Implications of lowering threshold of plasma troponin concentration in diagnosis of myocardial infarction: cohort study

The consensus statement on the universal definition of myocardial infarction (MI) recommends that an increase in plasma troponin concentration above the 99th centile of a normal reference population is used to confirm the diagnosis. Despite this guidance, lowering the diagnostic threshold for troponin remains a highly contentious issue, with clinicians uncertain as to whether the benefits of improved sensitivity will outweigh problems that might arise from reduced specificity.

The Global Task Force for the Universal Definition of Myocardial Infarction and the National Academy of Clinical Biochemistry recommend the 99th centile as the diagnostic threshold where assay precision can be shown with a coefficient of variation of ≤ 10% at this concentration. Currently few assays are able to meet these precision criteria at the diagnostic threshold, but the authors of this study¹ recently showed that the introduction of a sensitive troponin I assay halved the rate of recurrent MI and death in patients presenting with suspected acute coronary syndrome and a small increase in plasma troponin concentration.

A recent statement from the Biochemistry Group of the Global Task Force for the Universal Definition of Myocardial Infarction represents a change in position, with the recommendation that the 99th centile be adopted as the diagnostic threshold for current sensitive troponin assays irrespective of whether or not the coefficient of variation is less than 10% at this concentration. 

This recommendation is based in part on modelling exercises that suggest assays with imprecision of up to 20% do not affect diagnostic accuracy. To determine the potential impact of this change in guidance on clinical practice, Mills et al have evaluated the relation between plasma troponin concentration, assay precision and clinical outcomes in a cohort of consecutive patients admitted to hospital with suspected acute coronary syndrome.

About 2,092 consecutive patients admitted with suspected acute coronary syndrome were stratified with a sensitive troponin I assay into three groups (< 0.012, 0.012-0.049, and ≥ 0.050µg/L) based on the 99th centile for troponin concentration (0.012µg/L; coefficient of variation 20.8%) and the diagnostic threshold (0.050µg/L; 7.2%).

The main outcome measure was one-year survival without events (recurrent MI, death) in patients grouped by troponin concentration.

Troponin I concentrations were < 0.012µg/L in 988 patients (47%), 0.012-0.049µg/L in 352 patients (17%) and ≥ 0.050µg/L in 752 patients (36%). Adoption of the 99th centile would increase the number of people receiving a diagnosis of MI from 752 to 1,104: a relative increase of 47%. 

At one year, patients with troponin concentrations of 0.012-0.049µg/L were more likely to be dead or readmitted with recurrent MI than those with troponin concentrations < 0.012µg/L (13% versus 3%, p < 0.001; odds ratio 4.7, 95% confidence interval 2.9 to 7.9). Compared with troponin ≥ 0.050µg/L, patients with troponin 0.012-0.049µg/L had a higher risk profile but were less likely to have a diagnosis of, or be investigated and treated for, acute coronary syndrome.

The authors conclude that lowering the diagnostic threshold to the 99th centile and accepting greater assay imprecision would identify more patients with acute coronary syndrome at risk of recurrent MI and death but would increase the diagnosis of MI by 47%. 

It remains to be established whether reclassification of these patients and treatment for MI would improve outcome.

Reference

1. Mills N, Lee KK, McAllister DA et al, BMJ 2012; 344:31533