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Associations of High-Sensitivity Troponin and Natriuretic Peptide Levels With Serious Adverse Events in SPRINT.

ABSTRACT: Background Assessing the risk of serious adverse events (SAEs) during hypertension treatment is important for understanding the benefit-harm trade-offs of lower blood pressure goals. It is unknown whether high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) provide information about SAEs. Methods and Results In SPRINT (Systolic Blood Pressure Intervention Trial), hs-cTnT and NT-proBNP were measured at baseline in 8828 (94.3%) and 8836 (94.4%) participants, respectively. Multivariable Cox proportional hazards models were used to evaluate hs-cTnT and NT-proBNP associations with a composite of SPRINT's SAEs of interest: hypotension, syncope, bradycardia, acute kidney injury, electrolyte abnormalities, and injurious falls. Elevations in hs-cTnT and NT-proBNP were associated with increased composite SAE risk (hazard ratio [HR] per 2-fold higher hs-cTnT: 1.15; 95% CI, 1.06‒1.25; HR per 2-fold higher NT-proBNP: 1.09; 95% CI, 1.05‒1.14). Compared with both hs-cTnT and NT-proBNP in the lower tertiles, both biomarkers in the highest tertile was associated with increased composite SAE risk (HR, 1.56; 95% CI, 1.32‒1.84). Composite SAE risk was higher in the intensive-treatment group than in the standard-treatment group for participants with both biomarkers in the lower tertiles, but similar between treatment groups for participants with both biomarkers in the highest tertile (P for interaction=0.008). Conclusions Elevations in hs-cTnT and NT-proBNP individually and in combination are associated with higher composite SAE risk in SPRINT. The differential impact of blood pressure treatment on SAE risk across combined biomarker categories may have implications for identifying individuals with more favorable benefit-harm profiles for intensive blood pressure lowering.

SUBMITTER: Ascher SB

PROVIDER: S-EPMC9075292 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:OBJECTIVES:An estimated 1.2 million annual emergency department (ED) visits for syncope/near syncope occur in the United States. Cardiac biomarkers are frequently obtained during the ED evaluation, but the prognostic value of index high-sensitivity troponin (hscTnT) and natriuretic peptide (NT-proBNP) are unclear. The objective of this study was to determine if hscTnT and NT-proBNP drawn in the ED are independently associated with 30-day death/serious cardiac outcomes in adult patients presenting with syncope. METHODS:A prespecified secondary analysis of a prospective, observational trial enrolling participants ? age 60 presenting with syncope, at 11 United States hospitals, was conducted between April 2013 and September 2016. Exclusions included seizure, stroke, transient ischemic attack, trauma, intoxication, hypoglycemia, persistent confusion, mechanical/electrical invention, prior enrollment, or predicted poor follow-up. Within 3 hours of consent, hscTnT and NT-proBNP were collected and later analyzed centrally using Roche Elecsys Gen 5 STAT and 2010 Cobas, respectively. Primary outcome was combined 30-day all-cause mortality and serious cardiac events. Adjusting for illness severity, using multivariate logistic regression analysis, variations between primary outcome and biomarkers were estimated, adjusting absolute risk associated with ranges of biomarkers using Bayesian Markov Chain Monte Carlo methods. RESULTS:The cohort included 3,392 patients; 367 (10.8%) experienced the primary outcome. Adjusted absolute risk for the primary outcome increased with hscTnT and NT-proBNP levels. HscTnT levels ? 5 ng/L were associated with a 4% (95% confidence interval [CI] = 3%-5%) outcome risk, and hscTnT > 50 ng/L, a 29% (95% CI = 26%-33%) risk. NT-proBNP levels ? 125 ng/L were associated with a 4% (95% CI = 4%-5%) risk, and NT-proBNP > 2,000 ng/L a 29% (95% CI = 25%-32%) risk. Likelihood ratios and predictive values demonstrated similar results. Sensitivity analyses excluding ED index serious outcomes demonstrated similar findings. CONCLUSIONS:hscTnT and NT-proBNP are independent predictors of 30-day death and serious outcomes in older ED patients presenting with syncope.

Project description:ObjectivesCardiac 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.DesignProspective cohort study.SettingFour US communities.ParticipantsA total of 9114 and 9108 participants from the Atherosclerosis Risk in Communities study for analyses of hs-cTnT and NT-proBNP, respectively.MeasurementsWe 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.ResultsAt 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).ConclusionMarkers 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.

Project description:BackgroundHigh-sensitivity troponin I (hs-Tnl) and B-type natriuretic peptide (BNP) are promising prognostic markers for coronary artery disease (CAD). This prospective cohort study investigated whether a combination of these cardiac biomarkers with conventional risk factors would add incremental value for the prediction of secondary major adverse cardiovascular events (MACEs) in patients with CAD, with and without type 2 diabetes mellitus (T2DM).MethodsBaseline plasma level of hs-Tnl and BNP was measured in 2275 Chinese patients with stable CAD. Patients were monitored for new-onset of MACE over a median of 51 months. Cox proportional hazard model and area under the receiver operating characteristic curve (AUC) were used to assess the association of cardiac biomarkers with MACE and their predictive values in relationship with or without T2DM.ResultsDuring the follow up period 402 (18%) patients experienced a new-onset MACE with hs-Tnl and BNP level significantly higher than in those without MACE. In multivariable analyses, patients with elevated hs-Tnl (hazard ratio, 1.75 [95% CI 1.41-2.17]; P?<?0.001) and BNP (hazard ratio, 1.42 [95% CI 1.15-1.75]; P?=?0.001) were significantly associated with an increased risk of MACE after adjustment for variables of a risk factor model of age, sex, T2DM and hypertension. The risk factor model had an AUC of 0.64 for MACE prediction. The AUC significantly increased to 0.68 by the addition of hs-Tnl to the risk factor model. Subgroup analyses showed that hs-Tnl and BNP remained significant predictors of MACE in both patients with and without T2DM in multivariable models with higher risk of MACE evident in those without T2DM. Among patients without T2DM, addition of each biomarker yielded greater predictive accuracy than in T2DM patients, with AUC further increased to 0.75 when a combination of hs-Tnl and BNP was added to the risk factor model (age, sex and hypertension).ConclusionsElevated hs-Tnl and BNP level are independent predictors of new-onset MACE in CAD patients, irrespective of diabetes status. Among CAD patients without T2DM, a combination of cardiac biomarkers hs-Tnl and BNP yield the greatest predictive value beyond conventional risk factors.

Project description:ObjectiveCardiovascular disease (CVD) is the major cause of morbidity and mortality in diabetes; yet, heterogeneity in CVD risk has been suggested in diabetes, providing a compelling rationale for improving diabetes risk stratification. We hypothesized that N-terminal prohormone brain natriuretic peptide (NTproBNP) and high-sensitivity troponin T may enhance CVD risk stratification beyond commonly used markers of risk and that CVD risk is heterogeneous in diabetes.Research design and methodsAmong 8,402 participants without prevalent CVD at visit 4 (1996-1998) of the Atherosclerosis Risk in Communities (ARIC) study there were 1,510 subjects with diabetes (mean age 63 years, 52% women, 31% African American, and 60% hypertensive).ResultsOver a median follow-up of 13.1 years, there were 540 incident fatal/nonfatal CVD events (coronary heart disease, heart failure, and stroke). Both troponin T ≥14 ng/L (hazard ratio [HR] 1.96 [95% CI 1.57-2.46]) and NTproBNP >125 pg/mL (1.61 [1.29-1.99]) were independent predictors of incident CVD events at multivariable Cox proportional hazard models. Addition of circulating cardiac biomarkers to traditional risk factors, abnormal electrocardiogram (ECG), and conventional markers of diabetes complications including retinopathy, nephropathy, and peripheral arterial disease significantly improved CVD risk prediction (net reclassification index 0.16 [95% CI 0.07-0.22]). Compared with individuals without diabetes, subjects with diabetes had 1.6-fold higher adjusted risk of incident CVD. However, participants with diabetes with normal cardiac biomarkers and no conventional complications/abnormal ECG (n = 725 [48%]) were at low risk (HR 1.12 [95% CI 0.95-1.31]), while those with abnormal cardiac biomarkers, alone (n = 186 [12%]) or in combination with conventional complications/abnormal ECG (n = 243 [16%]), were at greater risk (1.99 [1.59-2.50] and 2.80 [2.34-3.35], respectively).ConclusionsAbnormal levels of NTproBNP and troponin T may help to distinguish individuals with high diabetes risk from those with low diabetes risk, providing incremental risk prediction beyond commonly used markers of risk.

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Associations of High-Sensitivity Troponin and Natriuretic Peptide Levels With Serious Adverse Events in SPRINT.

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