Elevated Levels of Oxidized Low Density Lipoprotein Show a Positive Relationship With the Severity of Acute Coronary Syndromes

TLDR

Acute coronary syndromes are linked to inflammation of atherosclerotic plaques, and elevated oxidized LDL may contribute to this process. Ox‑LDL was quantified in 135 patients with AMI, UAP, or SAP and 46 controls using ELISA, and immunohistochemistry on 33 atherectomy specimens from SAP and UAP patients assessed ox‑LDL–positive macrophages. Ox‑LDL levels rose with acute coronary syndrome severity—highest in AMI, lower in UAP, lowest in SAP and controls—and ox‑LDL–positive macrophages were more abundant in unstable lesions, indicating a link between ox‑LDL and plaque instability.

Abstract

Background —There is accumulating data that acute coronary syndromes relate to recent onset activation of inflammation affecting atherosclerotic plaques. Increased blood levels of oxidized low density lipoprotein (ox-LDL) could play a role in these circumstances. Methods and Results —Ox-LDL levels were measured in 135 patients with acute myocardial infarction (AMI; n=45), unstable angina pectoris (UAP; n=45), and stable angina pectoris (SAP; n=45) and in 46 control subjects using a sandwich ELISA method. In addition, 33 atherectomy specimens obtained from a different cohort of patients with SAP (n=10) and UAP (n=23) were studied immunohistochemically for ox-LDL. In AMI patients, ox-LDL levels were significantly higher than in patients with UAP ( P <0.0005) or SAP ( P <0.0001) or in controls ( P <0.0001) (AMI, 1.95±1.42 ng/5 μg LDL protein; UAP, 1.19±0.74 ng/5 μg LDL protein; SAP, 0.89±0.48 ng/5 μg LDL protein; control, 0.58±0.23 ng/5 μg LDL protein). Serum levels of total, HDL, and LDL cholesterol did not differ among these patient groups. In the atherectomy specimens, the surface area containing ox-LDL–positive macrophages was significantly higher in patients with UAP than in those with SAP ( P <0.0001). Conclusions —This study demonstrates that ox-LDL levels show a significant positive correlation with the severity of acute coronary syndromes and that the more severe lesions also contain a significantly higher percentage of ox-LDL–positive macrophages. These observations suggest that increased levels of ox-LDL relate to plaque instability in human coronary atherosclerotic lesions.