Response by Lowry et al to Letter Regarding Article, “Influence of Age on the Diagnosis of Myocardial Infarction”

Abstract

We wish to thank Chen et al and Gibson et al for their thoughtful appraisal of our recent article, in which we evaluated the impact of age on the diagnostic performance of high-sensitivity cardiac troponin for myocardial infarction. 1 Chen et al highlight the importance of considering renal function when interpreting elevated cardiac troponin concentrations in older people. Two of every 5 patients with suspected myocardial infarction and renal impairment have cardiac troponin concentrations above the 99th centile upper reference limit. 2 This is thought to reflect underlying coronary or structural heart disease rather than impaired renal clearance. 3 We agree that the relationship between age and declining renal function is likely to partly explain the lower specificity of cardiac troponin in older people. In the same study population, we have previously demonstrated the lower specificity of an elevated cardiac troponin in patients with renal impairment compared with those without (70.9% [67.5-74.2] versus 92.1% [91.2-93.0]). 2 The authors' observations support our primary conclusion that age-specific thresholds are unlikely to improve the diagnostic accuracy of myocardial infarction in older populations, as such blunt transformations do not capture the complexity of the relationship between troponin, aging, and the development of comorbidities, including renal disease.Gibson et al highlight that there is more to a diagnosis of myocardial infarction than raised cardiac troponin concentrations. We fully agree. We adjudicated the diagnosis in 48 282 consecutive patients on the basis of all clinical information, investigations, and serial high-sensitivity cardiac troponin measurements to provide confidence in the distinction of myocardial infarction from injury. 1 We would highlight that, in patients with suspected acute coronary syndrome, the use of a presentation cardiac troponin concentration to identify patients at high or low probability of myocardial infarction, facilitating early rule-out or rule-in, is an established and internationally recognized component of diagnostic pathways.

Challenges and opportunities for biomarker discovery to predict imminent myocardial infarction

“…Atherosclerotic plaque rupture, the most common precursor of myocardial infarction, typically occurs in the hours or days prior to the onset of symptoms [3]. This is in stark contrast to the six-month interval between blood sampling and myocardial infarction evaluated here.…”