Units of Nephrology and Vascular Surgery, University and IRCCS Policlinico San Matteo, Pavia and Division of Nephrology S. Maugeri, Pavia, Italy
Sir,
Contradictory findings have recently been published, showing either a relation [1,2] or no relation [3] between plasma levels of homocysteine (Hcy) and vascular changes in dialysis patients. However, since Hcy accumulates in uraemic patients [4] and increased plasma Hcy levels are already present in the early stage of renal failure, a possible role for uraemia-associated hyperhomocysteinaemia (HHcy) should be considered. Recent data from a murine model of atherosclerosis showed that atherosclerotic lesions increased when mice were fed with a diet enriched in methionine but depleted in folate and vitamins B6 and B12 [5]. These changes were suppressed when diet was supplemented with folate and vitamins B6 and B12, implicating Hcy directly in atherosclerotic plaque progression.
In the present investigation, we evaluated whether plasma Hcy levels correlate with an index of generalized atherosclerosis (i.e. intimal wall thickness (IWT)) of the extracranial carotid artery (CA). We studied 85 patients (age 62.5±14 years, range 2278; dialysis duration 66.7±53.4 months, range 12238) who were on regular dialysis treatment (RDT) for at least 1 year. Patients with CA plaques were excluded. Standard bicarbonate dialysis was performed three times a week (180270 min/session to achieve a Kt/V >1.2). Plasma levels of total Hcy (including both homocysteinehomocysteine disulfide and mixed homocysteinecysteine disulfide) were measured by automated high performance liquid chromatography with reversed-phase and fluorescence detection in venous blood collected from fasting patients just before the start of a dialysis session. Serum total cholesterol and triglycerides were measured by a Technicon Chem 1 assay. All patients underwent ultrasound examination (Acuson instrument, 7.5 MHz, Milan, Italy) to evaluate IWT-CA (measured 10 mm distal from common carotid artery). Data are presented as mean±SD. Linear regression analysis was used to examine a possible relation between Hcy and other variables.
Plasma Hcy levels were increased in 71 out of 85 RDT patients (83.5%) RDT patients in comparison with the normal range 515 µmol/l. In RTD patients, IWT-CA (mm) averaged 0.68±0.23 on the right and 0.65±0.27 on the left side, overall 0.67±0.25. Patients with plasma Hcy levels greater than 15 µmol/l also showed a thicker ITW echostructure than patients with plasma Hcy levels within the normal range (0.71±0.09, n=71 vs 0.57±0.07, n=14; P<0.001). Linear regression analysis showed a significant positive relation between Hcy levels and mean IWT-CA (r=0.74; P<0.01) (Figure 1). IWT-CA was also correlated with age (r=0.57; P<0.03), dialysis duration (r=0.48; P<0.05), and systolic blood pressure (r=0.63; P<0.01). No significant correlation was found between IWT-CA thickness and plasma levels of cholesterol (r=0.14) or triglycerides (r=0.19).
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