Dataset Information

Sex-Specific Associations of Vascular Risk Factors With Abdominal Aortic Aneurysm: Findings From 1.5 Million Women and 0.8 Million Men in the United States and United Kingdom.

ABSTRACT: Background Large studies are required for reliable estimates of important risk factors for abdominal aortic aneurysm (AAA). This could guide targeted AAA screening programs, particularly in subgroups like women who are currently excluded from such programs. Method and Results In a cross-sectional study, 1.5 million women and 0.8 million men without known vascular disease attended commercial screening clinics in the United Kingdom or United States from 2008 to 2013. Measurements of vascular risk factors were related to AAA using logistic regression with correction for regression dilution bias. Screening detected 12 729 new AAA cases (0.6%). Compared with never smoking, current smoking was associated with 15 times the risk of AAA among women (risk ratio 15.0, 95% CI 13.2-17.0) and 7 times among men (7.3, 6.4-8.2). In women aged <75 years, the risk of AAA was nearly 30 times greater in current smokers (26.4, 20.3-34.2). In every age group, the prevalence of AAA in female smokers was greater than in male never-smokers. Positive log-linear associations with AAA for women and men were also observed for usual body mass index, usual systolic blood pressure, height, usual low-density lipoprotein cholesterol, and usual triglycerides. Conclusions Log-linear increases in the risks of AAA with traditional vascular risk factors should be considered when evaluating populations that may be at-risk for the development of AAA, and when considering potential treatments. However, at any given age, female smokers are at higher risk of AAA than male never-smokers, and a policy of screening male never-smokers but not higher-risk female smokers is questionable.

SUBMITTER: Carter JL

PROVIDER: S-EPMC7070225 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Sex-Specific Associations of Vascular Risk Factors With Abdominal Aortic Aneurysm: Findings From 1.5 Million Women and 0.8 Million Men in the United States and United Kingdom.

Carter Jennifer L JL Morris Dylan R DR Sherliker Paul P Clack Rachel R Lam Kin Bong Hubert KBH Halliday Alison A Clarke Robert R Lewington Sarah S Bulbulia Richard R

Journal of the American Heart Association 20200217 4

Background Large studies are required for reliable estimates of important risk factors for abdominal aortic aneurysm (AAA). This could guide targeted AAA screening programs, particularly in subgroups like women who are currently excluded from such programs. Method and Results In a cross-sectional study, 1.5 million women and 0.8 million men without known vascular disease attended commercial screening clinics in the United Kingdom or United States from 2008 to 2013. Measurements of vascular risk ...[more]

PMID: 32063115

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Project description:BackgroundAbdominal aortic aneurysm (AAA) is an important cause of cardiovascular mortality; however, its genetic determinants remain incompletely defined. In total, 10 previously identified risk loci explain a small fraction of AAA heritability.MethodsWe performed a genome-wide association study in the Million Veteran Program testing ≈18 million DNA sequence variants with AAA (7642 cases and 172 172 controls) in veterans of European ancestry with independent replication in up to 4972 cases and 99 858 controls. We then used mendelian randomization to examine the causal effects of blood pressure on AAA. We examined the association of AAA risk variants with aneurysms in the lower extremity, cerebral, and iliac arterial beds, and derived a genome-wide polygenic risk score (PRS) to identify a subset of the population at greater risk for disease.ResultsThrough a genome-wide association study, we identified 14 novel loci, bringing the total number of known significant AAA loci to 24. In our mendelian randomization analysis, we demonstrate that a genetic increase of 10 mm Hg in diastolic blood pressure (odds ratio, 1.43 [95% CI, 1.24-1.66]; P=1.6×10-6), as opposed to systolic blood pressure (odds ratio, 1.06 [95% CI, 0.97-1.15]; P=0.2), likely has a causal relationship with AAA development. We observed that 19 of 24 AAA risk variants associate with aneurysms in at least 1 other vascular territory. A 29-variant PRS was strongly associated with AAA (odds ratioPRS, 1.26 [95% CI, 1.18-1.36]; PPRS=2.7×10-11 per SD increase in PRS), independent of family history and smoking risk factors (odds ratioPRS+family history+smoking, 1.24 [95% CI, 1.14-1.35]; PPRS=1.27×10-6). Using this PRS, we identified a subset of the population with AAA prevalence greater than that observed in screening trials informing current guidelines.ConclusionsWe identify novel AAA genetic associations with therapeutic implications and identify a subset of the population at significantly increased genetic risk of AAA independent of family history. Our data suggest that extending current screening guidelines to include testing to identify those with high polygenic AAA risk, once the cost of genotyping becomes comparable with that of screening ultrasound, would significantly increase the yield of current screening at reasonable cost.

Project description:BACKGROUND:Thresholds for repair of abdominal aortic aneurysms vary considerably among countries. METHODS:We examined differences between England and the United States in the frequency of aneurysm repair, the mean aneurysm diameter at the time of the procedure, and rates of aneurysm rupture and aneurysm-related death. Data on the frequency of repair of intact (nonruptured) abdominal aortic aneurysms, in-hospital mortality among patients who had undergone aneurysm repair, and rates of aneurysm rupture during the period from 2005 through 2012 were extracted from the Hospital Episode Statistics database in England and the U.S. Nationwide Inpatient Sample. Data on the aneurysm diameter at the time of repair were extracted from the U.K. National Vascular Registry (2014 data) and from the U.S. National Surgical Quality Improvement Program (2013 data). Aneurysm-related mortality during the period from 2005 through 2012 was determined from data obtained from the Centers for Disease Control and Prevention and the U.K. Office of National Statistics. Data were adjusted with the use of direct standardization or conditional logistic regression for differences between England and the United States with respect to population age and sex. RESULTS:During the period from 2005 through 2012, a total of 29,300 patients in England and 278,921 patients in the United States underwent repair of intact abdominal aortic aneurysms. Aneurysm repair was less common in England than in the United States (odds ratio, 0.49; 95% confidence interval [CI], 0.48 to 0.49; P<0.001), and aneurysm-related death was more common in England than in the United States (odds ratio, 3.60; 95% CI, 3.55 to 3.64; P<0.001). Hospitalization due to an aneurysm rupture occurred more frequently in England than in the United States (odds ratio, 2.23; 95% CI, 2.19 to 2.27; P<0.001), and the mean aneurysm diameter at the time of repair was larger in England (63.7 mm vs. 58.3 mm, P<0.001). CONCLUSIONS:We found a lower rate of repair of abdominal aortic aneurysms and a larger mean aneurysm diameter at the time of repair in England than in the United States and lower rates of aneurysm rupture and aneurysm-related death in the United States than in England. (Funded by the Circulation Foundation and others.).

Project description:ObjectiveTo determine whether there is a relation between aortic diameter and morbidity and mortality in men screened for abdominal aortic aneurysm.DesignProspective cohort study.SettingHighland and Western Isles (a large, sparsely populated area of Scotland).Participants8146 men aged 65-74.Main outcome measuresMorbidity and mortality in relation to presence of abdominal aortic aneurysm and three categories of aortic diameter (≤ 24 mm, 25-29 mm, and ≥ 30 mm).ResultsWhen screened, 414 men (5.1%) had an aneurysm (diameter ≥ 30 mm), 669 (8.2%) an aortic diameter of 25-29 mm, and 7063 (86.7%) an aortic diameter of ≤ 24 mm. The cohort was followed up for a median of 7.4 (interquartile range 6.9-8.2) years. Mortality was significantly associated with aortic diameter: 512 (7.2%) men in the ≤ 24 mm group died compared with 69 (10.3%) in the 25-29 mm group and 73 (17.6%) in the ≥ 30 mm group. The mortality risk in men with an aneurysm or with an aorta measuring 25-29 mm was significantly higher than in men with an aorta of ≤ 24 mm. The increased mortality risk in the 25-29 mm group was reduced when taking confounders such as smoking and known heart disease into account. After adjustment, compared with men with an aortic diameter of ≤ 24 mm, the risk of hospital admission for cardiovascular disease and chronic obstructive pulmonary disease was significantly higher in men with aneurysm and those with aortas measuring 25-29 mm. Men with an aneurysm also had an increased risk of hospital admission for cerebrovascular disease, atherosclerosis, peripheral arterial disease, and respiratory disease. In men with aortas measuring 25-29 mm, the risk of hospital admission with abdominal aortic aneurysm was significantly higher than in men with an aorta of ≤ 24 mm (adjusted hazard ratio 6.7, 99% confidence interval 3.4 to 13.2) and this increased risk became apparent two years after screening.ConclusionsMen with abdominal aortic aneurysm and those with aortic diameters measuring 25-29 mm have an increased risk of mortality and subsequent hospital admissions compared with men with an aorta diameter of ≤ 24 mm. Consideration should be given to control of risk factors and to rescreening men with aortas measuring 25-29 mm at index scanning.

Dataset Information

Sex-Specific Associations of Vascular Risk Factors With Abdominal Aortic Aneurysm: Findings From 1.5 Million Women and 0.8 Million Men in the United States and United Kingdom.

Publications

Sex-Specific Associations of Vascular Risk Factors With Abdominal Aortic Aneurysm: Findings From 1.5 Million Women and 0.8 Million Men in the United States and United Kingdom.

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