Lp-PLA2 Activity During Iron Depletion Treatment in Primary IO Patients

Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory biomarker involved in atherosclerosis and cardiovascular disease (CVD). Iron stores may modify Lp-PLA2 as higher activity levels were observed in patients with primary iron overload (IO).

Aim: to evaluate the changes of Lp-PLA2 activity and other atherosclerosis markers in patients with primary IO after iron depletion.

Materials and Methods: The study initially included 20 male patients with primary IO, defined by liver histology, from which 7 were lost during follow-up and 13 completed the study (mean follow-up duration: 24±6 months). Phlebotomy treatment consisted in the removal of 1 unit of blood weekly or biweekly. We recorded traditional cardiovascular risk factors, high sensitivity C-reactive protein (hsCRP), and Lp-PLA2 activity. Longitudinal differences were tested by paired T or Wilcoxon tests. Linear regression was used to evaluate the relationship between changes in ferritin and in Lp-PLA2.

Results: HFE mutations were present in 77% of the patients. Besides ferritin concentration (-74%), ALT (-11%) and Lp-PLA2 activities (-14%) were reduced after iron depletion (all p<0.05). Linear regression showed that changes in ferritin levels explained a 60% of the variability in the changes of Lp-PLA2 activity (B=0.80, p=0.008, R2= 0.60).

Conclusion: Treatment by phlebotomy significantly reduced the levels of Lp-PLA2 activity besides its expected effects in liver markers. The implications of iron depletion for the reduction of CVD risk remain to be studied.

Keywords: iron overload, phlebotomy, Lp-PLA2, hsCRP.