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Elevated Troponin Linked to Higher All-Cause Mortality

High levels of cardiac troponin could serve as a forewarning of heightened susceptibility to death from any cause within a span of approximately 2 years, irrespective of any pre-existing or suspected cardiovascular disease, according to a new study.

Although high cardiac troponin levels are often seen in hospital patients who don’t have specific signs of a heart attack, the clinical significance has remained unclear, researchers said. The results of the new prospective observational study, published in the journal, Heart, could suggest that cardiac troponin has a role as a more general indicator of medium-term survival, they proposed.

To explore this in more depth, the research team, led by the University of Southampton, set out to assess the relationship between medium-term mortality and troponin concentration, regardless of whether there was a clinical indication for testing.

They tracked the survival of 20,000 consecutive inpatients and outpatients aged over 18 years who had undergone a troponin blood test for any reason between June and August 2017 at University Hospital Southampton NHS Foundation Trust. 

Almost one in ten (8.6%) of the cohort had been tested for troponin levels at the request of their supervising clinician, with the remainder (91.4%) only having had the assay performed as part of the study. Nearly half (46.7%) were outpatients, almost a quarter (24.7%) were inpatients, and 28.5% were emergency care patients. Mortality data was obtained via NHS Digital.

High Troponin Level Associated with Increased Mortality Risk

The median age of patients was 61 (range 43-74), and over half (52.9%) were women.

After accounting for age, sex, hospital location, and kidney function, the researchers found that an abnormally high cardiac troponin level was independently associated with a 76% heightened risk of death (HR 1.76, 95% CI 1.65 to 1.89), not only from cardiovascular disease, but also from other causes. The most common cause of death was cancer (46.3%), followed by cardiovascular disease (12.8%).

"Patients were nearly four times as likely to die if their cardiac troponin test result was high (44.8%) as those whose test results fell within the normal range (12.4%)," highlighted the authors.

Landmark analysis, excluding deaths within 30 days — a parameter used to define the likelihood that this was associated with the reason for their hospital stay — showed the link between cardiac troponin and heightened risk of death persisted. 

Troponin concentration out to a median follow up of 809 days was independently associated with medium-term cardiovascular and non-cardiovascular mortality, the authors pointed out, which they said indicated that the association "wasn’t driven purely by a short-term risk of death". 

In addition, the relationship persisted irrespective of the setting — outpatient, inpatient, or emergency department — where the cardiac troponin was taken. This demonstrated that cardiac troponin was a marker of prognosis for populations of stable patients in outpatients, acutely unwell patients, and patients with specific disease processes, both cardiovascular and non-cardiovascular.

Troponin a Marker of Medium-Term Prognosis

The authors stressed that as an observational study, they were unable to draw firm conclusions about cause and effect. They also acknowledged some limitations of the study, which included that the data came from just one hospital, and that potentially influential factors, such as personal background information and concurrent conditions, weren’t known.

It seemed "biologically implausible" that cardiac troponin level itself posed a heightened risk of death, and more likely that it represented a "broad spectrum" of health issues, including those as yet undiagnosed, which increased the risk, the authors proposed. The findings also suggested that cardiac troponin may have a "more general role as a marker of medium-term prognosis" outside heart attack, they said.

However, further research was required to confirm the findings across multiple settings, they emphasised, and to evaluate whether any intervention could adjust the increased risk demonstrated.

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