Carotid Siphon Calcifications Research Articles

Development and validation of a SCORing systEm for pre-thrombectomy diagnosis of IntraCranial Atherosclerotic Disease (Score-ICAD)

BackgroundEarly identification of intracranial atherosclerotic disease (ICAD) may impact the management of patients undergoing mechanical thrombectomy (MT). We sought to develop and validate a scoring system for pre-thrombectomy diagnosis of...

Increased Intracranial Arterial Pulsatility and Microvascular Brain Damage in Pseudoxanthoma Elasticum.

Carotid siphon calcification might contribute to the high prevalence of cerebrovascular disease in pseudoxanthoma elasticum through increased arterial flow pulsatility. This study aimed to compare intracranial artery flow pulsatility, brain volumes, and small-vessel disease markers between patients with pseudoxanthoma elasticum and controls and the association between arterial calcification and pulsatility in pseudoxanthoma elasticum. Fifty patients with pseudoxanthoma elasticum and 40 age- and sex-matched controls underwent 3T MR imaging, including 2D phase-contrast acquisitions for flow pulsatility in the assessment of ICA and MCA and FLAIR acquisitions for brain volumes, white matter lesions, and infarctions. All patients with pseudoxanthoma elasticum underwent CT scanning to measure siphon calcification. Flow pulsatility (2D phase-contrast), brain volumes, white matter lesions, and infarctions (3D T1 and 3D T2 FLAIR) were compared between patients and controls. The association between siphon calcification and pulsatility in pseudoxanthoma elasticum was tested with linear regression models. Patients with pseudoxanthoma elasticum (mean age, 57 [SD, 12] years; 24 men) had significantly higher pulsatility indexes (1.05; range, 0.94-1.21 versus 0.94; range, 0.82-1.04; P = .02), lower mean GM volumes (597 [SD, 53] mL versus 632 [SD, 53] mL; P < .01), more white matter lesions (2.6; range, 0.5-7.5 versus 1.1; range, 0.5-2.4) mL; P = .05), and more lacunar infarctions (64 versus 8, P = .04) than controls (mean age, 58 [SD, 11] years; 20 men). Carotid siphon calcification was associated with higher pulsatility indexes in patients with pseudoxanthoma elasticum (β = 0.10; 95% CI, 0.01-0.18). Patients with pseudoxanthoma elasticum have increased intracranial artery flow pulsatility and measures of small-vessel disease. Carotid siphon calcification might underlie the high prevalence of cerebrovascular disease in pseudoxanthoma elasticum.

Carotid Siphon Calcification Predicts the Symptomatic Progression in Branch Artery Disease With Intracranial Artery Stenosis-Brief Report.

Background:Arterial calcification in the aortic arch, carotid bifurcation, or siphon on computed tomography was associated with cardiovascular disease. The association between arterial calcification prevalence and progression of branch atheromatous disease (BAD) in intracranial artery atherosclerosis was little investigated.Methods:This study included 310 patients with ischemic stroke from one stroke center. Patients were divided into BAD (110) and non-BAD groups (200). Baseline characteristics, lipids, and arterial calcification were measured. The primary outcome was the prevalence of arterial calcification in BAD progression, and the secondary outcome was the prevalence of calcification in arterial stenosis. The association or correlation among calcification prevalence, lipid markers, and BAD progression was analyzed using logistic regression, receiver operating characteristic curve, and linear regression.Results:Our study found that carotid siphon calcification on computed angiography was more prevalent (P=0.01) in patients with BAD and also more prevalent (P<0.001) in intracranial artery stenosis, and its computed tomography values could independently predict the symptomatic progression (P=0.01). Furthermore, a strong linear correlation between oxidized lipid and calcification density was found (beta=−0.73, P=0.0048) in patients with BAD, a subtype (B-type) of intracranial arterial atherosclerotic disease.Conclusions:We found that carotid siphon calcification was associated with BAD and its computed tomography values could predict the symptomatic progression in patients with intracranial arterial atherosclerotic disease and BAD, indicating the important role of carotid calcification in B-type intracranial arterial atherosclerotic disease.Registration:URL: http://www.chictr.org.cn; Unique identifier: ChiCTR1800018315

Silent brain infarction is associated with carotid siphon calcification in ischemic stroke patients

BackgroundSilent brain infarction (SBI) had a higher prevalence in ischemic stroke patients than healthy population. Intracranial artery calcification, as the important component of atherosclerosis, is a known risk factor of ischemic stroke. Whether it is also the risk factor of SBI is uncertain. We aimed to assess the association between SBI and carotid siphon calcification (CSC) in ischemic stroke patients. MethodsWe retrospectively collected consecutive data of acute ischemic stroke patients with and without SBI by Magnetic Resonance Imaging (MRI) and calcification using non-contrast Computerized Tomography (NCCT). We used a histopathologically validated method to score the circularity, thickness, and morphology of calcification. Clinical characteristics, prevalence and pattern (intimal and medial) of CSC were compared between patients with and without SBI. The association of CSC and SBI was investigated by logistic regression analysis. ResultsTotally, 303 acute ischemic stroke patients were enrolled, of whom 260 (85.8%) had CSC. Patients with SBI were older (64.5 ± 10.4 years vs. 61.3 ± 12.1 years, P = 0.032), had a higher proportion of hypertension (77.5% vs. 65.7%, P = 0.035). Of the 260 CSC patients, there’s no significant difference except for hyperlipidemia between patients with SBI and without SBI. The prevalence of intimal pattern of CSC was higher in those with SBI (adjusted odds ratio 2.42, 95% CI 1.219–4.794). ConclusionsPatients with SBI at acute phase of ischemic stroke have more risk factors than mentioned previously. SBI associated with the intimal pattern of CSC which relate to the atherosclerosis process in symptomatic ischemic stroke patients.

Risk for Subsequent SARS-CoV-2 Infection and Severe COVID-19 Among Community-Dwellers With Pre-Existing Cervicocephalic Atherosclerosis: A Population-Based Study.

Background:COVID-19 patients may develop atherosclerosis-related complications. Whether a proportion of these patients already had asymptomatic cervicocephalic atherosclerosis before SARS-CoV-2 infection is not known. This study assessed whether pre-existing cervicocephalic atherosclerosis increased the susceptibility to SARS-CoV-2 infection or resulted in more severe or fatal COVID-19.Methods:Individuals enrolled in the Atahualpa Project cohort who received head CT (for assessing carotid siphon calcifications) and B-mode ultrasounds (for measurement of the carotid intima-media thickness) prior to the pandemic were eligible for this study. Among this cohort, those who also received serological tests for detection of SARS-CoV-2 antibodies and clinical evaluations for assessment of COVID-19 severity were enrolled. Multivariate logistic regression and exposure-effect models were fitted to assess the association between pre-existing atherosclerosis biomarkers, and SARS-CoV-2 seropositivity and COVID-19 severity.Results:Overall, 154 of 519 study participants (30%) had evidence of cervicocephalic atherosclerosis. A total of 325 (63%) individuals became SARS-CoV-2 positive, and 65 (23.5%) of seropositive individuals had severe or fatal COVID-19. The risk of SARS-CoV-2 seropositive status did not differ across individuals with and without atherosclerosis biomarkers (P = .360). Likewise, seropositive individuals with pre-existing atherosclerosis were not more prone to develop severe or fatal COVID-19 than those without evidence of atherosclerosis (P = .274). Average estimated exposure effects of pre-existing cervicocephalic atherosclerosis versus no atherosclerosis over SARS-CoV-2 seropositivity and COVID-19 severity were not significant.Conclusions:Pre-existing cervicocephalic atherosclerosis does not increase the risk of acquiring SARS-CoV-2 infection nor the severity of COVID-19 among seropositive individuals.

Variants of the Circle of Willis as seen on magnetic resonance angiography and carotid siphon calcifications in community-dwelling older adults.

Information on the association between anatomical variants of the Circle of Willis (CoW) and intracranial atherosclerotic disease (ICAD) is limited and results are controversial. In this population-based study, we aimed to assess whether an incomplete CoW is associated with high calcium content in carotid siphons (a reliable biomarker of ICAD) in community-dwelling older adults of Amerindian ancestry. Individuals aged ≥60 years enrolled in the Three Villages Study received a head computed tomography (CT) and magnetic resonance angiogram (MRA) of intracranial vessels. The CoW was classified in complete or incomplete according to the presence or absence of one A1 segment of the anterior cerebral artery or one or both P1 segments of posterior cerebral arteries. Calcium content in carotid siphons was rated as low or high. A multivariate logistic model was fitted to assess the independent association between incompleteness of the CoW and high calcium content in carotid siphons, after adjusting for demographics and cardiovascular risk factors. A total of 581 individuals were enrolled (mean age: 71 ± 8.4 years; 57% women). MRA revealed an incomplete CoW in 227 (39%) individuals, and high-resolution CT disclosed high calcium content in carotid siphons in 185 (32%). A risk factor logistic regression model showed no independent association between incompleteness of the CoW and high calcium content in carotid siphons (odds ratio: 0.91; 95% confidence interval: 0.62-1.34; p = 0.631). Study results disclosed no association between anatomical variants of the CoW and the presence of high calcium content in carotid siphons.

Prevalence and Correlates of Intracranial Atherosclerotic Disease Among Community-Dwelling Older Adults of Amerindian Ancestry. The Three Villages Study

BackgroundKnowledge on the prevalence and correlates of intracranial atherosclerotic disease (ICAD) is limited. We aimed to assess prevalence, clinical and neuroimaging correlates of ICAD in a cohort of older adults of Amerindian ancestry. MethodsThe study included 581 community-dwellers aged ≥60 years (mean age 71 ± 8.4 years; 57% women) living in rural Ecuadorian villages. ICAD was identified by means of CT determinations of carotid siphon calcifications (CSC) or MRA findings of significant stenosis of intracranial arteries. Fully-adjusted logistic regression models were fitted with biomarkers of ICAD as the dependent variables. ResultsA total of 205 (35%) of 581 participants had ICAD, including 185 with high calcium content in the carotid siphons and 40 with significant stenosis of at least one intracranial artery (20 subjects had both biomarkers). Increasing age, high fasting blood glucose, >10 enlarged basal ganglia-perivascular spaces and non-lacunar strokes were associated with high calcium content in the carotid siphons. In contrast, male gender, moderate-to-severe white matter hyperintensities, lacunar and non-lacunar strokes were associated with significant stenosis of intracranial arteries. Stroke was more common among subjects with any biomarker of ICAD than in those with no biomarkers (29% versus 9%, p < 0.001). Significant stenosis of intracranial arteries was more often associated with stroke than high calcium content in the carotid siphons, suggesting that CSC are more likely an ICAD biomarker than causally related to stroke. ConclusionsICAD prevalence in Amerindians is high, and is significantly associated with stroke. CSC and significant stenosis of intracranial arteries may represent different phenotypes of ICAD.

Vascular Calcification-Induced Cognitive Impairment in Pseudoxanthoma Elasticum

Background: With no approved effective therapies for cognitive impairment, the need for new targetable phenotypes is high. We hypothesize that medial arterial calcification of the intracranial arteries, which is a modifiable process, results in increased arterial pulsatility, brain damage, and cognitive decline. Pseudoxanthoma elasticum (PXE) is a monogenetic disorder which results in non-atherosclerotic medial arterial calcification and was therefore used to investigate the effect of medial calcification of the carotid siphon on arterial pulsatility, brain volumes, small vessel disease and cognition. Methods: Magnetic resonance imaging and neurocognitive testing in 50 PXE patients and 42 age-matched controls were performed to compare arterial pulsatility, brain volumes, small vessel disease burden and cognition. Also, in the PXE patients we tested the association of carotid siphon calcification, measured by computed tomography, with arterial pulsatility and its association with brain volumes, small vessel disease and cognition. Results: PXE patients had a significantly higher pulsatility index (1.05(0.94-1.20) vs. 0.94(0.82-1.04), p=0.01), lower grey matter volumes (598±53 vs. 632±53ml, p=0.004), more white matter lesions (WML) (2.6(0.5-7.6) vs. 1.1(0.5-2.4)ml, p=0.04) and more lacunar infarctions (total 64 vs. 8, p=0.04) than controls. Patients scored lower on concentration and processing speed, but higher on memory. Carotid siphon calcification was associated with higher pulsatility indexes (β:0.09, 95%CI: 0.01;0.18), more WMLs (β:5.7, 95%CI: 0.9;10.5) and infarctions (RR:2.8, 95%CI: 1.1;7.0). Higher pulsatility was associated with lower grey matter volumes (β:-54.1, 95%CI: -107.8;-0.5), more WMLs (β:15.5, 95%CI: 7.7;23.3) and lower concentration and processing speed (β:-0.9, 95%CI: -1.8;-0.1). Conclusions: In PXE patients, medial calcification of the carotid siphon, was associated with higher pulsatility index which might contribute to grey matter damage, small vessel disease and cognitive impairment, particularly involving concentration and processing speed. Since arterial calcification is a modifiable process, we identified a potential novel target for the treatment of cognitive impairment. Funding: Dr. Zwanenburg is supported by the European Reasearch Council under the European Union’s Seventh Framework Programme (FP7/2007-2013), grant agreement no. 337333. The research of Prof. Dr. Hendrikse has received funding from the European Research Council under the European Union's Horizon 2020 Programme (H2020)/ERC grant agreement n° 637024 (HEARTOFSTROKE) and H2020 grant agreement No 666881, SVDs@target. Declaration of Interest: J. Bartstra has nothing to disclose Dr. Spiering has nothing to disclose Dr. Kranenburg has nothing to disclose Dr. Geurts has nothing to disclose Dr. den Harder has nothing to disclose Dr. Witkamp has nothing to disclose Dr. Wolterink has nothing to disclose Dr. Zwanenburg reports grants from European research council, from null, during the conduct of the study. Dr. van Valen has nothing to disclose Dr. Koek has nothing to disclose Prof. dr. Mali has nothing to disclose Prof. dr. de Jong has nothing to disclose Prof. Dr. Hendrikse reports grants from European research council, from null, during the conduct of the study. Ethical Approval: The study was approved by the institutional review board of the UMCU (number 16-622/M-X) and written informed consent was obtained from all participants.

No association between the abdominal aorta diameter and cervicocephalic atherosclerosis—Potential non-atherosclerotic origins of abdominal aorta aneurysms?

The atherosclerotic origin of abdominal aorta (AA) aneurysms is controversial. Using the Atahualpa Project Cohort, we aimed to assess the relationship between the AA diameter and two surrogates of cervicocephalic atherosclerosis, including the carotid intima-media thickness (cIMT) and the presence of carotid siphon calcifications (CSC). Atahualpa residents aged ≥60 years undergoing ultrasound examinations of the abdominal aorta and the carotid arteries (to calculate the AA diameter and the cIMT), and head CT (to assess CSC severity) were included. Associations between AA diameter and cIMT and CSC severity were assessed by generalized linear models, after adjusting for relevant confounders. Of 256 participants, 64 (25%) had an increased cIMT and 85 (33%) had high calcium content in the carotid siphons. In univariate analysis, being male (p < 0.001) and having total cholesterol blood levels <240 mg/dL (p = 0.022) were associated with a higher AA diameter. Also in univariate analysis, the mean AA diameter was higher in individuals with an increased cIMT (p = 0.021), but such association disappeared in adjusted models. The AA diameter was not associated with high calcium content in the carotid siphons in either univariate or multivariate analyses. This population study shows no association between the AA diameter and cervicocephalic atherosclerosis in community-dwelling older adults, suggesting a non-atherosclerotic origin of AA aneurysms.

Distribution of Cervicocephalic Atherosclerotic Lesions and Their Correlation with Cardiovascular Risk Factors in a Population of Amerindians. The Atahualpa Project

BackgroundNo information is available on the distribution of cervicocephalic atherosclerosis in Amerindians. We aimed to assess the distribution of these lesions and their correlation with cardiovascular risk factors in Amerindians living in rural Ecuador. MethodsAtahualpa residents aged ≥40years underwent head CT for assessment of carotid siphon calcifications (CSC) and sonographic examination for measurement of the carotid intima media thickness (cIMT). CSC were used as a surrogate of intracranial atherosclerosis and the cIMT as a surrogate of extracranial atherosclerosis. Linear regression and multinomial logistic regression models were fitted to assess the association between cIMT and CSC, and to evaluate differences in risk factors across individuals with atherosclerosis involving both arterial beds when compared with those with extra- or intracranial atherosclerosis alone, or no atherosclerosis. ResultsOf 590 participants, 145 had high calcium content in the carotid siphons and 87 had a cIMT >1mm (25% versus 15%, P < .001). Thirty-eight (7%) individuals had atherosclerosis at both vascular beds, 107 (18%) had intracranial atherosclerosis, and 49 (8%) had extracranial atherosclerosis alone. The cIMT and CSC were independently associated (P = .008). When compared with participants without atherosclerosis, those with atherosclerosis at both vascular beds were older, more often male, hypertensive and diabetic. Subjects with intracranial atherosclerosis alone were older, and those with extracranial atherosclerosis alone reported less physical activity than those without atherosclerosis. ConclusionIntracranial atherosclerosis is more common than extracranial atherosclerosis in Amerindians. Traditional risk factors only explain a minority of cases of cervicocephalic atherosclerosis in this population.

Arterial Stiffness is Independently Associated with Severity of Carotid Siphon Calcifications in Community-Dwelling Older Adults: The Atahualpa Project

Knowledge on the association between arterial stiffness and intracranial atherosclerosis is limited. Here, we aimed to assess whether the aortic pulse wave velocity (PWV)-used as a surrogate of arterial stiffness-might independently predict severity of carotid siphon calcifications (CSCs), used as a marker of atherosclerosis. Of 437 Atahualpa residents aged 60 years or older, 300 (69%) underwent head computed tomography (CT) (for CSC assessment), brain magnetic resonance imaging (for identification of neuroimaging signatures of cerebral small vessel disease [SVD]), and aortic PWV determinations (for arterial stiffness estimation). Ordinal logistic regression models were constructed to predict severity of CSC (as the dependent variable) according to levels of aortic PWV after adjusting for demographics, cardiovascular risk factors, and neuroimaging signatures of SVD. Grade 1 CSC were noticed in 120 (40%) subjects, grade 2 in 84 (28%), grade 3 in 73 (24%), and grade 4 in 23 (8%). The mean PWV was 10.4 ± 1.8 m/s, which increased from 9.8 ± 1.3 to 11.1 ± 2.1 m/s in individuals with grades 1 and 4 CSC, respectively (P <.001). The most parsimonious ordinal logistic regression model adjusted for relevant confounders showed a significant association between aortic PWV and severity of CSC. In this model, a change of 1 unit of aortic PWV increased the odds of CSC severity by 1.22 (95% confidence interval 1.07-1.39; P = .004). The monotonically increased odds of aortic PWV among subjects with different grades of CSC, suggest that aortic PWV may be a marker for identifying candidates for CT screening in the search of CSC.

Enlarged perivascular spaces in the basal ganglia are independently associated with intracranial atherosclerosis in the elderly

Background and aimsEnlarged basal ganglia perivascular spaces (BG-PVS) are a marker of cerebral small vessel disease (SVD). The association between enlarged BG-PVS and atherosclerosis has been explored, but knowledge is limited to extracranial vessels. We aimed to assess whether enlarged BG-PVS correlate with carotid siphon calcifications (CSC), used as a surrogate of intracranial atherosclerosis. MethodsAtahualpa residents aged ≥60 years underwent head computed tomography (CT) for assessment of CSC, and brain magnetic resonance imaging (MRI) for evaluation of BG-PVS and other imaging markers of SVD. We evaluated the association between BG-PVS and CSC severity (dependent variable) using regression models adjusted for demographics and cardiovascular risk factors. ResultsOf 437 candidates, 354 (81%) were included. Grade 1 CSC were observed in 131 (37%), Grade 2 in 99 (28%), Grade 3 in 92 (26%), and Grade 4 in 32 (9%) subjects. MRI showed >10 enlarged BG-PVS in 97 (27%) participants, moderate-to-severe white matter hyperintensities in 81 (23%), lacunar infarcts in 39 (11%), and deep microbleeds in 28 (8%). Fully-adjusted models showed a significant association between enlarged BG-PVS and CSC severity. Individuals with Grade 4 CSC have 3 times de odds of having enlarged BG-PVS than those with Grade 1 CSC. Enlarged BG-PVS were observed in 20% versus 41% of individuals with Grade 1 and Grade 4 CSC, respectively. ConclusionsEnlarged BG-PVS often coexist with CSC, suggesting that a common pathogenetic mechanism may explain the occurrence of both conditions.

The Role of Brachial Pulse Pressure as an Indicator of Intracranial Atherosclerosis: The Atahualpa Project.

Carotid siphon calcifications (CSC) are an important imaging marker of systemic atherosclerosis. Routine assessment of asymptomatic CSC may allow the implementation of intervention strategies before catastrophic cerebrovascular events occur. To assess whether brachial PP determinations might independently predicts the presence and severity of CSC in community-dwelling adults. All Atahualpa residents aged ≥40years were invited for the practice of a non-enhanced CT scan of the head, and those who signed the informed consent and had no contraindications for this exam were enrolled. The brachial PP was calculated by subtracting the mean diastolic pressure from the mean systolic pressure obtained from three different readings with individuals in the sitting position. Of 830 eligible candidates, 663 (80%) were included. The mean brachial PP was 56.4±19.9mmHg; 182 persons (27.4%) had PP levels >65mmHg. CT revealed Grade 1 CSC in 356 (54%), Grade 2 in 141 (21%), Grade 3 in 128 (19%), and Grade 4 in 38 (6%) subjects. Predictive margins of PP (delta method) were significantly lower in individuals with Grade 1 CSC than in the other groups. In the best adjusted linear model, PP levels increased up to 11.7mmHg as the severity of CSC increased (β 11.71; 95% C.I. 5.36-18.08: p<0.001). This study provides evidence on the relationship between brachial PP levels and intracranial atherosclerosis. Calculation of the PP may be used for detecting candidates for CT screening, reducing costs during population-based surveys, particularly in remote areas.

Inverse relationship between the body mass index and severity of carotid siphon calcifications (another obesity paradox): Results from the Atahualpa Project

Background and aimsThe importance of the obesity paradox in the intracranial vasculature has not been explored. We assessed whether the body mass index (BMI) correlates with severity of carotid siphon calcifications (CSC) in community-dwelling adults. MethodsUsing a population-based study design, Atahualpa residents aged ≥40 years underwent head computed tomography (CT) for assessment of CSC. We evaluated the association between BMI and severity of CSC (dependent variable) using regression models adjusted for demographics and cardiovascular risk factors. ResultsOf 830 people enrolled in the Atahualpa Project, 651 (78%) were included. Mean BMI was 27.3 ± 5 kg/m2, with 39% being overweight and 27% obese. CT revealed high calcium content in the carotid siphon in 25% participants. In an adjusted model, individuals with normal weight had a trend for presenting with more severe CSC than those overweight (p = 0.06), and those ones had significantly more severe CSC than obese participants (p = 0.04). Predictive margins of BMI were higher in individuals with low calcium content in the carotid siphon. A contour plot with Shepard interpolation showed that the paradox disappeared in older individuals and in those with severe obesity, irrespective of age. ConclusionsBMI inversely associates with severity of CSC. This paradox is relevant in younger individuals and in those without severe obesity, irrespective of age.

Calcifications in the carotid siphon inversely associate with cognitive performance in stroke-free community dwellers living in rural Ecuador (The Atahualpa Project).

We aimed to assess whether carotid siphon calcifications (as seen on computed tomography) are associated with worse performance in the Montreal Cognitive Assessment in 584 stroke-free individuals living in rural Ecuador. Using mean Montreal Cognitive Assessment score of subjects with Grade 1 calcifications (23.1 ± 4.2) as the referent category, fully adjusted generalized linear models showed significant associations between severity of carotid siphon calcifications and cognitive performance (mean Montreal Cognitive Assessment scores: 20.2 ± 4.8 for Grade 2 (p = 0.004), 19.7 ± 5.3 for Grade 3 (p = 0.0001), and 18.8 ± 4.1 for Grade 4 (p = 0.02)). Predictive Montreal Cognitive Assessment score margins were higher in individuals with Grade 1 calcifications than in other groups. This study shows an inverse relationship between calcium content in the carotid siphon and cognitive performance in Amerindians.

Calcifications in the carotid siphon correlate with silent cerebral small vessel disease in community-dwelling older adults: A population-based study in rural Ecuador.

Using a population-based, cross-sectional design, we aimed to assess whether the presence of calcifications in the carotid siphon (as seen on computed tomography) is associated with silent markers of cerebral small vessel disease (on magnetic resonance imaging) in apparently healthy older adults living in Atahualpa, a rural Ecuadorian village. Stroke-free Atahualpa residents aged ≥60 years identified during a door-to-door survey underwent head computed tomography for assessment of carotid siphon calcifications, and brain magnetic resonance imaging for identification of white matter hyperintensities and silent lacunar infarcts. We evaluated the association between calcifications and markers of small vessel disease using logistic regression models adjusted for demographics and cardiovascular risk factors. The mean age of the 236 participants was 71 ± 8 years, and 139 (59%) were women. Computed tomography readings showed high calcium content in the carotid siphon in 64 individuals (27%), and magnetic resonance imaging showed moderate-to-severe white matter hyperintensities in 51 (30%) and lacunar infarcts in 28 (12%). In the univariate analysis, individuals with high calcium content were older and were more likely to have high fasting glucose levels than those with low calcium content. After adjusting for confounding variables, we found an independent association between high calcium content in the carotid siphon and moderate-to-severe white matter hyperintensities (OR 2.3, 95% CI 1.1-4.9, P = 0.035) as well as lacunar infarcts (OR 3.1, 95% CI 1.3-7.6, P = 0.013). The present study shows a direct relationship between calcium content in the carotid siphon and silent small vessel disease in an indigenous Latin American population. Geriatr Gerontol Int 2016; 16: 1063-1067.

Is Calcification of Intracranial Arteries Important and How?

Intracranial atherosclerosis is a well-recognized and common cause of stroke in Asian, black, and Hispanic individuals.1,2 Recent studies showed that intracranial occlusive disease is also a more common cause of stroke in white individuals than previously thought.3 In this issue of JAMA Neurology, Bos and colleagues4 provide evidence that intracranial carotid artery calcification is an important risk factor for stroke in an elderly white Dutch population. As part of the prospective, population-based Rotterdam study, the authors followed up 2323 individuals to determine the incidence of stroke (parenchymal brain hemorrhage or ischemic) after they had nonenhanced computed tomography (CT) scanning that imaged the coronary arteries, aortic arch, extracranial carotid arteries, and intracranial carotid arteries. The authors used calcification volume in these arteries as an indicator of atherosclerosis and correlated this with the risk for all stroke and ischemic stroke. They found that larger intracranial carotid calcification volume was independently associated with all stroke and that intracranial carotid calcification was a more important risk factor for stroke than aortic arch calcification or extracranial carotid calcification. The apparent discrepancy between the importance of intracranial carotid calcification as a major risk factor for stroke in this study and the low frequency of stroke caused by intracranial atherosclerosis in most studies of white patients is largely explained by the different design of these studies. Prior studies identified consecutive patients with stroke and determined the frequency of proximal intracranial atherosclerotic arterial stenosis. In the current study, intracranial carotid calcification (not stenosis) was measured and correlated with subsequent stroke regardless of the territory of the stroke. Data on the size, location (cortical or subcortical), and vascular territory of brain infarcts were not collected. While the current study suggests that intracranial carotid artery calcification is an important, previously seldom considered, risk factor for subsequent stroke in any vascular territory in white patients, the study did not show that the intracranial vascular lesions were the cause of the strokes. Many of the ischemic strokes in this study were almost surely not caused by intracranial carotid atherosclerosis because the strokes were either in a different vascular territory or were caused by other vascular diseases (eg, coexisting penetrating artery disease,5 a cardiac source of embolism). Moreover, at least 11% of the strokes in the study were hemorrhagic and no causal relationship has been established between intracranial arterial calcification and parenchymal brain hemorrhage. Recent interest in calcification of arteries has been spurred on by the strong association between coronary calcification detected by cardiac CT and the risk for future cardiac events.6 The situation appears to be different in relation to carotid artery disease in the neck where the presence of heavy calcification on spiral CT has been correlated with stable, noninflammatory, asymptomatic plaques.7 Whether intracranial arterial calcification is also associated with stable plaque that is unlikely to cause a distal stroke is unknown. What is known is that severe stenosis of an intracranial artery is strongly associated with a high risk for stroke distal to the stenosis in patients presenting with a transient ischemic attack or stroke.8 If the presence of severe intracranial carotid calcification implied coexistent severe arterial stenosis of the artery, that would provide some evidence of a potential causal link between calcification and risk for stroke attributable to the affected artery. However, the relationship between calcification of the intracranial carotid artery and coexistent stenosis is unsettled. Older pathological studies found that heavy calcification of the carotid siphon did not necessarily indicate stenosis of the lumen9; however, a more recent neuroimaging study showed that the positive predictive value of severe carotid siphon calcification on CT for a stenosis of greater than 50% on angiography was 86% using bone window measurements.10 It is also possible that intracranial carotid calcification may cause stroke without the presence of coexistent stenosis if calcification is associated with unstable plaque features that predispose to distal embolism. This study by Bos and colleagues4 raises important questions about the role of calcification in the pathophysiology of intracranial atherosclerosis and should reawaken interest in intracranial atherosclerosis as a cause of stroke inwhite individuals. The study indicates that intracranial carotidcalcification isamajor risk factor for stroke inwhite individuals but does not establish a pathophysiologic causal relationshipbetweenthe two.Establishing thatwill require further prospective studies that correlate the association between intracranial arterial calcification and stenosis more clearly, identifyatheroscleroticplaque featuresassociatedwith calcification thatmay be associatedwith a high risk for distal embolism, and classify ischemic strokes that occur in patientswith intracranial carotid calcification according to size, location (cortical or subcortical), vascular territory, and thecoexistenceofotherpotential causesof stroke.Muchworkneeds to be done. Related article page 405 Opinion

Carotid siphon calcification impact on revascularization and outcome in stroke intervention

ObjectiveThe degree of coronary artery calcification has been shown to predict outcomes in coronary artery disease. The impact of intracranial carotid artery calcification on the prognosis of acute ischemic stroke (AIS) is unknown. The authors sought to examine if the degree of intracranial carotid artery calcification influences reperfusion or outcomes in AIS intervention. MethodsAll anterior circulation large vessel occlusion AIS cases that underwent intra-arterial therapy from January 2009 to July 2012 were reviewed. Clinical and radiographic data were collected. Non-contrast brain CT scans were assigned a Calcium Extent Score (degree of calcification of the carotid wall circumference), Calcium Thickness Score (thickness of the calcified plaque), and total Carotid Siphon Calcium (CSC) Score (8-point scale). ResultsOne-hundred seventeen patients met inclusion criteria. The mean age was 65.4±15.6 years and 36% were male. Calcification was present in the intracranial carotid artery of 84 patients (71%). Inter-rater agreement for total CSC score was strong (Spearman's rho=0.883, p<0.001). The mean Calcium Extent Score was 1.5±1.3, Calcium Thickness Score 1.3±1.0 and total CSC Score 2.8±2.2. Reperfusion and mRS were not associated with CSC. Multivariate linear regression analysis revealed that older age, history of coronary disease and cervical internal carotid occlusion/near-occlusion were independently associated with higher total CSC scores. ConclusionExtensive calcification on the intracranial carotid artery does not have impact on reperfusion or clinical outcomes in AIS patients undergoing endovascular therapy. Higher CSC scores are associated with coronary artery disease, increasing age and cervical internal carotid artery occlusion/near-occlusion.

Calcium at the carotid siphon as an indicator of internal carotid artery stenosis

Carotid siphon calcification is often visible on unenhanced head CT (UCT), but the relation to proximal carotid artery stenosis (CAS) is unclear. We investigated the association of carotid siphon calcification with the presence of CAS. This IRB-waived retrospective study included 160 consecutive patients suspected of stroke (age 64 ± 14 years, 63 female) who underwent head UCT and CTA of the head and neck. CAS was rated on CTA as not present or present with non-significant (<50 %), moderate (50-69 %) or significant (≥70 %) stenosis. Presence, shape (on UCT) and volume (on CTA) of carotid siphon calcifications were related to CAS. Carotid siphon calcification was absent in 41 % of patients and bilateral in 94 % of those with calcifications. Presence, shape and volume of calcification resulted in odds ratios for having significant CAS of 10.1, 3.9 and 8.4, with 95 % CIs of 1.3-79.6, 1.1-14.1 and 2.6-26.8, respectively. Corresponding NPVs were 0.98, 0.98 and 0.96, while PPVs were 0.14, 0.07 and 0.29, respectively. Absence of calcification in the carotid artery siphon on UCT has high negative predictive value for carotid artery stenosis in patients with suspected stroke. However, siphon calcification is not a reliable indicator of significant carotid artery stenosis. • Many stroke patients do not have calcification in the carotid artery siphon. • Carotid stenosis ≥50 % is unlikely in stroke patients without siphon calcification. • Carotid siphon calcium is a poor indicator of significant carotid artery stenosis.

The correlation between carotid siphon calcification and lacunar infarction

The aim of this study was to evaluate the correlation between carotid siphon (CS) calcification and lacunar infarction caused by small-vessel disease. This retrospective study included 445 patients (M/F = 256:189) older than 40years (mean age 60.0 ± 12.3years, range 41-98years) without large intracranial lesions who had undergone both brain CT and MRI within an interval of 6months. The patients were classified into three groups according to the number of lacunar infarctions: group I-zero infarctions (n = 328), group II-one to three infarctions (n = 94), and group III-four or more infarctions (n = 23). The severity of CS calcification was evaluated on CT and scored on a five-point scale (0-none, 1-stippled, 2-thin continuous or thick discontinuous, 3-thick continuous, 4-double tracts), and the calcification scores on both sides were summed. An ANOVA test was used to compare calcification scores among the three groups, and a logistic regression test was used to evaluate the influence of CS calcification and known cerebrovascular risk factors on the occurrence of lacunar infarction. On the ANOVA test, total calcification scores were significantly different among the three groups (group I = 1.28 ± 1.99, group II = 3.31 ± 2.39, group III = 4.36 ± 2.08; P < 0.05). Higher rates of lacunar infarction were associated with higher CS calcification scores. On the logistic regression test, CS calcification, age, and hypertension were significant risk factors for lacunar infarction (P < 0.05). CS calcification was correlated with the occurrence of lacunar infarction. The degree of CS calcification may be used to predict the possibility of a future lacunar infarction.