hs-Troponins Mark Subclinical Disease, Predict Fibrosis, Heart Failure

Larry Hand

February 10, 2017

FALLS CHURCH, VA — Elevated levels of high-sensitivity troponin T (hs-cTnT) in middle age may be a biomarker of subclinical heart disease and a predictor cardiomyopathy, cardiovascular events, and heart failure[1].

Interestingly, elevated hs-cTnT levels, which indicate myocyte injury or death, can also predict later subclinical myocardial fibrosis, according to according to researchers in their report published online February 3, 2017 in Circulation.

"You can use very subtle measures in a population that's free of any known cardiovascular disease in the form of this myocyte death marker—high-sensitivity troponin T—and detect an early phenotype that's going to often go on to progress to symptomatic disease," senior author Dr Christopher deFillippi (Inova Heart and Vascular Institute, Falls Church, VA), told heartwire from Medscape.

First author Dr Stephen L Seliger (Inova Heart and Vascular Institute) and colleagues analyzed data on 6814 men and women 45 to 84 years old who have participated in the Multi-Ethnic Study of Atherosclerosis (MESA), conducted between July 2000 and September 2002.

The MESA investigators enrolled the participants at six centers in the US. The participants had extensive evaluations and laboratory tests in five separate exams. For the current study, investigators included participants who had complete cardiovascular magnetic resonance (CMR) evaluation at exams 1 and 5 and who stayed free of "clinically overt" cardiovascular disease.

"One of the strengths we had in this project was the incredibly rich data that was provided by the MESA cohort study," Seliger told heartwire. "We were able to examine that these markers were important not just above and beyond traditional risk factors but after even controlling for very highly accurate measures of structure and function using cardiac MRI methods. The breadth of the risk-factor characterization and the length of follow-up are real strengths of the study that make the results very robust."

The researchers identified 2831 participants with CMR exams at exams 1 and 5 who also had available hs-cTnT measurements and had no evidence coronary heart disease or heart-failure events. Of these participants:

  • 668 (23.5%) had >12% increase in left ventricular mass from baseline.

  • 387 (13.7%) had >8% increase in end diastolic volume.

  • 570 (20.1%) had >10% decline in ejection fraction.

Participants with the highest hs-cTnT levels, after adjustment, were more likely to be in those categories for left ventricular mass increase (odds ratio 1.5) and end diastolic volume increase, but not for ejection fraction decline.

The researchers followed participants with baseline CMR and hs-cTnT measurements for a median of 12 years, during which time 177 definite or probable heart-failure events, 234 coronary heart disease events, and 41 cardiovascular deaths occurred. They found progressively higher levels of hs-cTnT to be associated with greater risk of each event.

Specifically for heart failure, they found the unadjusted hazard ratio for participants in the highest category of hs-cTnT, compared with those with less than the limit of detection, to be 14.13 (95% CI 8.18–24.42), which remained significant after risk-factor and other adjustments.

As for replacement fibrosis, the researchers identified late gadolinium enhancement in 113 (6.3%) of 1753 participants through gadolinium-enhanced CMR at exam 5 who had experienced no cardiovascular event. After adjustment, the odds of late gadolinium-enhancement scar was almost 2.5 times as high in patients with the highest levels of hs-cTnT compared with participants with undetectable hs-cTnT.

"The fact that we could correlate biochemical evidence of myocyte-cell death with later evidence of replacement fibrosis is novel," deFillippi told heartwire . "It supports the concept that there may be turnover in loss of myocytes that are ultimately leading to symptoms many years later."

hs-cTnT can help to identify an early biochemical phenotype of those who are going to go on to have structural heart disease and ultimately symptoms and death, deFillippi said.

"If this biochemical process that was preceding all of this by many years could be detected in the form of myocyte death with high-sensitivity troponin T, it could be a nice target for preventive therapy," he said.

He added that the high-sensitivity cardiac troponin T assay is being used "as de facto standard" in Europe and much of the world since 2010 but hasn't been available as a clinical test in the US, where less sensitive assays have been used. The Food and Drug Administration approved the high-sensitivity assay as an indication for diagnosing MI, but no indication has been approved yet for risk stratifying or early identification, he said.

The National Heart, Lung, and Blood Institute supported this research. The authors reported no relevant financial relationships.

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