scholarly journals Trajectories of high-sensitivity cardiac troponin I in the two decades before cardiovascular death in Whitehall II

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
D M Kimenai ◽  
A Anand ◽  
M De Bakker ◽  
M Shipley ◽  
T Fujisawa ◽  
...  

Abstract Background High-sensitivity cardiac troponin may be a promising biomarker that could be used for personalised cardiovascular risk prediction and monitoring in the general population. Temporal changes in high-sensitivity cardiac troponin before cardiovascular death are largely unexplored. Purpose Using the longitudinal Whitehall II cohort, we evaluated whether three serial high-sensitivity cardiac troponin I measurements over 15 years improved prediction of cardiovascular death when compared to a single time point at baseline. Methods Whitehall II is an ongoing longitudinal observation cohort study of 10,308 civil servants, and we included participants who had at least one cardiac troponin measurement and outcome data available. We constructed time trajectories to evaluate the temporal pattern of cardiac troponin I in those who died from cardiovascular disease as compared to those who did not. Cox regression and joint models were used to investigate the association of cardiac troponin I in relation to cardiovascular death using single time point (at baseline) and repeated measurements (at baseline, 10 and 15 years), respectively. The discriminative ability was assessed by the concordance index. Results In total, we included 7,293 individuals (mean age of 58 years [SD 7] at baseline, 29.4% women). Of these, 5,818 (79.8%) and 4,045 (55.5%) individuals had a second and third cardiac troponin I concentration measured, respectively. Cardiovascular death occurred in 281 (3.9%) individuals during a median follow-up of 21.4 [IQR, 15.8 to 21.8] years. In the 21-year trajectories of cardiac troponin I, we observed higher baseline concentrations in those who died due to cardiovascular disease as compared to those who did not (median 5 [IQR, 2 to 9] ng/L versus 3 [IQR, 2 to 5] ng/L respectively, Figure). Cardiac troponin I was an independent predictor of cardiovascular death, and the hazard ratio (HR) derived from the joint model that included serial cardiac troponin measurements was higher than the HR derived from the single time point model (single time point model: adjusted HR 1.53, 95% Confidence Interval [CI] 1.37 to 1.70 per naturally log transformed unit of cardiac troponin I, versus repeated measurements model: adjusted HR 1.79, 95% CI 1.58 to 2.02). The discriminative ability of the cardiac troponin model improved when using repeated measurements (concordance index of unadjusted cardiac troponin models, single time point: 0.668 versus repeated measurements: 0.724). Conclusions Our study shows that cardiac troponin I trajectories were persistently higher among individuals who died from cardiovascular disease. Cardiac troponin I is a strong independent predictor of cardiovascular death, and incorporating repeated measurements of cardiac troponin improves cardiovascular risk prediction in the general population. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Cardiac troponin I measurements and analysis were supported by were supported by Siemens Healthineers. The study was supported by Health Data Research UK which receives its funding from HDR UK Ltd (HDR-5012) funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation and the Wellcome Trust. NLM is supported by the British Heart Foundation through a Senior Clinical Research Fellowship (FS/16/14/32023), Programme Grant (RG/20/10/34966) and a Research Excellence Award (RE/18/5/34216). The funders had no role in the study and the decision to submit this work to be considered for publication.

2014 ◽  
Vol 60 (1) ◽  
pp. 158-164 ◽  
Author(s):  
Erin A Bohula May ◽  
Marc P Bonaca ◽  
Petr Jarolim ◽  
Elliott M Antman ◽  
Eugene Braunwald ◽  
...  

Abstract BACKGROUND High-sensitivity assays for cardiac troponin enable more precise measurement of very low concentrations and improved diagnostic accuracy. However, the prognostic value of these measurements, particularly at low concentrations, is less well defined. METHODS We evaluated the prognostic performance of a new high-sensitivity cardiac troponin I (hs-cTnI) assay (Abbott ARCHITECT) compared with the commercial fourth generation cTnT assay in 4695 patients with non–ST-segment elevation acute coronary syndromes (NSTE-ACS) from the EARLY-ACS (Early Glycoprotein IIb/IIIa Inhibition in NSTE-ACS) and SEPIA-ACS1-TIMI 42 (Otamixaban for the Treatment of Patients with NSTE-ACS) trials. The primary endpoint was cardiovascular death or new myocardial infarction (MI) at 30 days. Baseline cardiac troponin was categorized at the 99th percentile reference limit (26 ng/L for hs-cTnI; 10 ng/L for cTnT) and at sex-specific 99th percentiles for hs-cTnI. RESULTS All patients at baseline had detectable hs-cTnI compared with 94.5% with detectable cTnT. With adjustment for all other elements of the TIMI risk score, patients with hs-cTnI ≥99th percentile had a 3.7-fold higher adjusted risk of cardiovascular death or MI at 30 days relative to patients with hs-cTnI <99th percentile (9.7% vs 3.0%; odds ratio, 3.7; 95% CI, 2.3–5.7; P < 0.001). Similarly, when stratified by categories of hs-cTnI, very low concentrations demonstrated a graded association with cardiovascular death or MI (P-trend < 0.001). Use of sex-specific cutpoints did not improve prognostic performance. Patients with negative fourth generation cTnT (<10 ng/L) but hs-cTnI ≥26 ng/L were at increased risk of cardiovascular death/MI compared to those with hs-cTnI <26 ng/L (9.2% vs 2.9%, P = 0.002). CONCLUSIONS Application of this hs-cTnI assay identified a clinically relevant higher risk of recurrent events among patients with NSTE-ACS, even at very low troponin concentrations.


2012 ◽  
Vol 58 (5) ◽  
pp. 930-935 ◽  
Author(s):  
Fred S Apple ◽  
Lyn M Steffen ◽  
Lesly A Pearce ◽  
MaryAnn M Murakami ◽  
Russell V Luepker

Abstract BACKGROUND We examined several novel biomarkers of different pathophysiologic pathways as predictors of cardiovascular mortality in participants enrolled in the Minnesota Heart Survey (MHS), a population-based study of cardiovascular disease (CVD) risk factors. METHODS In a nested case-control study within MHS, 7 biomarkers were assayed in serum samples from 211 patients identified after 8–15 years of follow-up who died of cardiovascular causes (cardiovascular heart disease, stroke, congestive heart failure) and 253 controls matched on age, sex, and study year. Logistic regression analysis, adjusted for age, race, sex, education, study year, smoking, abdominal obesity, diabetes, serum total cholesterol, systolic blood pressure, previous hospitalization for a CVD event, and other significant biomarkers, was used to evaluate the relations of biomarkers relative to the odds of CVD mortality. RESULTS Cases survived a median of 7.2 years after enrollment. Increased N-terminal pro-B type natriuretic peptide (NT-proBNP) (19% vs 4.3%), increased high-sensitivity C-reactive protein (hs-CRP) (71% vs 51%), and increased high-sensitivity cardiac troponin I (hs-cTnI) (8.7% vs 1.0%) were more common among cases than among controls (all P < 0.001 in unadjusted analyses). The adjusted odds of death were greater among cases compared to controls for increased NT-proBNP [odds ratio (OR) 5.67, 95% CI 2.17–15], hs-CRP (OR 1.73, 95% CI 1.03–2.89), and hs-cTnI (OR 8.53, 95% CI 1.68–43), and decreased ST2 (OR 1.92, 95% CI 1.05–3.48). CONCLUSIONS When measured by an hs-cTnI assay, cTnI is a key biomarker associated with increased cardiovascular death in a community sample when evaluated in a multiple biomarker analysis.


2011 ◽  
Vol 57 (8) ◽  
pp. 1146-1153 ◽  
Author(s):  
Peter A Kavsak ◽  
Liqin Xu ◽  
Salim Yusuf ◽  
Matthew J McQueen

BACKGROUND Past investigations regarding the utility of high-sensitivity cardiac troponin I (cTnI) assays have been focused primarily on the acute coronary syndrome setting. We assessed whether such assays can predict future ischemic cardiovascular events in a stable high-risk population. METHODS We quantified serum cTnI using an investigational high-sensitivity assay (hs-cTnI IUO, Beckman Coulter) in 2572 participants from the Heart Outcomes Prevention Evaluation (HOPE) study. The derived ROC curve cutoff and the 99th percentile for the hs-cTnI assay were assessed by Kaplan–Meier and Cox analyses for the primary outcome [composite of myocardial infarction (MI), stroke, and cardiovascular death] at 4.5 years of follow-up. We also assessed individual outcomes (MI, stroke, cardiovascular death) and the combined outcome (MI/cardiovascular death) by regression analyses to determine hazard ratios (HRs) and c statistics in models that included established risk factors, C-reactive protein, and N-terminal pro-B–type natriuretic peptide (NT-proBNP). RESULTS Participants with hs-cTnI >6 ng/L (ROC cutoff) were at higher risk for the primary outcome (HR 1.38, 95% CI 1.09–1.76; P = 0.008, adjusted models). For the individual outcomes, participants with hs-cTnI above the 99th percentile (≥10 ng/L) had higher risk for cardiovascular death (HR 2.15, 95% CI 1.32–3.52; P = 0.002) and MI (HR 1.49, 95% CI 1.05–2.10; P = 0.025) but not stroke (HR 1.38, 95% CI 0.76–2.47; P = 0.288, adjusted models). Addition of hs-cTnI to an established risk model with NT-proBNP also yielded a higher c statistic for the combined outcome of MI/cardiovascular death. CONCLUSIONS The investigational Beckman Coulter hs-cTnI assay provides prognostic information for future MI and cardiovascular death in a stable high-risk population.


2015 ◽  
Vol 61 (4) ◽  
pp. 646-656 ◽  
Author(s):  
Torbjørn Omland ◽  
James A de Lemos ◽  
Oddgeir L Holmen ◽  
Håvard Dalen ◽  
Jūratė Šaltytė Benth ◽  
...  

Abstract BACKGROUND A new, high-sensitivity assay for cardiac troponin I (hs-cTnI) permits evaluation of the prognostic value of cardiac troponins within the reference interval. Men have higher hs-cTnI concentrations than women, but the underlying pathophysiological mechanisms and prognostic implications are unclear. The aim of this study was to assess the potential impact of sex on the association between hs-cTnI and cardiovascular death. METHODS By use of the Architect STAT High-Sensitive Troponin assay, we measured hs-cTnI in 4431 men and 5281 women aged ≥20 years participating in the prospective observational Nord-Trøndelag Health Study (HUNT). RESULTS hs-cTnI was detectable in 98.5% of men and 94.7% of women. During a mean follow-up period of 13.9 years, 708 cardiovascular deaths were registered. hs-cTnI was associated with the incidence of cardiovascular death [adjusted hazard ratio (HR) per 1 SD in log hs-cTnI 1.23 (95% CI 1.15–1.31)], with higher relative risk in women than men [HR 1.44 (1.31–1.58) vs 1.10 (1.00–1.20); Pinteraction < 0.001]. This finding was mediated by both lower risk associated with low hs-cTnI concentrations in women than in men and higher risk associated with high concentrations of hs-cTnI in women than in men. Male sex was associated with a higher risk of cardiovascular death [HR 1.28 (1.11–1.49)], but after adjustment for hs-cTnI, this association disappeared [HR 0.87 (0.75–1.02)]. CONCLUSIONS The prognostic value of hs-cTnI concentrations in the general population is stronger in women than in men. Subtle impairment of cardiovascular status may contribute to higher hs-cTnI concentrations in men, reflecting sex-dependent differences in cardiovascular risk.


Author(s):  
Peter A. Kavsak ◽  
Tara Edge ◽  
Chantele Roy ◽  
Paul Malinowski ◽  
Karen Bamford ◽  
...  

AbstractObjectivesTo analytically evaluate Ortho Clinical Diagnostics VITROS high-sensitivity cardiac troponin I (hs-cTnI) assay in specific matrices with comparison to other hs-cTn assays.MethodsThe limit of detection (LoD), imprecision, interference and stability testing for both serum and lithium heparin (Li-Hep) plasma for the VITROS hs-cTnI assay was determined. We performed Passing-Bablok regression analyses between sample types for the VITROS hs-cTnI assay and compared them to the Abbott ARCHITECT, Beckman Access and the Siemens ADVIA Centaur hs-cTnI assays. We also performed Receiver-operating characteristic curve analyses with the area under the curve (AUC) determined in an emergency department (ED)-study population (n=131) for myocardial infarction (MI).ResultsThe VITROS hs-cTnI LoD was 0.73 ng/L (serum) and 1.4 ng/L (Li-Hep). Stability up to five freeze-thaws was observed for the Ortho hs-cTnI assay, with the analyte stability at room temperature in serum superior to Li-Hep with gross hemolysis also affecting Li-Hep plasma hs-cTnI results. Comparison of Li-Hep to serum concentrations (n=202), yielded proportionally lower concentrations in plasma with the VITROS hs-cTnI assay (slope=0.85; 95% confidence interval [CI]:0.83–0.88). In serum, the VITROS hs-cTnI concentrations were proportionally lower compared to other hs-cTnI assays, with similar slopes observed between assays in samples frozen <−70 °C for 17 years (ED-study) or in 2020. In the ED-study, the VITROS hs-cTnI assay had an AUC of 0.974 (95%CI:0.929–0.994) for MI, similar to the AUCs of other hs-cTn assays.ConclusionsLack of standardization of hs-cTnI assays across manufacturers is evident. The VITROS hs-cTnI assay yields lower concentrations compared to other hs-cTnI assays. Important differences exist between Li-Hep plasma and serum, with evidence of stability and excellent clinical performance comparable to other hs-cTn assays.


Author(s):  
Peter A. Kavsak ◽  
Shawn Mondoux ◽  
Andrew Worster ◽  
Janet Martin ◽  
Vikas Tandon ◽  
...  

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