Incident Abdominal Aortic Aneurysm Research Articles

Polygenic Risk Score Informed Clinical Model for Improving Abdominal Aortic Aneurysm Screening

Abdominal aortic aneurysm (AAA) is a complex disease with environmental and genetic risk factors. Polygenic risk scores (PRSs) based on disease-specific risk-associated single nucleotide variants (SNVs) have demonstrated effectiveness in stratifying individual-level disease risk for cardiovascular diseases. This prospective cohort study assessed associations of PRS of AAA (PRSAAA) with risk of incident AAA, analyzed the effectiveness of a combined clinical-genetic risk model, and explored the clinical utility of the model in identifying high-risk individuals for AAA screening. PRSAAA was calculated using 911,440 SNVs and PRS of coronary artery disease was calculated using 2,324,683 SNVs derived from mixed ancestry genome-wide association studies. The UK Biobank was used as the study cohort. All individuals with complete genetic data available and no diagnosis of AAA at the time of recruitment were included in the analysis and followed prospectively to assess for incident AAA. A PRS-informed clinical model, Prob-AAA, was developed using clinically significant variables and PRSAAA. Four hundred eighty-one thousand one hundred 5 individuals were included in the analysis with 2,668 incident AAA cases. Incident AAA increased from 0.30 to 0.93% between the lowest and highest decile of PRSAAA; similarly, severe AAA, requiring surgery and/or presenting with rupture, increased from 23 to 39% of incident AAA cases across deciles. PRSAAA was a predictor of incident AAA diagnosis (hazard ratio 2.06 [1.70-2.48]) independent of other clinical risk factors including male sex, older age, and smoking history. Prob-AAA was an independent predictor of incident AAA (hazard ratio 1.92 [1.69-2.20]), and identified 9.6% of cases of incident AAA compared to only 4.2% by PRSAAA. Current screening guidelines captured 5.7% of the overall cohort, with an incident AAA rate of approximately 3.2%. Among males not included by current guidelines, Prob-AAA identified an additional cohort, approximately 2% of the overall cohort, with a similar rate of incident AAA. Prob-AAA, a PRS-informed clinical model for AAA, improved upon the predictive power of current, clinical risk factor-informed, screening guidelines for AAA.

#1737 Kidney function, kidney function decline, and the risk of abdominal aortic aneurysm: the Stockholm CREAtinine Measurements (SCREAM) project

Abstract Background and Aims Small, cross-sectional, cohort studies suggest a relationship between low estimated glomerular filtration rate (eGFR) and risk of developing abdominal aortic aneurysm (AAA). We here explored the possible association between eGFR and annual eGFR decline with future risk of AAA in a large community-based sample. Method Observational study from the SCREAM project, including participants free from AAA history. We used Cox regression to explore associations between eGFR and the rate of incident AAA and fatal-AAA (followed by death within 30 days). Among those with repeated eGFR tests within a year, we used linear mixed models to explore associations between the annual slope in eGFR and AAA rates. Results We included 1 586,543 eligible participants (mean age 47 years, 53% female, median eGFR 97 ml/min/1.73 m2). During median 7.6 years, 5,248 (0.34%) participants experienced AAA, of which 317 were fatal. In multivariable analyses, compared with individuals with eGFR 90 mL/min/1.73 m2, the rates of AAA and fatal-AAA were higher across lower eGFR: for eGFR 30 mL/min/1.73 m2, the HR of AAA was 1.23 (95% CI 1.09-1.39), and for fatal-AAA was 2.59 (1.71-3.90); for eGFR 15 mL/min/1.73 m2, the HR of AAA was 1.58 (1.31-1.90) and for fatal-AAA was 3.92 (2.28-6.70). Total 639 607 participants had repeated eGFR measures within a year, and experienced 3,416 AAA events during median 8.8 years of follow-up. Compared with participants showing a stable eGFR slope (−1 to 1 mL/min/y), the rate of AAA was 10% higher (HR 1.10 [1.00-1.21]) in those with an eGFR decline of 1-3 mL/min/y, and 30% higher (HR 1.30 [1.03-1.65]) in those with an eGFR decline >3 mL/min/y. Conclusion Both a single point eGFR and the annual slope of eGFR decline were associated with future risks of AAA. The incidence rate of AAA, and particularly fatal AAA, was higher with greater severity of chronic kidney disease or speed of eGFR decline.

Metabolic syndrome and the risk of abdominal aortic aneurysm: A nationwide cohort study

Background and aimsThe association between metabolic syndrome (MetS) and abdominal aortic aneurysm (AAA) remains unclear. We investigated the potential association between AAA and MetS and its components in a large population-based cohort. MethodsWe used the Korean National Health Insurance Service database including 4,162,640 participants aged ≥50 years who received a routine health examination in 2009. Cox proportional hazards models were used to analyze the association between MetS and its components (elevated waist circumference, blood pressure, glucose, triglycerides, and reduced high-density lipoprotein cholesterol [HDL-C]) with AAA incidence, with adjustment for confounders. ResultsDuring a median 9.4 years of follow-up, 18,160 participants developed incident AAA. MetS was associated with an increased risk of AAA compared to the non-MetS group (adjusted hazard ratio [aHR], 1.38; 95% confidence interval [CI], 1.34–1.43). Among the individual components, elevated waist circumference, blood pressure, triglycerides, and reduced HDL-C were associated with increased AAA risk, while elevated glucose alone was associated with reduced AAA risk (aHR, 0.85; 95% CI, 0.82–0.87). AAA risk also increased linearly with the increasing number of MetS components, with the highest risk found in the presence of all 5 components (aHR, 1.98, 95% CI, 1.83–2.15). ConclusionsMetS and its individual components, with the exclusion of elevated glucose, were associated with higher risk of AAA. Further studies are warranted to elucidate the association between MetS and AAA.

Association of HIV Infection and Incident Abdominal Aortic Aneurysm Among 143 001 Veterans.

People with HIV (PWH) have an increased risk of cardiovascular disease. Previous cross-sectional data suggest there is a higher prevalence of abdominal aortic aneurysm (AAA) in PWH than in those without HIV. Whether PWH have an increased risk of incident AAA compared with those without HIV is unknown. We analyzed data among participants without prevalent AAA from the Veterans Aging Cohort Study, a prospective, observational, longitudinal cohort of veterans with HIV matched 1:2 with veterans without HIV infection. We calculated AAA rates by HIV status and assessed the association between HIV infection and incident AAA using Cox proportional hazards models. We defined AAA using the International Classification of Diseases, 9th or 10th revision, or Current Procedural Terminology codes and adjusted all models for demographic characteristics, cardiovascular disease risk factors, and substance use. Secondary analyses examined the association between time-varying CD4+ T-cell count or HIV viral load and incident AAA. Among 143 001 participants (43 766 with HIV), over a median follow-up of 8.7 years, there were 2431 incident AAA events (26.4% among PWH). Rates of incident AAA per 1000 person-years were similar among PWH (2.0 [95% CI, 1.9-2.2]) and people without HIV (2.2 [95% CI, 2.1-2.3]). There was no evidence that HIV infection increased the risk of incident AAA compared with no HIV infection (adjusted hazard ratio, 1.02 [95% CI, 0.92-1.13]). In adjusted analyses with time-varying CD4+ T-cell counts or HIV viral load, PWH with CD4+ T-cell counts <200 cells/mm3 (adjusted hazard ratio, 1.29 [95% CI, 1.02-1.65]) or HIV viral load ≥500 copies/mL (adjusted hazard ratio, 1.29 [95% CI, 1.09-1.52]) had an increased risk of AAA compared with those without HIV. HIV infection is associated with an increased risk of AAA among those with low CD4+ T-cell counts or elevated HIV viral load over time.

Abstract 12631: Phenome-Wide Prediction of Incident Circulatory Diseases Using Machine Learning-Derived Features From Retinal Imaging

Purpose: The retina is a window for assessment of cardiovascular health. Here, we performed machine learning-based assessment of retinal vascular density (RVD) from fundus photos, and combined this with retinal layer thicknesses from optical coherence tomography (OCT) imaging, to predict incident circulatory conditions. Methods: We utilized UK Biobank participant retinal fundus images (N=54,813), and OCT images (N=44,823). Deep-learning of fundus photos was used to remove poor-quality images and segment the retinal microvasculature to calculate RVD. Using the Topcon Segmentation algorithm, we quantified retinal layer thicknesses. We performed Cox survival analyses, separately associating RVD and retinal layer thicknesses with 130 circulatory conditions from Phecode ICD-9 and ICD-10 composite phenotypes (median 10 year follow-up), adjusting for age, sex, smoking, ethnicity, height, weight, and spherical equivalent. False Discovery Rate (FDR&lt;0.05) correction was performed to identify significant associations. Results: Participants’ mean age was 56 (SD 8 years), 55% were female, and 56% were non-smokers. Associations were observed for each SD of photoreceptor thinning with incident abdominal aortic aneurysms (HR 1.47, P=6e-6), peripheral vascular disease (HR 1.32, P=4e-5), nonhypertensive heart failure (HR 1.20, P=2.8e-6), myocardial infarction (HR 1.17, P=8e-7), cerebrovascular disease (HR 1.15, P=1.9e-5) and hypertension (HTN) (HR 1.09, P=1e-12). Each SD of lower RVD was associated with incident HTN (HR 1.15, P=3.8e-39) and hypertensive heart disease (HR 2.07, P=6e-4). Further incident heart failure analysis additionally adjusting for RVD, prevalent HTN, and type 2 diabetes identified a persistent association for photoreceptor thinning. Conclusions: Our results indicate that photoreceptor thinning and RVD from retinal imaging can serve as a biomarker for future cardiovascular conditions, independent of other common risk factors.

Symptomatic and Asymptomatic Peripheral Artery Disease and the Risk of Abdominal Aortic Aneurysm: The Atherosclerosis Risk in Communities (ARIC) Study

A prospective cohort study was performed at visit 1 (1987-1989) and a cross-sectional cohort study was performed at visit 5 (2011-2013) from four U.S. communities (Washington County, Md; suburban Minneapolis, Minn; Jackson, Miss; Forsyth County, NC) in the Atherosclerosis Risk in Communities (ARIC) study. Of 14,148 participants (55% female, 26% black, 1% with symptomatic peripheral arterial disease), after a median follow-up of 23 years, 3.7% had developed incident abdominal aortic aneurysms (AAAs). The presence of symptomatic peripheral artery disease (PAD) resulted in a higher hazard ratio (HR) of incident AAA (HR, 4.9), as did asymptomatic PAD with an ankle brachial index (ABI) of ≤0.9 (HR, 2.33) compared with the reference ABI of >1.1. The crude 15-year cumulative incidence of AAAs was 12% in the symptomatic PAD group, 4% in the asymptomatic PAD group with an ABI of <0.9, and 2% in the asymptomatic PAD group with an ABI of >1.1. The cross-sectional analysis demonstrated similar patterns for ultrasound-based AAAs, with odds ratio for AAAs of 2.5 for symptomatic PAD and 4.0 for asymptomatic PAD in a demographically adjusted model. These prospective and cross-sectional data showed an elevated risk of AAAs in patients with symptomatic and asymptomatic PAD. These data support the current recommendation of AAA screening for symptomatic PAD patients and suggest the potential extension to asymptomatic PAD patients as well.

Symptomatic and asymptomatic peripheral artery disease and the risk of abdominal aortic aneurysm: The Atherosclerosis Risk in Communities (ARIC) study

Background and aimsSymptomatic peripheral artery disease (PAD) is a risk factor for abdominal aortic aneurysm (AAA). However, data on the association of asymptomatic PAD with AAA are limited. We explored the association of symptomatic and asymptomatic PAD with AAA. MethodsWe primarily assessed a prospective association of symptomatic (based on clinical history) and asymptomatic (ankle-brachial index ≤0.9) PAD at baseline (1987–89 [ages 45–64 years]) with incident AAA in a biracial community-based cohort, the Atherosclerosis Risk in Communities Study. We secondarily investigated a cross-sectional association of PAD with ultrasound-based AAA (diameter≥3.0 cm) (2011–13 [ages 67–91 years]). ResultsOf 14,148 participants (55.1% female, 25.5% black, 0.9% with symptomatic PAD) in our prospective analysis (median follow-up 22.5 years), 530 (3.7%) developed incident AAA. Symptomatic PAD had a higher hazard ratio (HR) of incident AAA [4.91 (95%CI 2.88–8.37)], as did asymptomatic PAD with ABI≤0.9 [2.33 (1.55–3.51)], compared to the reference ABI>1.1–1.2 in demographically-adjusted models. Crude 15-year cumulative incidence of AAA in these three groups were 12.3%, 3.9%, and 1.5%, respectively. The associations remained significant after accounting for other potential confounders [corresponding HR 2.96 (95%CI 1.73–5.07) and 1.52 (95%CI 1.00–2.30), respectively]. The cross-sectional analysis demonstrated similar patterns with ultrasound-based AAA [odds ratio 2.46 (95%CI 1.26–4.81) for symptomatic PAD and 3.98 (1.96–8.08) for asymptomatic PAD in a demographically-adjusted model]. ConclusionsOur prospective and cross-sectional data show elevated risk of AAA in both symptomatic and asymptomatic PAD. Our data support the current recommendation of AAA screening in symptomatic PAD patients and suggest the potential extension to asymptomatic PAD patients as well.

Derivation and Validation of a 10-Year Risk Score for Symptomatic Abdominal Aortic Aneurysm: Cohort Study of Nearly 500 000 Individuals.

Abdominal aortic aneurysm (AAA) can occur in patients who are ineligible for routine ultrasound screening. A simple AAA risk score was derived and compared with current guidelines used for ultrasound screening of AAA. United Kingdom Biobank participants without previous AAA were split into a derivation cohort (n=401 820, 54.6% women, mean age 56.4 years, 95.5% White race) and validation cohort (n=83 816). Incident AAA was defined as first hospital inpatient diagnosis of AAA, death from AAA, or an AAA-related surgical procedure. A multivariable Cox model was developed in the derivation cohort into an AAA risk score that did not require blood biomarkers. To illustrate the sensitivity and specificity of the risk score for AAA, a theoretical threshold to refer patients for ultrasound at 0.25% 10-year risk was modeled. Discrimination of the risk score was compared with a model of US Preventive Services Task Force (USPSTF) AAA screening guidelines. In the derivation cohort, there were 1570 (0.40%) cases of AAA over a median 11.3 years of follow-up. Components of the AAA risk score were age (stratified by smoking status), weight (stratified by smoking status), antihypertensive and cholesterol-lowering medication use, height, diastolic blood pressure, baseline cardiovascular disease, and diabetes. In the validation cohort, over 10 years of follow-up, the C-index for the model of the USPSTF guidelines was 0.705 (95% CI, 0.678-0.733). The C-index of the risk score as a continuous variable was 0.856 (95% CI, 0.837-0.878). In the validation cohort, the USPSTF model yielded sensitivity 63.9% and specificity 71.3%. At the 0.25% 10-year risk threshold, the risk score yielded sensitivity 82.1% and specificity 70.7% while also improving the net reclassification index compared with the USPSTF model +0.176 (95% CI, 0.120-0.232). A combined model, whereby risk scoring was combined with the USPSTF model, also improved prediction compared with USPSTF alone (net reclassification index +0.101 [95% CI, 0.055-0.147]). In an asymptomatic general population, a risk score based on patient age, height, weight, and medical history may improve identification of asymptomatic patients at risk for clinical events from AAA. Further development and validation of risk scores to detect asymptomatic AAA are needed.

Association of Differential Leukocyte Count With Incident Abdominal Aortic Aneurysm Over 22.5 Years: The ARIC Study.

OBJECTIVE: Leukocytes contribute to the development of abdominal aortic aneurysm (AAA). We evaluated whether associations of differential leukocyte counts with AAA persist after accounting for traditional risk factors of AAA. APPROACH AND RESULTS: Among 11 217 adults from the Atherosclerosis Risk in Communities Study, we evaluated associations of differential leukocyte counts at baseline (1987–1989) with incident AAAs over a median follow-up of 22.5 years, using Cox proportional hazards regression. Each differential leukocyte count was categorized into 5 groups—below normal, tertiles within the normal range, and above normal, with the first tertile serving as the referent. We identified 377 incident AAAs through 2011, using hospital discharge diagnoses, linked Medicare records, or death certificates. At baseline, higher neutrophil, monocyte, and eosinophil counts were associated with higher risk of AAA, independent of smoking, other differential leukocyte counts, and other traditional risk factors. The association with incident AAA was the strongest for above normal neutrophil count, with an adjusted hazard ratio (95% CI) of 2.17 (1.29–3.64). Below normal neutrophil, lymphocyte, eosinophil and basophil counts were associated with higher risk of AAA with adjusted hazard ratio (95% CI) between 1.86 (1.04–3.35) and 1.62 (1.10–2.39). CONCLUSIONS: Higher neutrophil, monocyte, and eosinophil counts in midlife are associated with higher risk of AAA, even after accounting for traditional risk factors such as smoking, obesity, and atherosclerosis. This suggests the need to identify nontraditional risk factors and treatment strategies to mitigate the residual risk of AAA conferred by midlife inflammation. Whether immunosuppression is associated with higher risk of AAA needs further investigation.

Abstract P110: Proteomics Identified Novel Proteins Associated With Genetic Risk Of Abdominal Aortic Aneurysm: The Atherosclerosis Risk In Communities Study (ARIC)

Introduction: Abdominal aortic aneurysm (AAA) is a condition characterized by a weakened dilated vessel wall with the potential for lethal rupture. A recent genome-wide association study identified and replicated nine AAA-related variants (rs602633, rs4129267, rs3827066, rs1795061, rs10757274, rs10985349, rs9316871, rs6511720, and rs2836411), but pathways through which these loci may influence disease have not been elucidated. Hypothesis: AAA risk variants were hypothesized to be associated with plasma proteins with numerous roles including, but not limited to, inflammation and extracellular matrix remodeling. Methods: Data from participants of the community-based ARIC Study were used. Genomic DNA from whole blood was genotyped using the Affymetrix Genome-Wide Human SNP array 6.0. Concentrations of 4,870 proteins were determined using the SomaLogic aptamer-based capture array in plasma collected at visit 3 (1993-95). Outliers that were 6 standard deviations from the means were excluded. Race-specific multiple linear regression analysis evaluated associations between genetic variants and log base 2 transformed protein levels, with adjustment for age, sex, estimated glomerular filtration rate, field center, and ten principal components of ancestry. Identified proteins in whites (N=7,241) were then examined for replication in Black participants (N=1,671). Cox regression was used to evaluate the associations between identified proteins and incident AAA (n=454) over a median 21.2-year follow-up in all 11,064 participants. Results: In white participants twenty-six protein associations were identified for rs602633 ( PSRC1-CELSR2-SORT1 ), rs4129267 ( IL6R ), and rs3827066 ( PCIF1-ZNF335-MMP9 ) following Bonferroni correction ( p ≤5.13x10 -6 ). Associations were observed between rs4129267 and soluble interleukin-6 receptor subunit alpha (β=-0.339; p&lt;1.0E-200) and CRP (β=0.093; p=2.24E-7); rs602633 and granulin (β=0.184; p&lt;1.0E-200), complement C1q TNF-related protein-1 (β=0.115; p=2.17E-184), and neogenin (β=-0.031; p=5.60E-13); and rs3827066 and kit ligand (β=-0.045; p=2.41E-08). Five associations were replicated in Black participants ( p ≤1.9x10 -3 ). In the whole cohort, top quintiles of CRP (HR: 1.68; 95% CI: 1.22, 2.31), kit ligand (HR: 0.56; 95% CI: 0.40, 0.78) and neogenin (HR: 0.57 95% CI: 0.42, 0.78) were significantly related to incident AAA risk compared to corresponding bottom quintiles. Conclusions: Three of the nine AAA risk variants were associated with plasma protein concentrations, with the strongest associations for those involved in inflammation, endothelial dysfunction, and extracellular matrix remodeling. Granulin, complement C1q tumor necrosis factor-related protein-1, kit ligand, and neogenin represent novel targets for genetic risk of AAA and may link genetic susceptibility to disease pathogenesis.

Diabetes, its duration, and the long-term risk of abdominal aortic aneurysm: The Atherosclerosis Risk in Communities (ARIC) Study

Background and aimsWe aimed at comprehensively evaluate the independent association of diabetes and its duration with incident abdominal aortic aneurysm (AAA) and aortic diameter. Methods and resultsWe prospectively studied incident AAA according to baseline glycemic status (diabetes, prediabetes, normal glycemia) in 13,116 ARIC participants (1990–1992) and the time-varying exposure of duration post incident diabetes in 11,675 participants (1987–1989) using Cox models. Additionally, we cross-sectionally explored ultrasound-based abdominal aortic diameter by glycemic status and cumulative duration of diabetes in 4710 participants (2011–2013) using linear regression models. Over ~20 years of follow-up, diabetes (vs. normal glycemia) at baseline was independently associated with lower AAA risk (489 cases) (hazard ratio: 0.71 [95%CI 0.51–0.99]), especially after 10 years (hazard ratio: 0.58 [0.38–0.87]). Prediabetes did not demonstrate an independent association. The inverse association was more evident with longer duration of diabetes (p for trend = 0.045), with 30–50% lower risk in eight years after diabetes diagnosis. The cross-sectional analysis demonstrated smaller aortic diameters with longer duration of diabetes (e.g., −0.76 mm [−1.24, −0.28] in diabetes with 8–12 years) compared to non-diabetes, whereas prediabetes consistently showed nominally greater diameter. ConclusionsDiabetes, especially with longer duration, but not prediabetes, was independently associated with lower risk of AAA and smaller aortic diameter. Our findings suggest that long lasting clinical hyperglycemia plays an important role in the reduced AAA risk, and the reduced aortic diameter may be a structural mechanism behind this paradoxical association.

Lipoprotein(a) levels and risk of abdominal aortic aneurysm in the Women's Health Initiative

ObjectiveFew studies have prospectively examined the associations of lipoprotein(a) [Lp(a)] levels with the risk of abdominal aortic aneurysm (AAA), especially in women. Accounting for commonly recognized risk factors, we investigated the baseline Lp(a) levels and the risk of AAA among postmenopausal women participating in the ongoing national Women's Health Initiative. MethodsWomen's Health Initiative participants with baseline Lp(a) levels available who were beneficiaries of Medicare parts A and B fee-for-service at study enrollment or who had aged into Medicare at any point were included. Participants with missing covariate data or known AAA at baseline were excluded. Thoracic aneurysms were excluded owing to the different pathophysiology. The AAA cases and interventions were identified using the International Classification of Diseases, 9th and 10th revision, codes and Current Procedural Terminology codes from claims data. Hazard ratios were computed using Cox proportional hazard models according to the quintiles of Lp(a). ResultsThe mean age of the 6615 participants included in the analysis was 65.3 years. Of the 6615 participants, 66.6% were non-Hispanic white, 18.9% were black, 7% were Hispanic and 4.7% were Asian/Pacific Islander. Compared with the participants in the lowest Lp(a) quintile, those in higher quintiles were more likely to be overweight, black, and former or current smokers, to have hypertension, hyperlipidemia, and a history of cardiovascular disease, and to use menopausal hormone therapy and statins. During 65,476 person-years of follow-up, with a median of 10.4 years, 415 women had been diagnosed with an AAA and 36 had required intervention. More than one half had required intervention for a ruptured AAA. We failed to find a statistically significant association between Lp(a) levels and incident AAA. Additional sensitivity analyses stratified by race, with exclusion of statin users and alternative categorizations of Lp(a) using log-transformed levels, tertiles, and a cutoff of >50 mg/dL, were conducted, which did not reveal any significant associations. ConclusionsWe found no statistically significant association between Lp(a) levels and the risk of AAA in a large and well-phenotyped sample of postmenopausal women. Women with high Lp(a) levels were more likely to be overweight, black, and former or current smokers, and to have hypertension, hyperlipidemia, and a history of cardiovascular disease, or to use hormone therapy and statins compared with those with lower Lp(a) levels. These findings differ from previous prospective, case-control, and meta-analysis studies that had supported a significant relationship between higher Lp(a) levels and an increased risk of AAA. Differences in the association could have resulted from study limitations or sex differences.

Abstract P248: Smoking, Smoking Cessation, and Risk of Abdominal Aortic Aneurysm: The Atherosclerosis Risk in Communities Study

Introduction: Smoking is the strongest risk factor for abdominal aortic aneurysm (AAA), and male ever smokers who are recommended for one-time screening for AAA with ultrasonography at age of 65 to 75 years. However, the proportion of eligible individuals who receive this screening remains small (~1%). Few studies have evaluated the association of key smoking parameters with incident AAA by sex. Methods: In 14,889 ARIC participants free of a history of AAA at baseline (1987-89), we quantified the associations of smoking parameters (pack-years, duration, and intensity [pack/day]) with incident AAA (hospitalizations with AAA diagnosis [ICD code: 441.3, 441.4, 38.44, 39.71] or a death certificate ICD code: 441.3, 441.4, I71.3, I71.4) using Cox models. Years since quitting in former smokers were explored as time-varying variables. Results: Over a median follow-up of 20 years, there were 567 cases of AAA. The incident rate of AAA was 5.98 per 1,000 person-years in male current smokers and 2.65 per 1,000 person-years in female current smokers. Pack-years was significantly associated with incident AAA (HR 7.31 [95% CI 5.48-9.74] for those smoked ≥40 pack-years vs. never smokers) and the association was stronger in women than men (8.53 [5.03-14.45] vs. 5.97 [4.21-8.47], p-for-interaction =0.02). Both smoking duration and intensity showed significant associations with AAA. Smoking cessation demonstrated a graded association with lower risk of AAA in both sexes, but significantly increased risk lasted longer in men (2.16 [1.39-3.36] in 30-&lt;40 years after cessation) than in women (1.84 [0.76-4.46] in 20-&lt;30 years after cessation) (Table). Conclusions: All smoking parameters tested consistently show significant associations with incident AAA in both sexes. After cessation, the residual risk lasted at least 40 years in men and 20 years in women. Our results further emphasize the importance of smoking prevention and early cessation for preventing AAA and the potential need of AAA screening in female current smokers and recent quitters.

Abstract P440: Diabetes and the Long-term Risk of Abdominal Aortic Aneurysm: The Atherosclerosis Risk in Communities Study

Introduction: Diabetes mellitus is known to be related to lower risk of abdominal aortic aneurysm (AAA). However, the full spectrum of glycemic status including prediabetes and the duration of diabetes have not been extensively investigated in the context of AAA risk. Methods: We prospectively studied incident AAA (defined using outpatient records, hospitalization discharge, or death certificate) according to the baseline glycemic status defined using physician diagnosed diabetes, self-reported anti-diabetic medication use and glucose or hemoglobin A1c (diabetes, pre-diabetes, vs. normal glycemia) in 13,116 participants (1990-1992) and the time-varying exposure of duration of incident diabetes in 11,675 participants (1987-1989) using Cox models. We cross-sectionally explored ultrasound-based abdominal aortic diameter by glycemic status and cumulative duration of diabetes in 4,710 participants (2011-2013) using linear regression models. Results: There were 489 incident AAA cases during a median follow-up of ~20 years. Diabetes but not pre-diabetes (vs. normal glycemia) at baseline was independently associated with lower risk of AAA (HR: 0.71 [95%CI 0.51 - 0.99]). The association was largely driven by long-standing diabetes (≥10 years duration: HR: 0.58 [95%CI 0.38 - 0.87]). Longer duration of diabetes was associated with lower risk of AAA (Figure 1A), with 30-50% lower risk in 8 years after incident diabetes diagnosis, as well as smaller aortic diameter measured cross-sectionally (Figure 1B) compared to non-diabetes. Pre-diabetes consistently showed relatively greater diameter (e.g., +0.26 mm [-0.03, +0.54]). Conclusions: Diabetes (but not prediabetes) and its longer duration were independently associated with lower risk of AAA and smaller aortic diameter. Our findings suggest that the cumulative effects of hyperglycemia may play a role in the counterintuitively lower AAA risk. Reduced aortic diameter might be a structural mechanism of decreased AAA risk in diabetes. Figure 1A. Adjusted hazard ratio of incident AAA according to the duration of diabetes among incident cases as a time-varying exposure; Figure 1B. Adjusted difference in maximum diameter (mm) for diabetes vs. non-diabetes by cumulative duration of diabetes. Both models adjusted for age, sex, race, education, BMI, height, total cholesterol, HDL cholesterol, systolic blood pressure, diastolic blood pressure, anti-hypertensive medication, cholesterol-lowering medication, cigarette smoking pack-years, alcohol drinking, eGFR, prevalent peripheral artery disease, prevalent coronary heart disease, and prevalent stroke (time-varying covariates for Figure 1A and baseline covariates for Figure 1B).

Female sex hormones and risk of incident abdominal aortic aneurysm in Norwegian women in the HUNT study

ObjectiveThe delayed development of abdominal aortic aneurysm (AAA) in women compared with men might be secondary to a protective effect from endogenous estrogens. The role of postmenopausal hormone therapy remains unclear. The aim of the present study was to evaluate the effect of female sex hormones compared with other risk factors associated with AAA through a long-term study of a large female cohort. MethodsThe present prospective cohort study included 20,024 postmenopausal women from the Norwegian Nord-Trøndelag Health Study. A total of 201 cases of AAA were identified during a median follow-up period of 18 years (295,554 person-years; 1995-2014). The data were recorded from questionnaires, physical measurements, medical records, blood sample test results, and the Norwegian Cause of Death Registry. The effect of risk factors was evaluated in a multiple Cox regression analysis. Multiple imputation was performed for missing data (n = 50 data sets). The serum estradiol concentrations in women with and without incidental AAAs were compared. The median interval from blood sample collection to the AAA diagnosis was 7 years. ResultsCurrent smokers had >10-fold increased risk of incident AAA during the follow-up period (hazard ratio [HR], 10.9; 95% confidence interval [CI], 7.4-16.1). Positive associations were found for hypertension (HR, 2.0; 95% CI, 1.4-3.0) and coronary heart disease (HR, 2.2; 95% CI, 1.6-3.2). The HR associated with the current use of postmenopausal hormone therapy was 0.58 (95% CI, 0.6-1.5). No substantial difference in estradiol concentrations was found between women with and without AAA (P = .075). ConclusionsThe effect of female sex hormones on the risk of incident AAAs in women, as evaluated by the serum concentrations of estradiol and the use of postmenopausal hormone therapy, is clinically less important than the strong associations found with smoking, hypertension, and coronary heart disease.

Adherence to the Dietary Approaches to Stop Hypertension Dietary Pattern and Risk of Abdominal Aortic Aneurysm: Results From the ARIC Study.

BackgroundThe role of a healthy dietary pattern in the prevention of abdominal aortic aneurysms (AAA) is unknown. We aimed to evaluate the relationship between adherence to a Dietary Approaches To Stop Hypertension‐style dietary pattern and the risk of incident AAAs.Methods and ResultsDietary intake was assessed via a 66‐item food frequency questionnaire at baseline (1987–1989) and at visit 3 (1993–1995) in 13 496 participants enrolled in the ARIC (Atherosclerosis Risk in Communities) study without clinical AAA (mean age, 54 years). A dietary scoring index based on food times was constructed to assess self‐reported adherence to a dietary approaches to stop hypertension‐style dietary pattern. Participants were followed for incident clinical AAAs using hospital discharge diagnoses, Medicare inpatient and outpatient diagnoses, or death certificates through December 31, 2011. Cox proportional hazards models with covariate adjustment were used to estimate hazard ratios with 95% confidence intervals. During a median follow‐up of 23 years, there were 517 incident AAA cases. Individuals with a Dietary Approaches To Stop Hypertension‐style diet score in the highest quintile had a 40% lower risk of hospitalization for AAA than those in the lowest quintile (hazard ratioQ5 vs Q1: 0.60; 95% confidence intervals: 0.44, 0.83; P trend=0.002). In detailed analyses, higher consumption of fruits, vegetables, whole grains, low‐fat dairy, and nuts and legumes was related to a lower risk for AAA.ConclusionsGreater adherence to a Dietary Approaches To Stop Hypertension‐style dietary pattern was associated with lower risk for AAA. Higher consumption of fruits, vegetables, whole grains, low‐fat dairy as well as nuts and legumes may help to decrease the burden of AAAs.

Chronic kidney disease measures and the risk of abdominal aortic aneurysm

Background and aimsDespite its strong link to cardiovascular outcomes, the association of chronic kidney disease (CKD) with abdominal aortic aneurysm (AAA) has not been explicitly and comprehensively investigated. MethodsIn 10,724 participants in the Atherosclerosis Risk in Communities Study (aged 53–75 years during 1996–1998), we evaluated the associations of two key CKD measures - estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (ACR) - with incident AAA (AAA diagnosis in outpatient, hospitalization discharge, or death records). Additionally, we performed a cross-sectional analysis for the CKD measures and ultrasound-based abdominal aortic diameter in 4258 participants during 2011–2013. ResultsDuring a median follow-up of 13.9 years, 347 participants developed AAA. The demographically-adjusted hazard ratio (HR) was 4.44 (95% CI 1.58–12.49) for eGFR <30, 3.29 (1.89–5.72) for 30–44, 2.03 (1.29–3.19) for 45–59, and 1.62 (1.11–2.35) for 60–74 compared to eGFR ≥90 mL/min/1.73 m2 and was 2.49 (1.28–4.87) for ACR ≥300, 1.99 (1.40–2.83) for 30–299, and 1.46 (1.08–1.97) for 10–29 compared to ACR <10 mg/g. The associations were generally similar after accounting for additional confounders, such as smoking (although attenuated), or after stratifying by subgroups, including diabetes. The cross-sectional analysis also showed continuous positive associations of these CKD measures with aortic diameter, particularly at the distal aortic segment assessed. ConclusionsReduced eGFR and elevated albuminuria were independently associated with greater incidence of AAA and greater abdominal aortic diameter. Our results suggest the potential usefulness of CKD measures to identify persons at high risk of AAA and the need to investigate pathophysiological pathways linking CKD to AAA.

Evaluation of the relationship between plasma lipids and abdominal aortic aneurysm: A Mendelian randomization study.

Studies have reported that higher circulating levels of total cholesterol (TC), low-density lipoprotein (LDL) cholesterol and lower of high-density lipoprotein (HDL) cholesterol may be associated with increased risk of abdominal aortic aneurysm (AAA). Whether dyslipidemia causes AAA is still unclear and is potentially testable using a Mendelian randomization (MR) approach. We investigated the associations between blood lipids and AAA using two-sample MR analysis with SNP-lipids association estimates from a published genome-wide association study of blood lipids (n = 188,577) and SNP-AAA association estimates from European Americans (EAs) of the Atherosclerosis Risk in Communities (ARIC) study (n = 8,793). We used inverse variance weighted (IVW) MR as the primary method and MR-Egger regression and weighted median MR estimation as sensitivity analyses. Over a median of 22.7 years of follow-up, 338 of 8,793 ARIC participants experienced incident clinical AAA. Using the IVW method, we observed positive associations of plasma LDL cholesterol and TC with the risk of AAA (odds ratio (OR) = 1.55, P = 0.02 for LDL cholesterol and OR = 1.61, P = 0.01 for TC per 1 standard deviation of lipid increment). Using the MR-Egger regression and weighted median methods, we were able to validate the association of AAA risk with TC, although the associations were less consistent for LDL cholesterol due to wider confidence intervals. Triglycerides and HDL cholesterol were not associated with AAA in any of the MR methods. Assuming instrumental variable assumptions are satisfied, our finding suggests that higher plasma TC and LDL cholesterol are causally associated with the increased risk of AAA in EAs.

Abstract 055: Adherence to a DASH (Dietary Approaches to Stop Hypertension) Dietary Pattern and Risk of Abdominal Aortic Aneurysm

Background: Abdominal aortic aneurysms (AAAs) develop in up to 8% of men and 6% of women over a lifetime. Although they typically remain asymptomatic, rupture of an AAA carries high mortality. Smoking and hypertension have been identified as modifiable risk factors for developing an AAA. The role of diet, however, is yet unclear. Objective: To evaluate the relationship between adherence to a DASH-style dietary pattern and the risk of incident AAA in a large, community-based cohort of middle-aged adults. Methods: Dietary intake was assessed via a 66-item FFQ at two visits in 14,322 participants enrolled in the ARIC study (Atherosclerosis Risk in Communities) without clinical AAA, incomplete dietary/covariate information or extreme energy intake at baseline. Adherence to a DASH-style dietary pattern was assessed using a previously developed dietary scoring index. Participants were followed for incident clinical AAAs using hospital discharge diagnoses, Medicare outpatient diagnoses, or death certificates through December 31, 2011. Cox proportional hazards models with covariate adjustment were used to estimate hazard ratios (HR) with 95% confidence intervals (CIs). Results: During a median follow-up of 23 years, there were 539 incident AAA cases. Participants with a DASH diet score in the highest quintile had a 39% lower risk to develop AAAs than those in the lowest score quintile (HRQ5 vs. Q1: 0.61; 95% CI 0.45, 0.84; ptrend =0.004) after adjusting for sociodemographics, total caloric intake, smoking, physical activity, BMI, abdominal obesity, diabetes, hypertension, hypercholesterolemia and cardiovascular disease. Higher intake of fruits, vegetables, whole grains, low-fat dairy, and nuts and legumes was related to a decreased risk for AAA. Conclusions: Greater adherence to a DASH-style dietary pattern was found to be associated with lower incidence of AAA. Higher consumption of fruits, vegetables, whole grains, low-fat dairy as well as nuts and legumes may help to decrease the burden of AAA in U.S. adults.

Markers of vitamin D metabolism and incidence of clinically diagnosed abdominal aortic aneurysm: The Atherosclerosis Risk in Communities Study.

Little is known about whether markers of vitamin D metabolism are associated with the development of abdominal aortic aneurysm (AAA), though these markers have been linked to other cardiovascular diseases. We tested the hypotheses that risk of AAA is higher among individuals with low serum concentrations of 25-hydroxy vitamin D [25(OH)D], and among those with elevated concentrations of calcium, fibroblast growth factor 23 (FGF23), phosphorus, and parathyroid hormone (PTH) using data from a cohort of black and white individuals with long-term follow-up. Markers of vitamin D metabolism were measured using serum collected in 1990-1992 from ARIC study participants (mean ± SD age 56.9 ± 5.7 years, 43.2% male, 23.9% black). A total of 12,770 participants were followed until 2011 for incident AAA. Multivariable-adjusted Cox regression models were used. A total of 449 incident AAA events occurred over a median follow-up of 19.7 years. For the association between serum calcium and risk of incident AAA there was evidence of interaction by sex ( p-interaction 0.02). Among women, in the fully adjusted model, the hazard ratio (95% confidence interval) comparing the highest to lowest quartile was 2.43 (1.25-4.73), whereas in men it was 1.01 (0.72-1.43). Not associated with risk of incident AAA were 25(OH)D, FGF23, phosphorus, and PTH. In this large prospective cohort, there was little evidence that markers of vitamin D metabolism are associated with risk of incident AAA. The positive association of calcium with AAA among women may warrant further investigation and replication in other populations.