P1476IRON PARAMETERS PREDICT CARDIOVASCULAR EVENTS IN MAINTENANCE HEMODIALYSIS PATIENTS

Abstract

Abstract Background and Aims Previous studies revealed the association between iron deficiency and thromboembolic events, whereas the association between high serum ferritin and poor prognosis of cerebral haemorrhage was reported in the general population. Since few reports have revealed the relationship between iron parameters and cardiovascular events in hemodialysis (HD) patients so far, our purpose was to examine whether iron parameters predict cardiovascular events in HD patients based on the nation-wide database of patients undergoing dialysis in Japan. Method We enrolled 126,560 patients aged between 20 and 100 who had been on maintenance HD more than 1 year and three times weekly at the end of 2012. We divided baseline transferrin saturation (TSAT) levels into 3 categories (T1: <20, T2: 20-25, T3: >25%) and serum ferritin levels into quartile (Q1: <31, Q2: 31-73, Q3: 73-158, Q4: >158 ng/mL). The study outcomes were new onset of myocardial infarction (MI), cerebral infarction (CIF), and cerebral haemorrhage (CHM) and death due to these three diseases between 2012 and 2013. We performed multivariate logistic regression for the incident events and also employed Cox proportional hazards analyses for death. Multiple imputation method with 5 data sets was performed for missing values. Results During a 1-year follow-up, a total of 2,087 MI (373 deaths), 2,930 CIF (283 deaths), and 1,371 (359 deaths) CHM occurred. After adjustment for demographic and clinical factors, odd ratios (ORs) for MI and CIF were significantly higher among patients with T1 of TSAT than those with T3 (OR; 1.19 (95% confidence interval (CI), 1.07-1.33), 1.16 (95% CI, 1.06-1.27, respectively), and serum ferritin levels were not associated with those outcomes. On the other hand, TSAT was not associated with CHM, however, stepwise increase of OR with the increase of ferritin quartile was observed; patients with Q4 of ferritin had the highest risk for CHM (OR; 1.32 (95% CI, 1.12-1.57) as compared to Q1). In the multivariable Cox regression models, the hazard ratios (HRs) for death due to MI and CIF of the patients with T1 of TSAT were 1.28 (95% CI, 1.00-1.65) and 1.40 (95% CI, 1.06-1.86) as compared to T3, respectively. HR for death due to CHM in patients with Q1-Q4 of ferritin was 1.00 (Reference), 1.59 (95% CI, 1.12-2.25), 1.90 (95% CI, 1.35-2.67), 1.61 (95% CI, 1.13-2.29), respectively (Figure). Furthermore, high dose of erythropoietin stimulating agents was a risk factor of all three cardiovascular events and mortality. Conclusion Low TSAT levels predicted MI and CIF and high serum ferritin levels predicted CHM in HD patients. These results suggest that functional iron deficiency could affect thromboembolic events, while increase in storage iron could affect microvascular fragility.