New Evidence for Personalized Medicine with Cardiac Troponins
JACC in a Flash | Higher levels of high-sensitivity troponin (hsTnT) have been associated with an increased risk of all-cause mortality; a high percentage of patients with coronary heart disease (CHD) have been shown to have detectable levels of hsTNT, presumably putting them at high risk for mortality or adverse events. However, no studies have investigated the change in troponin levels for prediction of outcomes in a broad population of CHD patients who are clinically stable following an MI or unstable angina.
A team of investigators, led by Harvey D. White, MD, investigated the predictive role of troponins for long-term outcomes in patients with stable coronary heart disease enrolled in the Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) study. LIPID randomized these patients to either placebo or pravastatin 40 mg/day. Using an hsTnT assay, troponin I (TnI) levels were measured at baseline and at 1 year after MI or unstable angina.
Patients were categorized into tertiles according to baseline TnI: <0.006ng/ml (n = 2,967), ≥0.006-0.018ng/ml (n = 2,436), and ≥0.018ng/ml (n = 2,460). Notably, levels of TnI >0.04 ng/ml (99th percentile) were found in 8.4% of patients.
At 1 year, TnI increased in 23% of patients, was unchanged in 51.3%, and decreased in 25.7%. Baseline TnI levels were strongly related to the primary outcome (CHD event death; p < 0.001), as well as other CVD outcomes, including non-fatal MI, stroke, and heart failure. Pravastatin was responsible for reducing TnI levels by 0.003 ng/mL versus placebo (p = 0.002), but was deemed "clinically unimportant," by the investigators.
Ultimately, adding troponin I to the baseline risk model resulted in a modest improvement in the net reclassification index of 4.76%, and TnI levels added to the LIPID risk model remained an independent predictor of CHD death and MI after the addition of biomarkers BNP and hsCRP (TABLE).
Overall, troponin levels may identify patients at high global cardiovascular risk because baseline levels predicted CHD death, MI, heart failure, stroke, and total mortality," Dr. White and colleagues concluded. Further research is needed to determine whether measurement of baseline levels and change in TnI could guide therapy, for example by prompting more intensive risk factor modification."
While the results of the LIPID study are promising, Torbjørn Omland, MD, PhD, MPH, wrote in an accompanying editorial, "the clinical benefit of using cardiac troponins as a management criterion in [low-risk patients with stable coronary disease] remains unproven. Prospectively and intelligently designed trials testing interventions that are both pathophysiologically linked to cardiac troponin production and are effective in reducing risk associated with such pathophysiology in stable coronary artery disease will be required to definitively answer the decisive question of whether cardiac troponin measurements can translate into improved patient management."
White HD, Tonkin A, Simes J, et al. J Am Coll Cardiol. 2014;63:345-54.
Omland T. J Am Coll Cardiol. 2014;64:355-7.
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