scholarly journals Extreme Phenotype Approach Suggests Taste Transduction Pathway for Carotid Plaque in a Multi-Ethnic Cohort

Stroke ◽  
2020 ◽  
Vol 51 (9) ◽  
pp. 2761-2769
Author(s):  
Nicole D. Dueker ◽  
Brett Doliner ◽  
Hannah Gardener ◽  
Chuanhui Dong ◽  
Ashley Beecham ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ethnic Groups ◽  
Pathway Analysis ◽  
Carotid Plaque ◽  
Vascular Risk Factors ◽  
Plaque Burden ◽  
Vascular Risk ◽  
Data Set ◽  
Gene Set ◽  
Genome Wide

Background and Purpose: Carotid plaque is a heritable trait and a strong predictor of vascular events. Several loci have been identified for carotid plaque, however, studies in minority populations are lacking. Within a multi-ethnic cohort, we have identified individuals with extreme total carotid plaque area (TCPA), that is, higher or lower TCPA than expected based on traditional vascular risk factors (age, sex, smoking, diabetes mellitus, hypertension, etc). We hypothesized that these individuals are enriched with genetic variants accounting for the plaque burden that cannot be explained by traditional vascular risk factors. Herein, we sought to identify the genetic basis for TCPA using the multi-ethnic cohort. Methods: Three hundred forty participants (170 from each extreme group) from 3 race/ethnic groups (53% Hispanic, 29% non-Hispanic Black, and 18% non-Hispanic White) were genotyped using a genome-wide single-nucleotide polymorphism (SNP) array and imputed using 1000Genome data. SNP-based analyses using logistic regression and gene-based analyses using VEGAS2 were performed within each race/ethnic group and then meta-analyzed. Genes with P <0.001 were included in an overrepresentation enrichment pathway analysis using WebGestalt. Promising findings were tested for association with ischemic stroke using the MEGASTROKE Consortium data set. Results: No SNP or gene reached genome-wide significance. In the pathway analysis, GO:0050913 (sensory perception of bitter taste) gene set was significantly enriched ( P =4.5×10 −6 , false discovery rate=0.04), which was confirmed in MEGASTROKE ( P =0.01). Within the GO:0050913 gene set, 3 genes were associated with extreme TCPA in our study ( P <0.001): TAS2R20 , TAS2R50 , and ITPR3 . In TAS2R50 , rs1376251 is the top SNP and has been associated with myocardial infarction by others. In ITPR3 , a SNP with high regulatory potential (rs3818527, RegulomeScore=1f), and ITPR3 itself were among the top SNP-based and gene-based results and showed consistent evidence for association in all ethnic groups ( P <0.05). Conclusions: Extreme TCPA analysis identified new candidate genes for carotid plaque in understudied populations.

Sonographic Carotid Plaque Morphologic Characteristics and Vascular Risk Factors

2008 ◽  
Vol 27 (9) ◽  
pp. 1313-1319 ◽  
Author(s):  
Edoardo Vicenzini ◽  
Maria Chiara Ricciardi ◽  
Francesco Puccinelli ◽  
Marta Altieri ◽  
Nicola Vanacore ◽  
...  
Keyword(s):  
Risk Factors ◽  
Carotid Plaque ◽  
Vascular Risk Factors ◽  
Vascular Risk ◽  
Morphologic Characteristics

Abstract P372: Sex-Differences in Carotid Plaque Composition in Patients With Embolic Stroke of Undetermined Source

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Jae W Song ◽  
James E Siegler ◽  
Jesse Thon ◽  
John H Woo ◽  
Brett L Cucchiara
Keyword(s):  
Risk Factors ◽  
Sex Differences ◽  
Ischemic Stroke ◽  
Carotid Plaque ◽  
Vascular Risk Factors ◽  
Embolic Stroke ◽  
Vascular Risk ◽  
Plaque Composition ◽  
Plaque Volume ◽  
Male Sex

Introduction: Non-stenotic carotid plaque may be the cause of ischemic stroke in some patients with embolic stroke of undetermined source (ESUS). We examined sex-differences in carotid plaque composition in patients with ESUS. Methods: A retrospective cohort of anterior circulation acute ischemic stroke patients with CTA head/neck and meeting criteria for ESUS was identified. Carotid artery bifurcations (4cm segment) ipsilateral to the stroke were evaluated using a semi-automated segmentation software to measure total plaque volume and plaque subcomponents (calcium, intraplaque hemorrhage [IPH], and lipid rich necrotic core [LRNC]). Sex-differences in baseline vascular risk factors and plaque subcomponent volumes were tested by Mann-Whitney U tests or students t-tests for continuous variables and Fisher’s exact test for categorical variables. Associations of each plaque subcomponent were tested by multivariate linear regressions. Results: Of 94 patients, 55% were women. Mean age of the cohort was 65 years. Women had higher body mass indices than men (29.2 vs 26.3; p=0.02). There were no other significant differences in age or vascular risk factors between men and women. Overall plaque volume (p=0.001) was significantly greater in men as was the volume of calcification (p<0.001) and IPH (p=0.008) in carotid arteries ipsilateral to the stroke (Figure). No significant difference was detected in LRNC volume by sex (p=0.84). In multivariate analysis, male sex (β=45.9, 95% CI 18.0-73.7, p=0.002) and older age (β=1.85, 95% CI 0.73-3.0, p=0.001) were significantly associated with calcified plaque volume, and male sex (β= 6.7, 95% CI 2.6-10.8, p=0.002) with IPH. Neither age nor sex was significantly associated with LRNC. Conclusions: Sex-differences in carotid plaque composition in ESUS suggest the possibility of a differential contribution of non-stenotic carotid plaque to stroke mechanism in men versus women.

Abstract TMP96: Carotid Plaque Characteristics Correlated to Baseline Vascular Risk Factors in a Large Randomized Trial: Results from CREST-2

Stroke ◽  
2019 ◽  
Vol 50 (Suppl_1) ◽  
Author(s):  
Brajesh K Lal ◽  
Matthew Chrencik ◽  
Amir Khan ◽  
Michael Jones ◽  
John Huston ◽  
...  
Keyword(s):  
Risk Factors ◽  
Randomized Trial ◽  
Carotid Plaque ◽  
Vascular Risk Factors ◽  
Vascular Risk ◽  
Large Randomized Trial

The Spectrum of Cerebrovascular Disease and Associated Cognitive Decline

2019 ◽  
pp. 574-599
Author(s):  
Victoria J. Williams ◽  
Steven E. Arnold ◽  
David H. Salat
Keyword(s):  
Risk Factors ◽  
Cognitive Impairment ◽  
Cerebrovascular Disease ◽  
Cognitive Decline ◽  
Vascular Dementia ◽  
Structure And Function ◽  
Vascular Risk Factors ◽  
Vascular Health ◽  
Vascular Risk ◽  
And Function

Throughout the lifespan, common variations in systemic health and illness contribute to alterations in vasculature structure and function throughout the body, significantly increasing risk for cardiovascular and cerebrovascular disease (CVD). CVD is a prevalent cause of mortality in late life; it also promotes brain alterations, contributing to cognitive decline and, when severe, vascular dementia. Even prior to diseased states, individual variation in CVD risk is associated with structural and functional brain alterations. Yet, how cumulative asymptomatic alterations in vessel structure and function contribute to more subtle changes in brain tissue integrity and function that emerge in late life is unclear. Finally, vascular risk factors are associated with the clinical progression of neurodegenerative diseases such as Alzheimer’s disease (AD); however, recent theory posits that vascular degeneration may serve a contributory role in these conditions. This chapter reviews how lifespan changes in vascular health contribute to degenerative changes in neural tissue and the subsequent development of cognitive impairment and/or vascular dementia. It first discusses associations between vascular risk factors and cognition and also how declining vascular health may lead to cognitive impairment and dementia. Next, it identifies basic aspects of cerebrovascular anatomy and physiology sustaining tissue health and discusses how vulnerabilities of this system contribute to neurodegenerative changes. Finally, it reviews evidence of vascular contributions to AD and presents ideas for future research to better understand the full spectrum of cerebrovascular contributions to brain aging, cognitive decline, and dementia.

scholarly journals The impact of vascular risk factors on the thickness and volume of the choroid in AMD patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Elżbieta Krytkowska ◽  
Aleksandra Grabowicz ◽  
Katarzyna Mozolewska-Piotrowska ◽  
Zofia Ulańczyk ◽  
Krzysztof Safranow ◽  
...  
Keyword(s):  
Risk Factors ◽  
Vascular Risk Factors ◽  
Age Related Macular Degeneration ◽  
Control Group ◽  
Vascular Risk ◽  
Average Volume ◽  
Central Ring ◽  
Age Related ◽  
The Impact ◽  
Wet Amd

AbstractDisturbances in choroidal microcirculation may lead to the onset and progression of age-related macular degeneration (AMD). We aimed to assess changes in the choroidal volume and thickness in the macular region in AMD eyes and to investigate whether coexisting vascular risk factors alter choroidal status. We enrolled 354 AMD patients (175 dry, 179 wet AMD) and 121 healthy controls. All participants underwent a complete ophthalmologic examination and assessment of choroidal thickness and volume. A multivariate analysis adjusted for age, sex, and smoking status revealed that wet AMD was an independent factor associated with higher average thickness of the central ring area (ATC) and average volume of the central ring area (AVC) and lower choroidal vascularity index (CVI) compared to controls (β =  + 0.18, p = 0.0007, β =  + 0.18, p = 0.0008, respectively) and to dry AMD (β =  + 0.17, p = 0.00003 for both ATC and AVC and β =  − 0.30 p < 0.0001 for CVI). ATC, AVC and average volume (AV) were lower in AMD patients with hypertension and ischaemic heart disease (IHD). The duration of hypertension was inversely correlated with ATC, AVC and AV (Rs =  − 0.13, p < 0.05; Rs =  − 0.12; p < 0.05, Rs =  − 0.12; p < 0.05, respectively) while IHD duration negatively correlated with AV (Rs =  − 0.15, p < 0.05). No such associations were observed in the control group. Our findings show that the choroidal vascular system in eyes with AMD is much more susceptible to damage in the presence than in the absence of systemic vascular disease.

scholarly journals O4-10-05: The effect of vascular risk factors on cognition in older adults: Data from the AIBL study

2012 ◽  
Vol 8 (4S_Part_17) ◽  
pp. P635-P635
Author(s):  
Carolina Restrepo ◽  
Michael Saling ◽  
Paul Yates ◽  
Victor Villemagne ◽  
David Ames ◽  
...  
Keyword(s):  
Risk Factors ◽  
Older Adults ◽  
Vascular Risk Factors ◽  
Vascular Risk
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