High-Sensitivity Cardiac Troponin, Statin Therapy, and Risk of Coronary Heart Disease

Abstract

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 low-density lipoprotein cholesterol and no history of myocardial infarction 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 myocardial infarction or death from coronary heart disease (hazard ratio [HR]: 2.3; 95% confidence interval [CI]: 1.4 to 3.7) for the highest (≥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; 95% CI: 0.12 to 0.72 vs. HR: 1.95; 95% CI: 1.09 to 3.49; p < 0.001 for trend) and pravastatin (HR: 0.23; 95% CI: 0.10 to 0.53 vs. HR: 1.08; 95% CI: 0.53 to 2.21; p < 0.001 for trend). Pravastatin reduced troponin concentration by 13% (10% to 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.

Keywords: cardiac troponin; cardiovascular risk; primary prevention; statins.

Graphical abstract

Figure 1

Cumulative Incidence Plot for Primary Outcome of Nonfatal Myocardial Infarction or Death From Coronary Heart Disease, and Secondary Outcomes of Cardiovascular and Noncardiovascular Death Stratified by Quarter of Troponin at Baseline Higher troponin concentrations at baseline were associated with increased risk of coronary heart disease (CHD) at both 5- and 15-year follow-up. Compared to the lowest quarter (≤3.1 ng/l), patients in the highest quarter (≥5.2 ng/l) were at the highest risk for nonfatal myocardial infarction or death from CHD at 5 and 15 years (hazard ratio: 2.27; 95% confidence interval: 1.42 to 3.65; and hazard ratio: 1.54; 95% confidence interval: 1.16 to 2.05, respectively; p < 0.001 for both). Cardiovascular death was also associated with baseline troponin concentration (p < 0.001), but noncardiovascular death was not (p = 0.890).

Figure 2

Percent Change in High-Sensitivity Cardiac Troponin I and LDL Cholesterol Concentrations at 1 Year in Placebo and Pravastatin Groups Line of fit is a Pearson correlation (pravastatin group r = 0.20; p < 0.001). The ellipses are prediction ellipses with 95% confidence interval under the assumption the samples are bivariate normal to display linear correlation. LDL = low-density lipoprotein.

Figure 3

Change in Troponin Concentration at 1 Year Stratified by Treatment Allocation and Nonfatal Myocardial Infarction or Coronary Heart Disease Death at 5 Years (Top) Nonfatal myocardial infarction or death from coronary heart disease (CHD) at 5 years in those taking pravastatin (orange) and placebo (blue) stratified into fifths by change in troponin concentration in the placebo group: Q1 = >26% increase; Q2 = 2% to 25% increase; Q3 = 2% increase to 13% decrease; Q4 = 13% to 27% decrease; Q5 = ≥27% decrease. (Middle) Twice as many participants were in the lowest-risk group (Q5), with >27% reductions in troponin concentration (645 vs. 320 on placebo; p < 0.001), and 30% fewer were in the highest-risk group (Q1) with >26% increase in troponin concentration (223 vs. 320 on placebo; p < 0.001). (Bottom) Using participants in the placebo group whose troponin concentrations were unchanged as a referent (Q3), hazard ratios for the primary outcome were determined for each fifth after adjustment for age, body mass index, heart rate, systolic blood pressure, diastolic blood pressure, high-density lipoprotein and low-density lipoprotein (LDL) cholesterol, symptoms of angina, diabetes, hypertension, family history of premature coronary heart disease, minor electrocardiographic abnormalities, nitrate use, and smoking status. The risk of the primary endpoint in participants taking pravastatin was 5-fold lower in those with the greatest reduction in troponin concentration (hazard ratio: 0.23; 95% confidence interval: 0.10 to 0.53) compared to those with the greatest increase in troponin concentration (hazard ratio: 1.08; 95% confidence interval: 0.53 to 2.21; p < 0.001 for trend) despite similar reductions in LDL cholesterol concentration (22% to 28%).

Central Illustration

Novel Applications of Cardiac Troponins: Stratifying Risk and Guiding Therapy for Prevention of Cardiovascular Disease LDL = low-density lipoprotein.