Submitted to: Metabolism: Clinical and Experimental
Publication Type: Peer reviewed journal
Publication Acceptance Date: 3/19/2007
Publication Date: 6/14/2007
Citation: Wilson, J., Welsch, M., Allen, J., Thomson, J.L., Tulley, R., Lefevre, M. 2007. The association of homocysteine and related factors to brachial artery diameter and flow-mediated dilation. Metabolism: Clinical and Experimental. 56:641-648. Interpretive Summary: Cardiovascular disease is a serious, life-threatening, and costly disease for millions of Americans. Brachial artery flow-mediated dilation (BAFMD) is a non-invasive, painless method to measure cardiovascular disease in patients. However, studies relating BAFMD to other risk factors for cardiovascular disease are conflicting, especially concerning the amino acid homocysteine. To determine whether the relationship between BAFMD and homocysteine is affected by genetic variations in a key enzyme involved in the metabolism of homocysteine, 174 healthy subjects were examined for BAFMD, homocysteine, and genotype, as well as other traditional risk factors for cardiovascular disease. The data confirmed the presence of a relationship between BAFMD and homocysteine, and suggest that genotype has a significant effect on BAFMD even when homocysteine is taken into account. Armed with the knowledge that specific genotypes may increase the susceptibility of individuals to certain risk factors will allow public health officials and medical practitioners to target these individuals for more aggressive preventive and therapeutic measures in the fight against cardiovascular disease.
Technical Abstract: Brachial artery flow-mediated dilation (BAFMD) has been proposed as a measurement of the degree and severity of cardiovascular disease. The purpose of this study was to (1) evaluate the associations between BAFMD and homocysteine, folate, vitamin B12, vitamin B6, (2) examine the influence of 5,10-methylenetetrahydrofolate reductase (MTHFR) genotypes to homocysteine levels and BAFMD, and (3) evaluate the effect of homocysteine on the baseline diameter of the vessel versus BAFMD. A total of 174 healthy research subjects were examined for BAFMD, homocysteine, folate, vitamin B12, vitamin B6, and MTHFR genotype, nucleotide 677 C'T. The data indicated a significant inverse correlation between homocysteine and BAFMD (r=-0.1763, p=0.02). There was a significant difference in BAFMD between MTHFR genotype groups (p=0.01)(T/T versus C/C p=0.042; C/C versus C/T p=0.13; T/T versus C/T p=0.003). Homocysteine was significantly associated with the baseline brachial artery diameter (r=0.1878, p=0.013). The data confirmed a significant inverse correlation between baseline diameter and BAFMD (r=-0.3321, p=0.0001). Regression analysis indicated that the MTHFR genotype, homocysteine, and age were significant predictors of BAFMD (p = 0.0001, r2= 0.118). When the baseline brachial diameter was incorporated into the model, the effect of homocysteine on BAFMD disappeared. The present data indicate an association between homocysteine and BAFMD, and reduced BAFMD in individuals with the MTHFR nucleotide 677 T/T genotype, despite similar blood values for folate and homocysteine. Finally, the data suggest that the effect of homocysteine on vascular reactivity is in part a consequence of its influence on baseline brachial artery diameter.