Cardiovascular events are associated with mental stress-induced ischemia in patients with stable coronary heart disease

1. Cardiovascular deaths, non-fatal myocardial infarctions, and hospitalization due to heart failure occurred more frequently in patients with coronary heart disease (CHD) that experienced mental stress-induced ischemia than those that did not.

2. CHD patients who experienced ischemia with both mental and conventional stress had a similar frequency of coronary events to those who only experienced mental stress-induced ischemia. This in turn was more frequent than those who never experienced ischemia or who only had conventional stress-induced ischemia.

Evidence Rating Level: 2 (Good)

Study Rundown: Physical stress, such as that which occurs during an exercise stress test, can trigger myocardial ischemia in patients with stable coronary heart disease (CHD). This study attempted to identify if mental stress can trigger myocardial ischemia in CHD patients and if mental stress-induced ischemia is associated with future coronary events. The Mental Stress Ischemia Prognosis Study (MIPS) and Myocardial Infarction and Mental Stress Study 2 (MIMS2) had patients with stable CHD or recent myocardial infarction (MI) undergo conventional stress (exercise or pharmacology) and mental stress (public speaking) testing. Ischemia was measured by myocardial perfusion imaging with single-photon emission computed tomography (SPECT). Cardiovascular death, non-fatal MI, and heart failure hospitalizations over the following years were collected by hospital records. Of the 918 pooled participants (age = 60±10 years, 55% White, 40% Black, 34% women), 16% experienced mental stress-induced ischemia, 31% had conventional stress ischemia, and 10% had both. Cardiovascular deaths and non-fatal MIs were more frequent with those that experienced mental stress-induced ischemia than those that did not. Those experiencing ischemia from mental stress were more likely to have had a history of heart failure or reduced ejection fraction and were more likely to go on to have heart failure. Patients who experienced ischemia with both mental and conventional stress had similar numbers of coronary events to those who only experienced mental stress-induced ischemia, which was more events than those patients who never were ischemic or who only experienced conventional stress ischemia. One strength of the study was the individual study and pooled analysis of the data. Additionally, this study corrected for confounders like duration of exercise in its analysis. One limitation in the scope of this study is that the mental stress model used for this study may not necessarily correlate to everyday ambulatory stress-induced ischemia. Additionally, the model used a single mental stress event, but everyday stress may be composed of multiple sequential or cumulative events. As this study was conducted at a single institution, it may not be generalizable to all populations, notably non-White and non-Black populations which were underrepresented. Finally, this study does not identify the feasibility of translating mental stress-induced ischemia testing into clinical practice.

Click to read the study in JAMA

Click to read an accompanying editorial in JAMA

Relevant Reading: Mental Stress–Induced-Myocardial Ischemia in Young Patients With Recent Myocardial Infarction

In-Depth [prospective cohort]: 30-79 years old patients with stable CHD or 18-60 years old patients with a MI within 8 months were enrolled in MIPS and MIMS2, respectively. Patients with comorbidities, or who were pregnant, were excluded. Mental stress was induced by a standardized 3-minute public speaking task to at least 4 people. Physical stress was given via the Bruce protocol. If patients could not exercise, they received pharmacological stress in the form of regadenoson. Ischemia was recorded using SPECT imaging and interpreted by blinded readers. The primary end-point of this study was a sum of cardiovascular death and non-fatal MI, collected via the Social Security Death Index and hospital records. The secondary end-point was heart failure hospitalizations. 5% of MIPS (n=618) and 17% of MIMS2 (n=300) patients experienced mental stress-induced ischemia. 34% and 25% experienced conventional stress-induced ischemia, respectively. 10% of the total study population experience both mental and physical stress-induced ischemia. Those with mental stress-induced ischemia more frequently had a positive history of heart failure or had reduced ejection fraction. MIPS patients were followed for 6.0 years, during which their cohort of 618 patients experienced a total of 90 deaths due to cardiovascular causes or non-fatal MIs and 76 hospitalizations for heart failure. The 300 MIMS2 patients were followed for 4.6 years, during which they experienced 66 cardiovascular deaths or non-fatal MIs and 87 hospitalizations for heart failure. Cardiovascular deaths, non-fatal MIs, and hospitalizations for heart failure were more common in the mental stress-induced ischemia group than the non-mental stress-induced ischemia group (MIPS: 4.9 vs 2.2 per 100 patient-years, hazard ratio [HR] = 2.3, 95% CI = 1.5-3.6); MIMS2: 11.5 vs 3.7 per 100 patient-years, HR = 3.5, 95% CI = 2.1-5.6; pooled: 4.8 vs 2.3 per 100 patient-years, HR = 2.0, 95% CI = 1.1-3.7). The addition of mental stress-induced ischemia improved the association of conventional stress ischemia with coronary events (HR = 2.1, 95% CI = 1.5-3.1). Patients who experienced ischemia with both mental and conventional stress had more coronary events than those who did not (8.1 per 100 patient-years, HR = 3.8, 95% CI = 2.6-5.6) or only experienced conventional stress ischemia (HR = 2.7, 95% CI, 1.7-4.3), but an equal number to those who only experienced mental stress–induced ischemia (HR = 1.9, 95% CI = 0.98-3.6).

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