Oxidized phospholipids predict the presence and progression of carotid and femoral atherosclerosis and symptomatic cardiovascular disease: five-year prospective results from the Bruneck study.
OBJECTIVE
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.
Tsimikas
Sotirios
S
Department of Medicine, University of California San Diego, La Jolla, California 92093-0682, USA. stsimikas@ucsd.edu
Kiechl
Stefan
S
Willeit
Johann
J
Mayr
Manuel
M
Miller
Elizabeth R
ER
Kronenberg
Florian
F
Xu
Qingbo
Q
Bergmark
Claes
C
Weger
Siegfried
S
Oberhollenzer
Friedrich
F
Witztum
Joseph L
JL
D000368:Aged; D000375:Aging / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood* / Q000737:chemistry; D050197:Atherosclerosis / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood*; D002340:Carotid Artery Diseases / Q000097:blood*; D005260:Female; D005263:Femoral Artery; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D002537:Intracranial Arteriosclerosis / Q000097:blood*; D017270:Lipoprotein(a) / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D010641:Phenotype; D010743:Phospholipids / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D011237:Predictive Value of Tests; D011446:Prospective Studies
D001055:Apolipoproteins B; D015415:Biomarkers; D018836:Inflammation Mediators; D017270:Lipoprotein(a); D010743:Phospholipids