2.4.1 Subclinical atherosclerosis: oxidized LDL as a marker of asymptomatic cardiovascular disease

In 1998, Holvoet at the Katholieke Universiteit Leuven, Belgium demonstrated for the first time that elevated circulating levels of oxLDL were found in most untreated patients with both stable CAD and acute coronary syndromes (unstable angina and acute MI). In this study, oxLDL levels were measured in plasma with an ELISA procedure using the monoclonal antibody 4E6, originally developed by professor Holvoet and colleagues. Since Holvoet’s landmark discovery and the commercial introduction of the Mercodia oxLDL ELISAs, based on the same antibody, the literature has been extensive in providing further support for Holvoet’s 1998 findings and expanding the importance of oxLDL as a marker of cardiovascular disease.

Figure. Compared to controls, oxidized LDL levels ar elevated in patients with stable angina, unstable angina and acute myocardial infarction (AMI). Published data by Holvoet et al. (1998).

In 2002, Hulthe and Fagerberg at the Sahlgrenska University Hospital, Gothenburg, Sweden tested 391 clinically healthy 58-year old Swedish men from the AIR study and found that oxidized LDL was associated with subclinical atherosclerosis (clinically silent atherosclerotic changes in the carotid and femoral arteries assessed by ultrasound). Otherwise healthy patients with at least one plaque in the carotid or femoral arteries were shown to have higher oxidized LDL levels compared to patients with no plaques. The results support the concept that oxidatively modified LDL may play a major role in the development of atherosclerosis.

Furthermore, baseline oxidized LDL levels have also been found to predict the progression of subclinical atherosclerosis. In a study by Wallenfeldt and colleagues at the Sahlgrenska University Hospital, Gothenburg, Sweden in 2004, the oxLDL levels at entry of the study correlated significantly with the number and size of plaques at 3-year follow-up, demonstrating that oxLDL in plasma is a prognostic biomarker of the subclinical atherosclerosis development. Oxidized LDL at entry, but not LDL cholesterol, was associated with the number and size of plaques present, and proved to be a strong predictor of the progression of atherosclerosis in the carotid arteries.

Liu and colleagues at the Helsinki University Central Hospital, Finland analyzed the potential determinants of circulating oxLDL in familial combined hyperlipidemia (FCHL) family members without clinical CAD. FCHL is associated with early atherosclerosis and is responsible for more than 10% of premature CAD and is characterized by enhanced generation of free radicals. OxLDL was found to be independently associated with carotid intima media thickness in asymptomatic FCHL family members as well as being a potential marker for early atherosclerosis in FCHL.

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