Abstract P613: Genetic Risk of Vascular Risk Factors and Severity of Leukoaraiosis in Patients With Ischemic Stroke: The MRI-GENIE Study

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Huichun Xu ◽  
Brady Gaynor ◽  
Kathleen Ryan ◽  
Patrick McArdle ◽  
Martin Bretzner ◽  
...  

Introduction: Severity of leukoaraiosis detected on T2 MRI scans as white matter hyperintensities (WMH) is associated with infarct growth and poor poststroke outcomes in patients with acute ischemic stroke (AIS). Traditional vascular risk factors (VRF) such as age, hypertension (HTN), type 2 diabetes mellitus (T2D), and cigarette smoking are linked to WMH in large population-based studies, yet casual inferences for WMH in AIS patients are limited. We sought to examine the VRFs for evidence of causal relationships with WMH burden in AIS patients using mendelian randomization principles and polygenic risk score (PRS) methods. Method: We examined FLAIR MRIs obtained within 48 hours of AIS onset in 4,362 European Caucasian patients from the MRI-GENetics Interface Exploration (MRI-GENIE) study. WMH volume (WMHv) was measured using a fully automated deep-learning trained algorithm. We considered 13 VRFs: blood pressure (HTN, SBP, DBP, Pulse Pressure), lipid (total cholesterol, HDL, LDL, TG), BMI, T2D, atrial fibrillation, alcohol use and smoking. For each factor, we calculated a weighted PRS for each individual based on the most recent GWAS with various GWAS p-value cutoff. We then used linear regression to estimate associations between each PRS and log transformed WMHv, controlling for age, gender and principal components of genetic ancestries. Strata-specific estimates were combined using inverse-variance weighting based meta-analysis. Results: PRS of both SBP and DBP were positively and robustly associated with WMHv in the meta-analysis (p value of the association ranging from <0.001 to 0.046 for various SNP selection strategies (GWAS p-value cutoff ranging from p<1E-5 to p<1E-8)), unlike the PRS of other risk factors, although stratum-specific significance was achieved for some factors. Conclusion: Using mendelian randomization, our results lend further evidence that high blood pressure is a causal risk factor for WMH in AIS patients. This result is consistent with previous epidemiological studies of leukoaraiosis in stroke-free populations, and it supports universal control of HTN as common contributor to WMH burden and the overall brain health.

2018 ◽  
Vol 53 (24) ◽  
pp. 1515-1525 ◽  
Author(s):  
Cheng Wang ◽  
Jessica Redgrave ◽  
Mohsen Shafizadeh ◽  
Arshad Majid ◽  
Karen Kilner ◽  
...  

ObjectiveSecondary vascular risk reduction is critical to preventing recurrent stroke. We aimed to evaluate the effect of exercise interventions on vascular risk factors and recurrent ischaemic events after stroke or transient ischaemic attack (TIA).DesignIntervention systematic review and meta-analysis.Data sourcesOVID MEDLINE, PubMed, The Cochrane Library, Web of Science, The National Institute for Health and Care Excellence, TRIP Database, CINAHL, PsycINFO, SCOPUS, UK Clinical Trials Gateway and the China National Knowledge Infrastructure were searched from 1966 to October 2017.Eligibility criteriaRandomised controlled trials evaluating aerobic or resistance exercise interventions on vascular risk factors and recurrent ischaemic events among patients with stroke or TIA, compared with control.ResultsTwenty studies (n=1031) were included. Exercise interventions resulted in significant reductions in systolic blood pressure (SBP) −4.30 mm Hg (95% CI −6.77 to −1.83) and diastolic blood pressure −2.58 mm Hg (95% CI −4.7 to −0.46) compared with control. Reduction in SBP was most pronounced among studies initiating exercise within 6 months of stroke or TIA (−8.46 mm Hg, 95% CI −12.18 to −4.75 vs −2.33 mm Hg, 95% CI −3.94 to −0.72), and in those incorporating an educational component (−7.81 mm Hg, 95% CI −14.34 to −1.28 vs −2.78 mm Hg, 95% CI −4.33 to −1.23). Exercise was also associated with reductions in total cholesterol (−0.27 mmol/L, 95% CI −0.54 to 0.00), but not fasting glucose or body mass index. One trial reported reductions in secondary vascular events with exercise, but was insufficiently powered.SummaryExercise interventions can result in clinically meaningful blood pressure reductions, particularly if initiated early and alongside education.


Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Kanjana S Perera ◽  
Balakumar Swaminathan ◽  
Jackie Bosch ◽  
Robert G Hart ◽  

Background: Atherosclerotic stenosis of large IC arteries is an important cause of stroke. The prevalence of ICS in stroke population differs by ethnicity.We report the frequency of ICS among a global sample of patients with non-lacunar cryptogenic ischemic stroke (NLCIS) who did not have another identifiable cause for stroke i.e. cardioembolic, extracranial LAD, or other specific causes. Hypothesis: We hypothesized that the prevalence rates of ICS will differ according to global regions. Methods: Consecutive patients with recent ischemic stroke were retrospectively surveyed at 19 stroke centers in 19 countries to identify the frequency of IC imaging and its yield. Countries were grouped by World Bank regions. ICS was considered to be significant if there was >50% stenosis in the arteries proximal to the index stroke evidenced by MRA, CTA or TCD. Results: We identified a total of 2145 consecutive ischemic stroke patients among which 475 had NLCIS. IC arterial imaging was carried-out,on average, in 87% of patients. Of these 414 patients, 15% had stenosis proximal to the area of brain ischemia. The frequency of ICS among NLCIS patients was highest in East Asia (27%) and lowest in Pacific (4%). Patients with ICS in Latin America were significantly younger when compared to other 4 regions. Conclusion: IC arterial imaging is carried out in majority of stroke centers in patients with NLCIS, among whom the fraction of IS associated with ICS is substantial throughout the world, averaging about 15%. MRA / CTA had a higher yield than TCD. On average these patients have traditional vascular risk factors except for Latin American patients who are significantly younger with no vascular risk factors.


Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Daphne Antillon ◽  
Natalie Valle ◽  
Kaiwen Lin ◽  
Waimei Tai ◽  
Mary Ann Gallup ◽  
...  

Background: Recent nationally representative studies of stroke patients have revealed that vascular risk factors are not as aggressively controlled in women compared to men. Medically underserved minority populations are at particularly high risk for poor control of vascular risk factors; however, little is known about sex differences in this population. Methods: Sex-specific vascular risk factors and admission medications were assessed for 440 consecutive ischemic stroke patients (39% female) admitted to a safety-net public hospital in Los Angeles County. Multivariate logistic regression was used to determine sex differences in vascular risk factors, adjusting for age and race. Results: The mean age was 58.9 (SE 10.6) years, 58% were Hispanic, 7% were white, 13% were black, 20% were Asian, and 1% were Native American. Stroke classification (using modified TOAST) revealed the following distribution: 35% small vessel, 20% large vessel, 7% cardioembolic, 23% cryptogenic, 13% >1 possible etiology, and 3% other mechanisms (e.g. drug use). Women had higher mean glycosylated hemoglobin levels than men (8.0% vs 7.4%, p<0.01) and were more likely than men to have a history of type 2 diabetes (49% vs. 40% male, p=0.04), systolic blood pressure > 140 mm Hg (72% vs. 62%, p=0.03), total cholesterol > 200 mg/dL (46% vs. 36%, p=0.04), and low HDL levels (<40 mg/dL for men and <50 mg/dL for women)(83% vs. 79%, p <0.01). Men were more likely than women to have a previous history of stroke (19% vs. 13%, p = 0.05), smoking (49% vs 19%, p<0.01), and alcohol abuse (28% vs. 7%, p<0.01). After adjustment for race and age, women were more likely than men to have total cholesterol > 200 mg/dL (OR 1.56, 95% CI 1.05-2.31), BMI ≥ 30 kg/m 2 (OR 1.55, 95% CI 1.03-2.34), systolic blood pressure >140 mm Hg (OR 1.46, 95% CI 0.96-2.22), low HDL (1.26, 95% CI 0.76-2.08), and triglyceride level > 150 mg/dL (OR 1.09, 95% CI 0.74-1.63); however, the latter 3 were not significant. After adjustment for race and age, men were more likely than women to have a history of smoking (OR 4.54, 95% CI 2.78-7.14) and alcohol abuse (OR 5.56, 95% CI 2.86-11.11). Conclusions: In this multi-ethnic population with inadequate access to care, women are more likely than men to have obesity, hypertension, and dyslipidemia while men are more likely than women to smoke or abuse alcohol. Larger studies are necessary to validate these findings. In the meantime, interventions aimed at reducing the incidence of metabolic syndrome components among women and smoking and alcohol abuse among men in underserved communities are likely warranted.


2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Arkadiusz Siennicki-Lantz ◽  
Sölve Elmståhl

To assess an impact of vascular risk factors on ambulatory blood pressure measurement (ABPM) in the elderly, we followed up a population-based cohort of men from 68 until 82 years, when 104 survivors underwent ABPM.Results. At age 68, hypertension and high clinic blood pressure (CBP) did not predict ABPM level. Smoking and low ankle-brachial index (ABI) predicted higher ABPM variability and pulse pressure (PP), but not absolute ABPM values. At age 82, hypertension, high or increasing CBP, strongly positively correlated with all variables of ABPM. Carotid stenosis, low or declining ABI during followup, correlated with higher nocturnal ABPM and PP.Concluding. Hypertension and vascular risk factors in a cohort of 68-year-old men do not result in higher ABPM at age 82, possibly due to inflection point in their pressure development. Higher ABPM reflects instead an increasing CBP and aggravating atherosclerosis during the preceding decade in that part of the cohort with previously favorable risk factor status.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Elizabeth M Aradine ◽  
Yan Hou ◽  
Kathleen A Ryan ◽  
Prachi Mehndiratta ◽  
Michael S Phipps ◽  
...  

Introduction: Few studies have compared the proportion of ischemic strokes attributable to traditional vascular risk factors (population-attributable risk percent or PAR%) between genders and races. The PAR% is a function of the population prevalence and strength of association of a risk factor. Methods: A population-based case-control study of ischemic stroke in young adults ages 18-49 in the Baltimore-Washington region was used to study the prevalence, odds ratios, and PAR% of hypertension, diabetes, and smoking among blacks and whites. Logistic regression was used to calculate age-adjusted odds ratios. All analyses were stratified by gender. Results: There were 1044 cases and 1099 controls. Of the cases, 47% were black, 54% were women. Roughly a quarter to a third of all strokes in women were attributable to smoking. Due to the higher prevalence of hypertension and a higher odds ratio for hypertension in black men (OR 3.9, 95% CI 2.6-5.9) compared to white men (OR 1.8, 95% CI 1.3-2.6), there was a much higher PAR% for hypertension among black men than white men. See Table 1 for prevalence and Table 2 for PAR% stratified by gender and race. Conclusion: Traditional vascular risk factors have the potential to explain a high proportion of ischemic stroke in young adults. The high proportion of strokes in women attributable to smoking underscores the need for targeted smoking cessation interventions in this population. Diabetes and, especially, hypertension are important contributors to the excess population burden of ischemic stroke among blacks. These findings support the value of early screening and treatment for hypertension in young blacks.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Anne-Katrin Giese ◽  
Markus D Schirmer ◽  
Adrian V Dalca ◽  
Ramesh Sridharan ◽  
Lisa Cloonan ◽  
...  

Introduction: White matter hyperintensity (WMH) is a highly heritable trait and a significant contributor to stroke risk and severity. Vascular risk factors contribute to WMH severity; however, knowledge of the determinants of WMH in acute ischemic stroke (AIS) is still limited. Hypothesis: WMH volume (WMHv) varies across AIS subtypes and is modified by vascular risk factors. Methods: We extracted WMHv from the clinical MRI scans of 2683 AIS subjects from the MRI-Genetics Interface Exploration (MRI-GENIE) study using a novel fully-automated, volumetric analysis pipeline. Demographic data, stroke risk factors and stroke subtyping for the Causative Classification of Stroke (CCS) were performed at each of the 12 international study sites. WMHv was natural log-transformed for linear regression analyses. Results: Median WMHv was 5.7cm 3 (interquartile range (IQR): 2.2-12.8cm 3 ). In univariable analysis, age (63.1 ± 14.7 years, β=0.04, SE=0.002), prior stroke (10.2%, β=0.66, SE=0.08), hypertension (65.4%, β=0.75, SE=0.05), diabetes mellitus (23.1%, β=0.35, SE=0.06), coronary artery disease (17.6%, β=0.04, SE=0.002), and atrial fibrillation (14.6%, β=0.48, SE=0.07) were significant predictors of WMHv (all p<0.0001), as well as smoking status (52.2%, β=0.15, SE=0.05, p=0.005), race (16.5% Non-Caucasian, β=0.25, SE=0.07) and ethnicity (8.2% Hispanic, β=0.30, SE=0.11) (all p<0.01). In multivariable analysis, age (β=0.04, SE=0.002), prior stroke (β=0.56, SE=0.08), hypertension (β=0.33, SE=0.05), smoking status (β=0.16, SE=0.05), race (β=0.42, SE=0.06), and ethnicity (β=0.34, SE=0.09) were independent predictors of WMHv (all p<0.0001), as well as diabetes mellitus (β=0.13, SE=0.06, p=0.02). WMHv differed significantly (p<0.0001, unadjusted) across CCS stroke subtypes: cardioembolic stroke (8.0cm 3 , IQR: 4.2-15.4cm 3 ), large-artery stroke (6.9cm 3 , IQR: 3.1-14.7cm 3 ), small-vessel stroke (5.8cm 3 , IQR: 2.5-13.5cm 3 ), stroke of undetermined (4.7cm 3 , IQR: 1.6-11.0cm 3 ) or other (2.55cm 3 , IQR: 0.9-8.8cm 3 ) causes. Conclusion: In this largest-to-date, multicenter hospital-based cohort of AIS patients with automated WMHv analysis, common vascular risk factors contribute significantly to WMH burden and WMHv varies by CCS subtype.


Stroke ◽  
2019 ◽  
Vol 50 (5) ◽  
pp. 1310-1317 ◽  
Author(s):  
Dirk M. Hermann ◽  
Christoph Kleinschnitz

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