AGE-LDL levels also were significantly associated with an increasing intima-media thickness. Patients in the upper quartile of AGE-LDL were 7.82 times more likely to have high vs. normal intima-media thickness than were those in the lowest quartile; this risk was again highly significant.
In contrast, elevations in conventional biomarkers of cardiovascular disease among this cohort (unmodified LDL, diastolic blood pressure, and HbA1c levels) were much less strongly associated with increased intima-media thickness. “The majority of these associations carry an odds ratio of around a twofold increase in the risk of a heart attack, compared to normal levels. A twofold increase in risk is, in general, considered a strong predictor,” Dr. Lopes-Virella said in the interview.
But even after adjustment for all conventional risk factors, including lipids, blood pressure, and HbA1c, “Ox-LDL and AGE-LDL circulating as immune complexes have been shown to be extremely strong predictors of cardiovascular risk in type 1 diabetes. The tremendous strength of the prediction provided by Ox-LDL and AGE-LDL was quite surprising, but since we studied almost 500 patients, there is very little chance of [its] being just a random association.”
“Whether or not these findings can be applied to predict risk in patients with type 2 diabetes is unclear, since it is possible that the strength of the prediction in type 1 diabetes is related to the fact that type 1 diabetes is an autoimmune disease,” she noted in an interview. “We are doing similar measurements in the serum of patients with type 2 diabetes to see if the levels of Ox-LDL and AGE-LDL circulating as immune complexes are also strongly associated with or predictive of cardiovascular events in type 2 diabetes.”
She would also like to perform similar studies someday on patients without diabetes and in patients with autoimmune disorders other than type 1 diabetes.
The test could be commercialized, Dr. Lopes-Virella added. “Separating the immune complexes by chromatography is relatively simple. You dissociate the two parts of the complex (antigen and antibody moieties), and run an immunoassay against the modified lipoproteins in the antigen moiety.”