High-Sensitive Cardiac Troponin T as an Early Biochemical Signature for Clinical and Subclinical Heart Failure: MESA (Multi-Ethnic Study of Atherosclerosis).
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 before symptoms is fundamental to understanding the potential of this biomarker in a HF prevention strategy.


METHODS
We measured hs-cTnT at baseline among 4986 participants in MESA (Multi-Ethnic Study of Atherosclerosis), a cohort initially free of overt cardiovascular disease (CVD). Cardiac magnetic resonance imaging was performed at baseline. Repeat cardiac magnetic resonance was performed 10 years later among 2831 participants who remained free of interim CVD events; of these, 1723 received gadolinium-enhanced cardiac magnetic resonance for characterization of replacement fibrosis by late gadolinium enhancement. 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
Late gadolinium enhancement for replacement fibrosis was detectable in 6.3% participants without interim CVD events by follow-up cardiac magnetic resonance. A graded association was observed between higher baseline hs-cTnT categories and late gadolinium enhancement (≥7.42 ng/L versus <limit of detection [<3 ng/L]; adjusted odds ratio, 2.87; 95% confidence interval, 1.38-5.94). Higher hs-cTnT was also associated with a greater probability of an increase in LV mass >12% (highest category versus <limit of detection; odds ratio, 1.50; 95% confidence interval, 1.09-2.07), but not with decline in left ventricular ejection fraction. The risk of incident HF was greater for higher hs-cTnT (≥8.81 ng/L versus <limit of detection; adjusted hazards ratio, 5.59; 95% CI, 2.97-10.68).


CONCLUSIONS
hs-cTnT levels are associated with replacement fibrosis and progressive changes in left ventricular 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.
From Division of Nephrology (S.L.S.), Division of Cardiovascular Medicine (S.N.H.), and Department of Pathology (R.H.C.), University of Maryland School of Medicine, Baltimore; University of Washington, Department of Biostatistics, Seattle (R.K.); University of California at San Diego, Division of Cardiology, La Jolla (L.B.D.); Johns Hopkins University, Division of Cardiology, Baltimore, MD (J.A.C.L.); University of Texas Southwestern Medical Center, Division of Cardiology, Dallas (J.A.d.L.); Wake Forest School of Medicine, Department of Epidemiology and Prevention, Winston-Salem, NC (A.B.); and Inova Heart and Vascular Institute, Falls Church, VA (C.R.d.).
Stephen L
SL
Seliger
From Division of Nephrology (S.L.S.), Division of Cardiovascular Medicine (S.N.H.), and Department of Pathology (R.H.C.), University of Maryland School of Medicine, Baltimore; University of Washington, Department of Biostatistics, Seattle (R.K.); University of California at San Diego, Division of Cardiology, La Jolla (L.B.D.); Johns Hopkins University, Division of Cardiology, Baltimore, MD (J.A.C.L.); University of Texas Southwestern Medical Center, Division of Cardiology, Dallas (J.A.d.L.); Wake Forest School of Medicine, Department of Epidemiology and Prevention, Winston-Salem, NC (A.B.); and Inova Heart and Vascular Institute, Falls Church, VA (C.R.d.).
Susie N
SN
Hong
From Division of Nephrology (S.L.S.), Division of Cardiovascular Medicine (S.N.H.), and Department of Pathology (R.H.C.), University of Maryland School of Medicine, Baltimore; University of Washington, Department of Biostatistics, Seattle (R.K.); University of California at San Diego, Division of Cardiology, La Jolla (L.B.D.); Johns Hopkins University, Division of Cardiology, Baltimore, MD (J.A.C.L.); University of Texas Southwestern Medical Center, Division of Cardiology, Dallas (J.A.d.L.); Wake Forest School of Medicine, Department of Epidemiology and Prevention, Winston-Salem, NC (A.B.); and Inova Heart and Vascular Institute, Falls Church, VA (C.R.d.).
Robert H
RH
Christenson
From Division of Nephrology (S.L.S.), Division of Cardiovascular Medicine (S.N.H.), and Department of Pathology (R.H.C.), University of Maryland School of Medicine, Baltimore; University of Washington, Department of Biostatistics, Seattle (R.K.); University of California at San Diego, Division of Cardiology, La Jolla (L.B.D.); Johns Hopkins University, Division of Cardiology, Baltimore, MD (J.A.C.L.); University of Texas Southwestern Medical Center, Division of Cardiology, Dallas (J.A.d.L.); Wake Forest School of Medicine, Department of Epidemiology and Prevention, Winston-Salem, NC (A.B.); and Inova Heart and Vascular Institute, Falls Church, VA (C.R.d.).
Richard
R
Kronmal
From Division of Nephrology (S.L.S.), Division of Cardiovascular Medicine (S.N.H.), and Department of Pathology (R.H.C.), University of Maryland School of Medicine, Baltimore; University of Washington, Department of Biostatistics, Seattle (R.K.); University of California at San Diego, Division of Cardiology, La Jolla (L.B.D.); Johns Hopkins University, Division of Cardiology, Baltimore, MD (J.A.C.L.); University of Texas Southwestern Medical Center, Division of Cardiology, Dallas (J.A.d.L.); Wake Forest School of Medicine, Department of Epidemiology and Prevention, Winston-Salem, NC (A.B.); and Inova Heart and Vascular Institute, Falls Church, VA (C.R.d.).
Lori B
LB
Daniels
From Division of Nephrology (S.L.S.), Division of Cardiovascular Medicine (S.N.H.), and Department of Pathology (R.H.C.), University of Maryland School of Medicine, Baltimore; University of Washington, Department of Biostatistics, Seattle (R.K.); University of California at San Diego, Division of Cardiology, La Jolla (L.B.D.); Johns Hopkins University, Division of Cardiology, Baltimore, MD (J.A.C.L.); University of Texas Southwestern Medical Center, Division of Cardiology, Dallas (J.A.d.L.); Wake Forest School of Medicine, Department of Epidemiology and Prevention, Winston-Salem, NC (A.B.); and Inova Heart and Vascular Institute, Falls Church, VA (C.R.d.).
Joao A C
JAC
Lima
From Division of Nephrology (S.L.S.), Division of Cardiovascular Medicine (S.N.H.), and Department of Pathology (R.H.C.), University of Maryland School of Medicine, Baltimore; University of Washington, Department of Biostatistics, Seattle (R.K.); University of California at San Diego, Division of Cardiology, La Jolla (L.B.D.); Johns Hopkins University, Division of Cardiology, Baltimore, MD (J.A.C.L.); University of Texas Southwestern Medical Center, Division of Cardiology, Dallas (J.A.d.L.); Wake Forest School of Medicine, Department of Epidemiology and Prevention, Winston-Salem, NC (A.B.); and Inova Heart and Vascular Institute, Falls Church, VA (C.R.d.).
James A
JA
de Lemos
From Division of Nephrology (S.L.S.), Division of Cardiovascular Medicine (S.N.H.), and Department of Pathology (R.H.C.), University of Maryland School of Medicine, Baltimore; University of Washington, Department of Biostatistics, Seattle (R.K.); University of California at San Diego, Division of Cardiology, La Jolla (L.B.D.); Johns Hopkins University, Division of Cardiology, Baltimore, MD (J.A.C.L.); University of Texas Southwestern Medical Center, Division of Cardiology, Dallas (J.A.d.L.); Wake Forest School of Medicine, Department of Epidemiology and Prevention, Winston-Salem, NC (A.B.); and Inova Heart and Vascular Institute, Falls Church, VA (C.R.d.).
Alain
A
Bertoni
From Division of Nephrology (S.L.S.), Division of Cardiovascular Medicine (S.N.H.), and Department of Pathology (R.H.C.), University of Maryland School of Medicine, Baltimore; University of Washington, Department of Biostatistics, Seattle (R.K.); University of California at San Diego, Division of Cardiology, La Jolla (L.B.D.); Johns Hopkins University, Division of Cardiology, Baltimore, MD (J.A.C.L.); University of Texas Southwestern Medical Center, Division of Cardiology, Dallas (J.A.d.L.); Wake Forest School of Medicine, Department of Epidemiology and Prevention, Winston-Salem, NC (A.B.); and Inova Heart and Vascular Institute, Falls Church, VA (C.R.d.). Christopher.Defilippi@inova.org.
Christopher R
CR
deFilippi
D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D005006:Ethnicity; D005260:Female; D006333:Heart Failure / Q000175:diagnosis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020107:Troponin T / Q000378:metabolism*
D020107:Troponin T
cardiovascular MRI; cardiovascular events; epidemiology; heart failure; troponin T