Soluble CD40 ligand levels indicate lipid accumulation in carotid atheroma: an in vivo study with high-resolution MRI.
OBJECTIVE
The CD40/CD40 ligand pathway mediates inflammatory processes important in atherogenesis and the formation of the intraplaque lipid pool. We tested the hypothesis that plasma levels of soluble CD40 ligand are elevated in patients with evidence of a lipid pool on high-resolution magnetic resonance imaging (MRI) of carotid stenoses.


RESULTS
We recruited 49 patients with evidence of carotid atherosclerosis on ultrasonography; 3 patients could not undergo carotid MRI because of claustrophobia. The remaining 46 patients underwent high-resolution MRI of the carotid arteries. Two radiologists blinded to all other data determined the presence or absence of an intraplaque lipid pool based on the loss of signal between the 20-ms echo time (TE20) and the fat-suppressed TE55 fast spin-echo images. Plasma levels of soluble CD40 ligand were determined by ELISA. Baseline levels of soluble CD40 ligand were higher among patients with evidence of intraplaque lipid (n=14) than among those without it (n=32; median, 2.54 ng/mL; interquartile range [IQR], 1.85 to 3.52 vs median, 1.58 ng/mL; IQR, 1.21 to 2.39; P=0.02). In contrast, soluble CD40 ligand levels were not correlated with percent diameter stenosis (r=-0.19; P=0.21). The relative risk for intraplaque lipid associated with soluble CD40 ligand levels above the median was 6.0 (95% confidence interval, 1.15 to 31.23; P=0.03). The magnitude of this predictive effect did not substantially change after adjustment for traditional cardiovascular risk factors (relative risk, 5.12; 95% confidence interval, 0.78 to 33.73; P=0.09).


CONCLUSIONS
Plasma levels of soluble CD40 ligand may predict patients with features of high-risk atherosclerotic lesions. These data provide novel insight into the mechanism through which elevated levels of soluble CD40 ligand may reflect cardiovascular risk in humans and illustrate the potential value of interfacing high-resolution MRI with studies of vascular inflammation.
Blake
Gavin J
GJ
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass, USA.
Ostfeld
Robert J
RJ
Yucel
E Kent
EK
Varo
Nerea
N
Schönbeck
Uwe
U
Blake
Michael A
MA
Gerhard
Marie
M
Ridker
Paul M
PM
Libby
Peter
P
Lee
Richard T
RT
D000368:Aged; D001161:Arteriosclerosis / Q000097:blood* / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D023201:CD40 Ligand / Q000097:blood*; D002340:Carotid Artery Diseases / Q000097:blood* / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D016893:Carotid Stenosis / Q000000981:diagnostic imaging / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D050356:Lipid Metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D012307:Risk Factors; D016037:Single-Blind Method; D012995:Solubility; D014463:Ultrasonography
D018799:Intercellular Adhesion Molecule-1; D023201:CD40 Ligand