Does Anger Predict a Higher Likelihood of Cardiovascular Events?
Icilma V. Fergus, MD
Mostofsky E, Penner EA, Mittleman MA. Outbursts of anger as a trigger of acute cardiovascular events: a systematic review and meta-analysis [published online March 3, 2014]. Eur Heart J. doi:10.1093/eurheart/ehu033.
It seems reasonable to assume that anger, particularly the explosive variety, would be associated with stress to the cardiovascular (CV) system. Increased heart rate and blood pressure could conceivably increase myocardial work and oxygen demand along with stress factors, and may result in an adverse outcomes to the CV system. Some studies do not show a relationship with anger and CV events, while others1 have reported that episodes of anger are associated with a higher risk. The study by Mostofsky et al attempts to link anger as a precipitant to various CV events including higher risk of myocardial infarction (MI),2 acute coronary syndrome (ACS),3-5 ischemic6 and hemorrhagic stroke,7 and arrhythmia.8,9
There are many factors including cardiovascular risk factors that coexist and overlap in individuals who display anger, and this in part may explain some of the confounding findings seen in many studies. For instance, factors such as catecholamine overexpression with resultant sympathetic drive and deleterious effects associated with increased blood pressure and heart rate may be seen in anger,10 but may also present in other emotional states and be certainly precipitated by several other germane risk factors.
Thus, the question to answer is whether the anger episode correlates directly to the CV event, or do other inherent or underlying risk factors explain the effect? Anger releases epinephrine and norepinephrine, which increase blood pressure and pulse, constrict blood vessels, and make platelets stickier,10 and may be why anger is potentially associated with increased cardiac risk. Several studies have found that anger increases the risk of incident coronary heart disease (CHD), even as others found anger to be protective. Considering this variance in study outcomes, there could be several contributory mechanisms, including adjusting for different types of anger expression, which may be associated with opposing levels of cardiovascular risk. A prior study by Mostofsky et al examined whether distinct types of anger expression differentially predict incident CHD.11 In the Atherosclerosis Risk in Communities (ARIC) study, individuals who were the most prone to anger were 2.69 times more likely to have a heart attack or sudden death than those with the lowest anger ratings on a 40-point scale.12 Individuals who scored a moderate level on an anger scale were 35% more likely to experience a coronary event. Other studies also discuss the fact that anger and hostility are associated with worse CHD outcomes in both healthy and CHD populations.13,14
Considering the vast array of studies that have looked at the question of anger and CVD with varying outcomes, the present review also must be taken in the context of limitations on final interpretation of data. In this meta-analysis, there is inclusion of cross-sectional, retrospective, and prospective studies, as well as prospective cohort investigations. Some of the reviewed studies included for analysis were based on small sample sizes with few exposed cases; thus the results were often reported with low precision. Since there has been no previous systematic evaluation to compare the results and examine whether there is consistency for CV outcome across studies, in this study Mostofsky et al attempted to answer the direct question of whether anger is a predictor for CV events by filtering thousands of studies and narrowing them down to 9 for the final analysis.Study Design
This study was performed based on pooled data from studies conducted between January 1966 and June 2013. A meta-analysis protocol was followed throughout the design, implementation, analysis, and reporting processes.15 Several databases were utilized looking for the key words “anger,” “hostility,” “aggression,” “mental stress,” and “cardiovascular diseases.” Nine independent cross-over studies were extracted from a total of 6870 publications. These publications were further assessed excluding 1299 duplicates. Furthermore, an additional 5565 articles were excluded after the review of the title or abstract. Incidence rate ratios and 95% confidence intervals (CIs) were calculated with inverse-variance-weighted random-effect models. Studies were eligible for review based on 3 criteria: (1) the design was a cohort, a case–control, a self-controlled case series, or a case-crossover study; (2) the investigators reported relative risks and 95% CI for the association between outbursts of anger and CV events, and (3) the investigators evaluated hazard periods for triggers occurring within 1 month before event onset.
Statistical analyses were performed to pool the relative risks from individual studies,16 and to calculate heterogeneity across studies,17 between-study heterogeneity attributable to variability in the association rather than sampling variation,18,19 and publication bias.19-21 Stratified analyses were performed to evaluate the influences of incident versus recurrent events and MI versus ACS, and sensitivity analyses were performed to assess whether the results were driven by a single study. The absolute risk of cardiovascular events associated with anger was listed as low (5%), medium (10%), and high (20%) 10-year risk of coronary heart disease.21,22
After exclusion criteria were applied to the original 6000 studies, 9 studies, published between 1995 and 2013, were reviewed. Included in the 9 were 4 studies investigating MI/ACS, 2 on ischemic stroke, 2 on ventricular arrhythmias, and 1 on ruptured intracranial aneurysm. There was evidence of substantial heterogeneity between the studies (I2 = 92.5% for MI/ACS and 89.8% for ischemic stroke). A total of 4546 cases of MI were reviewed, 462 cases of ACS, 590 cases of ischemic stroke, 215 cases of hemorrhagic stroke, and 306 cases of arrhythmia.
There was a 4.74 (95% CI, 2.50-8.99; P <.001) times higher risk of MI or ACS in the 2 hours following outbursts of anger compared with other times based on the random effect meta-analysis in 4 studies. However, there was heterogeneity (Q = 39.80; P<.001; I2 = 92.5%). Despite the fact that a pooled estimate may not be appropriate due to differences, there appeared to be a higher evidence of MI/ACS risk following episodes of anger. As noted in the original paper, the results were stronger for studies of incident events (Incident Rates Ratio [IRR] = 5.47, 95% CI, 3.83-7.80; Q = 0.02; P = .86; I2 = 0%) than for studies including both incident and recurrent events (IRR = 4.17, 95% CI, 1.42-12.26; Q = 31.96; P< .001; I2 = 96.9% and higher for studies of ACS (IRR = 6.45, 95% CI, 4.80-8.99; Q = 1.24, P = .27; I2 = 19.1%) than studies of MI (IRR = 3.52, 95% CI, 1.54-8.06; Q = 6.47, P = .01; I2 = 84.5%).
With respect to other CNS events, the rate of ischemic stroke in the 2 hours following an outburst of anger was 3.62 (95% CI, 0.82-16.08; P = .09) times higher. Regarding ventricular arrhythmias, results were demonstrated in 2 studies with different designs including a meeting abstract, and thus could not be meta-analyzed but showed that there was a 3.20 (95% CI, 1.80-5.70) times higher rate of ventricular tachycardia or ventricular fibrillation in the hour following moderate levels of anger and 16.7 times higher (95% CI, 8.12-34.5) in the hour after intense anger. In addition, the relative risk of a CV event is increased with more frequent outbursts of anger and in people noted to have higher baseline cardiovascular risk.