Eur J Clin Invest 2011; 41 (5): 479–486
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 A2 (Lp-PLA2) 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 < 0·0005] while lower high-density lipoprotein (HDL) cholesterol (mean ± SD) (41 ± 9 vs. 52 ± 10 mg dL−1, P < 0·0005) in comparison with controls. Moreover, the triglycerides/HDL-cholesterol [3·2 (2·0–5·1) vs. 1·5 (1·0–1·9), P < 0·0005] ratio and oxidized low-density lipoprotein levels [94 (64–103) vs. 68 (59–70) IU L−1, P < 0·05] 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 < 0·05]. In addition, CETP and Lp-PLA2 activities were also increased in the patients (189 ± 31 vs. 155 ± 36% ml−1 h−1, P < 0·005; and 10·1 ± 2·9 vs. 8·2 ± 2·4 μmol mL−1 h−1, P < 0·05, 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 = 65·9, P < 0·0001, r2 = 0·35), as well as ferritin concentration of Lp-PLA2 activity (B = 3·7, P < 0·0001, r2 = 0·40) 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.