Cardiac troponin I is an independent predictor of coronary heart disease
High-Sensitivity Cardiac Troponin, Statin Therapy, and Risk of Coronary Heart Disease
Although clinical trials have established the benefits of statin therapy in asymptomatic subjects at high cardiovascular risk [1,2], the debate regarding the benefit/risk balance of drug interventions in the wider primary prevention setting continues [3-5]. In this regard, higher troponin concentrations may reflect subclinical coronary artery disease (CAD) and identify individuals at greatest risk who could benefit from such targeted preventative therapies.
To investigate this, this study evaluated whether cardiac troponin I concentrations at baseline or after 1 year of treatment can predict future coronary events, and be modified by statins. For this, data from the WOSCOPS trial had been used. WOSCOPS randomized 6,595 men ages 45 to 64 years with moderate hypercholesterolemia and no prior history of myocardial infarction (MI) to receive placebo or pravastatin 40 mg/day. The primary outcome was a composite of nonfatal MI and death from coronary heart disease (CHD). In addition, it was assessed whether troponin concentrations can reflect the response to therapy in the WOSCOPS primary prevention population.
- The median troponin concentration at baseline was 4.0 ng/L (IR 3.1-5.2 ng/L). Higher baseline troponin concentrations were associated with increased age, BMI, systolic blood pressure (SBP), and LDL-C concentrations, as well as with a higher prevalence of anginal symptoms and minor ECG abnormalities.
- Higher troponin concentrations at baseline were associated with increased risk of CHD at both 5- and 15-year follow-up. Compared with the lowest quarter (≤3.1 ng/L), patients in the highest quarter (≥5.2 ng/L) were at the highest risk for non-fatal MI or cardiovascular death at 5 and 15 years (HR 2.27, 95% CI: 1.42-3.65 and HR 1.54, 95% CI: 1.16-2.05, respectively, P<0.001 for both).
- The HR for the overall relative treatment effect for the primary endpoint at 5 years was 0.45 (95% CI: 0.32-0.65, P<0.001) and for the outcome of coronary death or hospitalised MI at 15 years was 0.68 (95% CI: 0.56-0.83, P<0.001).
- At 15 years, the absolute risk reduction in non-fatal MI or cardiovascular death was greatest in the highest quarter (9.0%) compared to the lower three quarters of baseline troponin (2.6-3.0%).
- At 1 year, participants taking pravastatin had a greater reduction in troponin concentration (19%, 95% CI: 17-20%) compared with those receiving placebo (6%, 95% CI: 4-8%, P<0.001).
- The absolute change in troponin concentration from baseline till 1 year with pravastatin was 2.0 ng/L (IR 1.2-2.8 ng/L, P<0.001). Change in troponin concentration on treatment correlated weakly with change in LDL-C (r=0.20, P<0.001).
- After adjustment for multiple variables the change in troponin concentration at 1 year was an independent predictor of non-fatal MI or cardiovascular death at both 5 and 15 years in both treatment arms.
- The risk of the primary endpoint in participants on pravastatin was 5-fold lower in those with the greatest reduction in troponin concentration (HR 0.23, 95% CI: 0.10-0.53) compared to those with the greatest increase in troponin concentration (HR 1.08, 95% CI: 0.53-2.21, P<0.001 for trend) despite similar reductions in LDL-C (22-28%).
- Compared to placebo, participants taking pravastatin with the greatest reduction in troponin at 1 year (highest quarter ≤38% reduction vs. lowest quarter >3% increase) had the largest reduction in cardiovascular events (HR 0.21, 95% CI: 0.08-0.52 and HR 0.82, 95% CI: 0.51-1.32, respectively, P=0.002). The reduction in events was similar across quarters of change in LDL-C (P=0.823).
Cardiac troponin I at baseline is an independent predictor of CHD events and concentrations reduce with statin therapy. Also, reductions in troponin concentrations after 1 year are associated with better outcomes independent of LDL-C levels. These findings suggest that high-sensitivity cardiac troponin may be useful for the identification of individuals at greatest risk, as well as for the assessment of their response to interventions for the prevention of CHD.
Editorial comment 
Jaffe and Wright comment on the relatively unexplored potential usefulness of hscTn assays in the assessment of long-term cardiovascular risk: ‘The hscTn findings are analogous to the situation with natriuretic peptides where higher, albeit normal, values have been used to identify those at risk for heart failure. Importantly, interventions in response to these minor increases improve outcomes.’ … ‘Ford et al. now provide provocative new insights into this fertile environment.’…’Neither baseline low-density lipoprotein cholesterol (LDL-C) nor its change over the first year was associated with adverse outcomes. Instead, outcomes tracked with changes in hscTn values.’ …. ’The values reported by Ford et al. are on the margin of the biological variation data assuming that biological variation does not increase to greater values over the course of 1 year. Thus, repeated testing as suggested by the authors or a longer period of observation before the second sample may be necessary.” They also point out that the data of Ford et al. suggests that possible other mechanisms besides lipid-related ones, may be important for patients receiving statins for primary prevention and they conclude: ‘In the long run, it should be possible to determine how to deploy hscTn analysis to allow values to be clinically relevant, including helping to assess those who may benefit from statin therapy. For now, these hscTn data open new vistas to begin to explore novel mechanisms to understand how to better use this important treatment. Furthermore, hscTn analysis has the potential to revolutionize our ability to study and improve primary prevention.’