High Sensitive Cardiac Troponin T as an Early Biochemical Signature for Clinical and Subclinical Heart Failure: The 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 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.
- Received September 18, 2016.
- Revision received December 23, 2016.
- Accepted January 24, 2017.