A pathobiologic link between risk factors profile and morphological markers of carotid instability.
OBJECTIVE
Although cardiovascular risk factors have been strongly linked to carotid intimal-media thickness, their association with plaque progression towards instability is poorly understood. We evaluated a large database of endarterectomy specimens removed from symptomatic and asymptomatic patients to determine the correlation between major cardiovascular risk factors and carotid plaque morphology.


METHODS
Incidence of thrombotic, vulnerable and stable plaques together with the degree of plaque inflammatory infiltration was evaluated in 457 carotid atherosclerotic lesions. Clinical records were reviewed in all cases for risk factors profile.


RESULTS
Thrombotic plaques were more frequently observed in patients affected by stroke (66.9%) as compared to TIA (36.1%) and asymptomatic patients (26.8%, p<0.001). Out of 457 carotid plaques removed during carotid endarterectomy, 181 (39.6%) were represented by thrombotic plaques, 72 (15.8%) by vulnerable plaques (thin cap fibroateroma) and 204 (44.6%) by stable plaques. At the multivariate analysis, a strong association was observed between hypertension, low HDL-cholesterol (HDL-C) and ratio of total to HDL-C >5 with vulnerable and thrombotic carotid plaques. Hypertension (p=0.001), hypercholesterolemia (p=0.05) and low HDL-C (p=0.001) significantly also correlated with the presence of high inflammatory infiltrate of the plaque. When multivariate analysis was restricted to asymptomatic patients, hypertension (p=0.009, OR 2.29), low HDL-cholesterol (p=0.01 OR 2.21) and the ratio of total to HDL-C >5 (p=0.03, OR 2.07) were confirmed to be the risk factors most significantly associated to unstable plaques. The relative risk to carry an unstable plaque for asymptomatic patients with high Framingham Risk Score as compared with those with low risk score was 2.06 (95% C.I., 1.26-3.36).


CONCLUSIONS
The present histopathological study identifies risk factors predictive of increased risk of carotid plaque rupture and thrombosis. Asymptomatic patients with high risk factors profile may constitute a specific target to reduce the likelihood of cerebrovascular accidents even in the presence of non-flow-limiting plaque.
Mauriello
Alessandro
A
Cattedra di Anatomia ed Istologia Patologica, Dipartimento di Biopatologia e Diagnostica per Immagini, Anatomic Pathology, University of Rome Tor Vergata, Via Montpellier 1, 00133 Roma, Italy. alessandro.mauriello@uniroma2.it
Sangiorgi
Giuseppe M
GM
Virmani
Renu
R
Trimarchi
Santi
S
Holmes
David R
DR
Kolodgie
Frank D
FD
Piepgras
David G
DG
Piperno
Giulia
G
Liotti
Doriana
D
Narula
Jagat
J
Righini
Paolo
P
Ippoliti
Arnaldo
A
Spagnoli
Luigi G
LG
D000368:Aged; D001792:Blood Platelets / Q000166:cytology; D002318:Cardiovascular Diseases / Q000175:diagnosis* / Q000378:metabolism*; D002339:Carotid Arteries / Q000378:metabolism* / Q000473:pathology*; D008076:Cholesterol, HDL / Q000378:metabolism; D004691:Endarterectomy / Q000379:methods; D016894:Endarterectomy, Carotid / Q000379:methods; D005260:Female; D006801:Humans; D006973:Hypertension / Q000473:pathology; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis / Q000473:pathology; D013927:Thrombosis / Q000473:pathology; D014057:Tomography, X-Ray Computed / Q000379:methods
D008076:Cholesterol, HDL