Troponin Testing Presents Problems in Kidney-Impaired People

High-sensitivity cardiac troponin I (hs-cTnI) assays left much to be desired for their performance among people with kidney impairment in a secondary trial analysis.

These newer assays flagged sixfold more patients as kidney function declined from an eGFR of at least 90 to less than 30 mL/min/1.73 m² (10% vs 66%, P<0.001), reported Nicholas Mills, MD, of the University of Edinburgh, and colleagues.

However, the proportion with acute type 1 myocardial infarction (MI) dropped precipitously across that same range of renal function, from 74% to 35% (P<0.001), they noted in a research letter in JAMA Internal Medicine.

In addition, the increase in identification did not correlate with better outcomes. Subsequent type 1 or 4b (more than 24 hours after percutaneous coronary intervention) MI or cardiovascular death were equally common at 1 year for patients treated before and after clinical use of the high-sensitivity test both with kidney impairment (25% vs 24%; adjusted HR 1.00, 95% CI 0.85-1.18) and without it (13% vs 11%; adjusted HR 0.89, 95% CI 0.73-1.08).

Patients reclassified as having elevated troponin with the more sensitive versus conventional assay also didn’t have better outcomes.

“The reasons for this are complex,” Mills and colleagues suggested. “Two-thirds of patients with kidney impairment and elevated hs-cTnI concentrations had a diagnosis other than type 1 myocardial infarction. In the absence of evidence from randomized trials, there is little guidance to inform clinical decisions for this heterogeneous group.”

Still, they concluded that hs-cTnI is effective at enabling the early rule out of MI in patients with kidney impairment.

The stakes for accurately ruling out MI without increasing unnecessary testing and admissions are incredibly high, both clinically and medicolegally, noted Keith Hemmert, MD, and Benjamin Sun, MD, MPP, both of the University of Pennsylvania in Philadelphia, in an accompanying editorial.

It’s not operationally feasible to use a conventional assay for one population and high-sensitivity assay for others, they pointed out.

“Without a clearer understanding of elevated hs-cTn values in patients with kidney impairment and alternative risk stratification tools that are easily implemented in the ED environment, such as a modified HEART score adapted to this population, the clinical and medicolegal risks associated with missed myocardial injury still favor a conservative approach of increased testing and closer monitoring for those with elevated hs-cTn results,” Hemmert and Sun argued.

Even for kidney-impaired patients with elevated troponin who do have type 1 MI, Mills and colleagues noted that “the available evidence is largely extrapolated from clinical trials in patients with broadly normal kidney function. Further research is therefore needed to convince clinicians of the safety and efficacy of these treatments in patients with kidney impairment.”

They analyzed data from High-STEACS (High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome), a stepped-wedge, cluster-randomized clinical trial of 46,927 consecutive patients with suspected acute coronary syndrome across 10 hospitals.

Hospitals tested each patient with suspected acute coronary syndrome with both conventional and hs-cTnI assays, but the centers were randomized to have the less sensitive assay’s results suppressed early or late during the study period.

Overall, hs-cTnI concentrations were elevated in 10,111 patients (22%), of whom 42% had kidney impairment.

“A limitation of this study is that it was not possible to discriminate between acute and chronic kidney injury,” the researchers noted. “While both are associated with cardiovascular risk, these conditions are distinct.”