Impacts of depression and emotional distress on cardiac disease

DEPRESSION AND MENTAL STRESS–INDUCED MYOCARDIAL ISCHEMIA

Of the numerous proposed pathophysiologic mechanisms explaining the adverse impact of depression on cardiac diseases, I would like to emphasize the clinical and research significance of mental stress–induced myocardial ischemia (MSIMI).

Myocardial ischemia is an important measure of the clinical manifestation of IHD. Ambulatory electrocardiographic monitoring yielded the insight that myocardial ischemia occurs frequently and transiently during daily living; it usually occurs in the context of a lower heart rate, is asymptomatic or silent, does not necessarily involve high-intensity physical activity, and commonly occurs in conjunction with increased negative emotions.^8,9

Over the past 2 to 3 decades, several laboratories have consistently demonstrated that mental stress testing elicits myocardial ischemia in patients with documented IHD.^8,10,11 The prevalence of MSIMI, defined by wall motion abnormality and/or significantly reduced ejection fraction, is comparable to that of exercise-induced myocardial ischemia in the laboratory setting.¹²

Differences from exercise-induced ischemia

MSIMI differs from exercise-induced ischemia in several notable ways. It occurs silently most of the time and rarely results in ischemic electrocardiographic changes. Mental stress induces greater frequency and severity of left ventricular dysfunction. Furthermore, mental stress testing causes a greater diastolic blood pressure response but a modest increase in heart rate, whereas exercise testing elicits a smaller elevation in diastolic blood pressure but a several-fold increase in heart rate.

A key mechanism: Transient coronary vasoconstriction

One of the underlying mechanisms by which mental stress induces myocardial ischemia in susceptible patients is transient coronary vasoconstriction. Yueng et al¹³ used an intracoronary Doppler catheter to assess the change in coronary blood flow during mental stress testing and endothelium-dependent vasodilation in a group of patients with IHD. Coronary artery responses varied from 38% constriction to 29% dilation, with changes in coronary blood flow ranging from a decrease of 48% to an increase of 42%. Interestingly, although it has been proposed that mental stress triggers release of catecholamines that induce coronary vasoconstriction, the direction and magnitude of the change were not predicted by changes in heart rate, blood pressure, or plasma norepinephrine level. The change in coronary perfusion was correlated, however, with the response to acetylcholine infusion.¹³

Dakak et al¹⁴ showed that while the coronary microcirculation dilated during mental stress testing in individuals without IHD, it failed to dilate during such testing in IHD patients, a response that is likely mediated by alpha-adrenergic receptor activation. Furthermore, systemic vascular resistance has been found to increase significantly during mental stress and to be positively correlated with increases in plasma epinephrine.¹⁵ In contrast, systemic vascular resistance was reduced significantly during exercise testing, and there was no relationship between the exercise-induced hemodynamic change and the plasma epinephrine level.¹⁵ Compared with exercise-induced ischemia, epinephrine-induced ischemia (which may occur during emotional distress) is marked by smaller increases in heart rate and rate-pressure product and by a marked increase in contractility.¹⁶

MSIMI predicts cardiac events

From a prognostic standpoint, MSIMI consistently predicts an increase in future adverse cardiac events.^11,17–19 In a sample of 132 IHD patients with a recent positive exercise test,¹¹ MSIMI was associated with an increase in cardiac events during 5-year follow-up (OR = 2.8; 95% CI, 1.0 to 7.7; P < .05) independent of patients’ age, history of prior MI, or baseline cardiac function. In contrast, exercise-induced ischemia was not predictive for adverse cardiac events (OR = 1.5; 95% CI, 0.6 to 3.9; P = .39) in this same sample.

Depression correlates with MSIMI occurrence

Adapted from American Heart Journal (Jiang W, et al. Depression and increased myocardial ischemic activity in patients with ischemic heart disease. Am Heart J 2003; 146:55–61.), copyright 2003, with permission from Elsevier.

The mean CES-D score was 8.2 (SD = 7.4; range, 0 to 47) and the median score was 7. Logistic regression models using restricted cubic splines revealed a curvilinear relation between CES-D scores and the probability of ischemia triggered by mental stress testing and exercise testing. For patients with CES-D scores less than or equal to 19 (81.5% of the study population), a 5-point increment in the CES-D score was associated with a roughly twofold increase in the likelihood of MSIMI (Figure 1A). For patients with CES-D scores greater than 19, the relation between scores and ischemia during mental stress tended to be inverse (Figure 1A), but these patients represented a small portion of the study sample (18.5%). In contrast, depression was not related to the occurrence of exercise-induced ischemia (Figure 1B). This finding strongly indicates that MSIMI may be a significant mechanism by which depression increases the risk of mortality and morbidity in patients with IHD. A few patients in this study had severe depressive symptoms (CES-D scores > 19), which makes interpretation of the result very diffi­cult. Because only 18.5% of the patients had CES-D scores greater than 19, this pattern of results needs to be confirmed in a sample with a greater representation of these more severely depressed patients.²⁰