Oxidized low‐density lipoprotein in plasma is a prognostic marker of subclinical atherosclerosis development in clinically healthy men

Abstract

Objective. To investigate the association between plasma oxidized low-density lipoprotein (OxLDL) and the progress of clinically silent atherosclerosis, as measured by ultrasound in the carotid arteries. Design. Prospective, observational study with more than 3 years of follow-up. Setting. One-centre study at university hospital. Material and methods. The subjects (n ¼ 326) were obtained by stratified sampling from a population sample of men who were 58 years old at baseline. Carotid artery intima-media thickness (IMT) was measured bilaterally by high-resolution B-mode ultrasound at baseline and after follow-up. Plasma OxLDL cholesterol concentrations and conventional cardiovascular risk factors were measured at study entry. Automated measurements of IMT were performed. Plaque occurrence and size were assessed (plaque status). Plasma OxLDL at entry was measured by a specific monoclonal antibody, mAb-4E6.Results. OxLDL at entry, but not LDL cholesterol, was associated with the number and size of plaques at follow-up (P ¼ 0.008), also after adjustment for plaque status at entry (P ¼ 0.033). The plasma OxLDL concentration at entry was associated with change in carotid artery IMT (r ¼ 0.17; P ¼ 0.002) and in a stepwise multiple regression analysis this association remained after adjustment for other cardiovascular risk factors (P ¼ 0.005). Conclusions. These results provide new information, supporting the concept that circulating OxLDL was associated with the silent phase of atherosclerosis progression in clinically healthy men independently of conventional risk factors.

Role of Inflammation in Atherosclerosis

“…In a prospective study, Shimada et al (114) observed 238 patients with CAD for a mean of 52 mo and showed that baseline levels of OxLDL-DLH3 were significantly higher in patients with the subsequent development of cardiac death, nonfatal myocardial infarction, and unstable angina. In a prospective study, Wallenfeldt et al (115) showed that baseline OxLDL-4E6 levels predicted the progression of carotid artery intimamedia thickness in asymptomatic and presumably healthy 58-y-old Swedish men, independent of other cardiovascular risk factors. In summary, OxLDL may serve as an attractive biomarker because it may provide a link between lipoprotein disorders and inflammation.…”

Air Pollution and Cardiovascular Disease

“…PM induces highdensity lipoprotein (HDL) dysfunction with loss of its anti-inflammatory properties (Araujo and Nel 2009). Oxidative transformation of LDL into ox-LDL is a key step in the initiation and progression of atherosclerosis (Stocker and Keaney 2004), and circulating levels of ox-LDL are therefore an early marker, and a risk factor for the disease (Wallenfeldt et al 2004). The correlation between PM exposure and circulating levels of ox-LDL on an individual level was shown by Jacobs et al, demonstrating a dose-dependent association between this parameter and the carbon load of airway macrophages, a personal marker for chronic exposure to fossil fuel derived ultrafine particles (Jacobs et al 2011).…”

Oxidized LDL impair adipocyte response to insulin by activating serine/threonine kinases

“…Interestingly, several studies have demonstrated that increased plasma oxLDL concentration is associated with the metabolic syndrome (45)(46)(47)(48). Although the actual extent of in vivo interactions between adipose tissue and lipoproteins is still to be defined, a bulk of data suggests that adipocytes could have a role in the metabolism of circulating lipoproteins including oxLDL.…”