on February 3, 2005
Published online before print February 3, 2005, doi: 10.1161/01.ATV.0000157981.57694.d2
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Submitted on August 13, 2004
Accepted on January 18, 2005
S-Adenosylmethionine and 5-Methyltetrahydrofolate Are Associated With Endothelial Function After Controlling for Confounding by Homocysteine. The Hoorn Study
A. M.W. Spijkerman ;
From the Institute for Research in Extramural Medicine (A.M.W.S., P.J.K., J.M.D., G.N., L.M.B., C.D.A.S.), Institute for Cardiovascular Research (A.M.W.S., Y.M.S., A.B., T.T., C.J.), Department of Internal Medicine (Y.M.S.), Department of Clinical Epidemiology and Biostatistics (P.J.K.), Department of Clinical Chemistry (T.T., C.J.), and Department of Endocrinology (R.J.H.), VU University Medical Center, Amsterdam; Department of Internal Medicine (R.M.A.H.), Hospital Kennemer Gasthuis, Haarlem; and Department of Internal Medicine (C.D.A.S.), Academic Hospital Maastricht, the Netherlands.
* To whom correspondence should be addressed. E-mail: y.smulders{at}vumc.nl.
Objective--To explore to what extent homocysteine, S-adenosylmethionine (SAM), S-adenosylhomocysteine, total folate, 5-methyltetrahydrofolate (5-MTHF), vitamin B12, and vitamin B6 are associated with endothelium-dependent, flow-mediated vasodilation (FMD), and whether these associations are stronger in individuals with diabetes or other cardiovascular risk factors.
Methods and Results--In this population-based study of 608 elderly people, FMD and endothelium-independent nitroglycerin-mediated dilation (NMD) were ultrasonically estimated from the brachial artery (absolute change in diameter [µm]). High SAM and low 5-MTHF were significantly associated with high and low FMD, respectively (linear regression coefficient, [95% confidence interval]): 48.57 µm (21.16; 75.98) and -32.15 µm (-59.09; -5.20), but high homocysteine was not (-15.11 µm (-42.99; 12.78). High SAM and low 5-MTHF were also significantly associated with high and low NMD, respectively. NMD explained the association of 5-MTHF with FMD but not of SAM. No interactions were observed for diabetes or cardiovascular risk factors.
Conclusions--In this elderly population, both SAM and 5-MTHF are associated with endothelial and smooth muscle cell function. The effect of homocysteine on endothelial function is relatively small compared with SAM and 5-MTHF. The relative impact of SAM, 5-MTHF, and homocysteine, and the mechanisms through which these moieties may affect endothelial and smooth muscle cell function need clarification. Both SAM and 5-MTHF are associated with endothelial and smooth muscle cell function whereas the effect of homocysteine is relatively small compared with SAM and 5-MTHF.
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