High risk of cardiovascular disease in iron overload patients

P>Introduction Iron overload (IO) is defined as an increase in storage iron, regardless of the presence or absence of tissue damage. Whether increased iron stores are involved in the pathogenesis of cardiovascular disease remains controversial. Objectives To study insulin resistance markers, lipoprotein profile, activities of anti and prooxidant enzymes and cholesteryl ester transfer protein (CETP) in patients with IO. Methods Twenty male patients with IO were compared with 20 sex- and age-matched controls. General biochemical parameters, lipoprotein profile, and activities of paraoxonase 1, employing two substrates, paraoxon (PON) and phenylacetate (ARE), lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) and CETP were determined. Results IO patients showed higher levels of HOMA-IR and triglycerides [median (Q1-Q3)] [128 (93-193) vs. 79(51-91) mg dL-1, P < 0 center dot 0005] while lower high-density lipoprotein (HDL) cholesterol (mean +/- SD) (41 +/- 9 vs. 52 +/- 10 mg dL-1, P < 0 center dot 0005) in comparison with controls. Moreover, the triglycerides/HDL-cholesterol [3 center dot 2 (2 center dot 0-5 center dot 1) vs. 1 center dot 5 (1 center dot 0-1 center dot 9), P < 0 center dot 0005] ratio and oxidized low-density lipoprotein levels [94 (64-103) vs. 68 (59-70) IU L-1, P < 0 center dot 05] were increased in the patient group. Although no difference was observed in ARE activity, PON activity was decreased in IO patients [246 (127-410) vs. 428 (263-516) nmol mL-1 min-1, P < 0 center dot 05]. In addition, CETP and Lp-PLA(2) activities were also increased in the patients (189 +/- 31 vs. 155 +/- 36% ml-1 h-1, P < 0 center dot 005; and 10 center dot 1 +/- 2 center dot 9 vs. 8 center dot 2 +/- 2 center dot 4 mu mol mL-1 h-1, P < 0 center dot 05, respectively). Associations between ferritin concentration and the alterations in lipid metabolism were also found. Multiple regression analyses identified HOMA-IR as independent predictor of CETP activity (B = 65 center dot 9, P < 0 center dot 0001, r2 = 0 center dot 35), as well as ferritin concentration of Lp-PLA(2) activity (B = 3 center dot 7, P < 0 center dot 0001, r2 = 0 center dot 40) after adjusting for confounding variables. Conclusions IO patients presented not only insulin resistance but also metabolic alterations that were related to elevated iron stores and are associated with high risk of cardiovascular disease.