Antibodies to oxidized low-density lipoprotein in patients following coronary artery revascularization.
BACKGROUND
Measurement of antibodies to oxidized low-density lipoprotein (AB-oxLDL) has been proposed as a way of identifying individuals at risk for cardiovascular disease beyond the determination of LDL cholesterol (LDL-c) alone. While this hypothesis is appealing, evidence that AB-oxLDL is a risk factor independent of LDL-c levels remains to be established.


RESULTS
We conducted a cross-sectional study of 158 hypercholesterolemic adults who underwent coronary revascularization. Patients were randomized in a clinical trial to a nurse case management (NURS) or an enhanced usual care (EUC) group. The goal in the NURS group was to achieve an LDL-c <85 mg/dl with pharmacotherapy and lifestyle advice. Six months after revascularization, serum and urine were collected to determine lipids, AB-oxLDL, urinary isoprostanes (an in-vivo marker of oxidative damage), oxygen-radical-absorbing capacity (ORAC) of serum, serum carotenoids, alpha-tocopherol and C-reactive protein (CRP). After 6 months of intervention, the NURS group had a mean (+/-SD) LDL-c of 84 (18) mg/dl compared with 105 (25) mg/dl in the EUC group (P < 0.001). In addition, AB-oxLDL was lower (median +/- 95% confidence interval, -202 milliunits (mU)/ml, -372 to -32, P = 0.02) in the NURS group (488 mU/ml, 399, 588) than in the EUC group (690 mU/ml, 544, 847). The difference in AB-oxLDL between groups persisted after adjustment for LDL-c (-316 mU/ml, -519 to -112, P = 0.005). Further adjustment for ORAC and alpha-tocopherol did not diminish the group effect. The groups did not differ significantly in serum antioxidants, urinary isoprostane excretion or CRP. In additional analyses, change in LDL-c from baseline was not associated with AB-oxLDL at 6 months.


CONCLUSIONS
Our results demonstrate lower AB-oxLDL in patients who achieve greater lipid reduction. However, AB-oxLDL appears to be independent of achieved LDL-c, ORAC levels or serum antioxidant levels. These results support the hypothesis that AB-oxLDL is independent of LDL-c level. Further prospective studies are needed to determine the prognostic value of AB-oxLDL.
Miller
Edgar R
ER
Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205-2233, USA. ermiller@jhmi.edu
Erlinger
Thomas P
TP
Blumenthal
Roger S
RS
Margolis
Simeon
S
Allen
Jerilyn K
JK
D000368:Aged; D000906:Antibodies / Q000097:blood* / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood* / Q000188:drug therapy / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy / Q000601:surgery; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008077:Lipoproteins, LDL / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009204:Myocardial Revascularization; D010084:Oxidation-Reduction / Q000187:drug effects; D011237:Predictive Value of Tests; D011446:Prospective Studies; D017382:Reactive Oxygen Species / Q000097:blood; D013223:Statistics as Topic; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D000906:Antibodies; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; D014280:Triglycerides; C099252:oxidized low density lipoprotein; D002097:C-Reactive Protein