Sex-specific normal values and determinants of infrarenal abdominal aortic diameter among non-aneurysmal elderly population.
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ABSTRACT:
SUBMITTER: Zhu F
PROVIDER: S-EPMC8423780 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:AimsThe artery contains numerous cell types which contribute to multiple vascular diseases. However, the heterogeneity and cellular responses of these vascular cells during abdominal aortic aneurysm (AAA) progression have not been well characterized.Methods and resultsSingle-cell RNA sequencing was performed on the infrarenal abdominal aortas (IAAs) from C57BL/6J mice at Days 7 and 14 post-sham or peri-adventitial elastase-induced AAA. Unbiased clustering analysis of the transcriptional profiles from >4500 aortic cells identified 17 clusters representing nine-cell lineages, encompassing vascular smooth muscle cells (VSMCs), fibroblasts, endothelial cells, immune cells (macrophages, T cells, B cells, and dendritic cells), and two types of rare cells, including neural cells and erythrocyte cells. Seurat clustering analysis identified four smooth muscle cell (SMC) subpopulations and five monocyte/macrophage subpopulations, with distinct transcriptional profiles. During AAA progression, three major SMC subpopulations were proportionally decreased, whereas the small subpopulation was increased, accompanied with down-regulation of SMC contractile markers and up-regulation of pro-inflammatory genes. Another AAA-associated cellular response is immune cell expansion, particularly monocytes/macrophages. Elastase exposure induced significant expansion and activation of aortic resident macrophages, blood-derived monocytes and inflammatory macrophages. We also identified increased blood-derived reparative macrophages expressing anti-inflammatory cytokines suggesting that resolution of inflammation and vascular repair also persist during AAA progression.ConclusionOur data identify AAA disease-relevant transcriptional signatures of vascular cells in the IAA. Furthermore, we characterize the heterogeneity and cellular responses of VSMCs and monocytes/macrophages during AAA progression, which provide insights into their function and the regulation of AAA onset and progression.
| S-EPMC8064434 | biostudies-literature
Project description:Current screening and detection of asymptomatic aortic aneurysms is based largely on uniform cut-point diameters. The aims of this study were to define normal aortic diameters in asymptomatic men and women in a community-based cohort and to determine the association between aortic diameters and traditional risk factors for cardiovascular disease. Measurements of the diameters of the ascending thoracic aorta (AA), descending thoracic aorta (DTA), infrarenal abdominal aorta (IRA), and lower abdominal aorta (LAA) were acquired from 3,431 Framingham Heart Study (FHS) participants. Mean diameters were stratified by gender, age, and body surface area. Univariate associations with risk factor levels were examined, and multivariate linear regression analysis was used to assess the significance of covariate-adjusted relations with aortic diameters. For men, the average diameters were 34.1 mm for the AA, 25.8 mm for the DTA, 19.3 mm for the IRA, and 18.7 mm for the LAA. For women, the average diameters were 31.9 mm for the AA, 23.1 mm for the DTA, 16.7 mm for the IRA, and 16.0 mm for the LAA. The mean aortic diameters were strongly correlated (p <0.0001) with age and body surface area in age-adjusted analyses, and these relations remained significant in multivariate regression analyses. Positive associations of diastolic blood pressure with AA and DTA diameters in both genders and pack-years of cigarette smoking with DTA diameter in women and IRA diameter in men and women were observed. In conclusion, average diameters of the thoracic and abdominal aorta by computed tomography are larger in men compared with women, vary significantly with age and body surface area, and are associated with modifiable cardiovascular disease risk factors, including diastolic blood pressure and cigarette smoking.
| S-EPMC3644324 | biostudies-literature
Project description:Several studies suggest that infrarenal aortic diameter is associated with lower-extremity peripheral artery disease (LE-PAD). However, data regarding the associations between infrarenal aortic diameter and LE-PAD are limited, especially in large sample populations and Asian or Chinese populations. Our analysis included 17279 Chinese hypertensive adults comprising 6590 men and 10689 women with a mean age of 64.74?±?7.41 years. Participants were selected from 22693 candidates from two large population-based cohort-studies. The primary noninvasive test for diagnosis of LE-PAD is the ankle-brachial index (ABI) at rest and typically an ABI???0.90 is used to define LE-PAD. The prevalence of LE-PAD was found to significantly decrease as the aortic diameter increased according to the tertile of the aortic diameter. LE-PAD was significantly more prevalent in the lowest tertile (OR?=?1.58, 95% CI?=?1.29-1.94, p?<?0.001) and similarly prevalent in the highest tertile (OR?=?0.92, 95% CI?=?0.73-1.16, p?=?0.49) when compared with the median tertile. No significant interactions between the aortic diameter and any of the stratified variables were found (all p?>?0.05). In conclusion, Small aortic diameter (as opposed to large aortic diameter) is significantly associated with LE-PAD in Chinese hypertensive adults.
| S-EPMC5674057 | biostudies-literature
Project description:Open repair of abdominal aortic aneurysms (AAAs) is occasionally performed in conjunction with additional procedures; however, how these concomitant procedures affect outcome is unclear. This study determined the frequency of additional procedures during elective open AAA repair and the effect on perioperative outcomes.All elective infrarenal open AAA repairs between January 2003 and November 2014 in the Vascular Study Group of New England (VSGNE) were identified. Patients were grouped by concomitant procedures, which included no concomitant procedure, renal artery bypass, lower extremity bypass, other abdominal procedure, or thromboembolectomy. Analyses were performed using multivariable logistic regression.Of 1314 patients who underwent elective AAA repair, 153 (11.6%) had a concomitant procedure, including renal bypass in 27 (2.1%), lower extremity bypass in 28 (2.1%), other abdominal procedures in 64 (4.9%), and thromboembolectomy in 48 (3.7%). Independent risk factors for 30-day mortality were renal bypass (odds ratio [OR], 7.2; 95% confidence interval [CI], 1.9-27.7), other abdominal procedures (OR, 4.8; 95% CI, 1.6-14.1), and thromboembolectomy (OR, 8.8; 95% CI, 3.1-24.9). Deterioration of renal function was predicted by renal bypass (OR, 5.1; 95% CI, 2.1-12.4) and thromboembolectomy (OR, 3.7; 95% CI, 1.8-7.6). Lower extremity bypass and thromboembolectomy were predictive of postoperative leg ischemia (OR, 8.9; 95% CI, 2.7-29.0; OR, 11.2; 95% CI, 4.4-28.8, respectively), and thromboembolectomy was also predictive of postoperative bowel ischemia (OR, 4.4; 95% CI, 1.6-12.0).Performing additional procedures during infrarenal open AAA repair is associated with increased morbidity and mortality in the postoperative period. Careful deliberation of the operative risks and the necessity of the additional interventions are therefore advised during operative planning. This study also highlights the importance of avoiding perioperative thromboembolic events.
| S-EPMC5025327 | biostudies-literature
Project description:Several reports suggest unexpectedly high rates of late abdominal aortic aneurysm (AAA) rupture occur after endovascular AAA repair (EVAR). However, a population-based study examining causes of late death after EVAR vs open surgical repair has not been performed.We performed a retrospective cohort study of patients undergoing infrarenal AAA repair using information from the Medicare inpatient hospital discharge records (MedPAR files), physician claim files (Part B files, 20% sample), and Medicare Denominator Files for the years 2001 to 2004. Using the Social Security Death Index, we identified all "late" deaths, defined as deaths occurring >30 days and after hospital discharge. We used the National Death Index to identify cause of death information; in particular, those deaths that were likely caused by late rupture. We compared causes of late death and survival between EVAR and open repair using Wilcoxon log-rank and rank-sum tests.Between 2001 and 2004, 13,971 patients underwent AAA repair (6119 EVAR, 7852 open repair). After a mean follow-up of 1.6 years in the EVAR cohort and 1.9 years in the open cohort, mortality rates were similar across repair type (15.4% EVAR, 15.9% open repair), with an adjusted odds ratio for death after open repair of 0.98 (95% confidence interval, 0.90-1.07). Of the 2194 documented deaths, 523 occurred before discharge or <or=30 days, and 1671 occurred >30 days and after hospital discharge. Cause of death information for the 1671 late deaths was available from the National Death Index for 1515 (91%). The 15 most common codes for causes of late death were dominated by cardiac disease (atherosclerotic heart disease, acute myocardial infarction) and pulmonary disease (lung cancer, respiratory failure). Causes of late death with specific mention of aneurysm were identified in 37 patients (2.4% of all deaths), but this event was not more common in EVAR or open repair (15 [0.3%] in the EVAR group, 22 [0.3%], in the open repair group; P = .71).Late deaths from aneurysm rupture after EVAR or open repair appear to be relatively infrequent and similarly distributed across procedure type. Our results emphasize that the effectiveness of EVAR is comparable to open AAA repair in preventing aneurysm-related death.
| S-EPMC5292250 | biostudies-literature
Project description:Progressive dilation of the infrarenal aortic diameter is a consequence of the ageing process and is considered the main determinant of abdominal aortic aneurysm (AAA). We aimed to investigate the genetic and clinical determinants of abdominal aortic diameter (AAD). We conducted a meta-analysis of genome-wide association studies in 10 cohorts (n = 13 542) imputed to the 1000 Genome Project reference panel including 12 815 subjects in the discovery phase and 727 subjects [Partners Biobank cohort 1 (PBIO)] as replication. Maximum anterior-posterior diameter of the infrarenal aorta was used as AAD. We also included exome array data (n = 14 480) from seven epidemiologic studies. Single-variant and gene-based associations were done using SeqMeta package. A Mendelian randomization analysis was applied to investigate the causal effect of a number of clinical risk factors on AAD. In genome-wide association study (GWAS) on AAD, rs74448815 in the intronic region of LDLRAD4 reached genome-wide significance (beta = -0.02, SE = 0.004, P-value = 2.10 × 10-8). The association replicated in the PBIO1 cohort (P-value = 8.19 × 10-4). In exome-array single-variant analysis (P-value threshold = 9 × 10-7), the lowest P-value was found for rs239259 located in SLC22A20 (beta = 0.007, P-value = 1.2 × 10-5). In the gene-based analysis (P-value threshold = 1.85 × 10-6), PCSK5 showed an association with AAD (P-value = 8.03 × 10-7). Furthermore, in Mendelian randomization analyses, we found evidence for genetic association of pulse pressure (beta = -0.003, P-value = 0.02), triglycerides (beta = -0.16, P-value = 0.008) and height (beta = 0.03, P-value < 0.0001), known risk factors for AAA, consistent with a causal association with AAD. Our findings point to new biology as well as highlighting gene regions in mechanisms that have previously been implicated in the genetics of other vascular diseases.
| S-EPMC9558840 | biostudies-literature
Project description:Abdominal aortic aneurysm (AAA) is a vascular disease characterized by weakening of the vascular walls. Male sex is a risk factor for AAA, and peak AAA incidence occurs in men 10 years earlier than in women. However, the growth rate of AAA is faster in women, and women have a higher mortality due to AAA rupture. The mechanisms underlying sex-related differences in AAA remain unknown. Herein, we evaluated the effects of ovariectomy (OVX) on AAA in rats. Upon evaluation of the effects of OVX and AAA induction, AAA incidence rate and the aneurysm diameter increased in the OVX group. However, the histopathology in the developed AAA wall was not different between groups. When the effects of OVX on the vascular wall without AAA induction were evaluated, elastin and collagen levels were significantly decreased. Furthermore, the level of matrix metalloproteinase-9 significantly increased in the OVX group. According to our results, it is speculated that decreased levels of collagen and elastin fibers induced by OVX might be involved in increased incidence rate and diameter of AAA. Weakening of the vascular wall before the onset of AAA might be one reason for the faster rate of AAA growth in women.
| S-EPMC6892790 | biostudies-literature
Project description:Abdominal aortic aneurysm (AAA) is a common disease with often life-threatening consequences. This vascular disorder is responsible for 1-2% of all deaths in men aged 65 years or older. Autoimmunity may be responsible for the pathogenesis of AAA. Although it is well documented that infiltrating T cells are essentially always present in AAA lesions, little is known about their role in the initiation and/or progression of the disease. To determine whether T cells infiltrating AAA lesions contain clonally expanded populations of T cells, we amplified ?-chain TCR transcripts by the nonpalindromic adaptor-PCR/V?-specific PCR and/or V?-specific PCR, followed by cloning and sequencing. We report in this article that aortic abdominal aneurysmal lesions from 8 of 10 patients with AAA contained oligoclonal populations of T cells. Multiple identical copies of ?-chain TCR transcripts were identified in these patients. These clonal expansions are statistically significant. These results demonstrate that ?? TCR(+) T lymphocytes infiltrating aneurysmal lesions of patients with AAA have undergone proliferation and clonal expansion in vivo at the site of the aneurysmal lesion, in response to unidentified self- or nonself Ags. This evidence supports the hypothesis that AAA is a specific Ag-driven T cell disease.
| S-EPMC4009497 | biostudies-literature
Project description:BackgroundSagittal abdominal diameter (SAD) is an anthropometric index associated with visceral adiposity. It remains unclear whether SAD and its socio-economic correlates differ in women and men, which limits the epidemiological and clinical applications of the SAD measurement. The aims of this study are to examine the sex differences in SAD and its socio-economic correlates.MethodsA complex stratified multistage clustered sampling design was used to select 6975 men and 7079 women aged 18 years or more from the National Health Nutrition and Examination Survey 2011-2016, representative of the US civilian non-institutionalized population. SAD was measured in accordance to the standard protocols using a two-arm abdominal caliper. The sex differences in SAD and its socio-economic correlates were evaluated by performing weighted independent t tests and weighted multiple regression.ResultsSAD was lower in women than in men in the entire sample, as well as in all the subgroups characterized by age, race, birth place, household income, and body mass index except for non-Hispanic blacks and those with household income < $20,000. Adjusted for other characteristics, age, birth place, household income, and body mass index were associated with SAD in both women and men. Black women were associated with higher SAD then white women (p < .0001), and Hispanic and Asian men were associated with lower SAD than white men (both p < .01). Women born in other countries were more likely to have lower SAD than women born in the US (p < .0001), and so were men (p = .0118). Both women and men with a household income of <$75,000 had higher SAD than those with an income of over $75,000. The associations of age, race, and household income with SAD differed in women and men.ConclusionSAD is lower in women than in men, in the general population as well as in the most socio-economic subgroups. While socio-economic correlates of SAD are similar in women and men, the associations of age, race, and household income with SAD vary across sex.
| S-EPMC7953618 | biostudies-literature
Project description:ImportanceAbdominal aortic aneurysms affect more than 3% of US older adults.ObjectiveTo test whether doxycycline reduces the growth of abdominal aortic aneurysm over 2 years as measured by maximum transverse diameter.Design, setting, and participantsParallel, 2-group, randomized clinical trial that was conducted at 22 US clinical centers between May 2013 and January 2017, and enrolled patients 50 years or older with small (3.5-5.0 cm for men, 3.5-4.5 cm for women) infrarenal aneurysms. The final date of follow-up was July 31, 2018.InterventionsPatients were randomized to receive twice daily for 2 years doxycycline 100 mg orally (as capsules) (n = 133) or placebo (n = 128).Main outcomes and measuresThe primary outcome was change in abdominal aortic aneurysm maximum transverse diameter measured from CT images at baseline and follow-up at 2 years. Patients were assigned ranks based on the maximum transverse diameter (measured or imputed) of the aorta and also if they underwent aneurysm repair or died. The ranks were converted to scores having a normal distribution to facilitate the primary analysis ("normal scores").ResultsOf 261 patients randomized, no follow-up CT scans were obtained on 7 (3%), leaving a final analysis set of 129 patients assigned to doxycycline and 125 to placebo (mean [SD] age, 71.0 years [7.4 years], 35 women [14%]). The outcome normal scores used in the primary analysis were based on maximum transverse diameter (measured or imputed) in 113 patients (88%) in the doxycycline group and 112 patients (90%) in the placebo group; aneurysm repair in 13 (10%) and 9 (7%), and death in 3 (2%) and 4 (3%), respectively. The primary outcome, normal scores reflecting change in aortic diameter, did not differ significantly between the 2 groups, mean change in normal scores, 0.0262 vs -0.0258 (1-sided P = .71). Mean (SD) baseline maximum transverse diameter was 4.3 cm (0.4 cm) for doxycycline and 4.3 cm (0.4 cm) for placebo. At the 2-year follow-up, the change in measured maximum transverse diameter was 0.36 cm (95% CI, 0.31 to 0.40 cm) for 96 patients in the doxycycline group vs 0.36 cm (95% CI, 0.30 to 0.41 cm) for 101 patients in the placebo group (difference, 0.0; 95% CI, -0.07 to 0.07 cm; 2-sided P = .93). No patients were withdrawn from the study because of adverse effects. Joint pain occurred in 84 of 129 patients (65%) with doxycycline and 79 of 125 (63%) with placebo.Conclusions and relevanceAmong patients with small infrarenal abdominal aortic aneurysms, doxycycline compared with placebo did not significantly reduce aneurysm growth at 2 years. These findings do not support the use of doxycycline for reducing the growth of small abdominal aortic aneurysms.Trial registrationClinicalTrials.gov Identifier: NCT01756833.
| S-EPMC7251450 | biostudies-literature