High Sensitive Cardiac Troponin T as an Early Biochemical Signature for Clinical and Subclinical Heart Failure

The Multi-Ethnic Study of Atherosclerosis

Stephen L. Seliger, Susie N. Hong, Robert H. Christenson, Richard Kronmal, Lori B. Daniels, Joao A C Lima, James A de Lemos, Alain Bertoni, Christopher R. deFilippi

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

BACKGROUND—: Although small elevations of high sensitive cardiac troponin T (hs-cTnT) are associated with incident heart failure (HF) in the general population, the underlying mechanisms are not well defined. Evaluating the association of hs-cTnT with replacement fibrosis and progression of structural heart disease prior to symptoms is fundamental to understanding the potential of this biomarker in a HF prevention strategy. METHODS—: We measured hs-cTnT at baseline among 4,986 participants in the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort initially free of overt cardiovascular disease (CVD). Cardiac magnetic resonance (CMR) imaging was performed at baseline. Repeat CMR was performed 10 years later among 2,831 participants who remained free of interim CVD events; of these 1,723 received gadolinium-enhanced CMR for characterization of replacement fibrosis by late gadolinium enhancement (LGE). Progression of subclinical CVD was defined by 10-year change in left ventricular structure and function. Associations of hs-cTnT with incident HF, CV-related mortality, and coronary heart disease were estimated using Cox regression models. RESULTS—: LGE for replacement fibrosis was detectable in 6.3% participants without interim CVD events by follow-up CMR. A graded association was observed between higher baseline hs-cTnT categories and LGE (≥7.42 ng/L vs <limit of detection [LOD: < 3 ng/L], adjusted odds ratio [OR]=2.87, 95% CI: 1.38, 5.94). Higher hs-cTnT was also associated with a greater probability of an increase in LV mass >12% (highest category vs <LOD), OR=1.50, 95% confidence interval[CI]:1.09-2.07), but not with decline in LV ejection fraction. The risk of incident HF was greater for higher hs-cTnT (≥8.81 ng/L vs <LOD, adjusted hazards ratio [HR] 5.59, 95%CI, 2.97 - 10.68). CONCLUSIONS—: hs-cTnT levels are associated with replacement fibrosis and progressive changes in LV structure in CVD free adults, findings that may precede HF symptoms by years. Minor elevations of hs-cTnT may represent a biochemical signature of early subclinical cardiac disease, providing an opportunity for targeted preventive interventions.

Original languageEnglish (US)
JournalCirculation
DOIs
StateAccepted/In press - Feb 27 2017

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Troponin T
Atherosclerosis
Heart Failure
Gadolinium
Cardiovascular Diseases
Fibrosis
Magnetic Resonance Spectroscopy
Heart Diseases
Confidence Intervals
Left Ventricular Function
Proportional Hazards Models
Coronary Disease
Biomarkers
Magnetic Resonance Imaging
Mortality

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

High Sensitive Cardiac Troponin T as an Early Biochemical Signature for Clinical and Subclinical Heart Failure : The Multi-Ethnic Study of Atherosclerosis. / Seliger, Stephen L.; Hong, Susie N.; Christenson, Robert H.; Kronmal, Richard; Daniels, Lori B.; Lima, Joao A C; de Lemos, James A; Bertoni, Alain; deFilippi, Christopher R.

In: Circulation, 27.02.2017.

Research output: Contribution to journalArticle

Seliger, Stephen L. ; Hong, Susie N. ; Christenson, Robert H. ; Kronmal, Richard ; Daniels, Lori B. ; Lima, Joao A C ; de Lemos, James A ; Bertoni, Alain ; deFilippi, Christopher R. / High Sensitive Cardiac Troponin T as an Early Biochemical Signature for Clinical and Subclinical Heart Failure : The Multi-Ethnic Study of Atherosclerosis. In: Circulation. 2017.
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abstract = "BACKGROUND—: Although small elevations of high sensitive cardiac troponin T (hs-cTnT) are associated with incident heart failure (HF) in the general population, the underlying mechanisms are not well defined. Evaluating the association of hs-cTnT with replacement fibrosis and progression of structural heart disease prior to symptoms is fundamental to understanding the potential of this biomarker in a HF prevention strategy. METHODS—: We measured hs-cTnT at baseline among 4,986 participants in the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort initially free of overt cardiovascular disease (CVD). Cardiac magnetic resonance (CMR) imaging was performed at baseline. Repeat CMR was performed 10 years later among 2,831 participants who remained free of interim CVD events; of these 1,723 received gadolinium-enhanced CMR for characterization of replacement fibrosis by late gadolinium enhancement (LGE). Progression of subclinical CVD was defined by 10-year change in left ventricular structure and function. Associations of hs-cTnT with incident HF, CV-related mortality, and coronary heart disease were estimated using Cox regression models. RESULTS—: LGE for replacement fibrosis was detectable in 6.3{\%} participants without interim CVD events by follow-up CMR. A graded association was observed between higher baseline hs-cTnT categories and LGE (≥7.42 ng/L vs 12{\%} (highest category vs <LOD), OR=1.50, 95{\%} confidence interval[CI]:1.09-2.07), but not with decline in LV ejection fraction. The risk of incident HF was greater for higher hs-cTnT (≥8.81 ng/L vs <LOD, adjusted hazards ratio [HR] 5.59, 95{\%}CI, 2.97 - 10.68). CONCLUSIONS—: hs-cTnT levels are associated with replacement fibrosis and progressive changes in LV structure in CVD free adults, findings that may precede HF symptoms by years. Minor elevations of hs-cTnT may represent a biochemical signature of early subclinical cardiac disease, providing an opportunity for targeted preventive interventions.",
author = "Seliger, {Stephen L.} and Hong, {Susie N.} and Christenson, {Robert H.} and Richard Kronmal and Daniels, {Lori B.} and Lima, {Joao A C} and {de Lemos}, {James A} and Alain Bertoni and deFilippi, {Christopher R.}",
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T1 - High Sensitive Cardiac Troponin T as an Early Biochemical Signature for Clinical and Subclinical Heart Failure

T2 - The Multi-Ethnic Study of Atherosclerosis

AU - Seliger, Stephen L.

AU - Hong, Susie N.

AU - Christenson, Robert H.

AU - Kronmal, Richard

AU - Daniels, Lori B.

AU - Lima, Joao A C

AU - de Lemos, James A

AU - Bertoni, Alain

AU - deFilippi, Christopher R.

PY - 2017/2/27

Y1 - 2017/2/27

N2 - BACKGROUND—: Although small elevations of high sensitive cardiac troponin T (hs-cTnT) are associated with incident heart failure (HF) in the general population, the underlying mechanisms are not well defined. Evaluating the association of hs-cTnT with replacement fibrosis and progression of structural heart disease prior to symptoms is fundamental to understanding the potential of this biomarker in a HF prevention strategy. METHODS—: We measured hs-cTnT at baseline among 4,986 participants in the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort initially free of overt cardiovascular disease (CVD). Cardiac magnetic resonance (CMR) imaging was performed at baseline. Repeat CMR was performed 10 years later among 2,831 participants who remained free of interim CVD events; of these 1,723 received gadolinium-enhanced CMR for characterization of replacement fibrosis by late gadolinium enhancement (LGE). Progression of subclinical CVD was defined by 10-year change in left ventricular structure and function. Associations of hs-cTnT with incident HF, CV-related mortality, and coronary heart disease were estimated using Cox regression models. RESULTS—: LGE for replacement fibrosis was detectable in 6.3% participants without interim CVD events by follow-up CMR. A graded association was observed between higher baseline hs-cTnT categories and LGE (≥7.42 ng/L vs 12% (highest category vs <LOD), OR=1.50, 95% confidence interval[CI]:1.09-2.07), but not with decline in LV ejection fraction. The risk of incident HF was greater for higher hs-cTnT (≥8.81 ng/L vs <LOD, adjusted hazards ratio [HR] 5.59, 95%CI, 2.97 - 10.68). CONCLUSIONS—: hs-cTnT levels are associated with replacement fibrosis and progressive changes in LV structure in CVD free adults, findings that may precede HF symptoms by years. Minor elevations of hs-cTnT may represent a biochemical signature of early subclinical cardiac disease, providing an opportunity for targeted preventive interventions.

AB - BACKGROUND—: Although small elevations of high sensitive cardiac troponin T (hs-cTnT) are associated with incident heart failure (HF) in the general population, the underlying mechanisms are not well defined. Evaluating the association of hs-cTnT with replacement fibrosis and progression of structural heart disease prior to symptoms is fundamental to understanding the potential of this biomarker in a HF prevention strategy. METHODS—: We measured hs-cTnT at baseline among 4,986 participants in the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort initially free of overt cardiovascular disease (CVD). Cardiac magnetic resonance (CMR) imaging was performed at baseline. Repeat CMR was performed 10 years later among 2,831 participants who remained free of interim CVD events; of these 1,723 received gadolinium-enhanced CMR for characterization of replacement fibrosis by late gadolinium enhancement (LGE). Progression of subclinical CVD was defined by 10-year change in left ventricular structure and function. Associations of hs-cTnT with incident HF, CV-related mortality, and coronary heart disease were estimated using Cox regression models. RESULTS—: LGE for replacement fibrosis was detectable in 6.3% participants without interim CVD events by follow-up CMR. A graded association was observed between higher baseline hs-cTnT categories and LGE (≥7.42 ng/L vs 12% (highest category vs <LOD), OR=1.50, 95% confidence interval[CI]:1.09-2.07), but not with decline in LV ejection fraction. The risk of incident HF was greater for higher hs-cTnT (≥8.81 ng/L vs <LOD, adjusted hazards ratio [HR] 5.59, 95%CI, 2.97 - 10.68). CONCLUSIONS—: hs-cTnT levels are associated with replacement fibrosis and progressive changes in LV structure in CVD free adults, findings that may precede HF symptoms by years. Minor elevations of hs-cTnT may represent a biochemical signature of early subclinical cardiac disease, providing an opportunity for targeted preventive interventions.

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