Oxidized phospholipids predict the presence and progression of carotid and femoral atherosclerosis and symptomatic cardiovascular disease: five-year prospective results from the Bruneck study.

Abstract

OBJECTIVES:

The purpose of this work was to determine the predictive value of oxidized phospholipids (OxPLs) present on apolipoprotein B-100 particles (apoB) in carotid and femoral atherosclerosis.

BACKGROUND:

The OxPLs are pro-inflammatory and pro-atherogenic and may be detected using the antibody E06 (OxPL/apoB).

METHODS:

The Bruneck study is a prospective population-based survey of 40- to 79-year-old men and women initiated in 1990. Plasma levels of OxPL/apoB and lipoprotein (a) [Lp(a)] were measured in 765 of 826 (92.6%) and 671 of 684 (98.1%) subjects alive in 1995 and 2000, respectively, and correlated with ultrasound measures of carotid and femoral atherosclerosis.

RESULTS:

The distribution of the OxPL/apoB levels was skewed to lower levels and nearly identical to Lp(a) levels. The OxPL/apoB and Lp(a) levels were highly correlated (r = 0.87, p < 0.001), and displayed long-term stability and lacked correlations with most cardiovascular risk factors and lifestyle variables. The number of apolipoprotein (a) kringle IV-2 repeats was inversely related to Lp(a) mass (r = -0.48, p < 0.001) and OxPL/apoB levels (r = -0.46, p < 0.001). In multivariable analysis, OxPL/apoB levels were strongly and significantly associated with the presence, extent, and development (1995 to 2000) of carotid and femoral atherosclerosis and predicted the presence of symptomatic cardiovascular disease. Both OxPL/apoB and Lp(a) levels showed similar associations with atherosclerosis severity and progression, suggesting a common biological influence on atherogenesis.

CONCLUSIONS:

This study suggests that pro-inflammatory oxidized phospholipids, present primarily on Lp(a), are significant predictors of the presence and extent of carotid and femoral atherosclerosis, development of new lesions, and increased risk of cardiovascular events. The OxPL biomarkers may provide valuable insights into diagnosing and monitoring cardiovascular disease.

• Authors: Sotirios Tsimikas, Stefan Kiechl, Johann Willeit, Manuel Mayr, Elizabeth R Miller, Florian Kronenberg, Qingbo Xu, Claes Bergmark, Siegfried Weger, Friedrich Oberhollenzer, Joseph L Witztum
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 47 Issue 11 Pg. 2219-28 (Jun 06 2006) ISSN: 1558-3597 [Electronic] United States
• PMID: 16750687 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins B
• Biomarkers
• Inflammation Mediators
• Lipoprotein(a)
• Phospholipids

Topics

• Aged
• Aging (blood)
• Apolipoproteins B (blood, chemistry)
• Atherosclerosis (blood)
• Biomarkers (blood)
• Cardiovascular Diseases (blood)
• Carotid Artery Diseases (blood)
• Female
• Femoral Artery
• Humans
• Inflammation Mediators (blood)
• Intracranial Arteriosclerosis (blood)
• Lipoprotein(a) (blood, genetics)
• Male
• Middle Aged
• Oxidation-Reduction
• Phenotype
• Phospholipids (analysis, blood, metabolism)
• Predictive Value of Tests
• Prospective Studies