Influence of Biochemical Alterations on Arterial Stiffness in Patients With End-stage Renal Disease

From INSERM Unit 337 (J.B., M.E.S.) and the Department of Biochemistry, Hôpital Broussais (K.D., N.M.), Paris; and Service de Néphrologie-Hémodialyse, Hôpital Manhes, Fleury-Mérogis (A.P.G., G.M.L.), France.

Correspondence to Pr Michel E. Safar, Hôpital Broussais, Service de Médecine Interne, 96, rue Didot, 75674 Paris, Cedex 14, France. E-mail blacher{at}hbroussais.fr

Abstract—The incremental elastic modulus of the common carotid and radial arteries is increased in patients with end-stage renal disease (ESRD), independently of blood pressure, wall stress, and the presence of atherosclerotic alterations. Whether biochemical factors may be involved in the arterial changes and related to renal dysfunction remain largely ignored. To assess this question, we measured aortic (carotid-femoral), upper-limb (carotid-radial), and lower-limb (femoral-tibial) pulse wave velocity (PWV) in 74 ESRD patients undergoing hemodialysis in comparison with 57 control subjects similar in age, sex ratio, and mean blood pressure. We evaluated arterial blood presure by sphygmomanometry, aortic calcifications and cardiac mass by echography, and routine biochemical parameters, total plasma homocysteine, and plasma endothelin levels by standard techniques. In the population of patients with ESRD, on the basis of multiple stepwise regression analysis, aortic PWV was positively and independently correlated with systolic blood pressure (P<.0001), age (P<.0001), prevalence of aortic calcification (P=.0004), and the prevalence of diabetes mellitus (P=.0043). Upper-limb PWV was influenced exclusively by mean blood pressure (P<.0001). Lower-limb PWV was positively and independently correlated with plasma total homocysteine (P=.0004) and plasma endothelin (P=.0187) only. At any vascular site, PWV was not independently correlated with tobacco consumption; plasma levels of cholesterol, triglyceride, fibrinogen, or hemoglobin; body mass index; or the presence of bilateral nephrectomy. Finally, plasma homocysteine was independently correlated with cardiac mass (P=.0022). This study provides evidence that in ESRD patients, the stiffness of the arterial wall and cardiac mass are strongly influenced by biochemical factors related to the kidney alterations and are independent of age and blood pressure level. Increased plasma endothelin and homocysteine may be specifically involved in the vascular damage of lower limbs.

Key Words: end-stage renal disease • pulse wave velocity • homocysteine • endothelin

This article has been cited by other articles:

				J. Maizel, I. Six, M. Slama, C. Tribouilloy, H. Sevestre, S. Poirot, P. Giummelly, J. Atkinson, G. Choukroun, M. Andrejak, et al. Mechanisms of Aortic and Cardiac Dysfunction in Uremic Mice With Aortic Calcification Circulation, January 20, 2009; 119(2): 306 - 313. [Abstract] [Full Text] [PDF]

				W. Lieb, M. G. Larson, E. J. Benjamin, X. Yin, G. H. Tofler, J. Selhub, P. F. Jacques, T. J. Wang, J. A. Vita, D. Levy, et al. Multimarker Approach to Evaluate Correlates of Vascular Stiffness: The Framingham Heart Study Circulation, January 6, 2009; 119(1): 37 - 43. [Abstract] [Full Text] [PDF]

				P. Raggi and M. Kleerekoper Contribution of Bone and Mineral Abnormalities to Cardiovascular Disease in Patients with Chronic Kidney Disease Clin. J. Am. Soc. Nephrol., May 1, 2008; 3(3): 836 - 843. [Abstract] [Full Text] [PDF]

				D. Levy, S.-J. Hwang, A. Kayalar, E. J. Benjamin, R. S. Vasan, H. Parise, M. G. Larson, T. J. Wang, J. Selhub, P. F. Jacques, et al. Associations of Plasma Natriuretic Peptide, Adrenomedullin, and Homocysteine Levels With Alterations in Arterial Stiffness: The Framingham Heart Study Circulation, June 19, 2007; 115(24): 3079 - 3085. [Abstract] [Full Text] [PDF]

				N. Iwai, K. Kajimoto, Y. Kokubo, and H. Tomoike Extensive Genetic Analysis of 10 Candidate Genes for Hypertension in Japanese Hypertension, November 1, 2006; 48(5): 901 - 907. [Abstract] [Full Text] [PDF]

				S. Briese, S. Wiesner, J. C. Will, A. Lembcke, B. Opgen-Rhein, R. Nissel, K.-D. Wernecke, J. Andreae, D. Haffner, and U. Querfeld Arterial and cardiac disease in young adults with childhood-onset end-stage renal disease--impact of calcium and vitamin D therapy Nephrol. Dial. Transplant., July 1, 2006; 21(7): 1906 - 1914. [Abstract] [Full Text] [PDF]

				J.-S. Shao, J. Cai, and D. A. Towler Molecular Mechanisms of Vascular Calcification: Lessons Learned From The Aorta Arterioscler Thromb Vasc Biol, July 1, 2006; 26(7): 1423 - 1430. [Abstract] [Full Text] [PDF]

				T. Takenaka and H. Suzuki New strategy to attenuate pulse wave velocity in haemodialysis patients Nephrol. Dial. Transplant., April 1, 2005; 20(4): 811 - 816. [Abstract] [Full Text] [PDF]

				M. M. Mitsnefes, T. R. Kimball, S. A. Witt, B. J. Glascock, P. R. Khoury, and S. R. Daniels Abnormal Carotid Artery Structure and Function in Children and Adolescents With Successful Renal Transplantation Circulation, July 6, 2004; 110(1): 97 - 101. [Abstract] [Full Text] [PDF]

				C. J. G. Kelly, A. Speirs, G. W. Gould, J. R. Petrie, H. Lyall, and J. M. C. Connell Altered Vascular Function in Young Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 742 - 746. [Abstract] [Full Text] [PDF]

				J. L. Tycho Vuurmans, W. H. Boer, W.-J. W. Bos, P. J. Blankestijn, and H. A. Koomans Contribution of Volume Overload and Angiotensin II to the Increased Pulse Wave Velocity of Hemodialysis Patients J. Am. Soc. Nephrol., January 1, 2002; 13(1): 177 - 183. [Abstract] [Full Text] [PDF]

				C. Libetta, G. Villa, S. Pirrelli, V. Sepe, E. Gori, M. Zucchi, and A. D. Canton Homocysteine plasma levels correlate with intimal carotid artery thickness in haemodialysis patients Nephrol. Dial. Transplant., December 1, 2001; 16(12): 2444 - 2445. [Full Text] [PDF]

				R. A.J.M. van Dijk, J. A. Rauwerda, M. Steyn, J. W.R. Twisk, and C. D.A. Stehouwer Long-Term Homocysteine-Lowering Treatment With Folic Acid Plus Pyridoxine Is Associated With Decreased Blood Pressure but Not With Improved Brachial Artery Endothelium-Dependent Vasodilation or Carotid Artery Stiffness: A 2-Year, Randomized, Placebo-Controlled Trial Arterioscler Thromb Vasc Biol, December 1, 2001; 21(12): 2072 - 2079. [Abstract] [Full Text] [PDF]

				A. Farazaneh-Far Aortic stiffness and calcification Eur. Heart J., January 2, 2001; 22(2): 181 - 181. [PDF]

				A Farzaneh-Far, D Proudfoot, C Shanahan, and P L Weissberg Vascular and valvar calcification: recent advances Heart, January 1, 2001; 85(1): 13 - 17. [Full Text]

				M. E. Safar, J. Blacher, J. J. Mourad, and G. M. London Stiffness of Carotid Artery Wall Material and Blood Pressure in Humans : Application to Antihypertensive Therapy and Stroke Prevention Stroke, March 1, 2000; 31(3): 782 - 790. [Abstract] [Full Text] [PDF]

				J. J. van der Heijden-Spek, J. A. Staessen, R. H. Fagard, A. P. Hoeks, H. A. S. Boudier, and L. M. Van Bortel Effect of Age on Brachial Artery Wall Properties Differs From the Aorta and Is Gender Dependent : A Population Study Hypertension, February 1, 2000; 35(2): 637 - 642. [Abstract] [Full Text] [PDF]

				L. A. Bortolotto, M. E. Safar, E. Billaud, C. Lacroix, R. Asmar, G. M. London, and J. Blacher Plasma Homocysteine, Aortic Stiffness, and Renal Function in Hypertensive Patients Hypertension, October 1, 1999; 34(4): 837 - 842. [Abstract] [Full Text] [PDF]

				J. Lambert, M. van den Berg, M. Steyn, J. A. Rauwerda, A. J.M. Donker, and C. D.A. Stehouwer Familial hyperhomocysteinaemia and endothelium-dependent vasodilatation and arterial distensibility of large arteries Cardiovasc Res, June 1, 1999; 42(3): 743 - 751. [Abstract] [Full Text] [PDF]

				K. Demuth, N. Moatti, O. Hanon, M. O. Benoit, M. Safar, and X. Girerd Opposite Effects of Plasma Homocysteine and the Methylenetetrahydrofolate Reductase C677T Mutation on Carotid Artery Geometry in Asymptomatic Adults Arterioscler Thromb Vasc Biol, December 1, 1998; 18(12): 1838 - 1843. [Abstract] [Full Text] [PDF]