Phenotypic and genotypic risk factors for cardiovascular events in an incident dialysis cohort

Cardiovascular disease (CVD) remains the major cause of death in patients with end-stage renal disease ( ESRD). Traditional risk factors do not explain the high prevalence of CVD in this population, and other non-traditional cardiovascular ( CV) risk markers have now been described. Therefore, the potential relationship between CVD and phenotypic and genotypic risk markers was investigated prospectively in incident dialysis patients cohort. The 279 patients ( 244 on hemodialysis, 35 on peritoneal dialysis) within the Diamant Alpin Dialysis Cohort Study were investigated. Phenotypic and genotypic parameters were determined at dialysis initiation, patients monitored over a 2-year period, and CV events ( morbidity and mortality) recorded. Globally, 82 CV events occurred and 26 patients (9.3%) died from CVD, whereas 28 (10%) died from non-CV causes. Previous CV events were strongly predictive of CV events occurrence, whatever patients had had one ( hazard ratio (HR) 2, 95% confidence intervals (CI) 1.1 - 3.5) or more ( HR 3.9, 95% CI 2.1 - 7.1) CV accidents before starting dialysis. Both lipoprotein( a) ( HR 1.67, 95% CI 1 - 2.5) and total plasma homocysteine at cutoff 30 mu mol/l ( HR 1.7, 95% CI 1.1 - 2.8) were independent predictors of CV events outcome. In the subgroup of patients with homocysteine <30 mu mol/l, methylenetetrahydrofolate reductase ( MTHFR) TT was the sole biological parameter predictive of CV event outcome ( HR 2.5, 95% CI 1.1 - 10, P = 0.03). ESRD patients who enter chronic dialysis with a previous CV event, high total homocysteinemia levels, or MTHFR 677TT genotype must be considered at high risk of incident CV events.