Arterial stiffness is rapidly induced by raising the plasma homocysteine concentration with methionine


      Homocysteine appears to be causally related to cardiovascular disease and shown to induce endothelial dysfunction. An adverse effect on large elastic arteries has not been reported. In 18 healthy middle-aged subjects, systemic arterial compliance (SAC) was measured over 5 h after a standard methionine load. Arterial pressure waves from the carotid artery and aortic flow were measured non-invasively and SAC calculated. Differences in mean SAC values when plasma homocysteine concentrations were raised with a methionine containing meal and on another day when a control meal was eaten were highly significant. SAC fell (arterial stiffness increased) by 22% at 2.5 h and by 19% at 5 h (treatment×time interaction: P=0.003 and 0.004, respectively). Adjustment for confounders (age, arterial pressure, BMI, LDL cholesterol) did not affect conclusions. Thus, arterial stiffness in the central elastic arterial system increased rapidly at high plasma homocysteine concentrations.


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        • Wald D.S.
        • Laws M.
        • Morris J.K.
        Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis.
        BMJ. 2002; 325: 1202-1206
        • Woo K.S.
        • Chook P.
        • Lolin Y.I.
        • Sanderson J.E.
        • Metrwewli C.
        • Celermajer D.S.
        Folic acid improves arterial endothelial function in adults with hyperhomocysteinemia.
        J. Am. Coll. Cardiol. 1999; 34: 2002-2006
        • Tawakol A.
        • Omland T.
        • Gerhard M.
        • Wu J.T.
        • Creager M.A.
        Hyperhomocyst(e)inemia is associated with impaired endothelium-dependent vasodilation in humans.
        Circulation. 1997; 95: 1119-1121
        • Chao C.-L.
        • Kuo T.-L.
        • Lee Y.-T.
        Effects of methionine-induced hyperhomocysteinemia on endothelium-dependent vasodilation and oxidative status in healthy adults.
        Circulation. 2000; 101: 485-490
        • Hanratty C.G.
        • McAuley D.F.
        • McGrath L.T.
        • Young I.S.
        • Johnston G.D.
        Hyperhomocysteinaemia in young adults is not associated with impaired endothelial function.
        Clin. Sci. 2001; 100: 61-72
        • Tawakol A.
        • Forgione M.A.
        • Stuehlinger M.
        • Alpert N.M.
        • Cooke J.P.
        • Loscalzo J.
        • et al.
        Homocysteine impairs coronary microvascular dilator function in humans.
        J. Am. Coll. Cardiol. 2002; 40: 1051-1058
        • Meaume S.
        • Rudnichi A.
        • Lynch A.
        Aortic pulse wave velocity as a marker of cardiovascular disease in subjects over 70 years old.
        J. Hypertens. 2001; 19: 871-877
        • Liu Z.
        • Brin K.P.
        • Yin F.C.
        Estimation of total arterial compliance: an improved method and evaluation of current methods.
        Am J. Physiol. 1986; 251: H588-H600
        • Chambers J.C.
        • Obeid O.A.
        • Kooner J.S.
        Physiological increments in plasma homocysteine induce vascular endothelial dysfunction in normal human subjects.
        Arterioscler Thromb Vasc Biol. 1999; 19: 2922-2927
        • Smilde T.J.
        • van den Berkmortel F.W.P.J.
        • Boers G.H.J.
        • Wollersheim H.
        • de Boo T.
        • van Langen H.
        • et al.
        Carotid and femoral artery wall thickness and stiffness in patients at risk for cardiovascular disease, with special emphasis on hyperhomocysteinemia.
        Arteriscler Thromb Vasc Biol. 1998; 18: 1958-1963
        • Liang Y.-L.
        • Teede H.
        • Kotsopoulos D.
        • Shiel L.
        • Cameron J.D.
        • Dart A.M.
        • et al.
        Clin. Sci. 1998; 95: 669-679
      1. Lehman ED, Hopkins KD, Rawesh A, Joseph RC, Kongola K, Coppack SW, et al. Relation between number of cardiovascular risk factors/events and noninvasive doppler ultrasound assessments of arterial compliance. Hypertension 1998;32:565–9.

      2. McVeigh G, Brenna G, Hayes R. Vascular abnormalities in non-insulin-dependent diabetes mellitus identified by arterial waveform analysis. Am. J. Med. 1993;14:424–30.

        • Gatzka C.D.
        • Cameron J.D.
        • Kingwell B.A.
        • Dart A.M.
        Relation between coronary artery disease, aortic stiffness and left ventricular structure in a population sample.
        Hypertension. 1998; 32: 575-578
        • Dart A.M.
        • Kingwell B.A.
        Pulse pressure—a review of mechanisms and clinical relevance.
        J. Am. Coll Cardiol. 2001; 37: 975-984
        • Nestel P.J.
        • Shige H.
        • Pomeroy S.
        • Cehun M.
        • Chin-Dusting J.
        Post-prandial remnant lipids impair arterial compliance.
        J. Am. Coll. Cardiol. 2001; 37: 1929-1935
        • Wilkinson I.B.
        • MacCallum H.
        • Cockroft J.R.
        • Webb D.J.
        Inhibition of basal nitric oxide synthesis increases augmentation index and pulse wave velocity in vivo.
        Br. J. Clin. Pharmacol. 2002; 53: 189-192
        • Faraci F.M.
        Hyperhomocysteinemia. A million ways to lose control.
        Arterioscler Thromb Vasc Biol. 2003; 23: 371-373