Elevated troponin linked to mental stress ischaemia

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Some people with heart disease experience a restriction of blood flow to the heart in response to psychological stress. Usually silent (not painful), the temporary restriction in blood flow, called ischaemia, is an indicator of greater mortality risk. Cardiologists at Emory University School of Medicine have discovered that people in this group tend to have higher levels of troponin – a protein whose increased presence in the blood that is a sign of recent damage or stress to the heart muscle– all the time, independently of whether they are experiencing stress or chest pain at that moment.

The results were presented by cardiology research fellow Dr Muhammad Hammadah, at the American College of Cardiology Scientific Sessions as part of the Young Investigator Awards competition. Hammadah works with Dr Arshed Quyyumi and Dr Viola Vaccarino and colleagues at the Emory Clinical Cardiovascular Research Institute.

“Elevated troponin levels in patients with coronary artery disease may be a sign that they are experiencing repeated ischaemic events in everyday life, with either psychological or physical triggers,” Hammadah says.

Doctors test for troponin in the blood to tell whether someone has recently had a heart attack. But the levels seen in this study were lower than those used to diagnose a heart attack: less than a standard cutoff of 26 picograms per milliliter, in a range that only a high-sensitivity test for troponin could detect.

The Emory team studied 587 people with known coronary artery disease who were asked to undergo both a mental stress test, involving public speaking on an uncomfortable topic, and a conventional exercise test on a treadmill. Blood flow to the heart was monitored by SPECT imaging. A few people were unable to exercise at a high heart rate and had to have a pharmacological stress test with a drug that dilates the coronary arteries.

The study found 16% of participants developed mental stress-induced ischemia and 35% developed conventional – either exercise or pharmacological – stress induced ischemia. In the mental stress ischemia group, the average baseline (that is, before stress) levels of troponin were markedly higher than in the rest: 5.9 picograms per milliliter compared to 4.1.

“This is the first study to date showing the effects of mental stress-induced ischemia on a marker of myocardial damage, however subtle that damage may be,” Hammadah says. “Although this difference in troponin levels between those with and without ischemia is small, the difference has been shown by other investigators to predict increased risk of future heart attacks and death.”

The study found that 75% of participants who developed mental stress ischemia developed ischemia in response to exercise as well. Baseline troponin levels were also higher in the exercise-induced ischemia group: 5.4 pg/mL compared to 3.9.
When doctors tested for troponin 45 and 90 minutes after the mental stress test, they detected a small average increase in the mental stress ischemia group that was not statistically significant. The exercise test did result in a significant increase in troponin in the exercise-induced ischemia group. This may be because the exercise test lasts longer and puts more demands on the heart, Hammadah says.

In a separate study also presented at the ACC meeting, Emory investigators have shown that elevated troponin levels can predict mortality over the next few years, even in those without apparent coronary artery disease. The group examined was the Emory Cardiovascular Biobank: patients undergoing cardiac catheterisation, but excluding those who were experiencing a heart attack. In this situation, troponin levels more than 10 pg/mL (the highest quartile) are bad news, meaning a four times higher risk of death in three years, and 11 times higher for those without visible coronary artery disease.

“High hs-TnI may reflect the presence of vulnerable plaques undetectable on angiogram, that are still capable of rupturing and causing death,” the researchers conclude.

Background: High sensitive cardiac troponin I (hs-cTnI) is a marker of myocardial necrosis and elevated levels of hs-cTnI have been associated with exercise in patients with coronary artery disease (CAD) and predict adverse outcomes. Whether hs-cTnI is related to inducible ischemia during mental stress testing remains unknown. We hypothesized that hs-cTnl is associated with mental stress induced myocardial ischemia in CAD patients.
Methods: 587 patients with stable CAD underwent 99mTc sestamibi myocardial perfusion imaging during both mental stress testing, using a public speaking task, and, as a control condition, with conventional (pharmacologic or exercise) stress testing. Ischemia was defined as a new or worsening impairment in myocardial perfusion within each myocardial segment using a 17-segment model. Plasma hs-cTnI (Abbott Inc.) was measured at rest, 45 min and 90 min after the mental stress test, and 30 min after conventional stress testing.
Results: Mean age of the subjects was 63±9 years, 76% were male, 32% diabetic, 31% with prior myocardial infarction, with a median (IQR) hs-cTnI level of 4.3 (2.9-7.3) pg/mL. Overall, 16% (n=94) and 34.8% (n=204) of patients developed myocardial ischemia during mental and conventional stress, respectively. Baseline circulating hs-cTnI levels were higher in patients who developed ischemia during mental stress [5.9 (3.9-8.3) vs 4.1 (2.7-7.0), p<0.001] and during conventional stress [5.4 (3.9-9.3) vs 3.9 (2.5-6.5), p<0.001]. After adjusting for traditional CAD risk factors, patients with high hs-cTnI (≥ median) had more than doubled the odds of mental (OR, 2.4, 95% CI, 1.5 – 4, p<0.001) and conventional (OR, 2.6, 95% CI, 1.8-3.7, p<0.001) stress-induced ischemia. The associations with mental stress and conventional stress ischemia were independent of each other. There were no significant changes in hs-cTnI levels after either stress condition. Conclusion: Myocardial ischemia, both with mental stress and with conventional stress, is associated with higher baseline levels of hs-cTnI. These results suggest that hs-cTnI levels may be a marker of repeated or chronic ischemic burden with both psychological or physical triggers during everyday life.


Abstract 2 Background: High-sensitivity Troponin-I (hs-TnI) as a marker of myocardial injury is predictive of adverse outcomes in patients with coronary artery disease (CAD). Whether the relationship between hs-TnI and outcomes is dependent on underlying CAD severity is unknown. Methods: 2826 patients without AMI (mean age 62, 64% male, 17% Black) who underwent cardiac catheterization were recruited into the Emory Biobank. Plasma hs-TnI was measured at enrollment (Abbott, Chicago IL). CAD severity was quantified using the Gensini score. Cox proportional hazard model was used to analyze the association between quartiles hs-TnI and all-cause death. Results: High hs-cTnI (≥median 4.7 pg/mL) was associated with male gender, Black race, diabetes, hypertension, obstructive CAD (CAD with ≥50% stenosis), lower ejection fraction, and lower HDL levels. In multivariable analysis, subjects in the highest quartile of hs-cTnI (>10 pg/mL) had a 4.0-fold increase in the risk of all-cause death (95%CI [2.7,6.0]) compared to those in the lowest quartile, at a median follow-up period of 3.2 years. Even in the subset of patients without CAD (Gensini=0, n=865), hs-cTnI remained predictive of all-cause death, HR 11.0 (95%CI [4.9, 24.7]) compared to the lowest quartile.
Conclusions: Hs-TnI level is strongly predictive of all-cause death, independent of underlying CAD severity. High hs-TnI may reflect the presence of vulnerable plaques undetectable on angiogram, that are still capable of rupturing and causing death.

Emory University material
Scientific Sessions abstract 1
Scientific Sessions abstract 2

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