Anger, increased cardiovascular risk, and homocysteine

Summarized by Robert W. Griffith, MD
January 22, 2001 (Reviewed: February 18, 2003)

Introduction

It is well accepted that high blood levels of homocysteine are associated with an increased risk of atherosclerosis and coronary artery pathology, and also that hostility is associated with the development of coronary heart disease. Animal models show that homocysteine can cause direct damage to the vasculature, inducing pre-atherosclerotic changes in the endothelium and proliferation of smooth muscle cells. A study conducted at Ohio State University, USA, has "completed the triangle", linking anger and hostility in healthy adults with elevated homocysteine levels.

Method

64 healthy adults (33 women, 31 men, mean age 49.2 +/- 7.2 years) were enrolled. Volunteers with a previous history of heart or valvular disease, diabetes, hypertension, obesity, gastrointestinal disorders, or cancer were rejected.

The participants completed the Cook-Medley hostility questionnaire and the Spielberg Anger Expression questionnaire. These have been shown to have internal consistency, test-retest reliability, and documented validity. Blood sampling after at least 30 minutes' rest were analyzed for total homocysteine concentration using fluorescence high-pressure liquid chromatography.

The Spielberg Anger Expression questionnaire distinguished between the inhibition of anger (anger-in) and the outward expression of anger (anger-out). Separate one-way analyses of variance were done to test potential gender effects, plasma homocysteine levels, hostility, anger-in, and anger-out. These were followed by calculations of Pearson correlation coefficients and a stepwise regression analysis.

Results

Men were found to have significantly higher resting homocysteine levels than women, and were significantly higher in hostility and anger-in. This was an expected finding.

In both men and women, total hostility scores were positively related to homocysteine concentrations to a significant degree (r=0.29, p=0.02).

In the men participants, anger-in scores were positively associated with homocysteine levels (r=0.42, p=0.01). No such correlations were found for the women. There were no correlations between homocysteine levels and anger-out for either men or women.

Stepwise regression analysis showed that, after adjusting for hostility and anger-in, there were no significant gender-differences in homocysteine concentrations.

Comment

These findings provide a possible explanation for the way in which anger and hostility can be related to coronary heart disease. Blood levels of homocysteine are known to be regulated by genetic, dietary, and hormonal factors. Age-related increases may be due to dietary deficiencies of folic acid or vitamin B12, or waning estrogen levels. Moderate physical exercise is associated with lower homocysteine levels, whereas cigarette smoking is associated with higher levels. However, the association of hostility and anger-in with raised homocysteine levels reported here is new.

Hostility and anger are related to increased sympathetic nervous system activity during stress; this response is greater in men than in women, perhaps explaining the well-documented differences between plasma homocysteine levels in men and women. In fact, the regression analysis done on the data in this study support this role for sympathetic activity in the cascade:

• anger/hostility, causing
• increased sympathetic activity, causing
• elevated homocysteine levels, causing
• endothelial and smooth muscle changes, causing
• coronary heart disease

Of course, one might consider substituting 'LDL-cholesterol' for 'homocysteine' in the above cascade.¹

As the evidence mounts in favor of such a cascade (be it focused around homocysteine or cholesterol), it becomes clear that health professionals can attempt to intervene at various stages, to reduce the likelihood a serious cardiovascular event. Perhaps helping people to manage their anger better would be one of the more worthwhile interventions.

Source

• Plasma homocysteine concentrations are positively associated with hostility and anger CM. Stoney, TO. Engebretson, Life Sciences, 2000, vol. 66, pp. 2267--2275

Footnotes
1. Serum lipids and their relationships with hostility and angry affect and behaviors in men JC. Richards, A. Hof, M. Alvarenga, Health Psychol , 2000, vol. 19, pp. 4--8

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