High-Sensitivity Troponin Assays May Help With Response to Statins and Other Meds

New findings add to mounting evidence that high-sensitivity troponin assays may be useful in assessing risk and evaluating therapeutic response.

Blood Draw

Not only do levels of cardiac troponin I measured by a high-sensitivity assay predict coronary risk in a primary prevention population, but reductions in the concentrations—which seem to be achievable with statin therapy—track better with risk than do reductions in LDL cholesterol, according to an analysis of the WOSCOPS trial.

The findings, published in the December 27, 2016, issue of the Journal of the American College of Cardiology, add to mounting evidence that high-sensitivity troponin assays—which are not yet available in the United States but are used widely elsewhere to aid in the diagnosis of acute MI—may have clinical utility in assessing risk in the general population and evaluating response to various therapies.

“What this study adds is evidence that we can modify risk and modify troponin as a surrogate of risk with interventions that we know are effective,” senior author Nicholas Mills, MD (BHF/University Centre for Cardiovascular Science, Edinburgh, Scotland), told TCTMD.

The investigators had hypothesized that statins would be able to modify troponins by reducing plaque vulnerability, but “what we found was there was a really striking and consistent reduction in cardiac troponin across the entire study population, suggesting that statins might have effects on cardiac troponin concentrations in otherwise healthy individuals through a number of different mechanisms beyond an effect purely on plaque stabilization,” Mills added.

It is “unmistakable and irrefutable” that high-sensitivity troponin assays are useful for identifying risk in the general population, James Januzzi Jr, MD (Massachusetts General Hospital, Boston), who was not involved in the study, commented to TCTMD. But, he said, there remain open questions about whether these assays can improve the treatment of patients to prevent the onset of ischemic heart disease, what interventions might be effective, and what processes are causing troponin levels to be elevated in the first place.

“Whether risk can be modified through a therapeutic intervention triggered by an elevated highly sensitive troponin [level] remains to be proven in a prospective randomized trial,” he said. “But I do think that it is likely, it is plausible to expect that a well-designed clinical trial with a therapy that targets the specific pathology that troponin predicts would very likely reduce the risk in these patients quite substantially.”

The current study suggests that statins might be an effective therapy for lowering troponin concentrations and modifying risk, but Januzzi pointed out that troponin levels can be raised for a variety of reasons—not just coronary disease but also multiple types of myocardial injury. In other cohorts, these other causes of troponin elevations might be more important.

“While I would love to say that for every patient with an elevated troponin you should just put a statin on board, it may vary somewhat based on the reason that the troponin is elevated,” he explained. “So it’s almost certainly going to be a mixture of clinical judgment, history, physical, and biomarker testing to best decide whether a patient gets statins for their ischemic heart disease versus an ARNI [angiotensin receptor neprilysin inhibitor] for heart muscle disease versus diabetes care for their out of control diabetes. All of these different processes may lead to troponin elevations, so clinical judgment will always be necessary in order to best interpret the results of the test and intervene accordingly.”

‘Never Had a Test That Tracks Risk in This Way’

For the study, Mills along with lead author Ian Ford, PhD (University of Glasgow, Scotland), and colleagues examined data from the WOSCOPS trial, which randomized middle-aged men with elevated LDL cholesterol and no history of MI to placebo or pravastatin 40 mg/day for 5 years. The main results showed that statin therapy reduced the risk of various cardiovascular endpoints, with extended follow-up out to 15 years demonstrating a persistent effect.

“This and other similar trials established the benefits of intervention in asymptomatic high-risk subjects, but debate continues over the merits of drug therapy in the wider primary prevention setting,” Mills et al note. “One approach to resolve this issue has been the search for biomarkers that enhance risk prediction.”

In WOSCOPS, plasma cardiac troponin I was measured using the high-sensitivity ARCHITECTSTAT assay (Abbott Laboratories). The current analysis included 3,318 patients who had measurements both at baseline and 1 year.

As seen in prior studies, baseline troponin was an independent predictor of MI or death from coronary heart disease at 5 years when comparing patients with the highest levels (5.2 ng/L or greater) with those with the lowest levels (3.1 ng/L or less; HR 2.27; 95% CI 1.42-3.65).

Patients assigned to pravastatin had a greater reduction in troponin through the first year of follow-up compared with those taking placebo (19% vs 6%; P < 0.001).

The change in troponin concentrations was independently associated with MI or coronary heart disease death at both 5 and 15 years in both treatment arms. In the pravastatin arm, in fact, the risk of that endpoint was five-fold lower in patients who had more than a 27% relative drop in troponin than in those who had more than a 26% increase in troponin levels, despite similar reductions in LDL cholesterol across groups.

“This ability to identify those that have responded to treatment I think is where this is going to change entirely our approach to cardiovascular risk management,” Mills said. “We’ve never had a test that tracks risk in this way.”

An Entirely New Application

Januzzi noted that a recent analysis of the ARIC study—like the current study—showed that serial measurements of high-sensitivity troponin can help predict cardiovascular disease. “These studies are really identifying a clear signal that highly sensitive troponin may very well have utility in community-based testing,” he said.

In addition, he continued, “Some have actually suggested that this application may be even more of a step forward for highly sensitive troponin than its application in patients with chest pain, where there’s definitely benefit . . . in evaluating patients with myocardial infarction. But we use troponins already in that population. This is an entirely new indication and application.”

Mills agreed with Januzzi about the need for prospective studies to identify the best ways to use information from high-sensitivity troponin assays for improving patient care. He noted that WOSCOPS included only men, underscoring the need to validate the findings in women. It would also be useful, he said, to explore other interventions aside from statins.

”In Europe, we’ve been using these tests to guide patient care for a number of years now [in the setting of chest pain], and it’s become rapidly apparent to us that these tests have much wider potential in the risk assessment of our patients,” Mills said.

Todd Neale is the Associate News Editor for TCTMD and a Senior Medical Journalist. He got his start in journalism at …

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  • Ford I, Shah ASV, Zhang R, et al. High-sensitivity cardiac troponin, statin therapy, and risk of coronary heart disease. J Am Coll Cardiol. 2016;68:2719-2728.

  • The study was supported by the British Heart Foundation and by an investigator-initiated research grant from Abbott Laboratories.
  • Mills reports being supported by the Butler Senior Clinical Research Fellowship and Chair awards from the British Heart Foundation and serving as a consultant for Abbott Laboratories, Beckman-Coulter, Roche Diagnostics, and Singulex.
  • Ford reports no relevant conflicts of interest.
  • Januzzi reports being an associate editor for the Journal of the American College of Cardiology but having no involvement with decisions regarding the current study. He reports conducting research with some manufacturers of high-sensitivity troponin assays, but not with Abbott Laboratories.