Non-transferrin-bound iron is associated with plasma level of soluble intercellular adhesion molecule-1 but not with in vivo low-density lipoprotein oxidation.
BACKGROUND
Excess body iron is associated with increased cardiovascular disease risk, possibly via non-transferrin-bound iron (NTBI)-mediated enhancement of inflammation and oxidation of low-density lipoprotein (LDL).


METHODS
We assessed this proposed atherosclerotic mechanism of body iron by determining the relationship of levels of serum iron parameters, including NTBI, with plasma markers of inflammation and LDL oxidation in 232 subjects who visited the outpatient clinic for hemochromatosis family screening.


RESULTS
Plasma level of soluble intercellular adhesion molecule-1 (sICAM-1) was positively related to ferritin (standardized beta coefficient 0.16) and to NTBI (0.185) and negatively to total iron-binding capacity (TIBC, -0.166). Significant higher levels of sICAM-1 were found for subjects in the highest quartile of NTBI compared to the lowest quartile of NTBI (122 microg/L (107-141) and 106 microg/L (89-125), median (interquartile range), p<0.001). Odds ratio of subjects having sICAM-1 level above 134 microg/L (75th percentile) in the highest and lowest quartile of NTBI amounted 2.3. White blood cell count was positively related to ferritin (0.149). High-sensitivity C-reactive protein, interleukin-6, interleukin-8, oxidized LDL, oxidized LDL/apolipoprotein B and IgG and IgM antibodies to oxidized LDL were not related to any of the markers of iron status.


CONCLUSIONS
Excess body iron, reflected by elevated serum ferritin and NTBI and decreased TIBC, is associated with increased plasma level of sICAM-1 but not with markers of in vivo LDL oxidation.
van Tits
L J H
LJ
Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. B.vantits@aig.umcn.nl
Jacobs
E M G
EM
Swinkels
D W
DW
Lemmers
H L M
HL
van der Vleuten
G M
GM
de Graaf
J
J
Stalenhoef
A F H
AF
D000328:Adult; D050197:Atherosclerosis / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D005260:Female; D005838:Genotype; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D007501:Iron / Q000097:blood*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D010084:Oxidation-Reduction; D012307:Risk Factors; D012995:Solubility; D014168:Transferrin / Q000378:metabolism
D015415:Biomarkers; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D014168:Transferrin; C099252:oxidized low density lipoprotein; D018799:Intercellular Adhesion Molecule-1; D007501:Iron