Mounting evidence that troponin predicts CVD

A group of 3,300 male participants, randomized to receive pravastatin 40 mg or placebo, were followed for 5 years. Troponin I was measured at baseline and one year later. Authors found that troponin alone can anticipate coronary heart disease; and more importantly its levels were reduced by pravastatin, independently of the LDL lowering effect.

I anticipate troponin measurements to be clinically useful in the future in assessing CVD risk and response to therapy, like statins and PKSK9 inhibitors, especially in high risk individuals (diabetes, chronic kidney disease, prior MI, smoking, etc)

Take home message is nicely emphasized in the diagram below:

GT



J of the American College of Cardiology

WOSCOPS

December 2016

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Background: Cardiac troponin is an independent predictor of cardiovascular mortality in individuals without symptoms or signs of cardiovascular disease. The mechanisms for this association are uncertain, and a role for troponin testing in the prevention of coronary heart disease has yet to be established.

Objectives: This study sought to determine whether troponin concentration could predict coronary events, be modified by statins, and reflect response to therapy in a primary prevention population.

Methods: WOSCOPS (West of Scotland Coronary Prevention Study) randomized men with raised LDL and no history of MIR to pravastatin 40 mg once daily or placebo for 5 years. Plasma cardiac troponin I concentration was measured with a high-sensitivity assay at baseline and at 1 year in 3,318 participants.

Results: 

Baseline troponin was an independent predictor of MI or death from coronary heart disease (HR: 2.3, 1.4-3.7) for the highest (β‰₯5.2 ng/l) versus lowest (≀3.1 ng/l) quarter of troponin (p < 0.001).

There was a 5-fold greater reduction in coronary events when troponin concentrations decreased by more than a quarter, rather than increased by more than a quarter, for both placebo (HR: 0.29, 0.12-0.72 vs. HR: 1.95, 1.09-3.49; p < 0.001 for trend) and pravastatin (HR: 0.23, 0.10-0.53 vs. HR: 1.08, 0.53-2.21; p < 0.001 for trend).

Pravastatin reduced troponin concentration by 13% (10%-15%; placebo adjusted, p < 0.001) and doubled the number of men whose troponin fell more than a quarter (p < 0.001), which identified them as having the lowest risk for future coronary events (1.4% over 5 years).

Conclusions: 

Troponin concentration predicts coronary events, is reduced by statin therapy, and change at 1 year is associated with future coronary risk independent of cholesterol lowering.

Serial troponin measurements have major potential to assess cardiovascular risk and monitor the impact of therapeutic interventions.


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MORE INFORMATION FROM THE ARTICLE:

WOSCOPS (West of Scotland Coronary Prevention Study) was a trial of statin-based LDL-lowering therapy in men ages 45-64 years with raised serum cholesterol concentrations. The trial participants had no history of myocardial infarction and were randomized to receive pravastatin or placebo for an average of 5 years. Treatment reduced the risk of a range of cardiovascular endpoints by about one-third, and extended follow-up over 15 years revealed that the risk reduction persisted long term.

Cardiac troponin is a specific marker of myocardial injury and an independent predictor of cardiovascular mortality in patients with and without cardiovascular disease. Novel high-sensitivity assays can now accurately measure plasma cardiac troponin I concentrations in everyone. Higher troponin concentrations may reflect subclinical coronary artery disease and identify those at greatest risk who could benefit from targeted preventative therapies. The aims of this study were to determine whether cardiac troponin I concentrations could predict future coronary events, be modified by statins, and assess response to therapy in WOSCOPS.

We observed a strongspecific, and independent association between baseline and 1-year change in plasma troponin I concentration and the onset of coronary heart disease over 5 and 15 years in WOSCOPS. Troponin concentrations were reduced by pravastatin therapy, which doubled the number of men whose troponin fell by more than a quarter and were at the lowest risk for future coronary events. Thus, pravastatin treatment caused similar relative risk reductions in each category of troponin change and increased the propensity for troponin concentrations to fall, leading to additive decrements in future risk that appeared to be independent of LDL cholesterol lowering.

We conclude that high-sensitivity cardiac troponin assays can be used to predict future risk of coronary heart disease and to assess response to statin therapy. Therefore, serial troponin measurements appear to have major potential to monitor risk and assess the impact of established or novel therapeutic interventions on future coronary heart disease risk.

The association between troponin and coronary heart disease risk is nonlinear, with an apparent threshold at 5.2 ng/l that identifies those 2 to 3 times more likely to have a coronary event over 15 years. This is consistent with findings from other cohorts using the same assay, in which receiver-operating curve analysis identified a threshold of 6 ng/l in a randomized trial population with established coronary heart disease and 7 ng/l in men who participated in the Scottish Heart Health Study.

Although LDL cholesterol level is currently used to select patients for statin therapy and to monitor treatment response, it was notable that neither baseline nor change in LDL cholesterol predicted future coronary events. Importantly, pravastatin more than doubled the likelihood of a reduction in troponin concentration and this appeared to be independent of LDL cholesterol lowering. 

In addition to reducing serum cholesterol concentrations, statins reduce the levels of other oxidized proteins, improve endothelial nitric oxide bioavailability, and slow progression of atherosclerosis. Our observations suggest the preventative effects of statin therapy are mediated in part by these other mechanisms.

Cardiac troponin I is an independent predictor of coronary heart disease events in middle-aged hypercholesterolemic men without prior myocardial infarction. Troponin concentrations are reduced by statin therapy, and reductions in troponin concentrations are associated with better outcomes independent of LDL cholesterol lowering. These findings suggest that high-sensitivity cardiac troponin has major potential to identify those at greatest risk and to assess their response to interventions for the prevention of coronary heart disease.

Finally, serial high-sensitivity troponin concentrations may represent a new paradigm in the assessment of the efficacy and safety of novel cardiovascular and noncardiovascular therapies.