Homocysteine is putative risk factor for coronary heart disease (CHD). It is an amino acid associated with endothelial damage, which may cause direct injury to intimal cells and assist in the deposition of lipoproteins within atherosclerotic lesions. Homocysteine is bound to lipoproteins. Although several psychological characteristics are associated with CHD, few investigations of psychological risk factors and homocysteine exist. We have shown that homocysteine increases during stress, and that hostility is positively associated with resting homocysteine. The major goals of this proposal are to investigate the etiological significance of stress-induced and personality-associated elevations in homocysteine; to evaluate the relationship between lipids and homocysteine during stress; and to test one viable mechanism for homocysteine reactivity. Study 1 will test whether the stress-associated increases in homocysteine are etiologically meaningful, by comparing individuals with above average risk for CHD (based on American Heart Association/American College of Cardiology recommendations and family history), to those at below average risk. This study will also build on our earlier findings, by comparing homocysteine reactivity among high hostile individuals to low hostile individuals. Study 2 will test whether individuals with exaggerated homocysteine reactivity have greater stress-induced alterations in vitamin B6, vitamin B12, and folate than do those with smaller homocysteine reactivity. An additional purpose of this study will be to test whether individuals given B vitamin supplements for 4 weeks prior to an acute stressor display smaller elevations in stress-induced homocysteine, relative to individuals given placebo. Because homocysteine is bound to lipoproteins, and because it appears to modify the atherogenicity of low density lipoprotein, both studies will test the relationships between homocysteine and lipid reactivity. The results of this research will extend the available but limited data testing the impact of stress and hostility on homocysteine concentrations; will allow one test of the etiological significance of stress-related homocysteine elevations; will allow us to examine the relationship between lipid reactivity and homocysteine reactivity; and will test a viable mechanism for the homocysteine elevations.
