Importance of homocysteine, lipoprotein (a) and non-classical cardiovascular risk factors (fibrinogen and advanced glycation end-products) for atherogenesis in uraemic patients

Classical cardiovascular risk factors do not explain the 1. The results of a meta-analysis, including primarily full risk of cardiovascular disease (CVD) in the general retrospective observational studies, have suggested that population. Additional risk factors therefore probably each 5 mM increment in tHcy is associated with a exist. Increasing evidence suggests that homocysteine, >50% greater risk for CVD 2. Some prospective lipoprotein (a), fibrinogen and advanced glycation end- observational studies 3–6 , but not all 7,8, have products are potential candidates. This review is aimed confirmed this graded association between tHcy and at summarizing data linking these factors with cardio- CVD. On the other hand, a graded dose–response vascular risk in epidemiological and interventional relationship between fasting plasma tHcy level and studies of patients with renal disease. Since data to overall mortality has recently been reported in coronestablish the basis for the measurement and the therapy ary patients 9. It should be noted that hyperhomoof these risk factors are incomplete in renal disease cyst(e)inaemia is also associated with a greater risk of patients, in each case we will first review the evidence venous thromboembolic disease, as recently reported and strategies for intervention based on studies in the by a large meta-analysis 10. Although thermolabile general population. We will then review the role, and methylene tetrahydrofolate reductase (MTHFR) genothe approach to therapy of these factors in three groups type homozygosity mutation (C677� T transition) is (except for advanced glycation end-products): (i) associated with higher fasting tHcy levels, conflicting patients with chronic renal insufficiency (CRI ) (with results have been reported concerning the association nephrotic syndrome (NS) and without NS); (ii) between the thermolabile MTHFR genotype and CVD patients treated with haemodialysis (HD); and (iii) in the general population 11,12. peritoneal dialysis (PD) patients. In typical Western populations, supplementation with both 0.5–5 mg daily folic acid and about 0.5 mg daily vitamin B12 should reduce blood tHcy concentraHomocysteine