Comment 
Share 
Cite
Print
Text size
Download slides
La Jolla, CA - Circulating levels of oxidized LDL (OxLDL)-specific markers strongly reflect the presence of ACS and may offer a new predictive marker and clues to the links between the immune system, cholesterol, and artery plaque rupture, an article in the Feb 5 issue of the Journal of the American College of Cardiology indicates.1
In a small prospective study, researchers, led by Dr Sotirios Tsimikas (University of California at San Diego), measured circulating oxidized-LDL levels through immunoassay in patients with MI (n=8), unstable angina (n=15), stable coronary artery disease (n=17), angiographically normal coronary arteries (n=8), and healthy subjects (n=18). Measurements were taken at entry into study, at discharge for the MI group, and then at 30-, 120-, and 210-day follow-up.
The concept that oxidized LDL is involved in the creation of foam cells has been around for 20 years, but its role in the clinical arena has remained unclear. "There's a whole body of experimental data in animal models, but now these measures are finally being applied to patient populations," said Tsimikas in a press statement.
Tsimikas's group measured immunoglobin (Ig)M OxLDL autoantibody titers, LDL autoantibody immune complexes (LDL-ICs), and minimally oxidized LDL, measured by antibody E06. Tracking the rise and fall of these blood markers over time, the researchers found the markers showed significant changes from baseline in the ACS patients, both those having MI and those with unstable angina, while not varying significantly for those without ACS.
Percent increase from baseline for antibody titers in MI and UA groups at 30 days|
Patient group |
IgM OxLDL (%) |
IgM LDL-IC (%) |
OxLDL-E06 (%) |
|
MI | 48 (p<0.001) | 60 (p<0.01) | 36 (p=0.015) |
|
UA | 20 (p<0.001) | 26 (p<0.01) | NS |
Lp(a)
In parallel with the rise in OxLDL-E06 antibody in the MI group, there was a 2-fold rise in Lp(a). There was no significant change over time in Lp(a) in any other group. The levels of OxLDL-E06 correlated extremely well with Lp(a) in all groups across the entire study (r=0.91, p<0.00001)
The authors find this correlation to be of "considerable interest." It suggests that Lp(a) has a strong affinity for oxidized phospholipids, a toxic byproduct of cellular injury such as plaque disruption and myocyte death.
PCI effect?
The authors note that their study is relatively small and that since the majority of the ACS patients underwent PCI, it is possible that plaque disruption due to the PCI itself affected the circulating levels of oxidized LDL. It would be impossible in this study to distinguish between plaque disruption due to PCI and spontaneous plaque rupture.
They also note the lack of pre-presentation levels of the OxLDL markers, which leaves open the possibility that these are not direct contributors to plaque disruption but are only epiphenomena. The authors counter this suggestion by pointing out that previous studies have documented a direct relationship between OxLDL and the clinical presentation.
The authors propose prospective studies in larger roups of patients to evaluate whether these measurements will provide long-term prognostic information.
"Since these markers change only in people who have acute coronary syndromes, we may be able to apply them before people have events and maybe predict risk," Tsimikas said.
