Oxidized low-density lipoprotein (oxLDL)/beta(2)-glycoprotein I (beta2GPI) complexes have been implicated in atherogenesis. oxLDL/beta2GPI complexes were measured in 339 patients with suspected acute coronary syndromes. Approximately 68% had angiographically documented coronary artery disease (CAD) and significantly higher mean + or - SD levels of oxLDL/beta2GPI (3.75 + or - 6.31 U/mL) than patients with normal coronary arteries (2.21 + or - 3.03 U/mL; P = .0026). Patients with severe CAD had significantly higher mean + or - SD levels of oxLDL/beta2GPI (8.71 + or - 12.87 U/mL) compared with the overall mean of 3.25 U/mL (P < .05) and a significantly higher rate (28.9%) of adverse events than the overall rate of 11.2% (P < .05). Patients with adverse events had higher mean + or - SD levels of oxLDL/beta2GPI (4.05 + or - 5.38 U/mL) than patients without adverse events (3.15 + or - 5.53; P = .029). The relative risk for adverse events in higher oxLDL/beta2GPI quartiles was 3.1 (95% confidence interval, 1.0-9.1; P = .06) for quartile 3 and 3.5 (95% confidence interval, 1.2-10.4; P = .02) for quartile 4. Our results support the concept that oxLDL/beta2GPI complexes are associated with severity of CAD and a 3.5-fold increased risk for adverse outcomes.
Antiphospholipid antibodies (aPLs) have been implicated in atherogenesis. We studied 344 patients with acute coronary syndromes; approximately 40% were aPL+ in 1 or more tests and 60% aPL-. In 215 patients, coronary artery disease (CAD) was angiographically documented, with 43.7% positive for aPL vs 34.9% of patients without CAD positive for aPLs. Anti-beta(2)-glycoprotein I (beta2GPI; 54%) and anti-oxidized low-density lipoprotein (oxLDL)/beta2GPI (48%) were most frequent, accounting for 87% of all aPL+ CAD cases. aPLs correlated with severity of CAD (P = .012). Adverse events occurred in 16.7% of patients with CAD, more frequently in patients who were aPL+ (P = .0006; relative risk, 2.9; 95% confidence interval, 1.5-5.6). Patients who were aPL+ with severe CAD had more adverse events than patients who were aPL- with severe CAD (P = .005) and aPL+ patients undergoing revascularization procedures (P = .001). Vascular events occurred in 21.7% of aPL+ patients compared with 7.1% of aPL- patients (P = .005). Anti-beta2GPI and anti-oxLDL/beta2GPI were associated with CAD severity and adverse outcomes.
Background: Testing for the antiphospholipid syndrome (APS) using anticardiolipin antibodies (aCL) has been problematic. Titers may¯uctuate or even become negative. Anti-beta 2-glycoprotein I assays (ab2-GPI) may be more reliable for diagnosis. Methods: In a prospective, blinded study over a nine-month period we retested all patients seen for routine follow-up visits in our clinic who had previously been evaluated for aCL-associated illnesses. Patients were strati®ed into two groups: group AÐpatients previously positive () for aCL; group BÐpatients previously negative (7) for aCL. Both groups were further classi®ed according to disease severity. Patients were retested for both aCL and ab2-GPI (isotypes G, M, A for each) using uniform testing standards. Results: 118 patients with previously positive aCL (group A) were retested. Repeat aCL were positive in 52a118 (44%), ab2-GPI positive in 69a118 (58%) and 82a118 (69.5%) were positive for one or both assays. In patients with serious organ damage (92% with documented APS), 48.6% were aCL positive, 64% positive for ab2-GPI, and 75.7% were positive for one or both assays. When only one assay was positive, ab2-GPI was most frequent (P 0.0096). Overall, IgA ab2-GPI was the most frequent isotype found (60.9%).On retesting of 73 aCL-negative patients (group B), 9a73 (12%) were aCL positive, 27a73 (36%) were ab2-GPI positive, with 24a73 (32.9%) having isolated ab2-GPI. Of those positive for ab2-GPI, IgA ab2-GPI was present in 74.1%. Many of these patients had documented APS. Conclusion: Based on our data, ab2-GPI assays are superior to aCL assays for diagnosis of APS. The combined use of both assays enhance positive testing results in up to 75% of patients with APS at any stage of illness. ACL negative patients suspected of having APS should be retested for both ab2-GPI and aCL. IgA ab2-GPI appears to be the most important isotype detected. Lupus (2000) 9, 33±41
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