Extent and characteristics of carotid plaques and brain parenchymal loss in asymptomatic patients with no indication for revascularization

Abstract

Background and aims: Extent of subclinical atherosclerosis has been associated with brain parenchymal loss in community-dwelling aged subjects. Identification of patient-related and plaque-related markers could identify subjects at higher risk of brain atrophy, independent of cerebrovascular accidents. Aim of the study was to investigate the relation between extent and characteristics of carotid plaques and brain atrophy in asymptomatic patients with no indication for revascularization.

Methods and results: Sixty-four patients (aged 69 ± 8 years, 45% females) with carotid stenosis <70% based on Doppler flow velocity were enrolled in the study. Potential causes of cerebral damage other than atherosclerosis, including history of atrial fibrillation, heart failure, previous cardiac or neurosurgery and neurological disorders were excluded. All subjects underwent carotid computed tomography angiography, contrast enhanced ultrasound for assessment of plaque neovascularization and brain magnetic resonance imaging for measuring brain volumes. On multivariate regression analysis, age and fibrocalcific plaques were independently associated with lower total brain volumes (β = -3.13 and β = -30.7, both p < 0.05). Fibrocalcific plaques were also independently associated with lower gray matter (GM) volumes (β = -28.6, p = 0.003). On the other hand, age and extent of carotid atherosclerosis were independent predictors of lower white matter (WM) volumes.

Conclusions: WM and GM have different susceptibility to processes involved in parenchymal loss. Contrary to common belief, our results show that presence of fibrocalcific plaques is associated with brain atrophy.

Keywords: Brain atrophy; Brain magnetic resonance imaging; Brain volumes; CC-IMT, common carotid intima media thickness; CEUS, contrast enhanced ultrasound; CV, cardiovascular; Cardiovascular risk factors; Carotid atherosclerosis; GFR, glomerular filtration rate; GM, gray matter; TBV, total brain volume; TPA, total plaque area; Vulnerable plaque; WM, white matter.

Fig. 1

Brain volumes of two representative subjects. Panels A-C show respectively a transverse, sagittal and coronal reconstruction of 3D T1-weighted brain scan from the same patient. The subject had a total normalized brain volume of 1451 mL, with 759 mL of grey matter and 692 mL of white matter. Panels D-F show an ultrasound, contrast enhanced ultrasound (CEUS) and computed tomography angiography (CTA) of the right carotid bulb of the same patient. The plaque (white arrows) appears to be lipid rich, as showed by hypoechogenic images in B-mode ultrasound. The plaque also had a lower attenuation in CTA images (274HU). Panels G-I show brain images from a different patient reconstructed at comparable levels. The second subject had more pronounced reduction of cerebral volumes, with a total brain volume of 1341 mL, a grey matter volume of 700 mL and white matte volume of 641 mL. Panels L-N show ultrasound, CEUS and CTA images of the right carotid bifurcation of the second subject. This time the plaque (white arrows) appears markedly fibrocalcific, as demonstrated by posterior acoustic shadows (white arrowheads) in ultrasound images. CTA demonstrates a high attenuation, with a plaque density of 1368HU. In CTA images, the blue line delimitated the contour of the carotid artery, while the blue line showed the lumen of the artery. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Association between cardiovascular risk factors and cerebral volumes. Panels A-C show the significant associations between brain volumes and age; panels D and E the correlation between brain volumes and renal function; panel F the association between grey matter volume and overall cardiovascular risk. WM = white matter; GM = grey matter; eGFR = estimated glomerular filtration rate; FRS = 10-year Framingham risk score.

Fig. 3

Associations between carotid atherosclerosis features and cerebral volumes. Panels A and B show the association between atherosclerotic burden estimated as number of carotid segments involved by the atherosclerotic process and total brain volume and white matter volume. Panels C and D show the significant inverse correlation between plaque density and total and grey matter volumes; the last two panels show the significant association between plaque composition evaluated with ultrasound and total and grey matter volumes. WM = white matter; GM = grey matter; HU = Hounsfield’s unit.