Abstract 71: Sex and Genetic Predisposition Synergistically Influence Risk of Stroke and Myocardial Infarction in Middle-Aged Persons Without Risk Factors

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Guido J Falcone ◽  
Julian Acosta ◽  
Audrey C Leasure ◽  
Kevin N Vanent ◽  
Rommell B Noche ◽  
...  
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Genetic Predisposition ◽  
Genetic Risk ◽  
Vascular Risk Factors ◽  
Vascular Risk ◽  
Uk Biobank ◽  
Middle Aged ◽  
High Genetic Risk ◽  
The Uk

Background and Hypothesis: Driven by aging-related physiological changes, the incidence of stroke and myocardial infarction rises rapidly in persons aged >40 years. A significant proportion of these acute vascular events (AVE) take place in persons without vascular risk factors. We tested the hypothesis that sex and genetic predisposition synergistically increase the risk of AVE in middle-aged persons without vascular risk factors. Methods: We analyzed data from the UK Biobank, a prospective longitudinal study that enrolled persons aged 40 to 69 years. Our analysis was restricted to middle-aged participants, defined as those aged 40 to 60 years. Prevalent and incident cases of stroke (ischemic and hemorrhagic) and myocardial infarction were included. To quantify the genetic predisposition to sustain an AVE, we constructed a polygenic risk score using 68 independent (R 2 <0.1) genetic variants known to associate (p<5x10 -8 ) with AVE. Participants were classified as having low, intermediate or high genetic risk according to tertiles of the score. We used Cox models for association and interaction testing. Results: Of the 502,536 study participants enrolled in the UK Biobank, 303,295 (60%) did not have any vascular risk factors. During the follow-up period, there were 5,746 AVEs, including 1,954 strokes and 3,792 myocardial infarctions. The cumulative risk of AVE was 0.12% (n=352), 0.46% (n = 1,386) and 1.32% (n = 4,008) at ages 40, 50 and 60 years (test-for-trend p<0.001). The risk of AVE was 3 times greater in men than women (HR 3.30, 95%CI 3.08 - 3.53). Compared to persons with low genetic risk, those with intermediate and high genetic risk had a 22% (HR 1.22, 95%CI 1.13 - 1.32) and 52% (HR 1.52, 95%CI 1.41 - 1.65) increase in risk of AVE, respectively. There was significant synergy (interaction) between sex and genetic predisposition: compared to females with low genetic risk, males with high genetic risk had 4 times (HR 3.91, 95%CI 3.58 - 4.26) the risk of AVE (interaction analysis p<0.001). Conclusion: Genetic information constitutes a promising tool to risk stratify middle-aged persons without vascular risk factors. The synergistic effect of sex and genetic predisposition points to specific subgroups that could benefit from aggressive preventive interventions.

scholarly journals Midlife vascular risk factors and risk of incident dementia: Longitudinal cohort and Mendelian randomization analyses in the UK Biobank

2021 ◽  
Author(s):  
Rainer Malik ◽  
Marios K. Georgakis ◽  
Julia Neitzel ◽  
Kristiina Rannikmäe ◽  
Michael Ewers ◽  
...  
Keyword(s):  
Risk Factors ◽  
Mendelian Randomization ◽  
Vascular Risk Factors ◽  
Vascular Risk ◽  
Uk Biobank ◽  
Longitudinal Cohort ◽  
Incident Dementia ◽  
The Uk

scholarly journals RISK LOCI IDENTIFICATION OF NOVEL GENETIC RISK FACTORS FOR ATRIAL SEPTAL DEFECT USING THE UK BIOBANK

2021 ◽  
Vol 77 (18) ◽  
pp. 479
Author(s):  
Alex Gyftopoulos ◽  
Yi-Ju Chen ◽  
James A. Perry ◽  
Charles C. Hong
Keyword(s):  
Risk Factors ◽  
Atrial Septal Defect ◽  
Genetic Risk ◽  
Septal Defect ◽  
Genetic Risk Factors ◽  
Uk Biobank ◽  
The Uk

scholarly journals White matter hyperintensities across the adult lifespan: relation to age, Aβ load, and cognition

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Antoine Garnier-Crussard ◽  
Salma Bougacha ◽  
Miranka Wirth ◽  
Claire André ◽  
Marion Delarue ◽  
...  
Keyword(s):  
Risk Factors ◽  
Working Memory ◽  
Executive Functions ◽  
White Matter Hyperintensities ◽  
Vascular Risk Factors ◽  
Age Group ◽  
Vascular Risk ◽  
Middle Aged ◽  
Adult Lifespan ◽  
Middle Aged Adults

Abstract Background White matter hyperintensities (WMH) are very frequent in older adults and associated with worse cognitive performance. Little is known about the links between WMH and vascular risk factors, cortical β-amyloid (Aβ) load, and cognition in cognitively unimpaired adults across the entire lifespan, especially in young and middle-aged adults. Methods One hundred and thirty-seven cognitively unimpaired adults from the community were enrolled (IMAP cohort). Participants underwent (i) a comprehensive neuropsychological assessment of episodic memory, processing speed, working memory, and executive functions; (ii) brain structural T1 and FLAIR MRI scans used for the automatic segmentation of total and regional (frontal, parietal, temporal, occipital, and corpus callosum) WMH; and (iii) a Florbetapir-PET scan to measure cortical Aβ. The relationships of total and regional WMH to age, vascular risk factors, cortical Aβ, and cognition were assessed within the whole sample, but also splitting the sample in two age groups (≤ or > 60 years old). Results WMH increased with age across the adult lifespan, i.e., even in young and middle-aged adults. Systolic blood pressure, diastolic blood pressure, and glycated hemoglobin were all associated with higher WMH before, but not after, adjusting for age and the other vascular risk factors. Higher frontal, temporal, and occipital WMH were associated with greater Aβ, but this association was no longer significant when adjusting for age and vascular risk factors. Higher total and frontal WMH were associated with worse performance in executive functions, with no interactive effect of the age group. In contrast, there was a significant interaction of the age group on the link between WMH and working memory, which was significant within the subgroup of young/middle-aged adults only. Adding cortical Aβ load in the models did not alter the results, and there was no interaction between WMH and Aβ on cognition. Conclusion WMH increased with age and were associated with worse executive functions across the adult lifespan and with worse working memory in young/middle-aged adults. Aβ load was weakly associated with WMH and did not change the relationship found between WMH and executive functions. This study argues for the clinical relevance of WMH across the adult lifespan, even in young and middle-aged adults with low WMH.

Silent Cerebral White Matter Lesions and Their Relationship With Vascular Risk Factors in Middle-Aged Predialysis Patients With CKD

2006 ◽  
Vol 47 (2) ◽  
pp. 241-250 ◽  
Author(s):  
Alberto Martinez-Vea ◽  
Esther Salvadó ◽  
Alfredo Bardají ◽  
Cristina Gutierrez ◽  
Ana Ramos ◽  
...  
Keyword(s):  
Risk Factors ◽  
White Matter ◽  
White Matter Lesions ◽  
Vascular Risk Factors ◽  
Cerebral White Matter ◽  
Vascular Risk ◽  
Middle Aged ◽  
Cerebral White Matter Lesions

scholarly journals Prevalence of dementia in African–Caribbean compared with UK-born White older people: two-stage cross-sectional study

2011 ◽  
Vol 199 (2) ◽  
pp. 119-125 ◽  
Author(s):  
Simon Adelman ◽  
Martin Blanchard ◽  
Greta Rait ◽  
Gerard Leavey ◽  
Gill Livingston
Keyword(s):  
Risk Factors ◽  
Older People ◽  
Vascular Risk Factors ◽  
Country Of Birth ◽  
Vascular Risk ◽  
Cross Sectional ◽  
Caribbean Country ◽  
African Caribbean ◽  
The Uk ◽  
Prevalence Of Dementia

BackgroundPreliminary studies in the UK, all using screening instruments of unknown cultural validity, indicate that there may be an increased prevalence of dementia in African–Caribbean people, possibly related to vascular risk factors and potentially amenable to preventative measures.AimsTo determine the prevalence of dementia in older people of African–Caribbean country of birth compared with their White UK-born counterparts.MethodA total of 218 people of African–Caribbean country of birth and 218 White UK-born people aged ⩾60 years were recruited from five general practices in North London. Those who screened positive for cognitive impairment using a culturally valid instrument were offered a standardised diagnostic interview. Two independent assessors diagnosed dementia according to standard operationalised criteria.ResultsAfrican–Caribbean participants were 2 years younger, and those with dementia nearly 8 years younger than their White counterparts. The prevalence of dementia was significantly higher in the African–Caribbean (9.6%) than the White group (6.9%) after adjustment for the confounders age and socioeconomic status (odds ratio (OR) = 3.1, 95%CI 1.3–7.3, P = 0.012).ConclusionsThere is an increased prevalence of dementia in older people of African–Caribbean country of birth in the UK and at younger ages than in the indigenous White population. These findings have implications for service provision and preventive interventions. Further research is needed to explore the role of vascular risk factors and social adversity in the excess of dementia in this population.

scholarly journals Stroke, vascular risk factors and depression

2001 ◽  
Vol 178 (1) ◽  
pp. 23-28 ◽  
Author(s):  
R. Stewart ◽  
M. Prince ◽  
M. Richards ◽  
C. Brayne ◽  
A. Mann
Keyword(s):  
Risk Factors ◽  
Geriatric Depression Scale ◽  
Depression Scale ◽  
Vascular Risk Factors ◽  
Vascular Risk ◽  
Geriatric Depression ◽  
Community Based ◽  
Blood Tests ◽  
Mediating Factor ◽  
The Uk

BackgroundStroke, hypertension and diabetes are common in older Caribbean-born populations in the UK who may be at risk of depression secondary to vascular disease.AimsWe examined the association between stroke, vascular risk factors and depression in a community-based Caribbean-born population aged 55–75 years.MethodVascular risk factors were identified by interview, examination and blood tests. Depression was categorised using the Geriatric Depression Scale. Disablement was assessed as a potential mediating factor.ResultsPhysical illness and disablement were strongly associated with depression, independent of disablement. Previous stroke was associated with depression, independent of disablement. No vascular risk factors were associated with depression.ConclusionsThe risk of depression associated with stroke was not explained by disablement. However, the hypothesis that vascular risk factors are important in the genesis of depression was not supported.

P3823Body mass index or waist and hip circumference as predictors of outcome in the UK biobank

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
P Pellicori ◽  
B Stanley ◽  
S Iliodromiti ◽  
C A Celis-Morales ◽  
D M Lyall ◽  
...  
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Body Fat ◽  
Uk Biobank ◽  
Anthropometric Indices ◽  
All Cause Mortality ◽  
History Of ◽  
Cv Disease ◽  
The Uk

Abstract Background Controversies exist about the relationship between body habitus and mortality, especially for patients with cardiovascular disease. Purpose We evaluated the relations between different anthropometric indices and mortality amongst participants with and without cardiovascular (CV) risk factors, or established CV disease (stroke, myocardial infarction and/or heart failure), enrolled in the UK Biobank. Methods The UK Biobank is a large prospective study which, between 2006 and 2010, enrolled 502,620 participants aged 38–73 years. Participants filled questionnaires and had a medical history recorded, physical measurements done and biological samples taken. The UK Biobank is routinely linked to national death registries and updated on a quarterly basis. Data on death were coded according to the International Classification of Diseases, 10th Revision (ICD-10). The primary end-point was all-cause mortality (ACM) across three subgroups of men and women: those with, or without, one or more CV risk factors (smoking, diabetes and/or hypertension), and those with CV disease (history of stroke, myocardial infarction and/or heart failure) at recruitment. Presence, or absence, of CV risk factors and diagnoses of CV disease were self-reported by participants at enrolment. Associations between anthropometric indices (body mass index (BMI), waist circumference (WC), waist to hip ratio (WHiR), and waist to height ratio (WHeR)) and the risk of all-cause mortality were analysed using Cox regression models. Results After excluding those with history of cancer at baseline (n=45,222), 453,046 participants were included (median age: 58 (interquartile range: 50 - 63) years; 53% women), of whom 150,732 had at least one CV risk factor, and 17,884 established CV disease. During a median follow-up of 5 years, 6,319 participants died. Baseline BMI had a U-shaped relationship with ACM, with higher nadir-values for those with CV risk factors or CV disease, for both sexes (figure). WC, WHiR and WHeR (measures of central distribution of body fat) had more linear associations with ACM, regardless of CV risk factors, CV disease and sex. Conclusions For adults with or without CV risk factors or established CV disease, measures of central distribution of body fat are more strongly and more linearly associated with ACM than BMI. WC, or WHiR, rather than BMI, appear to be more appropriate variables for risk stratification.

DO DEMOGRAPHIC AND VASCULAR RISK FACTORS PREDICT COGNITIVE CHANGE IN 11,070 UK BIOBANK PARTICIPANTS?

2017 ◽  
Vol 13 (7) ◽  
pp. P1556
Author(s):  
Chloe Fawns-Ritchie ◽  
Simon R. Cox ◽  
Marcus Richards ◽  
John Gallacher ◽  
John M. Starr ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cognitive Change ◽  
Vascular Risk Factors ◽  
Vascular Risk ◽  
Uk Biobank

scholarly journals Effect of n-3 polyunsaturated fatty acids on ischemic heart disease and cardiometabolic risk factors: a two-sample Mendelian randomization study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Bayi Xu ◽  
Zhixia Xu ◽  
Duanmin Xu ◽  
Xuerui Tan
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Blood Pressure ◽  
Fatty Acids ◽  
Cardiometabolic Risk ◽  
Mendelian Randomization ◽  
Meta Analysis ◽  
Cardiometabolic Risk Factors ◽  
Uk Biobank ◽  
The Uk

Abstract Background The cardioprotective ability of n-3 polyunsaturated fatty acids (PUFAs) is controversial. Most studies suggest a specific role for PUFAs in cardioprotection from ischemic heart disease (IHD). However, few studies have used genetic biomarkers of n-3 PUFAs to examine their potential relationships with IHD. This study aimed to use Mendelian randomization to evaluate whether genetically-predicted n-3 PUFAs affect IHD and cardiometabolic risk factors (CRFs). Methods Genetic variants strongly (p < 5 × 10–8) and independently (r2 > 0.1) associated with n-3 PUFAs were derived from the CHARGE Consortium (including 8,866 subjects of European ancestry) and were used as instrumental variables (IVs) for evaluating the effect of n-3 PUFAs, including α-linolenic acid (ALA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). Data on the associations between the IVs and IHD, myocardial infarction, and CRFs (including diabetes, lipids, blood pressure, body mass index, and waist-to-hip ratio (WHR)) were obtained from the UK Biobank SOFT CAD GWAS with the CARDIoGRAMplusC4D 1000 Genomes-based GWAS (113,937 IHD cases and 339,115 controls), the Myocardial Infarction Genetics and CARDIoGRAM Exome consortia (42,335 MI cases and 78,240 controls), the DIAbetes Genetics Replication And Meta-analysis consortium (26,676 diabetes mellitus cases and 132,532 controls), the Global Lipids Genetics Consortium (n = 196,475), the International Consortium for Blood Pressure (n = 69,395), and the meta-analysis of GWAS for body fat distribution in the UK Biobank and Genetic Investigation of Anthropometric Traits (n = 694,649). Results Genetically-predicted higher ALA was associated with lower risk of IHD, type 2 diabetes (T2D), and lower serum lipids. The effect size per 0.05-unit increase (about 1 standard deviation) in plasma ALA level) was − 1.173 (95% confidence interval − 2.214 to − 0.133) for IHD. DPA and EPA had no association with IHD but were associated with a higher risk of T2D, higher levels of lipids or WHR. DHA had no association with IHD or CRFs. Conclusions Our study suggests a benefit of ALA for IHD and its main risk factors. DHA, DPA, and EPA had no association with IHD but were partly associated with increasing cardiometabolic risk factors.

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