Low levels of IgM antibodies to phosphorylcholine predict cardiovascular disease in 60-year old men: effects on uptake of oxidized LDL in macrophages as a potential mechanism.
OBJECTIVE
We here determine the role of IgM antibodies against phosphorylcholine (anti-PC) in prediction of cardiovascular disease (CVD) and on macrophage uptake of Oxidized LDL (OxLDL).


METHODS
From a screening of 4232 subjects, 60-year-old (2039 men and 2193 women), 211 incident cases of CVD (myocardial infarction, ischemic stroke, or hospitalized angina pectoris) and 633 age- and sex-matched controls were identified through a 5-7 year follow-up. Serum levels of IgM anti-PC was determined by ELISA. Anti-PC was extracted from pooled human IgM and the effect of anti-PC on the uptake of OxLDL was studied by FACScan.


RESULTS
Relative risks (RR) with 95% confidence intervals (CI) by quartiles of anti-PC levels with quartile 4 set as the reference value (RR = 1.0) and adjusted for smoking, BMI, type II diabetes, hypercholesterolaemia, and high blood pressure yielded an excess risk for CVD only for those within the lowest quartile of anti-PC values with an RR of 1.37 (CI 0.87-2.16). However, for men stronger associations were noted with increasing multivariately adjusted RRs from quartile 4 to quartile 1. Subjects within quartile 1 (values below 29.7 U/ml) had a significantly increased RR of 1.96 (CI 1.09-3.55). Further adjustments for hsCRP gave essentially the same results. No excess risk was noted for women. Specific anti-PC could be extracted from IgM and these antibodies inhibited macrophage uptake of OxLDL.


CONCLUSIONS
Low IgM anti-PC could be a novel risk marker for CVD among men. One possible mechanism could be inhibition of uptake of oxLDL in macrophages.
de Faire
Ulf
U
Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, S-171 77 Stockholm, Sweden. ulf.defaire@ki.se
Su
Jun
J
Hua
Xiang
X
Frostegård
Anna
A
Halldin
Mats
M
Hellenius
Mai-Lis
ML
Wikström
Max
M
Dahlbom
Ingrid
I
Grönlund
Hans
H
Frostegård
Johan
J
D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology*; D002460:Cell Line; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood / Q000494:pharmacology*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D010767:Phosphorylcholine / Q000276:immunology*; D011379:Prognosis; D012306:Risk; D012737:Sex Factors; D013548:Sweden
D015415:Biomarkers; D007075:Immunoglobulin M; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D010767:Phosphorylcholine