Cardiac Troponin Concentration Independently Associated With Medium-Term Mortality

Cardiac troponin (cTn) concentration is independently associated with medium-term cardiovascular and noncardiovascular mortality, especially among patients tested for cTn I (cTnI) without clinical indication, according to study findings published in Heart.

Increasing sensitivity of the cTnI assays has led to increasing evidence that elevated cTn concentrations are associated with adverse prognosis in multiple chronic conditions outside the context of type 1 myocardial infarction. Therefore, investigators sought to evaluate the relationship between cTnI concentration and medium-term mortality regardless of clinical indication for testing for cTnI.

They conducted a prospective observational study that included 20,000 consecutive in-hospital and outpatient patients from the original CHARIOT study (ClinicalTrials.gov Identifier: NCT03047785). CHARIOT included 20,000 unselected patients (unaware they were involved in a study as per study protocol) aged 18 years or older who received a blood test for any reason at the University Hospital Southampton NHS Foundation Trust from the end of June 2017 almost to the end of August 2017. Overall, patients had a median age of 61 (IQR, 43-74) years and 52.9% were women.

Overall, supervising clinicians requested cTnI assay in 1718 patients (8.6%). The assay was performed as part of the CHARIOT study in the remaining 18,282 patients with their first blood test, and the result was not released to the patient or their clinical team.

Researchers in the CHARIOT study used the Beckman Coulter Access AccuTnI+3 assay (Beckman Coulter, Brea, California, USA) which approaches the level of sensitivity required for a high sensitivity assay but does not meet criteria as defined by the International Federation of Clinical Chemistry.

Across a median of 809 days, 14.1% of patients died (median age, 77 years). Among those who died, 55.3% were men. Among the 1718 patients for whom cTnI assay was requested, 210 died (7.4% of the 2825 who died overall). The most common causes of death were malignancy (46.3%), cardiovascular mortality (12.8%), and old age (7.8%).

Patients with cTnI concentration above the upper limit of normal (ULN; manufacturer’s recommended upper limit; n=1085) experienced significantly higher mortality (45.3% vs 12.3%; P <.001 log rank). The log₁₀ cTnI concentration was independently associated with mortality in multivariable Cox regression analysis (hazard ratio, 1.76; 95% CI, 1.65-1.88). Regression analysis included sex, age, estimated glomerular filtration rate, clinical location (inpatient, outpatient, emergency department), and whether cTnI was requested by clinical team.

Study limitations include the lack of extensive demographic and comorbidity data that may include important variables known to affect cTn concentrations. Additionally, the assay used for testing as a high sensitivity assay does not meet the accepted qualifications as a true high sensitivity assay.

“In a cohort of 20,000 patients, the majority of whom had cTn testing performed without a clinical indication, a cTn concentration was independently associated with mortality out to a median of 809 days for both cardiovascular and non-cardiovascular causes,” the investigators wrote. “Landmark analysis demonstrated that this relationship was not driven purely by short-term mortality. In addition, those patients who had cTn requested for clinical reasons had a lower hazard mortality.”

Disclosure: This research was supported by Beckman Coulter. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.