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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:ImportanceElevated high-sensitivity cardiac troponin T (hscTnT) and N-terminal pro-B-type natriuretic peptide (NTproBNP) levels are associated with risk of heart failure (HF) and mortality among individuals in the general population. However, it is unknown if this risk is modifiable.ObjectiveTo test the hypothesis that elevated hscTnT and NTproBNP levels would identify individuals with the greatest risk for mortality and HF and the largest benefit associated with intensive systolic blood pressure (SBP) lowering.Design, setting, and participantsThis is a nonprespecified post hoc analysis of the multicenter, prospective, randomized clinical Systolic Blood Pressure Intervention Trial (SPRINT), conducted from October 20, 2010, to August 20, 2015. A total of 9361 patients without diabetes with increased risk for cardiovascular disease were randomized to receive intensive vs standard SBP lowering. Statistical analysis was performed on an intention-to-treat basis from September 30, 2019, to July 29, 2021.InterventionsParticipants were randomized to undergo intensive (<120 mm Hg) or standard (<140 mm Hg) SBP lowering. High-sensitivity cardiac troponin T and NTproBNP levels were measured from stored specimens collected at enrollment, with elevated levels defined as 14 ng/L or more for hscTnT (to convert to micrograms per liter, multiply by 0.001) and 125 pg/mL or more for NTproBNP (to convert to nanograms per liter, multiply by 1.0).Main outcomes and measuresThe primary outcome of this ancillary study was HF and mortality.ResultsOf the 9361 participants enrolled in SPRINT, 8828 (5578 men [63.2%]; mean [SD] age, 68.0 [9.5] years) had measured hscTnT levels and 8836 (5585 men [63.2%]; mean [SD] age, 68.0 [9.5] years) had measured NTproBNP levels; 2262 of 8828 patients (25.6%) had elevated hscTnT levels, 3371 of 8836 patients (38.2%) had elevated NTproBNP, and 1411 of 8828 patients (16.0%) had both levels elevated. Randomization to the intensive SBP group led to a 4.9% (95% CI, 1.7%-7.5%) absolute risk reduction (ARR) over 4 years in death and HF (421 events) for those with elevated hscTnT and a 1.7% (95% CI, 0.7%-2.5%) ARR for those without elevated levels. Similarly, for those with elevated NTproBNP, the ARR for death and HF over 4 years was 4.6% (95% CI, 2.3%-6.5%) vs 1.8% (95% CI, 0.9%-2.5%) in those without elevated levels. For those with elevated levels of both biomarkers, the ARR for death and HF over 4 years was 7.8% (95% CI, 3.3%-11.3%) vs 1.7% (95% CI, 0.8%-2.3%) in those with neither biomarker elevated. No significant treatment group by biomarker category interactions were detected.Conclusions and relevanceIntensive SBP control led to large absolute differences in death and HF among patients with abnormal hscTnT and NTproBNP levels. These findings demonstrate that risk associated with elevation of these biomarkers is modifiable with intensive BP control. A prospective, randomized clinical trial is needed to evaluate whether these biomarkers may help guide selection of patients for intensive SBP lowering.Trial registrationClinicalTrials.gov Identifier: NCT01206062.

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:ImportanceSex-specific differences in the commonly used cardiac biomarkers high-sensitivity cardiac troponin (hs-cTn) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are apparent. There is an absence of medical literature delineating the concentration differences for these biomarkers in transgender individuals without cardiac disease.ObjectiveTo determine the distribution of hs-cTn and NT-proBNP in healthy transgender people.Design, setting, and participantsIn this cross-sectional prospective study, healthy transgender individuals prescribed testosterone or estradiol for 12 months or more were recruited from internal medicine and primary care clinics that specialize in transgender medical care between November 1, 2017, and July 1, 2018.ExposuresTestosterone or estradiol for 12 months.Main outcomes and measuresConcentrations for hs-cTnI (troponin I), hs-cTnT (troponin T), and NT-proBNP were measured.ResultsTransgender people prescribed testosterone (n = 79; mean [SD] age, 28.8 [7.8] years) or estrogen (n = 93; mean [SD] age, 35.1 [11.7] years) were recruited. The concentration of hs-cTn was significantly higher in transgender men relative to transgender women. For Abbott hs-cTnI levels, the median (IQR) concentration observed in transgender men and women was 0.9 (0.6-1.7) ng/L and 0.6 (0.3-1.0) ng/L, respectively. Results were similar across 2 additional hs-cTn assays. In contrast, NT-proBNP level was higher in transgender women. The median (IQR) NT-proBNP concentration was significantly higher in transgender women ( 49 [32-86] ng/L) than in transgender men (17 [13-27] ng/L).Conclusions and relevanceFindings of this cross-sectional study suggest that the differences in concentration for hs-cTn and NT-proBNP between transgender men and women were similar to what is observed between cisgender men and women. Sex hormones, rather than sex assigned at birth, may be a stronger driver of the observed concentration differences between healthy men and women for biomarkers of cardiac disease.

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.

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

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