Carotid Atherosclerotic Calcification Characteristics Relate to Post-stroke Cognitive Impairment

Background: Together with cerebral small vessel disease (CSVD), large vessel atherosclerosis is considered to be an equally important risk factor in the progression of vascular cognitive impairment. This article aims to investigate whether carotid atherosclerotic calcification is associated with the increased risk of post-stroke cognitive impairment (PSCI).Methods: A total of 128 patients (mean age: 62.1 ± 12.2 years, 37 women) suffering from ischemic stroke underwent brain/neck computer tomography angiography examination. The presence and characteristic of carotid calcification (size, number and location) were analyzed on computer tomography angiography. White matter hyperintensity (WMH) was assessed using Fazekas scales. PSCI was diagnosed based on a battery of neuropsychological assessments implemented 6−12 months after stroke.Results: Among 128 patients, 26 developed post-stroke dementia and 96 had carotid calcification. Logistic regression found carotid calcification (odds ratio [OR] = 7.15, 95% confidence interval [CI]: 1.07–47.69) and carotid artery stenosis (OR = 6.42, 95% CI: 1.03–40.15) both significantly increased the risk for post-stroke dementia. Moreover, multiple, thick/mixed, and surface calcifications exhibited an increasing trend in PSCI (Ptrend = 0.004, 0.016, 0.045, respectively). The prediction model for post-stroke dementia including carotid calcification (area under curve = 0.67), WMH (area under curve = 0.67) and other covariates yielded an area under curve (AUC) of 0.90 (95% CI: 0.82–0.99).Conclusion: Our findings demonstrated that the quantity and location of carotid calcifications were independent indicators for PSCI. The significant role of large vessel atherosclerosis in PSCI should be concerned in future study.

Assessing robustness of carotid artery CT angiography radiomics in the identification of culprit lesions in cerebrovascular events

Radiomics, quantitative feature extraction from radiological images, can improve disease diagnosis and prognostication. However, radiomic features are susceptible to image acquisition and segmentation variability. Ideally, only features robust to these variations would be incorporated into predictive models, for good generalisability. We extracted 93 radiomic features from carotid artery computed tomography angiograms of 41 patients with cerebrovascular events. We tested feature robustness to region-of-interest perturbations, image pre-processing settings and quantisation methods using both single- and multi-slice approaches. We assessed the ability of the most robust features to identify culprit and non-culprit arteries using several machine learning algorithms and report the average area under the curve (AUC) from five-fold cross validation. Multi-slice features were superior to single for producing robust radiomic features (67 vs. 61). The optimal image quantisation method used bin widths of 25 or 30. Incorporating our top 10 non-redundant robust radiomics features into ElasticNet achieved an AUC of 0.73 and accuracy of 69% (compared to carotid calcification alone [AUC: 0.44, accuracy: 46%]). Our results provide key information for introducing carotid CT radiomics into clinical practice. If validated prospectively, our robust carotid radiomic set could improve stroke prediction and target therapies to those at highest risk.

Correlating Ex Vivo Carotid Calcification Measurements With Cerebrovascular Symptoms

Background and Purpose: The purpose of this study is to examine the ability of ex vivo derived Agatston, Volume, and Density-Volume calcium scores or calcium density measurements to differentiate between carotid plaques based on preoperative cerebrovascular symptomatology. Methods: Thirty-eight carotid plaques were acquired from standard endarterectomy. Micro-computed tomography was performed on the ex vivo samples. Image series were downsampled to represent the resolution of clinical multidetector computed tomography. Agatston, Volume, and Density-Volume carotid calcium scores were then calculated using coronary methodologies. The fractions of low- and high-density calcification were also determined. Results: The coronary calcium scores could not differentiate between carotid plaques from asymptomatic versus symptomatic patients. However, plaques from asymptomatic patients contained significantly lower fractions of low-density calcification and higher fractions of high-density calcification. Conclusions: Screening for carotid calcium density in noncontrast computed tomography could reflect plaque stability.

Added value of femoral artery atherosclerosis for determining severity of white matter lesion by carotid atherosclerosis: a magnetic resonance imaging study

Background Previous studies reported that single vascular atherosclerosis was an effective indicator for white matter lesions (WMLs). Purpose To investigate the added value of femoral atherosclerosis for determining severity of WMLs by carotid atherosclerosis using three-dimensional vessel wall magnetic resonance imaging (MRI). Material and Methods Elderly individuals without cardiovascular symptoms within the previous six months were recruited. The plaque features of carotid and femoral arteries were evaluated and compared between individuals with WML score ≤ 3 and those with WML score > 3. Logistic regression and receiver operating characteristic (ROC) analyses were used to determine the value of plaque features in discriminating WMLs with score > 3. Results In total, 112 individuals (49 men, mean age 72.0±5.6 years) were included. Participants with a WML score > 3 showed a significantly greater carotid wall area and femoral artery stenosis and higher incidence of carotid calcification and femoral artery calcification and lipid-rich necrotic cores (LRNC) compared to those with a WML score ≤ 3 (all P < 0.05). Carotid artery calcification and femoral artery calcification, LRNC, and stenosis were found to be significantly associated with severe WMLs before and after adjustment for clinical factors (odds ratio 1.51–3.79, all P < 0.05). ROC analysis showed, in discriminating severe WMLs, the area under the curve increased from 0.615 to 0.754 after combining femoral artery LRNC and stenosis with carotid calcification compared to the carotid calcification alone. Conclusion Characteristics of femoral artery atherosclerosis determined by vessel wall MRI have added value for carotid atherosclerosis in determining the severity of WMLs.

Elevated serum sortilin is related to carotid plaque concomitant with calcification

Aim: To explore whether elevated serum sortilin was associated with calcified carotid plaque and ischemic stroke. Methods: A total of 171 patients with cardiovascular risk factors were enrolled. Ultrasonography was performed to evaluate calcified plaques and noncalcified plaques. Serum sortilin concentration was measured by ELISA. Results: Serum sortilin level was higher in patients with calcified carotid plaque and positively related to carotid plaque burden, but not with ischemic stroke during the follow-up. Multivariable logistic regression analysis revealed serum sortilin level was an independent determinant for calcified carotid plaque (p = 0.001). Receiving operating characteristic analysis showed an area under the curve of sortilin for carotid calcification was 0.759. Conclusion: Higher serum sortilin level was associated with carotid calcification and severe carotid plaque score.

Abstract TP482: Carotid Calcification Predicts Systemic Vascular Events

Background and Objective: It is well known that systemic arterial calcifications progress simultaneously. And coronary calcifications are a well-known predictor of coronary event in the future. Impact of carotid artery calcifications for cerebral stroke is still controversial among various articles, and the relationship between carotid artery calcifications and systemic vascular events are not known either. In this study, we aim to examine if the carotid calcification can be used as a predictor of systemic vascular events. Methods: This is a prospective study, which enrolled 199 subjects who have already suffered from vascular events, including carotid stenosis, coronary syndromes or stroke. We collected data at entry on risk factors, blood examination, and whole-body computed tomography analysis to assess the calcifications of carotid, coronary, aorta (three distinct part; arch, abdominal, and bifurcation) and renal artery using modified Agatston calcium score (ACS) for each vessel. According to the median carotid ACS, subjects were divided into two groups. And during 5 years of follow up period, cerebrovascular events, coronary events and other systemic vascular events were counted. Results: Carotid ACS has a stronger correlation with aortic ACS than coronary ACS. Hypertension and low renal function have significant impact on increasing carotid ACS, while a diabetes mellitus increase coronary calcification. On Kaplan-Meier estimates, subjects with higher carotid ACS (higher group) suffered more systemic vascular events than lower group (p=0.03, log rank correlation coefficient), and hazard ratio was 1.88 (95%CI; 1.02-3.46). There was no significant difference in the risk of cerebral or coronary events, however, higher group have tendency to be treated for aortic or peripheral arterial disease in the follow up period (HR6.86, 0.9-54.7). Conclusion: Carotid ACS have strong correlation with systemic large vascular bed including aorta, and can be a useful tool to extract a subject who will be suffered from systemic vascular event in the future.

Assessment of relationship between extracranial and intracranial carotid calcifications—a retrospective cone beam computed tomography study

Objectives: Cone beam CT scans in current day dental practice are highly collimated yet involve areas along the course of the extracranial carotid artery. Detecting an extracranial carotid calcification on small volume scans leaves the dentist with two questions: whether the patient is likely to have intracranial carotid calcifications and whether the patient warrants further medical attention. This study aimed to assess the presence of intracranial carotid artery calcifications (ICAC) in the presence of extracranial carotid artery calcifications (ECAC). Methods: 450 CBCT scans were retrospectively evaluated for ECAC and ICAC. Erby et al’s classification was modified to classify calcifications as mild, moderate, and severe. The presence of ICAC when ECAC were present was evaluated in all three orthogonal planes. The risk of ICAC in the presence of ECAC was calculated as odds ratio and the association between the two was calculated using a χ2 test. Results: The odds ratio for bilateral ICAC in the presence of bilateral ECAC was 15.09. The odds ratio for left ICAC/right ICAC in the presence of left/ right ECAC was 0.833 and 2.564, respectively. The number and severity of calcifications increased with age. The χ2 test showed that there was a strong association (p < 0.001) between bilateral ECAC with bilateral ICAC. Conclusions: The results of this group of patients showed that there is an increased presence of ICAC in the presence of ECAC.

3045Role of osteogenic circulating endothelial progenitor cells in dissemination of large arterial calcification in rheumatoid arthritis

Background Rheumatoid arthritis is associated with both abnormal bone metabolism and atherogenesis but mechanistic links were missing. Aim This study aimed to investigate the role of osteocalcin (OCN)-expressing circulating endothelial progenitor cells (EPC)s in the severity and dissemination of systemic arterial calcifications in rheumatoid arthritis. Methods We performed flow cytometry studies in 145 consecutive patients with rheumatoid arthritis to determine osteogenic circulating levels of OCN-positive (OCN+) CD34+KDR+ and OCN+CD34+, versus conventional early EPC CD34+CD133+KDR+. Total calcium load of the thoracic aorta (ascending plus descending) and the carotid arteries were assessed by non-contrast computed tomography (CT) and contrast CT angiography. Results Osteogenic EPCs OCN+CD34+KDR+ (P=0.002) and OCN+CD34+ were strikingly associated with the clustered presence of aortic and carotid calcification (P=0.002 and 0.001 respectively, Figure). Multivariable analyses revealed that circulating OCN+CD34+KDR+ (B=14.4 [95% CI 4.0 to 24.8], P=0.007) and OCN+CD34+ (B=9.6 [95% CI 4.9 to 14.3], P<0.001) remained independently associated with increased aortic calcium load. OCN+CD34+ EPC (B=0.8 [95% CI 0.1 to 1.5], P=0.023), but not OCN+CD34+KDR+ EPC (B=1.2 [95% CI −0.2 to 2.6], P=0.09) was further independently associated with carotid calcium load. In comparison, conventional early EPC CD34+CD133+KDR+ had no significant association with aortic or carotid calcium load (P=0.46 and 0.88, respectively). Conclusions Circulating level of osteogenic EPC is associated with promulgated aortic and carotid calcification in patients with rheumatoid arthritis, suggesting a potential mechanistic role of the bone-vascular axis in pro-atherogenicity of rheumatic diseases. Acknowledgement/Funding General Research Fund, Hong Kong Research Grants Council