-
1.
Stress Cardiac Biomarkers, Cardiovascular and Renal Outcomes, and Response to Canagliflozin.
Vaduganathan, M, Sattar, N, Xu, J, Butler, J, Mahaffey, KW, Neal, B, Shaw, W, Rosenthal, N, Pfeifer, M, Hansen, MK, et al
Journal of the American College of Cardiology. 2022;(5):432-444
Abstract
BACKGROUND Circulating biomarkers reflecting different mechanistic pathways may identify at-risk individuals with diabetes who may benefit from sodium-glucose cotransporter-2 (SGLT2) inhibitors. OBJECTIVES The purpose of this study was to determine if high-sensitivity cardiac troponin T (hs-cTnT), soluble suppression of tumorigenesis-2 (sST2), and insulin-like growth factor binding protein 7 (IGFBP7) levels, either alone or in combination, may modify the treatment benefits of canagliflozin. METHODS In the CANVAS (CANagliflozin cardioVascular Assessment Study) biomarker substudy, we evaluated the prognostic significance of baseline biomarker measurements, the long-term trajectory of each, and response to canagliflozin on key cardiovascular and kidney outcomes. RESULTS Among the 4,330 study participants, baseline hs-cTnT, sST2, and IGFBP7 were available in 3,503 (81%), 3,084 (71%), and 3,577 (83%). In total, 39% had elevated hs-cTnT ≥14 pg/mL, 6% had sST2 >35 ng/mL, and 49% had IGFBP7 >96.5 ng/mL. Canagliflozin significantly slowed increases of hs-cTnT (P = 0.027) and sST2 (P = 0.033) through 6 years. Each biomarker was significantly associated with cardiovascular and kidney outcomes, independent of clinical covariates. Canagliflozin reduced heart failure and kidney events regardless of baseline biomarker concentration. Patients with hs-cTnT ≥14 ng/L and those with sST2 >35 ng/mL derived greater relative benefit for major adverse cardiovascular events (MACE) (both Pinteraction ≤0.05). A panel of all 3 biomarkers predicted each cardiac and kidney outcome evaluated; participants with an increasing number of abnormal circulating biomarkers appeared to have greater relative reductions in MACE from canagliflozin treatment (Pinteraction trend = 0.005). CONCLUSIONS Canagliflozin delays longitudinal rise in hs-cTnT and sST2 compared with placebo out to 6 years. Canagliflozin reduced heart failure and kidney events regardless of baseline biomarker concentration. Elevated cardiovascular biomarkers, either alone or in combination, may identify individuals who may derive greater MACE benefit from SGLT2 inhibition. CANVAS (CANagliflozin cardioVascular Assessment Study; NCT01032629).
-
2.
Factors associated with baseline and serial changes in circulating NT-proBNP and high-sensitivity cardiac troponin T in a population-based cohort (Dallas Heart Study).
Puleo, CW, Ayers, CR, Garg, S, Neeland, IJ, Lewis, AA, Pandey, A, Drazner, MH, de Lemos, JA
Biomarkers in medicine. 2021;(16):1487-1498
-
-
Free full text
-
Abstract
Aim: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) associate with structural heart disease and heart failure risk in individuals without known cardiovascular disease (CVD). However, few data are available regarding whether factors influencing levels of these two biomarkers are similar or distinct. We performed serial measurement of NT-proBNP and hs-cTnT in a contemporary multiethnic cohort with extensive phenotyping, with the goal of identifying their respective biological determinants in a population without known or suspected CVD. Methods: We evaluated 1877 participants of the Dallas Heart Study who had NT-proBNP and hs-cTnT measured and were free from clinical CVD at the each of its two examinations (2000-2002 and 2007-2009). Variables collected included demographic and risk factors, high-sensitivity C-reactive protein, body composition via dual-energy x-ray absorptiometry, coronary artery calcium by computed tomography, and cardiac dimensions and function by cardiac MRI. Linear regression was used to identify associations of these factors with each biomarker at baseline and with changes in biomarkers over follow-up. Results: NT-proBNP and hs-cTnT were poorly correlated at baseline (Spearman rho 0.083, p = 0.015), with only moderate correlation between change values (rho 0.18, p < 0.001). hs-cTnT positively associated and NT-proBNP inversely associated with male gender and black race. At baseline, both NT-proBNP and hs-cTnT associated with left ventricular end-diastolic volume and wall thickness, but only NT-proBNP associated with left atrial size. Changes in cardiac dimensions between phases were more strongly associated with changes in NT-proBNP than hs-cTnT. NT-proBNP was more strongly associated with high-sensitivity C-reactive protein and measures of body composition than hs-cTnT. Conclusion: Among individuals without CVD in the general population, NT-proBNP and hs-cTnT are nonredundant biomarkers that are differentially associated with demographic and cardiac factors. These findings indicate that hs-cTnT and NT-proBNP may reflect different pathophysiological pathways.
-
3.
Predictive Value of High-Sensitivity Troponin T for Systolic Dysfunction and Infarct Size (Six Months) After ST-Elevation Myocardial Infarction.
Mohammad, MA, Koul, S, Smith, JG, Noc, M, Lang, I, Holzer, M, Clemmensen, P, Jensen, U, Engstrøm, T, Arheden, H, et al
The American journal of cardiology. 2018;(5):735-743
Abstract
The association of markers of myocardial injury and dysfunction with infarct size (IS) and ejection fraction (EF) are well documented. However, limited data are available on the newer high-sensitivity troponin assays and comparison with morphologic and functional assessment with cardiac magnetic resonance imaging. We aimed to examine the associations of high-sensitivity cardiac Troponin-T (hs-cTnT), creatine kinase MB iso-enzyme (CKMB), and N-terminal pro B-type Natriuretic Peptide (NT-proBNP) to IS and EF at 6 months. Blood samples from 119 ST-segment elevation myocardial infarction patients from the Rapid Endovascular Catheter Core Cooling Combined With Cold Saline solution as an Adjunct to Percutaneous Coronary Intervention for the Treatment of Acute Myocardial Infarction trial were collected at baseline, 6, 24, and 48 hours after admission. Cardiac magnetic resonance was performed at 4 ± 2 days and 6 months. The association of biomarker levels to IS and EF was tested with Pearson's correlation coefficients and linear regression models with bootstrap resampling. The correlation coefficient of biomarker to IS was (CKMB: r = 0.71); (NT-proBNP: r = 0.55); (hs-cTnT: r = 0.80); and for EF (CKMB: r = 0.57); (NT-proBNP: r = 0.48); and (peak hs-cTnT: r = 0.68). IS and EF at 4 ± 2 days had the strongest correlations with IS and EF at 6 months respectively (IS: r = 0.84) and (EF: r = 0.74). Receiver operating characteristic of peak hs-cTnT for predicting EF ≤40% at 6 months was 0.87 compared with 0.75 for early IS. Early EF was a negative predictor of late EF <40%, 1-area under curve = 0.93. In conclusion, high-sensitivity Troponin T is a rapid, cheap, generally available tool for accurate prediction of systolic dysfunction in patients 6 months after first-time ST-segment elevation myocardial infarction.
-
4.
Biomarker-Based Risk Model to Predict Cardiovascular Mortality in Patients With Stable Coronary Disease.
Lindholm, D, Lindbäck, J, Armstrong, PW, Budaj, A, Cannon, CP, Granger, CB, Hagström, E, Held, C, Koenig, W, Östlund, O, et al
Journal of the American College of Cardiology. 2017;(7):813-826
Abstract
BACKGROUND Currently, there is no generally accepted model to predict outcomes in stable coronary heart disease (CHD). OBJECTIVES This study evaluated and compared the prognostic value of biomarkers and clinical variables to develop a biomarker-based prediction model in patients with stable CHD. METHODS In a prospective, randomized trial cohort of 13,164 patients with stable CHD, we analyzed several candidate biomarkers and clinical variables and used multivariable Cox regression to develop a clinical prediction model based on the most important markers. The primary outcome was cardiovascular (CV) death, but model performance was also explored for other key outcomes. It was internally bootstrap validated, and externally validated in 1,547 patients in another study. RESULTS During a median follow-up of 3.7 years, there were 591 cases of CV death. The 3 most important biomarkers were N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and low-density lipoprotein cholesterol, where NT-proBNP and hs-cTnT had greater prognostic value than any other biomarker or clinical variable. The final prediction model included age (A), biomarkers (B) (NT-proBNP, hs-cTnT, and low-density lipoprotein cholesterol), and clinical variables (C) (smoking, diabetes mellitus, and peripheral arterial disease). This "ABC-CHD" model had high discriminatory ability for CV death (c-index 0.81 in derivation cohort, 0.78 in validation cohort), with adequate calibration in both cohorts. CONCLUSIONS This model provided a robust tool for the prediction of CV death in patients with stable CHD. As it is based on a small number of readily available biomarkers and clinical factors, it can be widely employed to complement clinical assessment and guide management based on CV risk. (The Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial [STABILITY]; NCT00799903).
-
5.
Impact of Modifiable Risk Factors on B-type Natriuretic Peptide and Cardiac Troponin T Concentrations.
Srivastava, PK, Pradhan, AD, Cook, NR, Ridker, PM, Everett, BM
The American journal of cardiology. 2016;(3):376-81
-
-
Free full text
-
Abstract
Alcohol use, physical activity, diet, and cigarette smoking are modifiable cardiovascular risk factors that have a substantial impact on the risk of myocardial infarction, stroke, and cardiovascular death. We hypothesized that these behaviors may alter concentrations of cardiac troponin, a marker of myocyte injury, and B-type natriuretic peptide, a marker of myocyte stress. Both markers have shown strong association with adverse cardiovascular outcomes. In 519 women with no evidence of cardiovascular disease, we measured circulating concentrations of cardiac troponin T, using a high-sensitivity assay (hsTnT), and the N-terminal fragment of B-type natriuretic peptide (NT-proBNP). We used logistic regression to determine if these behaviors were associated with hsTnT ≥ 3 ng/l or with NT-proBNP in the highest quartile (≥ 127.3 ng/l). The median (Q1 to Q3) NT-proBNP of the cohort was 68.8 ng/l (40.3 to 127.3 ng/l), and 30.8% (160 of 519) of the cohort had circulating hsTnT ≥ 3 ng/l. In adjusted models, women who drank 1 to 6 drinks/week had lower odds of having a hsTnT ≥ 3 ng/l (odds ratio 0.58, 95% confidence interval 0.34 to 0.96) and lower odds of having an elevated NT-proBNP (odds ratio 0.55, 95% confidence interval 0.32 to 0.96). We were subsequently able to validate the results for B-type natriuretic peptide in a large independent cohort. In conclusion, our results suggest that regular alcohol consumption is associated with lower concentrations of hsTnT and NT-proBNP, 2 cardiovascular biomarkers associated with cardiovascular risk, and raise the hypothesis that the beneficial effects of alcohol consumption may be mediated by direct effects on the myocardium.
-
6.
Sample Size in Clinical Cardioprotection Trials Using Myocardial Salvage Index, Infarct Size, or Biochemical Markers as Endpoint.
Engblom, H, Heiberg, E, Erlinge, D, Jensen, SE, Nordrehaug, JE, Dubois-Randé, JL, Halvorsen, S, Hoffmann, P, Koul, S, Carlsson, M, et al
Journal of the American Heart Association. 2016;(3):e002708
Abstract
BACKGROUND Cardiac magnetic resonance (CMR) can quantify myocardial infarct (MI) size and myocardium at risk (MaR), enabling assessment of myocardial salvage index (MSI). We assessed how MSI impacts the number of patients needed to reach statistical power in relation to MI size alone and levels of biochemical markers in clinical cardioprotection trials and how scan day affect sample size. METHODS AND RESULTS Controls (n=90) from the recent CHILL-MI and MITOCARE trials were included. MI size, MaR, and MSI were assessed from CMR. High-sensitivity troponin T (hsTnT) and creatine kinase isoenzyme MB (CKMB) levels were assessed in CHILL-MI patients (n=50). Utilizing distribution of these variables, 100 000 clinical trials were simulated for calculation of sample size required to reach sufficient power. For a treatment effect of 25% decrease in outcome variables, 50 patients were required in each arm using MSI compared to 93, 98, 120, 141, and 143 for MI size alone, hsTnT (area under the curve [AUC] and peak), and CKMB (AUC and peak) in order to reach a power of 90%. If average CMR scan day between treatment and control arms differed by 1 day, sample size needs to be increased by 54% (77 vs 50) to avoid scan day bias masking a treatment effect of 25%. CONCLUSION Sample size in cardioprotection trials can be reduced 46% to 65% without compromising statistical power when using MSI by CMR as an outcome variable instead of MI size alone or biochemical markers. It is essential to ensure lack of bias in scan day between treatment and control arms to avoid compromising statistical power.
-
7.
Clinical Presentation, Management and Outcome of Japanese Patients With Acute Myocardial Infarction in the Troponin Era - Japanese Registry of Acute Myocardial Infarction Diagnosed by Universal Definition (J-MINUET) - .
Ishihara, M, Fujino, M, Ogawa, H, Yasuda, S, Noguchi, T, Nakao, K, Ozaki, Y, Kimura, K, Suwa, S, Fujimoto, K, et al
Circulation journal : official journal of the Japanese Circulation Society. 2015;(6):1255-62
Abstract
BACKGROUND New criteria for diagnosis of acute myocardial infarction (AMI) were proposed in 2000 as a universal definition, in which cardiac troponin (cTn) was the preferred biomarker. A large number of patients formerly classified by creatine kinase (CK) as unstable angina are now ruled-in by cTn as non-ST-elevation myocardial infarction (NSTEMI). METHODS AND RESULTS The Japanese registry of acute Myocardial INfarction diagnosed by Universal dEfiniTion (J-MINUET) is a prospective and multicenter registry conducted in 28 institutions. We enrolled 3,283 consecutive patients with AMI diagnosed by cTn-based criteria who were admitted to participating institutions within 48 h of symptom onset. There were 2,262 patients (68.9%) with STEMI and 1,021 (31.1%) with NSTEMI. CK was not elevated more than twice the upper limit of normal in 458 patients (44.9%) with NSTEMI (NSTEMI-CK). Although there was no significant difference in the in-hospital mortality of STEMI and NSTEMI with CK elevation (NSTEMI+CK) patients (7.1% vs. 7.8%, P=0.57), it was significantly lower in patients with NSTEMI-CK than in those with STEMI or NSTEMI+CK (1.7%, P<0.001 for each). CONCLUSIONS J-MINUET revealed the clinical presentation, management and outcomes of Japanese patients with AMI in the current cTn era. We should be aware of the difference between AMI diagnosed by CK-based criteria and AMI diagnosed by cTn-based criteria when using universal definitions for the diagnosis of AMI.
-
8.
High-sensitivity cardiac troponin I and B-type natriuretic Peptide as predictors of vascular events in primary prevention: impact of statin therapy.
Everett, BM, Zeller, T, Glynn, RJ, Ridker, PM, Blankenberg, S
Circulation. 2015;(21):1851-60
-
-
Free full text
-
Abstract
BACKGROUND Cardiac troponin and B-type natriuretic peptide (BNP) concentrations are associated with adverse cardiovascular outcome in primary prevention populations. Whether statin therapy modifies this association is poorly understood. METHODS AND RESULTS We measured high-sensitivity cardiac troponin I (hsTnI) in 12 956 and BNP in 11 076 participants without cardiovascular disease in the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) trial before randomization to rosuvastatin 20 mg/d or placebo. Nearly 92% of participants had detectable circulating hsTnI, and 2.9% of men and 4.1% of women had levels above proposed sex-specific reference limits of 36 and 15 ng/L, respectively. hsTnI concentrations in the highest tertile were associated with a first major cardiovascular event (adjusted hazard ratio [aHR], 2.19; 95% confidence interval, 1.56-3.06; P for trend <0.001). BNP levels in the highest tertile were also associated a first cardiovascular event (aHR, 1.94; 95% confidence interval, 1.41-2.68; P for trend <0.001). The risk of all-cause mortality was elevated for the highest versus the lowest tertiles of hsTnI (aHR, 2.61; 95% confidence interval, 1.81-3.78; P for trend <0.001) and BNP (aHR, 1.45; 95% confidence interval, 1.03-2.04; P for trend 0.02). Rosuvastatin was equally effective in preventing a first cardiovascular event across categories of hsTnI (aHR range, 0.50-0.60) and BNP (aHR range, 0.42-0.67) with no statistically significant evidence of interaction (P for interaction=0.53 and 0.20, respectively). CONCLUSIONS In a contemporary primary prevention population, baseline cardiac troponin I and BNP were associated with the risk of vascular events and all-cause mortality. The benefits of rosuvastatin were substantial and consistent regardless of baseline hsTnI or BNP concentrations. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.
-
9.
Cardiomyocyte injury induced by hemodynamic cardiac stress: Differential release of cardiac biomarkers.
Irfan, A, Reichlin, T, Twerenbold, R, Fischer, C, Ballarino, P, Nelles, B, Wildi, K, Zellweger, C, Rubini Gimenez, M, Mueller, M, et al
Clinical biochemistry. 2015;(18):1225-9
Abstract
OBJECTIVE We explored whether hemodynamic cardiac stress leads to a differential release of cardiomyocyte injury biomarkers, used in the diagnosis of acute myocardial infarction (AMI). METHODS In an observational international multicenter study, we enrolled 831 unselected patients presenting with symptoms suggestive of AMI to the emergency department. The final diagnosis was adjudicated by two independent cardiologists. Hemodynamic cardiac stress was quantified by levels of B-type natriuretic peptide (BNP). Spearman's rho correlation was used to analyze the correlations between BNP and high-sensitivity cardiac troponin T (hs-cTnT), Siemens cTnI-Ultra (cTnI-ultra), CK-MB and Myoglobin. Patients were categorized according to the extent of hemodynamic cardiac stress as quantified by BNP tertiles. RESULTS Among all patients, the positive pair-wise correlation with BNP was strongest with hs-cTnT and cTnI-ultra (r=0.58 and 0.50, respectively), moderate for Myoglobin (r=0.43), and weakest with CK-MB (r=0.25; p<0.001 for each). Similar pattern of correlations was also observed among AMI patients. Among patients diagnosed with non-cardiac cause of chest pain (n=385, 46%) and cardiac but non-coronary (n=109, 13%), BNP had significant positive correlations with hs-cTnT, cTnI-ultra and Myoglobin (p<0.05), but not with CK-MB (p=NS). A similar pattern of stronger correlation between BNP and hs-cTnT, cTnI-ultra and Myoglobin as compared to that with CK-MB was also observed within the higher BNP tertile range. There was no correlation between BNP and other biomarkers within the 1st BNP tertile group. CONCLUSION Hemodynamic cardiac stress, as quantified by BNP, as a likely cause of cardiomyocyte injury, is more closely reflected by concentrations of hs-cTnT, cTnI-ultra and Myoglobin than CK-MB.
-
10.
ICD Shock, Not Ventricular Fibrillation, Causes Elevation of High Sensitive Troponin T after Defibrillation Threshold Testing--The Prospective, Randomized, Multicentre TropShock-Trial.
Semmler, V, Biermann, J, Haller, B, Jilek, C, Sarafoff, N, Lennerz, C, Vrazic, H, Zrenner, B, Asbach, S, Kolb, C
PloS one. 2015;(7):e0131570
Abstract
BACKGROUND The placement of an implantable cardioverter defibrillator (ICD) has become routine practice to protect high risk patients from sudden cardiac death. However, implantation-related myocardial micro-damage and its relation to different implantation strategies are poorly characterized. METHODS A total of 194 ICD recipients (64±12 years, 83% male, 95% primary prevention of sudden cardiac death, 35% cardiac resynchronization therapy) were randomly assigned to one of three implantation strategies: (1) ICD implantation without any defibrillation threshold (DFT) testing, (2) estimation of the DFT without arrhythmia induction (modified "upper limit of vulnerability (ULV) testing") or (3) traditional safety margin testing including ventricular arrhythmia induction. High-sensitive Troponin T (hsTnT) levels were determined prior to the implantation and 6 hours after. RESULTS All three groups showed a postoperative increase of hsTnT. The mean delta was 0.031±0.032 ng/ml for patients without DFT testing, 0.080±0.067 ng/ml for the modified ULV-testing and 0.064±0.056 ng/ml for patients with traditional safety margin testing. Delta hsTnT was significantly larger in both of the groups with intraoperative ICD testing compared to the non-testing strategy (p≤0.001 each). There was no statistical difference in delta hsTnT between the two groups with intraoperative ICD testing (p = 0.179). CONCLUSION High-sensitive Troponin T release during ICD implantation is significantly higher in patients with intraoperative ICD testing using shock applications compared to those without testing. Shock applications, with or without arrhythmia induction, did not result in a significantly different delta hsTnT. Hence, the ICD shock itself and not ventricular fibrillation seems to cause myocardial micro-damage. TRIAL REGISTRATION ClinicalTrials.gov NCT01230086.