GLASGOW and EDINBURGH, SCOTLAND — In a study of middle-aged men with hypercholesterolemia who were randomized to pravastatin or placebo, those whose cardiac troponin subtype I (troponin I) levels dropped as opposed to increased at 1 year were much less likely to have a nonfatal MI or die from coronary heart disease (CHD) during follow-up.
Moreover, in this analysis of data from the West of Scotland Coronary Prevention Study (WOSCOPS), change in troponin I levels predicted future coronary events independent of cholesterol lowering.
These preliminary findings are being described as "exciting," "provocative," and even "revolutionary."
"Serial troponin measurements have major potential to assess cardiovascular risk and monitor the impact of therapeutic interventions," Dr Ian Ford (University of Glasgow, Scotland) and colleagues conclude, in their study published online December 19, 2016 in the Journal of the American College of Cardiology.
"These results are tremendously exciting and could revolutionize the way we manage patients at risk of coronary heart disease," senior author Dr Nicholas L Mills (University of Edinburgh, Scotland) told heartwire from Medscape in an email. "While blood cholesterol levels and blood pressure are important and associated with the risk of developing heart disease, troponin is a direct measure of injury to the heart," he added. In the future, cardiac troponin I tests may help doctors identify apparently healthy individuals who have silent heart disease.
Ford et al "provide provocative new insights," Drs Allan S Jaffe and R Scott Wright (Mayo Clinic, Rochester, MN) echo in an accompanying editorial. "As opposed to what one might have anticipated, these investigators found no association with changes in LDL cholesterol but a strong relationship to changes in [high-sensitivity] hs-troponin I results."
This "counterintuitive" finding doesn't take away from the importance of LDL-cholesterol reduction with statin therapy or definitively demonstrate that the benefit of statins is mainly via mechanisms other than lowering LDL cholesterol, Dr John W McEvoy (Johns Hopkins University School of Medicine, Baltimore, MD), who was not involved with this study, cautioned to heartwire in an interview.
But he too agrees that "nevertheless, this is very exciting data . . . and does position this biomarker as a potential dynamic marker of . . . change in risk over time and overall cardiovascular well-being."
Potential "Exciting" New Biomarker for Primary Prevention
The hs-troponin I assay was introduced into clinical practice in 2013 and is widely used worldwide outside of the US (where it is not yet approved) to diagnose MI, Mills noted. However, it is unclear whether this test could play a role in primary prevention of CHD.
The researchers aimed to investigate whether troponin I levels could predict future coronary events, be modified by statins, or reflect the response to statin therapy in participants in WOSCOPS.
The trial randomized 6595 men who were 45 to 64 years old with moderate LDL cholesterol and no prior MI to receive placebo or 40-mg/day pravastatin.
Now, 20 years later, 3318 participants had sufficient serum from blood samples taken at baseline and 1 year to be able to measure troponin I levels, using the Architect Stat high-sensitivity troponin I assay (Abbott Laboratories).
The test has a limit of detection of 1.2 ng/L and an upper reference limit (99th percentile value) of 34 ng/L in men.
The participants were divided into quartiles of troponin-I levels: <3.1 ng/L, 3.2–3.9 ng/L, 4.0–5.1 ng/L, and >5.2 ng/L. Only seven participants had undetectable levels, and 48 participants (1.5%) had values above 34 ng/mL.
Compared with participants in the lowest troponin I quartile, those in the highest quartile had a 2.3-fold higher risk of nonfatal MI or death from CHD at 5 years (HR 2.27, 95% CI 1.42–3.65); they had a 1.5-fold higher risk of these outcomes at 15 years (HR 1.54, 95% CI 1.16–0.05; P<0.001 for both).
Participants who received pravastatin or placebo had a 5-fold greater reduction in coronary events when their troponin concentrations decreased by more than a quartile, rather than increased by more than a quartile.
Pravastatin reduced troponin concentration by 13% and doubled the number of men whose troponin fell more than a quartile (P<0.001); these men had the lowest risk for future CHD (1.4% over 5 years).
Need Further Study, FDA Approval of hs-Troponin Assays
The findings in the current study are consistent with those that McEvoy and colleagues reported from their observational study based on data from ARIC. That study showed that patients who had increases in cardiac troponin subunit T (troponin T) levels were at increased risk of death, CHD, and especially heart failure, McEvoy noted.
"It is likely that the effectiveness of interventions, such as exercise or blood-pressure–lowering therapies, could also be monitored using serial troponin testing, but further research is needed to formally evaluate this," Mills observed.
Moreover, before this approach could be applied in clinical practice, prospective studies are needed to determine whether it is possible to consistently quantify small changes in cardiac troponin I concentration in response to treatment in individuals.
The researchers plan to continue this line of research to answer some of these questions. The British Heart Foundation has recently provided funding for a 5-year research program at the University of Edinburgh, Mills divulged, "to generate the evidence now required to provide clinicians with guidance as to how to use high-sensitivity cardiac troponin testing in the risk assessment of patients for the prevention of coronary heart disease."
"High-sensitivity cardiac troponin analysis has the potential to revolutionize our ability to study and improve primary prevention," Jaffe and Wright write. "Now it is time for us to get them into use in the United States."
The study was supported by a special project grant from the British Heart Foundation and by an investigator-initiated research grant from Abbott Laboratories. Mills is supported by awards from the British Heart Foundation. Disclosures for the coauthors are listed in the paper. Jaffe is a consultant for Roche, Beckman, Siemens, Abbott, Alere, NeurogenomeX, Sphingotec, Outpost Medical, theheart.org, and Novartis. Wright is a consultant for Sanofi, Pfizer, AstraZeneca, the Medicines Company, and Boehringer Ingelheim. McEvoy reports receiving National Institutes of Health grant funding.
Heartwire from Medscape © 2016 Medscape, LLC
Cite this: Drop in Troponin I, Not Cholesterol, Predicts CHD Risk in WOSCOPS - Medscape - Dec 21, 2016.