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carotid_artery_atherosclerotic_disease

Carotid artery atherosclerotic disease

Intracranial atherosclerosis related large vessel occlusions (ICAS-O) are challenging to diagnose and manage. The degree of intracranial carotid artery calcification may assist pre-thrombectomy diagnosis of ICAS and guide treatment strategy.


The aim of a study was to report the relationship between cognitive function and risk factors at baseline and during follow-up in the Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS) trial.

Subjects in the SAMMPRIS trial were included in this study. In order to have an assessment of cognitive function independent of stroke, patients with a stroke as a qualifying event whose deficits included aphasia or neglect were excluded from these analyses as were those with a cerebrovascular event during follow-up. The Montreal Cognitive Assessment (MoCA) score was used to assess cognitive impairment at baseline, 4 months, 12 months and closeout. Cognitive impairment was defined as MoCA < 26. A multivariate analysis was performed to determine what risk factors were independent predictors of cognitive function at baseline, 12 months and closeout. Among patients randomized to aggressive medical management only, the percentage of patients with cognitive impairment was compared between patients in versus out of target for each risk factor at 12 months and closeout.

Of the 451 patients in SAMMPRIS, 371 patients met the inclusion criteria. MoCA < 26 was present in 55% at baseline. Older age and physical inactivity were associated with cognitive impairment at baseline. Older age, non-white race, lower baseline body mass index, and baseline cognitive impairment were associated with cognitive impairment at 12 months. In the aggressive medical management group, at 12 months, physical inactivity during follow-up was the strongest risk factor associated with cognitive impairment.

Cognitive impairment is common in patients with severe symptomatic intracranial atherosclerosis. Physical inactivity at baseline and during follow-up is a strong predictor of cognitive impairment 1).


A study investigated whether inhalation of fine airborne particulate matters (PM2.5) causes ICA and whether omega-3 fatty acids (O3FA) attenuated the development of ICA.

Twelve but not 6 week exposure significantly increased triglycerides (TG) in normal chow diet (NCD), while PM2.5 enhanced all lipid profiles (TG, low density lipoprotein (LDL) and cholesterol (CHO)) after both 6 and 12-week exposure with high-cholesterol diet (HCD). PM2.5 exposure for 12 but not 6 weeks significantly induced middle cerebral artery (MCA) narrowing and thickening, in association with the enhanced expression of inflammatory cytokines, (interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interferon gamma (IFN-γ)), vascular cell adhesion molecule 1 (VCAM-1) and inducible nitric oxide synthase (iNOS). O3FA significantly attenuated vascular alterations, even without favorable changes in lipid profiles, in association with reduced expression of IL-6, TNF-α, MCP-1, IFN-γ, VCAM-1 and iNOS in brain vessels.

PM2.5 exposure for 12 weeks aggravates ICA in a dietary model (HCD + short-term L-NAME), which may be mediated by vascular inflammation. O3FA dietary supplementation prevents ICA development and inflammatory reaction in cerebral vessels.

Adult Sprague-Dawly rats were under filtered air (FA) or PM2.5 exposure with NCD or HCD for 6 or 12 weeks. Half of the HCD rats were treated with O3FA (5 mg/kg/day) by gavage. A total of 600 mg NG-nitro-L-arginine methyl ester (L-NAME, 3 mg/mL) per rat was administered over two weeks as supplementation in the HCD group. Blood lipids, including LDL, CHO, TG and high density lipoprotein (HDL), were measured at 6 and 12 weeks. ICA was determined by lumen diameter and thickness of the MCA. Inflammatory markers, IL-6, TNF-α, MCP-1, IFN-γ, VCAM-1 and iNOS were assessed by real-time PCR for mRNA and Western blot for protein expression 2).

References


Because atherosclerotic factors and antithrombotic agents sometimes induce cerebral microbleeds (CMBs), patients with cerebral large artery disease (CLAD) tend to have more CMBs than control subjects. On the other hand, VEGF contributes to the disruption of the blood-brain barrier, and it may induce parenchymal edema and bleeding. We conducted a study to evaluate the role of vascular endothelial growth factor (VEGF) in the occurrence of CMBs in patients with CLAD.

CLAD is defined as stenosis or occlusion of either the carotid artery or the middle cerebral artery of 50% or more. We prospectively registered patients with CLAD who were hospitalized in our neurocenter. Biological backgrounds, atherosclerotic risk factors, administration of antithrombotics before hospitalization, and levels of cytokines and chemokines were evaluated. Susceptibility-weighted imaging or T2*-weighted MR angiography was used to evaluate CMBs. The Brain Observer MicroBleed Scale (BOMBS) was used for CMB assessments. Images were analyzed with regard to the presence or absence of CMBs. We also examined plasma VEGF concentrations using a commercial ELISA kit. Because more than half showed plasma VEGF levels below assay detection limits (3.2 pg/mL), the patients were dichotomized by plasma VEGF levels into two groups (above and below the detection limit). After univariate analyses, logistic regression analysis was conducted to determine the factors associated with the CMBs after adjustment for age, sex, the presence of hypertension, and administration of antithrombotic agents. A similar analysis with CMBs separated by location (cortex, subcortex, or posterior circulation) was also conducted.

Sixty-six patients (71.1 ± 8.9 years, 53 males and 13 females) were included in this study. Plasma VEGF levels were not correlated with age, sex, and atherosclerotic risk factors; however, patients with VEGF levels >3.2 pg/mL tended toward more frequent CMBs (60.0 vs. 32.6%, in the presence and absence of CMBs, p = 0.056). With regard to the location of CMBs, those in the cortex and/or at the gray-white junction were observed more frequently in the patients with VEGF levels >3.2 pg/mL after multivariable analyses (odds ratio: 3.80; 95% confidence interval: 1.07-13.5; p = 0.039).

In patients with CLAD, elevated plasma VEGF might be associated with CMBs, especially those located in the cortex and/or at the gray-white junction 3).


Studies in Carotid artery atherosclerotic disease have demonstrated that plaque morphology can contribute to identification of patients at high risk of carotid artery atherosclerosis as well as the degree of stenosis in those with carotid atherosclerosis. Neovascularization of carotid plaques is associated with plaque vulnerability.

Communication of inwardly projecting neovessels with the lumen and inflammation synergistically contribute to intraplaque hemorrhage (IPH) and symptomatic presentations in patients with carotid stenosis and are more specific than the vasa vasorum. This condition could be a new therapeutic target, and regression of luminal neovessel sprouting and inflammation may help to prevent IPH development and a symptomatic presentation 4).


A study tested the hypothesis that inflammation and oxidative stress determined carotid IMT in patients with OSA. The carotid IMT, mean systolic and diastolic pressure (night and morning) were significantly higher and the level of thiols and high-density lipoprotein were significantly lower in our 121 OSA patients than in 27 controls (P < 0.05). The apnea/hypopnea index was correlated positively with E-selectin (r = 0.222, P = 0.014), total cholesterol (r = 0.185, P = 0.042), low-density lipoprotein (r = 0.264, P = 0.003) and HbA1c levels (r = 0.304, P = 0.001), but inversely with high-density lipoprotein level (r = -0.203, P = 0.025) in the 121 patients with OSA. In OSA subjects, multiple linear regression analysis revealed that age, systolic blood pressure and intercellular cell adhesion molecule-1 level associated independently with carotid IMT. Besides both age and systolic blood pressure, our study demonstrated that intercellular cell adhesion molecule-1 level was associated significantly with carotid IMT in those patients who had OSA but without metabolic syndrome 5).

Diagnosis

The determination of the wall thickness [intima-media thickness (IMT)], the delineation of the atherosclerotic carotid plaque, the measurement of the diameter in the common carotid artery (CCA), as well as the grading of its stenosis are important for the evaluation of the atherosclerosis disease. All these measurements are also considered to be significant markers for the clinical evaluation of the risk of stroke. A number of CCA segmentation techniques have been proposed in the last few years either for the segmentation of the intima-media complex (IMC), the lumen of the CCA, or for the atherosclerotic carotid plaque from ultrasound images or videos of the CCA.

Three-dimensional ( 3D three-dimensional ) black blood imaging magnetic resonance (MR) imaging is a noninvasive and accurate way to quantify moderate to severe carotid artery atherosclerotic disease. With fast acquisition and large coverage, 3D three-dimensional BB black blood MR imaging has the potential to become an alternative imaging approach in evaluating the severity of atherosclerosis 6).

1)
Turan TN, Al Kasab S, Smock A, Cotsonis G, Bachman D, Lynn MJ, Nizam A, Derdeyn CP, Fiorella D, Janis S, Lane B, Montgomery J, Chimowitz MI; MBChB for the SAMMPRIS Investigators. Impact of Baseline Features and Risk Factor Control on Cognitive Function in the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis Trial. Cerebrovasc Dis. 2019 Feb 14;47(1-2):24-31. doi: 10.1159/000497245. [Epub ahead of print] PubMed PMID: 30763948.
2)
Guan L, Geng X, Shen J, Yip J, Li F, Du H, Ji Z, Ding Y. PM2.5 inhalation induces intracranial atherosclerosis which may be ameliorated by omega 3 fatty acids. Oncotarget. 2017 Dec 16;9(3):3765-3778. doi: 10.18632/oncotarget.23347. eCollection 2018 Jan 9. PubMed PMID: 29423081; PubMed Central PMCID: PMC5790498.
3)
Ogata T, Dohgu S, Takano K, Inoue T, Arima H, Takata F, Kataoka Y, Tsuboi Y. Increased Plasma VEGF Levels in Patients with Cerebral Large Artery Disease Are Associated with Cerebral Microbleeds. Cerebrovasc Dis Extra. 2019 Apr 30;9(1):25-30. doi: 10.1159/000497215. [Epub ahead of print] PubMed PMID: 31039570.
4)
Horie N, Morofuji Y, Morikawa M, Tateishi Y, Izumo T, Hayashi K, Tsujino A, Nagata I. Communication of inwardly projecting neovessels with the lumen contributes to symptomatic intraplaque hemorrhage in carotid artery stenosis. J Neurosurg. 2015 Jun 19:1-8. [Epub ahead of print] PubMed PMID: 26090834.
5)
Chang YT, Lin HC, Chang WN, Tsai NW, Huang CC, Wang HC, Kung CT, Su YJ, Lin WC, Cheng BC, Su CM, Chen TY, Chiang YF, Lu CH. Impact of inflammation and oxidative stress on carotid intima-media thickness in obstructive sleep apnea patients without metabolic syndrome. J Sleep Res. 2016 Nov 28. doi: 10.1111/jsr.12477. [Epub ahead of print] PubMed PMID: 27896929.
6)
Zhao H, Wang J, Liu X, Zhao X, Hippe DS, Cao Y, Wan J, Yuan C, Xu J. Assessment of Carotid Artery Atherosclerotic Disease by Using Three-dimensional Fast Black-Blood MR Imaging: Comparison with DSA. Radiology. 2014 Oct 3:132687. [Epub ahead of print] PubMed PMID: 25286322.
carotid_artery_atherosclerotic_disease.txt · Last modified: 2019/05/01 11:54 by administrador