Carotid artery stiffness in patients with end-stage renal disease: no effect of long-term homocysteine-lowering therapy.
BACKGROUND
The excess of cardiovascular disease in end-stage renal disease (ESRD) patients is unexplained, but could relate to altered intrinsic vascular wall properties, such as increased arterial stiffness, which could be mediated by hyperhomocysteinemia. We investigated potential determinants of carotid artery stiffness in ESRD patients and the effect of long-term homocysteine-lowering treatment.


METHODS
Fifty-four patients on maintenance dialysis treatment were studied at baseline. Fourty-one patients completed the treatment protocol, which consisted of a 12-week treatment with folic acid 5 mg daily with or without betaine 4 g per day, and of 1 or 5 mg of folic acid thereafter for 40 weeks. Both phases were randomized. Compliance and distensibility coefficients (CC and DC) and the stiffness index (beta) of the common carotid artery were determined at baseline and after 52 weeks of treatment using a non-invasive vessel wall movement detector system.


RESULTS
At baseline, plasma total homocysteine was elevated (44.1+/-33.7 micromol/l), but showed no relationship with CC, DC or beta. Age and mean arterial pressure (MAP) were the only independent determinants of CC and DC, whereas beta was associated with age only. Plasma homocysteine showed a sustained decrease after therapy (20.7+/-9.0 micromol/l at week 52). No significant changes occurred in CC (from 0.59+/-0.21 to 0.60+/-0.22 mm2/kPa; p = 0.47), in DC (from 14.9+/-6.1 to 15.3+/-6.2 10(-3)/kPa; p = 0.55), or in beta (from 10.9+/-4.7 to 11.2+/-4.4; p = 0.64). No independent determinants were detected for the change in CC, whereas the change in DC was inversely related to the change in MAP (stand. r = -0.58; p<0.0002). The decrease in MAP after therapy was significant (p = 0.003) and was related to the dialysis mode (p = 0.003) and smoking status (p = 0.02).


CONCLUSIONS
Folic acid treatment of hyperhomocysteinemia has no major effect on carotid artery stiffness in chronic dialysis patients. The results do, however, emphasize the importance of tight blood pressure control in these patients.
van Guldener
C
C
Department of Internal Medicine, University Hospital and Institute for Cardiovascular Research, Vrije Universiteit, Amsterdam, The Netherlands.
Lambert
J
J
ter Wee
P M
PM
Donker
A J
AJ
Stehouwer
C D
CD
D000367:Age Factors; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000502:physiology; D001916:Brachial Artery / Q000503:physiopathology; D017536:Carotid Artery, Common / Q000503:physiopathology*; D003187:Compliance / Q000187:drug effects; D016232:Endothelins / Q000097:blood; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000503:physiopathology* / Q000628:therapy; D011736:Pyridoxine / Q000097:blood; D012044:Regression Analysis; D006435:Renal Dialysis; D014664:Vasodilation / Q000187:drug effects*; D014805:Vitamin B 12 / Q000097:blood; D014841:von Willebrand Factor / Q000378:metabolism
D015415:Biomarkers; D016232:Endothelins; D014841:von Willebrand Factor; D006710:Homocysteine; D011736:Pyridoxine; D014805:Vitamin B 12