Troponin release during sepsis linked to early—but not late—death risk

Myocardial injury in sepsis patients was associated with a heightened risk of short-term mortality but not one-year mortality, according to a study in Circulation: Cardiovascular Quality and Outcomes.

But despite the leveling off of death risk, these patients were at a 25 percent increased risk of developing new or worsening cardiovascular disease (CVD) within one year of hospital admission, reported lead author Jos F. Frencken, MD, and colleagues.

Frencken et al. studied 1,124 patients with sepsis who were admitted to two Dutch intensive care units (ICUs) between 2011 and 2013. They tested high-sensitivity cardiac troponin I (hs-cTnI) levels each of the first four days and considered any elevated measurement an indicator of myocardial injury.

Sixty percent of patients had elevated troponin levels on the first day of their ICU stay and an additional 7 percent had elevated levels at some other point within the first four days. Compared to patients without high hs-cTnI levels, they demonstrated a 72 percent increased risk of all-cause death within 14 days but not after that point.

“Regardless of whether this association is causal or merely prognostic, troponin release during sepsis could act as an important alarm signal for physicians, identifying patients at high risk of cardiovascular complications, and future studies should evaluate whether they may benefit from preventative strategies,” the researchers wrote.

Although previous studies have noted a mortality increase after sepsis, Frencken and colleagues pointed out this prior evidence was limited by small sample sizes, single troponin measurements, and a lack of long-term follow-up or proper adjustment for confounders.

One novel finding of their study, they said, is the nonlinear relationship between troponin levels and mortality risk.

“Prior studies either categorized troponin concentrations or simply assumed a linear outcome relation, and these approaches may lead to loss of information or even erroneous conclusions,” they wrote.

For this cohort, troponin levels above 100 nanograms per liter didn’t pose a significant risk difference versus concentrations between 26 and 100 ng/L.

“Perhaps high hs-cTnI concentrations no longer accurately reflect deterioration of cardiac function, or perhaps active medical treatment blunts the effects of underlying myocardial dysfunction,” the authors wrote. “Nonetheless, increased short-term mortality has now repeatedly been reported across various clinical settings, and it is thus essential that future studies attempt to uncover the underlying pathogenesis of myocardial injury during sepsis. This may lead to therapies (such as heart rate control or antiplatelet therapy) aimed at improving (short-term) survival.”

To evaluate the onset of new or worsening CVD after hospital admission, the researchers linked patients to insurance information for medications. However, they acknowledged using CVD prescriptions as a proxy for actual CVD may allow for some cases to be misclassified.