Adipocyte fatty acid binding protein in atherosclerotic plaques is associated with local vulnerability and is predictive for the occurrence of adverse cardiovascular events.
OBJECTIVE
There is an increasing need for translational studies identifying molecular targets contributing to atherosclerotic plaque destabilization. Local molecular plaque markers that are related to plaque vulnerability may hold predictive value to identify patients who are at increased risk to suffer from cardiovascular events. Animal studies revealed that adipocyte fatty acid binding protein (FABP4) is associated with the progression of atherosclerosis; however, FABP4 expression studies in human atherosclerotic plaques are lacking. We investigated FABP4 expression in carotid atherosclerotic lesions in relation to plaque composition and future cardiovascular events.


RESULTS
Atherosclerotic plaques were obtained from 561 patients undergoing carotid endarterectomy (CEA). Plaques were analysed for the presence of macrophages, lipid core, smooth-muscle cells, collagen, calcification, and intraplaque haemorrhage. Patients were followed for 3 years after CEA. The primary outcome was defined as the composite of vascular death, vascular event, and surgical or percutaneous vascular intervention. Fatty acid binding protein levels correlated with unstable plaque characteristics and symptomatic lesions. Patients with increased FABP4 plaque levels showed a two-fold increased risk [HR = 1.99, 95% confidence interval (95% CI) (1.30-3.04)] (P = 0.005) to reach the primary outcome during follow-up. Increased FABP4 levels related to primary outcome, independent from general cardiovascular risk factors [HR = 1.33, 95% CI (1.08-1.65)] (P = 0.008).


CONCLUSIONS
FABP4 levels in atherosclerotic lesions are associated with an unstable plaque phenotype and an increased risk for cardiovascular events during follow-up. Besides risk stratification for adverse future cardiovascular events, the outcome of the present study supports the relevance of exploring FABP4 antagonists as a potential pharmaceutical intervention to treat atherosclerotic disease progression.
Experimental Cardiology Laboratory, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands. w.peeters-2@umcutrecht.nl
Wouter
W
Peeters
Dominique P V
DP
de Kleijn
Aryan
A
Vink
Sander
S
van de Weg
Arjan H
AH
Schoneveld
Siu Kwan
SK
Sze
Peter J
PJ
van der Spek
Jean-Paul P M
JP
de Vries
Frans L
FL
Moll
Gerard
G
Pasterkamp
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000097:blood* / Q000401:mortality / Q000473:pathology; D016757:Death, Sudden, Cardiac / Q000209:etiology; D018450:Disease Progression; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality; D058226:Plaque, Atherosclerotic / Q000097:blood* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D020521:Stroke / Q000401:mortality
D015415:Biomarkers; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins