High risk of cardiovascular disease in iron overload patients.
BACKGROUND
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.


OBJECTIVE
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 < 0·0005] 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-PLA(2) 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, r(2) = 0·35), as well as ferritin concentration of Lp-PLA(2) activity (B = 3·7, P < 0·0001, r(2) = 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.
Tomàs Meroño, Department of Clinical Biochemistry, School of Pharmacy and Biochemistry, University of Buenos Aires, Argentina. tomasmero@yahoo.com.ar
Tomás
T
Meroño
Leonardo
L
Gómez
Leonardo G
LG
Rosso
Patricia
P
Sorroche
Laura
L
Boero
Jorge
J
Arbelbide
Fernando
F
Brites
D000328:Adult; D001118:Argentina; D043303:Aryldialkylphosphatase / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000378:metabolism*; D016022:Case-Control Studies; D053480:Cholesterol Ester Transfer Proteins / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D019190:Iron Overload / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged
D053480:Cholesterol Ester Transfer Proteins; D008074:Lipoproteins; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human