Myocardial ischemia during mental stress: role of coronary artery disease burden and vasomotion

Abstract

Background: Mental stress-induced myocardial ischemia (MSIMI) is associated with adverse prognosis in patients with coronary artery disease (CAD), yet the mechanisms underlying this phenomenon remain unclear. We hypothesized that compared with exercise/pharmacological stress-induced myocardial ischemia (PSIMI) that is secondary to the atherosclerotic burden of CAD, MSIMI is primarily due to vasomotor changes.

Methods and results: Patients with angiographically documented CAD underwent 99mTc-sestamibi myocardial perfusion imaging at rest and following both mental and physical stress testing, performed on separate days. The severity and extent of CAD were quantified using the Gensini and Sullivan scores. Peripheral arterial tonometry (Itamar Inc) was used to assess the digital microvascular tone during mental stress as a ratio of pulse wave amplitude during speech compared with baseline. Measurements were made in a discovery sample (n = 225) and verified in a replication sample (n = 159). In the pooled (n = 384) sample, CAD severity and extent scores were not significantly different between those with and without MSIMI, whereas they were greater in those with compared with those without PSIMI (P < 0.04 for all). The peripheral arterial tonometry ratio was lower in those with compared with those without MSIMI (0.55 ± 0.36 versus 0.76 ± 0.52, P = 0.009). In a multivariable analysis, the peripheral arterial tonometry ratio was the only independent predictor of MSIMI (P = 0.009), whereas angiographic severity and extent of CAD independently predicted PSIMI.

Conclusions: The degree of digital microvascular constriction, and not the angiographic burden of CAD, is associated with MSIMI. Varying causes of MSIMI compared with PSIMI may require different therapeutic interventions that require further study.

Keywords: coronary disease; ischemia; mental stress; vasoconstriction.

Figure 1.

Angiographic burden of coronary artery disease stratified by ischemia status during mental and/or physical stress. P‐value compares the stated group with the group of patients without any ischemia (MSIMI [−]/PSIMI [−]). Panels A and B compare the angiographic severity of coronary artery disease between the groups, assessed by the Gensini and Sullivan coronary scoring systems, respectively. Panel C compares the angiographic extent of coronary artery disease defined by the Sullivan coronary scoring system. MSIMI indicates mental stress–induced myocardial ischemia; PSIMI, exercise or pharmacologic stress–induced myocardial ischemia.

Figure 2.

Digital microvascular response during the different phases of the mental stress task assessed as peripheral arterial tonometry (PAT) ratio in patients with and without mental stress–induced myocardial ischemia (MSIMI). The PAT ratio was calculated as the ratio of pulse wave amplitude during the specified phase of the mental stress task compared with the resting baseline. P‐value compares the PAT ratio at each phase between subjects with and without MSIMI.

Figure 3.

Digital microvascular response stratified by ischemia status during mental and/or physical stress. P‐value compares the stated group to the group of patients without any ischemia (MSIMI [−]/PSIMI [−]). MSIMI indicates mental stress–induced myocardial ischemia; PSIMI, exercise or pharmacologic stress–induced myocardial ischemia.

Figure 4.

Receiver operating characteristic (ROC) curves for prediction of physical stress–induced myocardial ischemia. The C‐statistic for a model predicting physical stress–induced myocardial ischemia (PSIMI) based on traditional risk factors and CAD severity was 0.66. With the addition of the PAT ratio during mental stress, the model improved to 0.70 (P<0.001). ACE indicates angiotensin‐converting enzyme; CABG, coronary artery bypass graft surgery; CAD, coronary artery disease; MI, myocardial infarction; PAT, peripheral arterial tonometry; PCI, percutaneous coronary intervention.

Figure 5.

Receiver operating characteristic (ROC) curves for prediction of mental stress–induced myocardial ischemia (MSIMI). The C‐statistics using the PAT ratio during the mental stress task improved the risk prediction of MSIMI) based on traditional risk factors and CAD severity from 0.62 to 0.72 (P<0.001). ACE indicates angiotensin‐converting enzyme; CABG, coronary artery bypass graft surgery; CAD, coronary artery disease; MI, myocardial infarction; PAT, peripheral arterial tonometry; PCI, percutaneous coronary intervention.