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

Abstract

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 micromol/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 micromol/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.

Risk Factors Associated with Cardiovascular Morbidity and Mortality in Spanish Incident Hemodialysis Patients: Two-Year Results from the ANSWER Study

“…A recent analysis of the European Renal Association-European Dialysis and Transplant Association Registry revealed that, despite the increased risk of death associated with HD, no excess of CV mortality is observed [26]. The incidence found in our study is very similar to those reported by the majority of previous studies in European populations, but lower than those observed in US populations [21,23,27]. Additionally, in our study the all-cause and CV mortality rates during the first year were constant, which differs with results from the DOPPS (higher mortality rate during the first 120 days) [27].…”

“…The Dialysis Outcomes and Practice Patterns study (DOPPS) [18,19] demonstrated that the characteristics of incident populations and HD techniques differ from one country to another. Published studies include large populations from the US [20,21], and small cohorts from Japan [22] and Europe [23]. The primary objective of the ANSWER study was to determine patients’ characteristics at HD initiation independently associated with CV morbidity and mortality, in order to find modifiable risk factors.…”

Complement receptor 1 gene polymorphism and cardiovascular disease in dialyzed end-stage renal disease patients

“…There is a high prevalence of CVD in patients with ESRD that cannot be explained by traditional risk factors alone. Several reports suggest a role of candidate genes in the pathogenesis of CVD in dialyzed patients [22]. Polymorphisms of genes that are involved in innate immunity might be particularly relevant in increased risk of CVD [23].…”

The intercellular adhesion molecule-1 (ICAM-1) gene polymorphism K469E in end-stage renal disease patients with cardiovascular disease

“…Several reports suggest a role of candidate genes in the pathogenesis of CVD in dialyzed patients [21]. Both renal failure and CVD are polygenic disorders with changes in multiple genes involved in their etiopathology.…”