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

BACKGROUND: Knowledge 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. METHODS: The 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. RESULTS: A 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. CONCLUSIONS: ICAD prevalence in Amerindians is high, and is significantly associated with stroke. CSC and significant stenosis of intracranial arteries may represent different phenotypes of ICAD.

Cerebral small vessel disease score and atherosclerosis burden - A population study in community-dwelling older adults.

OBJECTIVE: Cerebral small vessel disease (cSVD) and large artery atherosclerosis (LAA) are related to different pathogenetic mechanisms. However, relationships between single biomarkers of cSVD and LAA affecting isolated vascular beds have been reported. Using the Atahualpa Project cohort, we aimed to assess the association between cSVD score categories and LAA burden in community-dwelling older adults. PATIENTS AND METHODS: Atahualpa individuals aged ≥60 years undergoing assessment of the cSVD score and LAA in the peripheral, carotid extracranial, and intracranial vascular beds (n = 333) were included. Multivariate models were fitted to assess independent associations between the cSVD score and LAA burden. RESULTS: The cSVD score was 0 points in 62 % individuals, 1 point in 19 %, 2 points in 13 %, and 3-4 points in 7 %. LAA involved the extracranial carotid bed in 43 % individuals, the intracranial bed in 36 %, and the peripheral bed in 20 %. One vascular bed was involved in 111 (33 %) individuals, two beds in 75 (23 %), and three beds in 23 (7 %). The remaining 124 (37 %) had no atherosclerosis. Ordinal logistic regression models showed progressively greater associations between higher categories of cSVD score and the odds of having more beds involved with LAA. Multinomial logistic regression models showed associations between categories of cSVD score and LAA burden, but only when two or three vascular beds were involved. CONCLUSION: This study demonstrates robust associations between the cSVD score and LAA, which become evident at the upper end of the spectrum of cSVD score (3-4 points) and LAA burden (2-3 vascular beds involved).

Intracranial Atherosclerosis And The Earlobe Crease (Frank's Sign). A Population Study / Aterosclerosis Intracraneal Y Pliegue Auricular (Signo De Frank). Estudio Poblacional

ABSTRACT Background: The earlobe crease (ELC) has been linked to coronary artery disease and other vascular conditions, but there is no information on its association with intracranial atherosclerosis. Objective: This study aimed to assess the association between high calcium content in the carotid siphons (as a surrogate of intracranial atherosclerosis) and ELC in community-dwelling adults living in rural Ecuador. Methods: Atahualpa residents aged ≥40 years underwent head CT to estimate calcium content in the carotid siphons, and visual inspection of both earlobes to evaluate the presence of ELC. The association between both variables was assessed by logistic regression models, after adjusting for demographics and cardiovascular risk factors. Results: Of 651 enrolled individuals (mean age: 59.7±12.8 years; 54% women), 225 (35%) had ELC, and 143 (22%) had high calcium content in the carotid siphons. Univariate logistic regression showed a borderline (non-significant) association between high calcium content in the carotid siphons and ELC presence (OR: 1.44; 95% C.I.: 0.99 - 2.12; p=0.057), which disappeared when age (OR: 0.98; 95% C.I.: 0.65 - 1.48; p=0.923) and other covariables (OR: 0.97; 95% C.I.: 0.63 - 1.49; p=0.890) were added to the model. Conclusion: This population study shows no association between high calcium content in the carotid siphons and ELC presence.

RESUMEN Antecedentes: El pliegue auricular se ha relacionado con enfermedad coronaria y otras patologías vasculares, pero no hay información sobre su asociación con aterosclerosis intracraneal. Objetivo: Este estudio tuvo como objetivo evaluar la asociación entre el contenido de calcio en los sifones carotideos (como un sustituto de aterosclerosis intracraneal) y el pliegue auricular en adultos viven en zonas rurales de Ecuador. Métodos: Los residentes de Atahualpa de 40 años o más fueron sometidos a TC de cerebro para estimar el contenido de calcio en los sifones carotideos. Además, ambas orejas fueron examinadas para detectar la presencia de pliegues auriculares. La asociación entre ambas variables se evaluó mediante modelos de regresión logística, ajustados por factores demográficos y de riesgo cardiovascular. Resultados: De 651 individuos enrolados (edad media: 59,7±12,8 años, 54% mujeres), 225 (35%) tuvieron pliegues auriculares y 143 (22%) tuvieron alto contenido de calcio en los sifones carotideos. La regresión logística univariada mostró una asociación limítrofe (no significativa) entre el contenido de calcio en los sifones carotideos y la presencia de pliegue auricular (OR: 1.44, 95%IC: 0.99 - 2.12, p=0.057), que desapareció cuando la edad (OR: 0.98; 95% I.C.: 0,65 - 1,48; p=0,923) y otras covariables (OR: 0,97; 95% I.C.: 0,63 - 1,49; p=0,890) fueron agregadas al modelo estadístico. Conclusión: El presente estudio no mostró asociación entre el contenido de calcio en los sifones carotídeos y la presencia de pliegue auricular.

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

BACKGROUND: No 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. METHODS: Atahualpa 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. RESULTS: Of 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. CONCLUSION: Intracranial 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.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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 AIMS: Enlarged 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. METHODS: Atahualpa 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. RESULTS: Of 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. CONCLUSIONS: Enlarged 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.

INTRODUCTION: 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. AIM: To assess whether brachial PP determinations might independently predicts the presence and severity of CSC in community-dwelling adults. METHODS: All Atahualpa residents aged ≥40 years 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. RESULTS: Of 830 eligible candidates, 663 (80%) were included. The mean brachial PP was 56.4 ± 19.9 mmHg; 182 persons (27.4%) had PP levels >65 mmHg. 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 11.7 mmHg as the severity of CSC increased (ß 11.71; 95% C.I. 5.36-18.08: p < 0.001). CONCLUSION: 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 AIMS: The 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. METHODS: Using 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. RESULTS: Of 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. CONCLUSIONS: BMI 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.

AIM: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Carotid siphon geometry and variants of the circle of Willis in the origin of carotid aneurysms / Geometria do sifão carotídeo e variantes do polígono de Willis na origem de aneurismas da carótida

This study evaluated anatomical variants in the carotid siphon and of the circle of Willis in patients with aneurysms. We performed a retrospective analysis of cerebral angiographies. The Control Group was composed of patients without aneurysms. Posterior communicating artery (PcomA) aneurysms were more common in women (p<0.05), and the anterior communicating artery (AcomA) aneurysms in men (p<0.1). The incidence of fetal-type PcomA was higher in cases with co-occurring PcomA aneurysm (24 versus 8%, p<0.05). Patients with AcomA aneurysm had higher incidence of A1 hypoplasia (p<0.0001, OR=32.13, 95%CI 12.95-79.71) and lower frequency of fetal-type PcomA compared to their control counterparts (p=0.0125). The angle of carotid siphon was narrower in patients with PcomA aneurysm (27.3±19.1 versus 34.8±22.6, p=0.028). In conclusion, a narrower carotid siphon or the presence of fetal-type PcomA or A1 hypoplasia may cause hemodynamic stress, thereby promoting the formation of aneurysms in susceptible individuals.

O presente estudo avaliou as variantes anatômicas do sifão carotídeo e da parte posterior do polígono de Willis em pacientes com aneurismas. Foi realizada uma análise retrospectiva de angiografias cerebrais. O Grupo Controle foi composto por pacientes sem aneurismas. Aneurismas da artéria comunicante posterior (ACP) foram mais frequentes em mulheres (p<0,05), e aqueles da anterior (ACA) em homens (p<0,1). A incidência do tipo fetal da ACP foi maior nos casos com co-ocorrência de aneurisma da ACP (24 versus 8%, p<0,05). Pacientes com aneurisma da ACA tiveram maior incidência de hipoplasia A1 (p<0,0001, OR=32,13, IC95% 12,95-79,71) e menor frequência do da ACP fetal comparados com os controles (p=0,0125). O ângulo do sifão carotídeo era mais estreito em pacientes com aneurismas da ACP (27,3±19,1 versus 34,8±22,6, p=0,028). Em conclusão, um sifão carotídeo estreito e a presença de ACP fetal ou hipoplasia A1 podem causar estresse hemodinâmico, promovendo a formação de aneurismas em indivíduos suscetíveis.

The hydrokinetic parameters of shunts for hydrocephalus might be inadequate.

Long-term treatment of hydrocephalus continues to be dismal. Shunting is the neurosurgical procedure more frequently associated with complications, which are mostly related with dysfunctions of the shunting device, rather than to mishaps of the rather simple surgical procedure. Overdrainage and underdrainage are the most common dysfunctions; of them, overdrainage is a conspicuous companion of most devices. Even when literally hundreds of different models have been proposed, developed, and tested, overdrainage has plagued all shunts for the last 60 years. Several investigations have demonstrated that changes in the posture of the subject induce unavoidable and drastic differences of intraventricular hydrokinetic pressure and cerebrospinal fluid (CSF) drainage through the shunt. Of all the parameters that participate in the pathophysiology of hydrocephalus, the only invariable one is cerebrospinal fluid production at a constant rate of approximately 0.35 ml/min. However, this feature has not been considered in the design of currently available shunts. Our experimental and clinical studies have shown that a simple shunt, whose drainage capacity complies with this unique parameter, would prevent most complications of shunting for hydrocephalus.