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 vasc ular 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 homo cysteine-lowering treatment. Patients and methods: Fifty-four patients on m aintenance dialysis treatment were studied at baseline. Fourty-one patients completed the treatment protocol, which consisted of a 12-week treatment w ith 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. Co mpliance and distensibility coefficients (CC and DC) and the stiffness inde x (beta) of the common carotid artery were determined at baseline and after 52 weeks of treatment using a non-invasive vessel wall movement detector s ystem. Results: At baseline, plasma total homocysteine was elevated (44.1 /- 33.7 mu mol/l), but showed no relationship with CC, DC or beta. Age and mean arterial pressure (MAP) were the only independent determinants of CC a nd DC, whereas beta was associated with age only. Plasma homocysteine showe d a sustained decrease after therapy (20.7 +/- 9.0 mu mol/l at week 52). No significant changes occurred in CC (from 0.59 +/- 0.21 to 0.60 +/- 0.22 mm (2)/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 indep endent 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 < 0.0 002). 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). Co nclusion: Folic acid treatment of hyperhomocysteinemia has no major effect on carotid artery stiffness in chronic dialysis patients. The results do, h owever, emphasize the importance of tight blood pressure control in these p atients.