Natural History Of Abdominal Aortic Aneurysms Research Articles

Abdominal Aortic Aneurysm in Heart Transplant Recipients: New Insights from a 30-year Experience at a Single Center

The improvement in survival rates for heart transplant recipients (HTRs) has increased their risk of developing extracardiac diseases such as abdominal aortic aneurysms (AAAs). The purposes of this study were to evaluate the prevalence and to describe the clinical features and natural history of AAA in HTRs. A retrospective review of all patients (375) who underwent heart transplantation (HT) at our center over a 32-year period (1983-2015) was carried out. We identified 20 patients (5.3%) with AAA. All but one patient were male (95%), and most of them (80%) had a history of ischemic heart disease (IHD) prior to transplantation. The mean age of the patients with AAA at transplant was 57.2±7.3years (range: 42-62years). Seven of the 20 patients with AAA already had an AAA (30-55mm) prior to transplantation. The average aneurysm size at the time of diagnosis was 40.9±9.6mm, and the average patient age at the time of diagnosis was 62.2±8.3years. The mean linear expansion rate was 10.6±2.12mm/y, and the exponential expansion rate was 0.220±0.040year-1, respectively. The median follow-up time was 5.4years (range 0.1-27.4years). The median survival was 143months (95% confidence interval (CI) 65 to 180months) for the 20 HTRs with AAA and 68.8months (95% CI 46 to 88months) for the other HTRs. The natural history of AAA in HTR is characterized by an increased expansion rate. Male HTR with end-stage IHD are particularly at risk and should be closely followed-up after HT.

Alcohol Intake and Growth Rate of Abdominal Aortic Aneurysms in Men- results of a Prospective Population-based Randomised Screening Trial with up to Five Year Follow-up

Introduction: Abdominal aortic aneurysm (AAA) is a common disease with a pathological dilatation of the aortic wall, and the prevalence is up to 2% people above 50 years. Age, smoking, male sex, family history of AAA, and hypertension are known risk factors for developing AAAs. Recent studies suggested that moderate intake of alcohol was associated with a lower hazard rate of developing AAA. No studies have reported how alcohol affects the growth rate of AAAs. Therefore, the aim of this study was to investigate the association between alcohol intake and growth rate of AAAs. Methods: This study was based on data from VIVA, a population-based randomised screening trial of men aged 65-74 enrolling from October 2008 until July 2011. Study participants were randomly assigned 1:1 to screening or no screening. Lifestyle parameters, medical history and use of medication were self-reported. Ultrasound scans of the infrarenal abdominal aorta were performed by specially trained nurses, the maximal systolic inner-to-inner anterior-posterior diameter was measured. Ultrasound surveillance was annual and continued up to five years. Results: Analysing the association between the aneurysmal growth rate and intake of alcohol, we found in our crude analysis that an increase by one daily unit of alcohol intake increased the growth rate by 3.5% (estimate 1.035, CI 0.99-1.08). After adjusting for potential confounders, we found that an increase by one daily unit of alcohol increased the aneurysmal growth rate by 2.3% (estimate 1.023, Cl 0.98-1.07). Analysing the need for repair as a time-to-event analysis, we found in our crude analysis, that an increase by one unit of alcohol changed the hazard ratio by 1.08 (CI 0.99-1.17). In our adjusted analysis, we found a similar result of one unit of alcohol increasing the hazard ratio by 1.07 (Cl 0.98-1.17). Conclusion: Although no statistically significant associations were exposed, a constant trend for adjusted positive associations between alcohol intake and the natural history of AAA was noticed calling for clarifying larger studies or meta-analyses. Disclosure: Nothing to disclose

Association Between Diverticular Disease and Abdominal Aortic Aneurysms: Pooled Analysis of Two Population Based Screening Cohorts

The aetiology of abdominal aortic aneurysms (AAA) is multifactorial, and many risk factors are shared with diverticular disease. It is unknown whether an independent association exists between these conditions. Individuals enrolled in two Danish population based randomised AAA screening trials and assigned to cross sectional screening and evaluation of cardiovascular risk factors were identified. Diagnoses of diverticular disease were interrogated from a national patient registry covering the period from 1977 to the screening date. Adjusted odds ratios (aOR) and hazard ratios (aHR) with 95% CI were calculated as risk measures. 24,632 individuals (median age, 69 years) were included. At screening, 687 patients had pre-existing diverticular disease. Patients with diverticular disease were more likely to have AAA at screening compared with those without diverticular disease (5.2% vs 3.3%) (OR 1.61, 95% CI 1.14–2.27). This association persisted after adjusting for potential confounders (aOR 1.49, 95% CI 1.04–2.12) and on sensitivity analyses. The association was most pronounced for those with a diagnosis of diverticular disease for at least 10 years (aOR 2.56, 95% CI 1.49–4.38). Following screening, 6.2% of patients with diverticular disease and AAA experienced aneurysm rupture, compared with 2.2% of patients with AAA without diverticular disease (aHR 4.1, 95% CI 1.6–10.8). An association was found between diverticular disease and AAA in a large population based cohort. Biological causality remains to be established, and a potential impact of diverticular disease on the natural history of AAA needs to be explored further.

Association Between Diverticular Disease and Abdominal Aortic Aneurysms: Pooled Analysis of Two Population Based Screening Cohorts

The aetiology of abdominal aortic aneurysms (AAA) is multifactorial, and many risk factors are shared with diverticular disease. It is unknown whether an independent association exists between these conditions. Individuals enrolled in two Danish population based randomised AAA screening trials and assigned to cross sectional screening and evaluation of cardiovascular risk factors were identified. Diagnoses of diverticular disease were interrogated from a national patient registry covering the period from 1977 to the screening date. Adjusted odds ratios (aOR) and hazard ratios (aHR) with 95% CI were calculated as risk measures. 24,632 individuals (median age, 69 years) were included. At screening, 687 patients had pre-existing diverticular disease. Patients with diverticular disease were more likely to have AAA at screening compared with those without diverticular disease (5.2% vs. 3.3%) (OR 1.61, 95% CI 1.14-2.27). This association persisted after adjusting for potential confounders (aOR 1.49, 95% CI 1.04-2.12) and on sensitivity analyses. The association was most pronounced for those with a diagnosis of diverticular disease for at least 10 years (aOR 2.56, 95% CI 1.49-4.38). Following screening, 6.2% of patients with diverticular disease and AAA experienced aneurysm rupture, compared with 2.2% of patients with AAA without diverticular disease (aHR 4.1, 95% CI 1.6-10.8). An association was found between diverticular disease and AAA in a large population based cohort. Biological causality remains to be established, and a potential impact of diverticular disease on the natural history of AAA needs to be explored further.

Potential biomechanical roles of risk factors in the evolution of thrombus-laden abdominal aortic aneurysms.

Abdominal aortic aneurysms (AAAs) typically harbour an intraluminal thrombus (ILT), yet most prior computational models neglect biochemomechanical effects of thrombus on lesion evolution. We recently proposed a growth and remodelling model of thrombus-laden AAAs that introduced a number of new constitutive relations and associated model parameters. Because values of several of these parameters have yet to be elucidated by clinical data and could vary significantly from patient to patient, the aim of this study was to investigate the possible extent to which these parameters influence AAA evolution. Given that some of these parameters model potential effects of factors that influence the risk of rupture, this study also provides insight into possible roles of common risk factors on the natural history of AAAs. Despite geometrical limitations of a cylindrical domain, findings support current thought that smoking, hypertension, and female sex likely increase the risk of rupture. Although thrombus thickness is not a reliable risk factor for rupture, the model suggests that the presence of ILT may have a destabilizing effect on AAA evolution, consistent with histological findings from human samples. Finally, simulations support two hypotheses that should be tested on patient-specific geometries in the future. First, ILT is a potential source of the staccato enlargement observed in many AAAs. Second, ILT can influence rupture risk, positively or negatively, via competing biomechanical (eg, stress shielding) and biochemical (ie, proteolytic) effects. Although further computational and experimental studies are needed, the present findings highlight the importance of considering ILT when predicting aneurysmal enlargement and rupture risk.

Flow Mediated Dilatation and Progression of Abdominal Aortic Aneurysms

Objective/BackgroundBiomarker(s) for prediction of the future progression rate of abdominal aortic aneurysms (AAA) may be useful to stratify the management of individual patients. AAAs are associated with features of systemic inflammation and endothelial dysfunction. Flow mediated dilatation (FMD) of the brachial artery is a recognised non-invasive measurement for endothelial function. We hypothesised that FMD is a potential biomarker of AAA progression and reflects the temporal changes of endothelial function during AAA progression.MethodsIn a prospectively recruited cohort of patients with AAAs (Oxford Abdominal Aortic Aneurysm Study), AAA size was recorded by antero-posterior diameter (APD) (outer to outer) on ultrasound. Annual AAA progression was calculated by (ΔAPD/APD at baseline)/(number of days lapsed/365 days). FMD was assessed at the same time as AAA size measurement. Analyses of data were performed in the overall cohort, and further in subgroups of AAA by size (small: 30–39 mm; moderate: 40–55 mm; large: > 55 mm).ResultsFMD is inversely correlated with the diameter of AAAs in all patients (n = 162, Spearman’s r = −.28, p < .001). FMD is inversely correlated with AAA diameter progression in the future 12 months (Spearman’s r = −.35, p = .001), particularly in the moderate size group. Furthermore, FMD deteriorates during the course of AAA surveillance (from a median of 2.0% at baseline to 1.2% at follow-up; p = .004), while surgical repair of AAAs (n = 50 [open repair n = 22, endovascular repair n = 28)] leads to an improvement in FMD (from 1.1% pre-operatively to 3.8% post-operatively; p < .001), irrespective of the type of surgery.ConclusionFMD is inversely correlated with future AAA progression in humans. FMD deteriorates during the natural history of AAA, and is improved by surgery. The utility of FMD as a potential biomarker in the context of AAA warrants further investigation.

A mathematical model of aortic aneurysm formation.

Abdominal aortic aneurysm (AAA) is a localized enlargement of the abdominal aorta, such that the diameter exceeds 3 cm. The natural history of AAA is progressive growth leading to rupture, an event that carries up to 90% risk of mortality. Hence there is a need to predict the growth of the diameter of the aorta based on the diameter of a patient’s aneurysm at initial screening and aided by non-invasive biomarkers. IL-6 is overexpressed in AAA and was suggested as a prognostic marker for the risk in AAA. The present paper develops a mathematical model which relates the growth of the abdominal aorta to the serum concentration of IL-6. Given the initial diameter of the aorta and the serum concentration of IL-6, the model predicts the growth of the diameter at subsequent times. Such a prediction can provide guidance to how closely the patient’s abdominal aorta should be monitored. The mathematical model is represented by a system of partial differential equations taking place in the aortic wall, where the media is assumed to have the constituency of an hyperelastic material.

Modeling the Burden of Abdominal Aortic Aneurysm in the USA in 2013

Objectives: Abdominal aortic aneurysm (AAA) is a pathological condition characterized by an abnormal, localized dilatation of the lower part of the aorta. Due to a lack of data on the natural history of AAA and risk of death from other cardiovascular diseases attributable to AAA, the true number of AAA-attributable deaths may be higher than currently estimated. This study aims to produce more realistic estimates of the burden of AAA. Methods: A disease-modeling software, DisMod II, was used to assess the AAA burden via a multistate life table. Inputs included population, all-cause mortality, size- and sex-specific AAA prevalence, and relative risk of death estimates for persons with AAA compared with persons without AAA. Results: There were 2,347,339 prevalent cases of AAA in the USA in 2013 (95% CI: 2,131,964-2,524,116), resulting in 41,371 deaths attributable to AAA (95% CI: 34,090-49,234). Females constituted 21.1% of prevalent cases and 45.2% of deaths, compared with males constituting 78.9% of prevalent cases and 54.8% of deaths. Conclusions: This work shows that the burden of mortality attributable to AAA is more than twice the current estimates from the American Heart Association. Females account for a disproportionately high percentage of deaths despite constituting a low percentage of prevalent cases.

Structure, Mechanics, and Histology of Intraluminal Thrombi in Abdominal Aortic Aneurysms.

It has been recognized that the intraluminal thrombus (ILT) is a biologically active material contributing in the progression and rupture of abdominal aortic aneurysms (AAAs). To advance our understanding of the potential role of ILT in the natural history of AAAs, the structural, mechanical, and histological characteristics of ILTs have been studied with great interest over the past decade. Given that the ILT is evolving and changing its composition during AAA progression, attention has been paid to exploring the chemomechanical effects of ILT on the underlying wall properties. Various biomechanical and chemomechanical data, and related models have provided advanced insights into AAA pathogenesis which have served as a basis for clinical diagnosis. The goal of this review is to describe and summarize recent advances in the research of ILT found in the aorta in terms of structure, mechanics, and histology on a patient-specific basis. We point to some possible future studies which hopefully stimulate multidisciplinary research to address open problems.

Growth Rates of Small Abdominal Aortic Aneurysms Correlate with Clinical Events

Conclusions: There is a bimodal growth pattern of abdominal aortic aneurysms (AAAs). AAA-related events are associated with growth rates of at least 2 mm annually. Summary: It is well known there is variation in AAA growth rate, indicating that AAA expansion does not conform to simple mechanics of Laplace's Law. In the United Kingdom Small Aneurysm Trial, growth of AAAs ranged from −1.0 to 6.1 mm/y (Circulation 2004;110:16-21). Peripheral arterial disease and diabetes are known to be associated with slowed AAA growth and smoking with more rapid growth. Elastin peptide, a serum biomarker, appears to be associated with AAA expansion (Eur J Vasc Endovasc Surg 2008;36:273-80). Expansion associations with hypercholesterolemia, sex, and hypertension are less clear, whereas doxycycline, statins, and angiotensin-converting enzyme inhibitors may slow AAA growth. Some have demonstrated an association between increased AAA growth and rupture (J Vasc Surg 2003;37:280-4), whereas others have been unable to demonstrate such a relationship (J Vasc Surg 2002;35:666-71). In this report, the authors examine patterns of AAA growth and the relationship between aneurysm growth and specific risk factors (mean arterial pressure, history of hypertension, hypercholesterolemia, diabetes, smoking, ischemic heart disease, and sex) and aneurysm-related events (surgery or death). From 1984 to 2007, data for 1649 individuals with AAAs were collected prospectively in the Chichester AAA screening program. Data included serial aortic size measurements, blood pressure, risk factors for arterial disease, and medications. The authors adjusted growth rates for risk factor confounders using flexible hierarchical modeling. AAA growth distribution was analyzed using Silverman's test of multimodality. There were 1231 individuals with more than one scan over a surveillance interval of at least 3 months. AAAs demonstrated a bimodal growth pattern, with nearly 50% of all AAAs never progressing to surgery or rupture. Adjusted AAA growth rates >2 mm annually predicted AAA related events (surgery or death). Comment: Many believe the natural history of AAAs is inevitable progressive dilatation until rupture occurs or the patient dies from other causes. The data, however, indicate only 27.2% of monitored AAAs end up requiring repair, and patterns of expansion may relate to clinical events. This information, along with more sophisticated models of stress points on the AAA wall, may eventually allow better selection of patients for AAA repair. Perhaps someday there will be a cohort of patients, even with relatively large AAAs, that can be safely observed. Such knowledge would result in increased peace of mind for the patient and the physician as well as savings for the health care system.

Medical Therapy Approach for Treating Abdominal Aortic Aneurysm

Abdominal aortic aneurysm (AAA) is a common and deadly problem. The aortic diameter increases in association with a complex remodeling process that includes changes in the structure and content of key proteins, elastin and collagen. As these changes occur, the tissue mechanical properties also change. The natural history of AAA is progressive enlargement to a point of mechanical tissue failure, typically followed by death. Currently, the marker used to predict the risk of impending rupture is the largest transverse diameter. After reaching a diameter threshold of 5.5 cm, the aneurysm is surgically repaired. This criterion does not consider any patient-specific information or the known heterogeneity of the aneurysm that may, in some cases, lead to rupture before the aneurysm reaches the standard intervention threshold. Conversely, in many patients, continued observation beyond this threshold is safe. Although no medical treatment is yet approved, doxycycline has been shown to greatly reduce aortic aneurysm growth in animal models and has been shown to slow growth in several small clinical trials. Although larger prospective randomized trials are needed, one unknown is what effect doxycycline has on the structural integrity of the aortic wall. That is, does slowed aneurysm growth by doxycycline treatments, in fact, prevent rupture, or does the wall continue to weaken and the aneurysm instead ruptures at a smaller diameter? Research has begun to answer these questions before a large clinical trial begins.

Endovascular stent-grafts for the repair of infrarenal abdominal aortic aneurysms: a brief review.

In the United States nearly 1.5 million people have abdominal aortic aneurysms (AAAs). The natural history of AAAs is to enlarge and rupture. Rupture of an AAA results in an estimated 15,000 deaths per year. The major objective in the treatment of AAAs is to prevent aneurysm rupture and death. Endoluminal grafting for the treatment of aortic aneurysms is the most exciting topic in vascular surgery today. It is anticipated that approximately half of all aneurysms in the infrarenal abdominal and descending thoracic aorta will be repaired endovascularly in the future. Despite the enthusiasm for this technology, there are unanswered questions like the long-term fate of the device, management of endoleaks, and the ability to protect the patient from subsequent rupture. This article describes the two FDA approved devices in clinical use today and the indications, techniques, and potential pitfalls of endoluminal stent-grafting for the treatment of AAAs.

Association of intraluminal thrombus in abdominal aortic aneurysm with local hypoxia and wall weakening

Purpose: Our previous computer models suggested that intraluminal thrombus (ILT) within an abdominal aortic aneurysm (AAA) attenuates oxygen diffusion to the AAA wall, possibly causing localized hypoxia and contributing to wall weakening. The purpose of this work was to investigate this possibility. Methods: In one arm of this study, patients with AAA were placed in one of two groups: (1) those with an ILT of 4-mm or greater thickness on the anterior surface or (2) those with little (< 4 mm) or no ILT at this site. During surgical resection but before aortic cross-clamping, a needle-type polarographic partial pressure of oxygen (Po2) electrode was inserted into the wall of the exposed AAA, and the Po2 was measured. The probe was advanced, and measurements were made midway through the thrombus and in the lumen. Mural and mid-ILT Po2 measurements were normalized by the intraluminal Po2 measurement to account for patient variability. In the second arm of this study, two AAA wall specimens were obtained from two different sites of the same aneurysm at the time of surgical resection: group I specimens had thick adherent ILT, and group II specimens had thinner or no adherent ILT. Nonaneurysmal tissue was also obtained from the infrarenal aorta of organ donors. Specimens were subjected to histologic, immunohistochemical, and tensile strength analyses to provide data on degree of inflammation (% area inflammatory cells), neovascularization (number of capillaries per high-power field), and tensile strength (peak attainable load). Additional specimens were subjected to Western blotting and immunohistochemistry for qualitative evaluation of expression of the cellular hypoxia marker oxygen-regulated protein. Results: The Po2 measured within the AAA wall in group I (n = 4) and group II (n = 7) patients was 18% ± 9% luminal value versus 60% ± 6% (mean ± SEM; P <.01). The normalized Po2 within the ILT of group I patients was 39% ± 10% (P =.08 with respect to the group I wall value). Group I tissue specimens showed greater inflammation (P <.05) compared with both group II specimens and nonaneurysmal tissue: 2.9% ± 0.6% area (n = 7) versus 1.7% ± 0.3% area (n = 7) versus 0.2% ± 0.1% area (n = 3), respectively. We found similar differences for neovascularization (number of vessels/high-power field), but only group I versus control was significantly different (P <.05): 16.9 ± 1.6 (n = 7) vs 13.0 ± 2.3 (n = 7) vs 8.7 ± 2.0 (n = 3), respectively. Both Western blotting and immunohistochemistry results suggest that oxygen-regulated protein is more abundantly expressed in group I versus group II specimens. Tensile strength of group I specimens was significantly less (P <.05) than that for group II specimens: 138 ± 19 N/cm2 (n = 7) versus 216 ± 34 N/cm2 (n = 7), respectively. Conclusion: Our results suggest that localized hypoxia occurs in regions of thicker ILT in AAA. This may lead to increased, localized mural neovascularization and inflammation, as well as regional wall weakening. We conclude that ILT may play an important role in the pathology and natural history of AAA. (J Vasc Surg 2001;34:291-9.)

Successful repair of a ruptured abdominal aortic aneurysm in a cardiac transplant patient

The improvement in survival rates for heart transplant recipients (HTRs) has increased their risk of developing extracardiac diseases such as abdominal aortic aneurysms (AAAs). The purposes of this study were to evaluate the prevalence and to describe the clinical features and natural history of AAA in HTRs.A retrospective review of all patients (375) who underwent heart transplantation (HT) at our center over a 32-year period (1983–2015) was carried out.We identified 20 patients (5.3%) with AAA. All but one patient were male (95%), and most of them (80%) had a history of ischemic heart disease (IHD) prior to transplantation. The mean age of the patients with AAA at transplant was 57.2 ± 7.3 years (range: 42–62 years). Seven of the 20 patients with AAA already had an AAA (30–55 mm) prior to transplantation. The average aneurysm size at the time of diagnosis was 40.9 ± 9.6 mm, and the average patient age at the time of diagnosis was 62.2 ± 8.3 years. The mean linear expansion rate was 10.6 ± 2.12 mm/y, and the exponential expansion rate was 0.220 ± 0.040 year−1, respectively. The median follow-up time was 5.4 years (range 0.1–27.4 years). The median survival was 143 months (95% confidence interval (CI) 65 to 180 months) for the 20 HTRs with AAA and 68.8 months (95% CI 46 to 88 months) for the other HTRs.The natural history of AAA in HTR is characterized by an increased expansion rate. Male HTR with end-stage IHD are particularly at risk and should be closely followed-up after HT.