 80 to 89 mm Hg, a DBP <60 mm Hg was associated with incident CHD and mortality, but not with stroke. The DBP and incident CHD association was strongest with baseline hs-cTnT ≥14 ng/l (p value for interaction <0.001). Associations of low DBP with prevalent hs-cTnT and incident CHD were most pronounced among patients with baseline SBP ≥120 mm Hg., Conclusions: Particularly among adults with an SBP ≥120 mm Hg, and thus elevated pulse pressure, low DBP was associated with subclinical myocardial damage and CHD events. When titrating treatment to SBP <140 mm Hg, it may be prudent to ensure that DBP levels do not fall below 70 mm Hg, and particularly not below 60 mm Hg., Competing Interests: The other authors declare no commercial conflicts of interest (but receive National Institutes of Health grant funding)., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Patients with non-alcoholic fatty liver disease (NAFLD) are thought to be at increased risk of cardiovascular morbidity and mortality. However, the relationships between NAFLD and subclinical myocardial injury or structural heart disease are unknown., Methods: We conducted a cross-sectional analysis of 8668 participants from the Atherosclerosis Risk in Communities (ARIC) Study, who showed no clinical evidence of cardiovascular disease. We used levels of liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST] and gamma-glutamyl transpeptidase [GGT]), in the context of no history of elevated alcohol consumption as non-invasive surrogates of NAFLD. We used highly sensitive cardiac troponin T (hs-cTnT) and N-terminal pro-Brain natriuretic peptide (NT-proBNP) as biomarkers of myocardial damage and function., Results: In this population-based study (mean age 63 years, 60% women, 78% white), higher levels of ALT, AST, and GGT, even within the normal range, were significantly and independently associated with detectable (hs-cTnT >3 ng/L) and elevated (hs-cTnT ⩾14 ng/L) concentrations of hs-cTnT. The adjusted odds ratios (95% confidence interval) for elevated liver enzymes (vs. normal levels) with elevated hs-cTnT were: 1.65 (1.28-2.14) for ALT, 1.90 (1.36-2.68) for AST, and 1.55 (1.13-2.12) for GGT. Furthermore, there was evidence for inverse associations of ALT and AST with NT-proBNP., Conclusions: Our results suggest that elevated liver enzyme levels in the absence of elevated alcohol consumption may be associated with subclinical myocardial injury. The inverse association between NT-proBNP and both ALT and AST supports the recently described metabolic role of natriuretic peptides., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Epidemiologic data for cardiac abnormality predating decreased kidney function are sparse. We investigated the associations of high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) with end-stage renal disease (ESRD) risk in a community-based cohort., Study Design: A prospective cohort study., Setting & Participants: 10,749 white and black participants at the fourth visit (1996-1998) of the Atherosclerosis Risk in Communities (ARIC) Study with follow-up through 2010., Predictor: hs-cTnT (3, 6, 9, and 14ng/L) and NT-proBNP (41.6, 81.0, 142.5, and 272.5pg/mL) levels were divided into 5 categories at the same percentiles (32th, 57th, 77th, and 91th; corresponding to ordinary thresholds of hs-cTnT), with the lowest category as a reference., Outcomes: Incident ESRD defined as initiation of dialysis therapy, transplantation, or death due to kidney disease., Measurements: Relative risk and risk prediction of ESRD according to hs-cTnT and NT-proBNP levels based on Cox proportional hazards models., Results: During a median follow-up of 13.1 years, 235 participants developed ESRD (1.8 cases/1,000 person-years). hs-cTnT and NT-proBNP levels were associated with ESRD risk independently of each other and of potential confounders, including kidney function and albuminuria (adjusted HRs for highest category, 4.43 [95% CI, 2.43-8.09] and 2.28 [95% CI, 1.44-3.60], respectively). For hs-cTnT level, the association was significant even at the third category (HR for 6-8ng/L of hs-cTnT, 2.74 [95% CI, 1.54-4.88]). Their associations were largely consistent even among persons without decreased kidney function or history of cardiovascular disease. hs-cTnT and NT-proBNP levels both significantly improved ESRD prediction (C statistic differences of 0.0084 [95% CI, 0.0005-0.0164] and 0.0045 [95% CI, 0.0004-0.0087], respectively, from 0.884 with conventional risk factors)., Limitations: Relatively small number of ESRD cases and single measurement of hs-cTnT and NT-proBNP., Conclusions: hs-cTnT and NT-proBNP levels independently predicted ESRD risk in the general population, with more evident results for hs-cTnT. These results suggest the involvement of cardiac abnormality, particularly cardiac injury, in the progression of reduced kidney function and/or may reflect the useful property of hs-cTnT as an end-organ damage marker., (Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Structural changes in the heart are known risk factors for atrial fibrillation (AF). An association between high-sensitivity cardiac troponin T (hs-cTnT), a marker of myocardial cell damage measured with a high-sensitivity assay, and the risk of AF could have implications for AF risk stratification., Objective: To estimate the association between hs-cTnT and the risk of incident AF in the ARIC study, a prospective cohort of middle-aged adults from 4 US communities., Methods: Study included 10,584 participants (mean age 62.7 years) free of AF in 1996 to 1998 and followed through 2008. Atrial fibrillation was defined using International Classification of Diseases codes from hospitalizations and death certificates. Participants with undetectable hs-cTnT levels (58%) were assigned the lower limit of measurement (5 ng/L). Net reclassification improvement was used to examine the discriminative ability of hs-cTnT for 10-year AF risk prediction (categories: <5%, 5%-15%, and >15%)., Results: A total of 920 incident AF cases were observed for 109,227 person-years. After adjustment, a 1-SD difference in ln(hs-cTnT) was associated with a hazard ratio of 1.16 (95% CI 1.10-1.23). Compared with those with undetectable levels, participants with hs-cTnT ≥14 ng/L had a hazard ratio of 1.78 (95% CI 1.43-2.24). Addition of hs-cTnT to known AF predictors did not increase the c statistic appreciably (0.756 vs 0.758) or improve risk stratification (net reclassification improvement 0.4%, 95% CI -1.4% to 2.3%)., Conclusions: High-sensitivity cTnT level is associated with an increased incidence rate of AF but did not improve risk stratification., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Based on observational studies, there is a linear increase in cardiovascular risk with higher systolic blood pressure (SBP), yet clinical trials have not shown benefit across all SBP categories. We assessed whether troponin T measured using high-sensitivity assay was associated with cardiovascular disease within SBP categories in 11 191 Atherosclerosis Risk in Communities study participants. Rested sitting SBP by 10-mm Hg increments and troponin categories were identified. Incident heart failure hospitalization, coronary heart disease, and stroke were ascertained for a median of 12 years after excluding individuals with corresponding disease. Approximately 53% of each type of cardiovascular event occurred in individuals with SBP<140 mm Hg and troponin T ≥3 ng/L. Higher troponin T was associated with increasing cardiovascular events across most SBP categories. The association was strongest for heart failure and least strong for stroke. There was no similar association of SBP with cardiovascular events across troponin T categories. Individuals with troponin T ≥3 ng/L and SBP <140 mm Hg had higher cardiovascular risk compared with those with troponin T <3 ng/L and SBP 140 to 159 mm Hg. Higher troponin T levels within narrow SBP categories portend increased cardiovascular risk, particularly for heart failure. Individuals with lower SBP but measurable troponin T had greater cardiovascular risk compared with those with suboptimal SBP but undetectable troponin T. Future trials of systolic hypertension may benefit by using high-sensitivity troponin T to target high-risk patients., (© 2014 American Heart Association, Inc.)

Background: Patterns and determinants of temporal change in highly-sensitivity troponin-T (hs-cTNT), a novel measure of subclinical myocardial injury, among asymptomatic persons have not been well characterized., Methods: We studied 8571 ARIC Study participants, free of cardiovascular disease, who had hs-cTNT measured at two time-points, 6 years apart (1990-1992 and 1996-1998). We examined the association of baseline 10-year atherosclerotic cardiovascular (ASCVD) risk-group (<5%, 5-7.4%, ≥ 7.5%) and individual cardiac risk-factors with change across hs-cTNT categories using Poisson and Multinomial Logistic regression and with mean continuous hs-cTNT change using linear regression., Results: Mean age was 57 years and 43% were male. Mean (SD) 6-year hs-cTNT change was higher across increasing ASCVD risk-groups; +1.2 (6.1) ng/L [<5%], +2.1 (5.4) ng/L [5-7.4%], and +2.8 (8.8) ng/L [≥ 7.5%]. Major baseline determinants of temporal hs-cTNT increases were: age, male gender, hypertension, diabetes, and obesity. In addition, the relative risk (RR) of incident elevated hs-cTNT (≥ 14 ng/L) was 1.46 (95% CI 1.1-2.0) for persons with sustained hypertension compared to those who remained normotensive. Results for sustained obesity (RR 1.65 [1.19-2.29]) and hyperglycemia (RR 1.76 [1.16-2.67]) were similar. These associations were generally stronger after accounting for survival bias. However, smoking, LDL-cholesterol and triglycerides were not associated with hs-cTNT change. HDL-cholesterol was associated with declining hs-cTNT., Conclusions: Persons in higher ASCVD risk-groups were more likely to have increases in hs-cTNT over 6 years of follow-up. The modifiable risk-factors primarily driving this association were diabetes, hypertension, and obesity; particularly when they were persistently elevated over follow-up. Future studies are needed to determine whether modifying these risk factors can prevent progression of subclinical myocardial injury., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Aim: Clinical cardiovascular disease is a major risk factor for cognitive impairment and dementia. However, less is known about the association of subclinical myocardial damage with cognition and dementia. We sought to examine the associations of high-sensitivity cardiac troponin T (hs-cTnT) with cognition and dementia., Methods and Results: Cross-sectional analysis of cognition (baseline 1996-98) and prospective analysis of dementia (follow-up through 2010) in 9472 participants in the Atherosclerosis Risk in Communities study. High-sensitivity cardiac troponin T was measured using a novel highly sensitive assay with a lower limit of the blank of 3 ng/L. Cognitive function was assessed by three tests: the delayed word recall test (DWRT), the digit symbol substitution test (DSST), and the word fluency test (WFT). Dementia was defined using ICD-9 codes. Linear regression and Cox models were adjusted for traditional cardiovascular risk factors. The mean age of participants was 63 years, 59% were female, 21% were black, and 66% had hs-cTnT ≥3 ng/L. In cross-sectional analyses, higher hs-cTnT was associated with lower scores on the DSST (P-trend < 0.001) and the WFT (P-trend = 0.002), but not on the DWRT (P-trend = 0.089). Over a median of 13 years, there were 455 incident dementia hospitalizations. In prospective analyses, higher baseline concentrations of hs-cTnT were associated with an increased risk for dementia hospitalizations overall (P-trend < 0.001) and for vascular dementia (P-trend = 0.029), but not for Alzheimer's dementia (P-trend = 0.212)., Conclusion: Elevations in baseline concentrations of hs-cTnT were associated with lower cognitive test scores at baseline and increased dementia hospitalization risk during the follow-up. Our results suggest that subclinical myocardial injury is associated with cognition and dementia., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Objectives: The study sought to determine the 99th percentile upper reference limit for the high-sensitivity cardiac troponin T assay (hs-cTnT) in 3 large independent cohorts., Background: The presently recommended 14 ng/l cut point for the diagnosis of myocardial infarction using the hs-cTnT assay was derived from small studies of presumably healthy individuals, with relatively little phenotypic characterization., Methods: Data were included from 3 well-characterized population-based studies: the Dallas Heart Study (DHS), the Atherosclerosis Risk in Communities (ARIC) Study, and the Cardiovascular Health Study (CHS). Within each cohort, reference subcohorts were defined excluding individuals with recent hospitalization, overt cardiovascular disease, and kidney disease (subcohort 1), and further excluding those with subclinical structural heart disease (subcohort 2). Data were analyzed stratified by age, sex, and race., Results: The 99th percentile values for the hs-cTnT assay in DHS, ARIC, and CHS were 18, 22, and 36 ng/l (subcohort 1) and 14, 21, and 28 ng/l (subcohort 2), respectively. These differences in 99th percentile values paralleled age differences across cohorts. Analyses within sex/age strata yielded similar results between cohorts. Within each cohort, 99th percentile values increased with age and were higher in men. More than 10% of men 65 to 74 years of age with no cardiovascular disease in our study had cardiac troponin T values above the current myocardial infarction threshold., Conclusions: Use of a uniform 14 ng/l cutoff for the hs-cTnT assay may lead to over-diagnosis of myocardial infarction, particularly in men and the elderly. Clinical validation is needed of new age- and sex-specific cutoff values for this assay., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Among the various cardiovascular diseases, heart failure (HF) is projected to have the largest increases in incidence over the coming decades; therefore, improving HF prediction is of significant value. We evaluated whether cardiac troponin T (cTnT) measured with a high-sensitivity assay and N-terminal pro-B-type natriuretic peptide (NT-proBNP), biomarkers strongly associated with incident HF, improve HF risk prediction in the Atherosclerosis Risk in Communities (ARIC) study., Methods: Using sex-specific models, we added cTnT and NT-proBNP to age and race ("laboratory report" model) and to the ARIC HF model (includes age, race, systolic blood pressure, antihypertensive medication use, current/former smoking, diabetes, body mass index, prevalent coronary heart disease, and heart rate) in 9868 participants without prevalent HF; area under the receiver operating characteristic curve (AUC), integrated discrimination improvement, net reclassification improvement (NRI), and model fit were described., Results: Over a mean follow-up of 10.4 years, 970 participants developed incident HF. Adding cTnT and NT-proBNP to the ARIC HF model significantly improved all statistical parameters (AUCs increased by 0.040 and 0.057; the continuous NRIs were 50.7% and 54.7% in women and men, respectively). Interestingly, the simpler laboratory report model was statistically no different than the ARIC HF model., Conclusions: cTnT and NT-proBNP have significant value in HF risk prediction. A simple sex-specific model that includes age, race, cTnT, and NT-proBNP (which can be incorporated in a laboratory report) provides a good model, whereas adding cTnT and NT-proBNP to clinical characteristics results in an excellent HF prediction model.

Background and Purpose: Cerebrovascular and cardiovascular disease share common risk factors. Our goal was to determine whether levels of N-terminal brain natriuretic peptide (NT-proBNP) and cardiac troponin T measured with a highly sensitive assay (hs-cTnT) are associated with silent brain infarcts (BIs) and white matter lesions (WMLs) on MRI in the Atherosclerosis Risk in Communities (ARIC) study., Methods: At ARIC visit 3 (1993-1995), 1920 participants had brain MRI. NT-proBNP and hs-cTnT were measured in all individuals at ARIC visit 4 (1996-1998). Of 1920 individuals, 1112 had a follow-up MRI [2004-2006]). We analyzed the association of NT-proBNP and hs-cTnT with MRI-defined BI and WML on the initial MRI and incident BI and WML progression on the follow-up MRI in participants without heart failure, coronary heart disease, or stroke., Results: In the adjusted model, individuals in the highest NT-proBNP quartile had significantly more BI (odds ratio, 3.50; 95% confidence interval, 2.03-6.20), and WML (β-coefficient, 0.09; SE, 0.03) on the baseline MRI and more incident BI (odds ratio, 2.18; 95% confidence interval, 1.38-3.47) and WML progression (β-coefficient, 0.22; SE, 0.10) on the follow-up MRI. Individuals in the highest hs-cTnT category had more BI (odds ratio, 3.03; 95% confidence interval, 1.57-5.82) and WML (β-coefficient, 0.11; SE, 0.04) on the initial MRI and more WML progression (β-coefficient, 0.43; SE, 0.17) on the follow-up MRI., Conclusions: NT-proBNP and hs-cTnT are independently associated with silent MRI-defined BI and WML, suggesting that cardiovascular biomarkers may be useful to identify individuals with subclinical cerebral injury.

Background: High levels of cardiac troponin T, measured by a highly sensitive assay (hs-cTnT), are strongly associated with incident coronary heart disease and heart failure. To date, no large-scale genome-wide association study of hs-cTnT has been reported. We sought to identify novel genetic variants that are associated with hs-cTnT levels., Methods and Results: We performed a genome-wide association in 9491 European Americans and 2053 blacks free of coronary heart disease and heart failure from 2 prospective cohorts: the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study. Genome-wide association studies were conducted in each study and race stratum. Fixed-effect meta-analyses combined the results of linear regression from 2 cohorts within each race stratum and then across race strata to produce overall estimates and probability values. The meta-analysis identified a significant association at chromosome 8q13 (rs10091374; P=9.06×10(-9)) near the nuclear receptor coactivator 2 (NCOA2) gene. Overexpression of NCOA2 can be detected in myoblasts. An additional analysis using logistic regression and the clinically motivated 99th percentile cut point detected a significant association at 1q32 (rs12564445; P=4.73×10(-8)) in the gene TNNT2, which encodes the cardiac troponin T protein itself. The hs-cTnT-associated single-nucleotide polymorphisms were not associated with coronary heart disease in a large case-control study, but rs12564445 was significantly associated with incident heart failure in Atherosclerosis Risk in Communities Study European Americans (hazard ratio=1.16; P=0.004)., Conclusions: We identified 2 loci, near NCOA2 and in the TNNT2 gene, at which variation was significantly associated with hs-cTnT levels. Further use of the new assay should enable replication of these results.

Background: Application of cardiac troponin T (cTnT) as a marker of myocyte damage requires knowledge of its measurement variability. Using a highly sensitive assay for measurement, we evaluated the long-term storage stability of plasma cTnT at -70 °C and the sources of cTnT variability., Methods: Samples from the Atherosclerosis Risk in Communities study collected in 1996-1998 and 2005-2006 were assayed centrally to quantify variability in cTnT attributable to processing (replicates from same blood draw, n = 87), laboratory (replicates after freeze thaw, n = 29), short-term (n = 40) and long-term biological variation (repeat visit, n = 38), and degradation in frozen storage (n = 7677)., Results: Approximately 30% of this population-based cohort had cTnT concentrations below the detection limit (3 ng/L). Reliability coefficients for all paired comparisons exceeded 0.93 except for samples drawn 8 years apart (r = 0.36). Sources of cTnT variation (as CVs) were: laboratory, 2.1% and 11.2% in those with and without heart failure, respectively; processing, 18.3%; biological, 16.6% at 6 weeks and 48.4% at 8 years. The reference change value at 6 weeks (68.5%) indicated that 4 samples are needed to determine a homeostatic set point within ±25%. The estimated cTnT degradation rate over the first year in long-term frozen storage was 0.36 ng/L per year., Conclusions: cTnT was detectable in approximately 70% of community-dwelling middle-aged study participants and stable in -70 °C storage. The variability in cTnT attributable to 1 freeze-thaw cycle is of small magnitude. The observed high laboratory and intraindividual (biological) reliability of cTnT support its use for population-based research, and in clinical settings that rely on classification and serial measurements.

Background: We evaluated whether cardiac troponin T (cTnT) measured with a new highly sensitive assay was associated with incident coronary heart disease (CHD), mortality, and hospitalization for heart failure (HF) in a general population of participants in the Atherosclerosis Risk in Communities (ARIC) Study., Methods and Results: Associations between increasing cTnT levels and CHD, mortality, and HF hospitalization were evaluated with Cox proportional hazards models adjusted for traditional CHD risk factors, kidney function, high-sensitivity C-reactive protein, and N-terminal pro-B-type natriuretic peptide in 9698 participants aged 54 to 74 years who at baseline were free from CHD and stroke (and HF in the HF analysis). Measurable cTnT levels (≥0.003 μg/L) were detected in 66.5% of individuals. In fully adjusted models, compared with participants with undetectable levels, those with cTnT levels in the highest category (≥0.014 μg/L; 7.4% of the ARIC population) had significantly increased risk for CHD (hazard ratio=2.29; 95% confidence interval, 1.81 to 2.89), fatal CHD (hazard ratio=7.59; 95% confidence interval, 3.78 to 15.25), total mortality (hazard ratio=3.96; 95% confidence interval, 3.21 to 4.88), and HF (hazard ratio=5.95; 95% confidence interval, 4.47 to 7.92). Even minimally elevated cTnT (≥0.003 μg/L) was associated with increased risk for mortality and HF (P<0.05). Adding cTnT to traditional risk factors improved risk prediction parameters; the improvements were similar to those with N-terminal pro-B-type natriuretic peptide and better than those with the addition of high-sensitivity C-reactive protein., Conclusions: cTnT detectable with a highly sensitive assay was associated with incident CHD, mortality, and HF in individuals from a general population without known CHD/stroke.