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St George’s Vascular Institute, St James’ Wing, St George’s Hospital, Blackshaw Road, London SW17 0QT, UK (I. M. Nordon, R. J. Hinchliffe, I. M. Loftus, M. M. Thompson).
Pathophysiology and epidemiology of abdominal aortic aneurysmsIan M. Nordon, Robert J. Hinchliffe, Ian M. Loftus and Matt M. Thompson
Abstract | Abdominal aortic aneurysms (AAAs) are found in up to 8% of men aged >65 years, yet usually remain asymptomatic until they rupture. Rupture of an AAA and its associated catastrophic physiological insult carries overall mortality in excess of 80%, and 2% of all deaths are AAA-related. Pathologically, AAAs are associated with inflammation, smooth muscle cell apoptosis, and matrix degradation. Once thought to be a consequence of advanced atherosclerosis, accruing evidence indicates that AAAs are a focal representation of a systemic disease of the vasculature. Risk factors for AAAs include increasing age, male sex, smoking, and low HDL-cholesterol levels. Familial associations exist and although susceptibility genes have been described on the basis of candidate-gene studies, robust genetic studies have failed to discover causative gene mutations. The surgical management of AAAs has been revolutionized by minimally invasive endovascular repair. Ongoing randomized trials will establish whether endovascular repair confers a survival advantage over open surgery for patients with a ruptured AAA. In many countries, centralization of vascular surgical services has largely been driven by the improved outcomes of elective aneurysm surgery in specialized centers, the widespread adoption of endovascular techniques, and the introduction of screening programs.
Nordon, I. M. et al. Nat. Rev. Cardiol. 8, 92–102 (2011); published online 16 November 2010; doi:10.1038/nrcardio.2010.180
IntroductionAn abdominal aortic aneurysm (AAA) is a permanent, localized dilatation of the abdominal aorta (beginning at the level of the diaphragm and extending to its bifurcation into the left and right common iliac arteries) that exceeds the normal diameter by 50%, or >3 cm.1 Most AAAs are found in the infrarenal aorta, proximal to the aortic bifur-cation (Figure 1). The pathological processes involved in the formation of degenerative AAAs include upregula-tion of proteolytic pathways, apoptosis, oxidative stress, inflammation, and loss of arterial wall matrix.2 Although AAAs are focal lesions, a body of evidence indicates that the entire vascular tree is abnormal in patients with an AAA.3 Molecular and biomechanical changes found in the vasculature distant from the AAA are similar to those present in the aneurysm wall.4–6 AAAs are associated with generalized arteriomegaly and visceral artery ectasia, and are likely to be a local representation of systemic disease, with a distinct molecular and cellular profile, rather than simply a consequence of advanced atherosclerosis.
The risk of AAA rupture increases with aortic dia meter.7 Mortality after rupture is high; approximately 80% of those who reach hospital and 50% of those who undergo surgery for a ruptured AAA will die.8,9 The mainstay of manage-ment for AAAs is to diagnose the disease before rupture and offer elective aneurysm repair at an appropriate
juncture. Diagnosis is problematic, however, as most aneu-rysms are asymptomatic until rupture. The considerably reduced mortality after elective repair, as compared with that following rupture, has led to the develop ment of ultra-sound screening programs. Community-based screening services have been shown to reduce mortality from an AAA in men aged 65–79 years, but are not cost-effective in women in whom the prevalence of AAAs is lower.10–13
The epidemiology of AAAs is becoming more clearly defined with data evolving from centers involved in screening for AAA. Our understanding of the etio logy of aneurysms from vascular biology, genetics, and pro-teomic science is improving. An appreciation of factors that impact on surgical morbidity and mortality is also growing. In this Review, we explore the evidence that aneurysms are a local representation of a systemic disease. We also describe the epidemiology of AAA with particu-lar reference to screening studies, and examine specific risk factors for AAA development alongside patient and surgical determinants that impact on treatment outcome.
PathophysiologyAneurysmal disease represents a complicated and dynamic pathophysiological process rather than a static pathological problem. Three key processes contribute to the AAA phenotype: proteolysis, inflammation, and smooth muscle cell apoptosis.14 Understanding the factors that initiate aneurysmal degeneration and those that drive the transition from a minimally dilated abdominal aorta (3.0–3.9 cm) to a clinically relevant AAA (>4.0 cm) is criti-cal, but complex. The predisposition to AAA formation
Competing interestsM. M. Thompson declares associations with the following companies: Cook Medical and Medtronic. See the article online for full details of the relationships. The other authors declare no competing interests.
could have an embryological origin; elastin synthesis in the abdominal aorta almost ceases at birth and any impairment in fetal elastogenesis, owing to placental dys-function or micronutritional abnormality, is likely to have long-term effects.2 In addition, complex signaling path-ways during embryogenesis dictate smooth muscle cell phenotype and their future responses to factors currently implicated in AAA pathogenesis, such as transforming growth factor β.2
The formation of an AAA has historically been con-sidered to be a focal manifestation of advanced athero-sclerosis.15 This conventional theory has been challenged by evidence demonstrating that the entire vascular tree is abnormal in patients with aneurysmal disease.16 Atherosclerosis in AAA forms as a consequence of the altered luminal flow, rather than being the initiating factor in the development of the lesion.17 Multiple mechanisms are likely to be involved in the development of both AAA and atherosclerosis, and susceptibility to these conditions varies between individuals.18 If atherosclerosis was the dominant feature in AAA development then the sever-ity of aortic atherosclerosis would correlate with AAA develop ment, which is not the case.19
AAAs are characterized by dilatation of all layers of the arterial wall as a result of loss of elastin, smooth muscle cell apoptosis, and compensatory collagen deposi-tion.20 Alterations in the matrix composition observed in the aneurysmal aortic wall have been detected both in non aneurysmal aortic segments and in the inferior mesenteric vein.6,21 Patients with an AAA display bio-mechanical alterations in vessels distant from the AAA. The carotid arteries of these patients exhibit mild dila-tation and reduced distensibility compared with con-trols.16,22 The inferior mesenteric vein from patients with AAA demon strates reduced tensile strength and stiffness, analogous to those found in the arterial aneurysm wall.6 These findings all strongly suggest the systemic nature of the aneurysmal process.
Inflammation and matrix degradation in the vascula-ture are crucial for AAA formation.23 Reactive oxygen and nitrogen species could cause the progressive cell and tissue damage characteristic of oxidative stress that is implicit in AAA pathogenesis.24 Inhibition of these systemic stres-sors prevented AAA formation in an animal model, which demonstrates their importance in aneurysmal disease.25 However, antioxidant medication has no proven benefit in suppression of AAA formation in humans and, to date, none have been translated to successful pharmacological management of AAAs.26
The systemic dilating diathesis is most evident in the abdominal aorta owing to the inherent susceptibil-ity of this vessel.27 Aneurysm formation in a previously intact artery implies a local inability of the arterial wall to sustain the tensile stress imposed by the column of blood. The abdominal aorta is exposed to unique hemo-dynamic forces as it is located proximal to the first major branching of the vessel and is constrained by the renal arteries (proximally) and the iliac arteries (distally). The pulse wave of blood pressure (BP) increases as it travels from the aortic root to the bifurcation, a consequence
Key points
Abdominal aortic aneurysms are a local representation of a systemic disease ■process
Ruptured abdominal aortic aneurysms continue to be associated with high ■mortality
Screening programs target men aged >65 years, as this group is at highest risk ■of developing an abdominal aortic aneurysm
The diameter of an abdominal aortic aneurysm is currently the only validated ■measure of rupture risk
endovascular repair has substantially reduced perioperative morbidity and ■mortality of abdominal aortic aneurysms
Centralization of vascular surgical services has led to improved outcomes ■among patients with an abdominal aortic aneurysm
of the tapering of the vessel as it gives off branches.28 A relative paucity of elastin and collagen is present at this level,29 and the additive depletion of elastin associated with aging together with the fragile nutrient supply of the aorta, render it especially vulnerable to repetitive high wall stress.30
Figure 1 | Three-dimensional reconstruction of a CT angiogram showing a large abdominal aortic aneurysm and associated right common iliac artery aneurysm. This angiogram was of an asymptomatic male aged 76 years, obtained before endovascular repair.
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Development of an AAA is associated with generalized arteriomegaly.31 This tendency towards arterial dilata-tion has been demonstrated in vessels independent of athero sclerosis, including the brachial and external carotid arteries.3 Discrete popliteal aneurysms, which are rare in the healthy population, are found in up to 70% of patients with AAA and 55% of patients with arterio-megaly.32 The incidence of coronary artery ectasia is increased in associ ation with AAA.33 Coronary artery ectasia and AAA share similar histological features, with prominent medial elastin degeneration.34 The systemic dilating diathesis is not limited to the arterial system; venous changes, such as varicose veins and aneurysms in venous bypass allografts, are also increased in patients with AAA.35,36
Patients with an AAA have an increased incidence of inguinal herniation, postoperative incisional herniation, and diastasis recti.37,38 These associations could reflect systemic degradation of collagen fiber, which has been demonstrated in patients matched for hypertension and smoking.39 Patients with chronic obstructive pulmonary disease (COPD) might have a higher risk of AAA rupture than those without this condition. In COPD and AAA, the elastin content of the lung and aortic wall, respec-tively, is decreased.40 smoking is a strong risk factor for both diseases, and is examined in more detail below.
PrevalenceMost early studies describing the occurrence of AAAs were based on findings at postmortem examination or on population- based clinical case-series. These studies esti-mated that the prevalence of AAA could be as high as 6% in selected populations.41 Aneurysms are more prevalent in white males, and mortality increases with advancing age.42 Population-screening programs have been used to describe the epidemiology of AAA (Table 1).10,12,13,43,44 In men aged 65–80 years, these screening studies reported that the prevalence of AAA was between 4% and 8%. The prevalence is approximately six times greater in men than women.44 However, evidence exists indicating that the prevalence of AAA among women could be slowly increasing, with women now representing one-third of patients presenting with rupture.45 The reason for this
trend is not fully understood. One explanation is that the increase reflects a temporal change in the prevalence of smoking among women, which increased between 1950 and 1970, several decades after the widespread uptake of smoking by men.46
IncidenceThe mean annual incidence of new AAA diagnoses in Western populations is 0.4–0.67%.47–49 The incidence is lower in Asian populations by a factor of 10.50 The inci-dence of AAA rupture is increasing, accounting for 1–2% of all deaths, with approximately 7,000 men dying per year in the UsA (crude rate 11 in 100,000, 95% CI 10.9–11.0).51–53 Population-based data from sweden revealed an increase in the incidence of AAA rupture from 5.6 (95% CI 4.9–6.3) per 100,000 person-years in the period 1971–1986 to 10.6 (95% CI 8.9–12.4) per 100,000 person- years in the period 2000–2004, despite a doubling of elective AAA surgery.54 One possible explana tion for these obser-vations is the decreasing mortality from cardiac disease meaning that patients live longer than in the past, provid-ing the opportunity for AAAs to grow insidiously until rupture. The true magnitude of mortality related to aortic rupture is likely to be underestimated, particularly with the decreasing number of postmortem examinations carried out.
Risk factorsRisk factors for AAA have been described based on large-scale, cross-sectional studies. Risk factors can be associ-ated with AAA development, expansion, and rupture. The only modifiable factor associated with all three processes seems to be smoking.55 Whether or not the risk factors described below are causal is not known, as the triggers of AAA are still largely undefined. The mechanisms that initiate and stimulate the progression of AAA are likely to be multifactorial, with a combination of genetic pre-disposition and environmental and physio logical factors leading to the AAA phenotype.
epidemiological studies of AAA have concentrated on traditional risk factors for atherosclerotic disease (Table 2).56 Although a number of shared risk factors for atherosclerosis and AAAs exist, including smoking and hypertension, the strength of these associations varies between the two disease processes. A clear understanding of groups at high-risk for AAA development is important for targeted screening of this asymptomatic disease and to direct research into its pathogenesis.
AgeThe incidence of AAA increases with advancing age (Figure 2). Deaths from AAA rupture are rare below the age of 65 years. The age-specific prevalence of AAA is six times greater in men than women and the risk increases by 40% every 5 years after the age of 65 years.57
sexMen are at much higher risk of AAA than women. The reasons for this are unclear, but it is likely to be a function of hormonal factors, genetic susceptibility, and risk factor
Table 1 | Prevalence of AAA in screened populations
study (population) screened population
Number of scans performed
Number of AAAs* detected
Prevalence of AAA
Ashton et al. for the MASS group (UK)10
Men aged 65–74 years
27,147 1,333 4.9%
Norman et al. (Western Australia)12
Men aged 65–83 years
12,203 875 7.2%
Lindholt et al. (Viborg, Denmark)13
Men aged 64–73 years
4,816 191 4.0%
Ashton et al. (Chichester, UK)43
Men aged 65–80 years
2,216 170 7.7%
Scott et al. (Chichester, UK)44
Women aged 65–80 years
3,052 40 1.3%
*AAA was defined as maximal abdominal aortic diameter >3 cm. Abbreviation: AAA, abdominal aortic aneurysm.
exposure.52 When unruptured aneurysms are discovered in women there seems to be an association with family history, which is likely to be reflective of awareness on the part of the women.58 no evidence exists to suggest that screening women for AAA is cost-effective.59
Family historyFamily history is a risk factor for AAA development independent of atherosclerosis.60 since the first report of familial tendency for AAA by Clifton in 1977,61 several studies have reported a high prevalence of AAA among siblings of patients with AAA.62,63 Population-based series have found that a positive family history of AAA is associated with an approximately doubled risk of AAA compared with those without a family history.64 In a case–control study of 98 cases of AAA and 102 controls, a positive family history was associated with an increased risk of AAA (odds ratio [OR] 4.77, 95% CI 1.26–18.1).60 The comorbidities and sex of the index patient did not modify the relative risk (RR) associated with family history.
smokingsmoking is an irrefutable risk factor for AAA.65 smoking increases the RR of AAA 7.6-fold.66 Men who currently smoke more than 25 cigarettes per day have a 15-fold increased risk of AAA (hazard ratio [HR] 14.6, 95% CI 9.6–22) compared with men who have never smoked.67 The number of cigarettes smoked per day is relevant, but more important is the duration of smoking.47 each year of smoking increases the RR of AAA by 4% (95% CI 2–5%) in all populations.66 Those who continue to smoke have more rapid AAA expansion.68,69 A smoker’s risk of developing AAA continues for at least 10 years following smoking cessation. To date, however, no causative link has been proven between smoking and AAA formation.
The mechanism is independent of atherosclerosis and theories include disruption in collagen synthesis, altered expression of metalloproteinases, and the response to oxidative stress.70
Lipid levelsThe association between plasma lipid levels and AAA is complicated. Iribarren et al. reported that elevated serum cholesterol (>240 mg/dl) was associated with an OR of 2.82 for AAA (95% CI 2.13–3.72).71 However, a similar retrospective epidemiological study failed to reproduce this finding, rather identifying a protective effect of elevated levels of serum HDl.72 This protective effect might simply be a surrogate marker of cardio vascular health, as physical exercise is known to increase HDl chol esterol.73 The possible role of statin therapy for estab-lished AAA has been explored. Retrospective analysis of the Dutch AAA screening database proposed that statins could delay AAA growth,74 but this observation has yet to be proven in a prospective study. Data from the Tromsø study indicated that statin therapy increased the risk of AAA formation, although this result might be a confounder, and underscores the limitations of cohort studies.47
HypertensionIncreased BP is a commonly cited risk factor for AAA, but any association seems weak.75,76 Hypertension (systolic BP >160 mmHg, diastolic BP >95 mmHg) is associated with AAA risk, but only in women.47 Mean elevated BP has been cited as an independent risk factor for aneurysm rupture in men and women, and reflects the continuing hemodynamic burden on the aortic wall, which contrib-utes to wall weakness.77 Hypertension accelerated experi-mental AAA growth in a rat model, but no evidence exists for this effect in humans.78
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obesityCentral obesity is independently associated with AAA. In the prospective Health in Men study (Western Australia), specific anthropometric measures, particularly waist circum ference (OR 1.14, 95% CI 1.06–1.22) and waist–hip ratio (OR 1.22, 95% CI 1.09–1.37), were independently associated with AAA in a cohort of 12,203 screened men.79 This finding was reproduced in a selected patient cohort (n = 306) with coronary heart disease, among whom obesity (BMI >30 kg/m2) was independently associ ated with AAA (OR 2.0, 95% CI 1.2–3.4).80
other risk factorsHigh levels of alcohol intake (>30 g/day) have been associated with increased risk of AAA (OR 1.65, 95% CI 1.03–2.64).67 The strongest association was found in patients who drank spirits. The mechanism through which alcohol exposure increases the risk of AAA is unclear, but could be through upregulation of matrix metalloproteinases and focal elastin degradation.81
The relationship between trace metal exposure and AAA development has been explored without convincing findings.82 socioeconomic deprivation and geographi-cal origin have been cited as risk factors associated with AAA development;83 however, these factors could be surrogate markers of the influence of smoking, hospital attendance, and genetics.
diabetesDiabetes is a risk factor for atherosclerosis, but has been shown to be protective against the development of AAA.60,84 A pooled meta-analysis suggested a reduced rate of AAA among patients with diabetes compared with patients without diabetes (OR 0.65, 95% CI 0.6–0.7, P <0.001).85 Diabetes is also associated with a slower rate of
growth of established AAAs.84 Proposed mechanisms for the protective effect of diabetes include hyper insulinemia, hyperglycemia, and actions of the therapeutic agents used in the management of diabetes. These agents can stabi-lize mural thrombus, increase aortic wall stiffness, and decrease systemic inflammation.86–88
Genetic evidenceAAA development is genetically complex. evidence from family case series and twin studies have provided robust evidence that heritability contributes to AAA for-mation.89 The probability that a monozygotic twin of a person with an AAA will develop an aneurysm is 24%.90 The development of AAAs is unlikely to be related to a single gene mutation, and multiple genetic factors are implicated.91 susceptibility genes, rather than causal gene mutations, are likely to be important, particularly those regulating inflammatory mediators, tissue proteases, and smooth muscle cell biology.
Hypothesis-driven studies exploring candidate-gene associations have demonstrated some moderate risk effects associated with common variants in the genes for angiotensin- converting enzyme (RR 1.33, 95% CI 1.20–1.48), methylene tetrahydrofolate reductase (RR 1.14, 95% CI 1.08–1.210), and matrix metalloproteinase-9 (RR 1.09, 95% CI 1.01–1.180).92 Inconsistent results from various laboratories and patient populations limit translation of these findings to clinical practice.
Genome-wide association studiesGenome-wide association studies (GWAs) that employ array-based platforms, offer the greatest hope of clari-fying the genetic component of AAA development. A GWAs from Iceland, examining 1,292 patients with an AAA and 30,503 controls, identified an association between AAA and the rs7025486 allele on chromo-some 9q33 (OR 1.21, P = 4.6 × 10–10).93 This site encodes an inhibitor of cell growth and survival, leading to an increased susceptibility to smooth muscle cell apoptosis mediated by ras-GTPase. The results of another GWAs by the Aneurysm Consortium, analyzing DnA from patients with AAAs in new Zealand, Australia, and the UK are awaited.91
A single-nucleotide polymorphism on chromosome 9p21 was shown to be associated with AAA (RR 1.3) in a subgroup analysis of a worldwide GWAs for coro-nary heart disease.94 This finding has been reproduced in a separate cohort in Australia, and is associated with upregulation of long interspersed nuclear elements at the site of AAA.95
Rupture riskProspective studies have identified factors associated with AAA rupture.96 The most commonly used predictor of AAA rupture is the maximum diameter of the aneu-rysm. In the UK small Aneurysm Trial,77 the mean AAA diameter at rupture was 5 cm in women and 6 cm in men. After adjustment for age, initial AAA diameter, BMI, and height, the rate of AAA rupture was three times higher in women than in men. Consequently, the AAA diameter
threshold for elective surgical intervention might be lower for women than for men.
Biomarkers and biomechanics have been investigated for their utility in predicting AAA rupture, and although finite element analysis in particular shows promise,97 these techniques are not yet sufficiently specific to apply in general clinical practice. studies examining putative biomarkers for AAA rupture are scarce and have concen-trated on inflammation-sensitive plasma proteins, such as fibrinogen and α1-antitrypsin.98 elevation in the level of these markers is likely to be a consequence of rupture, rather than an actual predictor of risk.
surgery is usually deferred in patients at high operative risk until the AAA attains a diameter at which the risk of rupture is thought to outweigh the operative risk. little data on rupture risk of large AAAs are available. The UK small Aneurysm Trial demonstrated an estimated 1-year rupture risk of 1% for AAAs 4.0–5.5 cm in diameter.99 Further evidence from patients declared unfit for elective repair indicates 1-year rupture risks of 9.4%, 10.2%, and 32.5% for AAAs 5.5–5.9 cm, 6.0–6.9 cm, and >7.0 cm in diameter, respectively.100
AAA growth rate has been suggested to have an indepen dent impact on rupture risk. enlargement of >1 cm per year has been used as an independent indica-tion for AAA repair in small aneurysm trials.99 Growth rates in excess of 2 mm per year are associated with AAA-related events, whereas aneurysms growing at <1.5 mm per year are unlikely to become clinically important.101 Other factors demonstrated to be independently and signifi cantly associated with AAA rupture risk are female sex (OR 4.5, 95% CI 1.98–10.2), smoking (OR 2.1, 95% CI 0.95–4.67), and high BP (mean BP >110 mmHg) (OR 1.04, 95% CI 1.02–1.07).77 Hypertension (OR 1.04) and active smoking (OR 2.11) are risk factors for AAA rupture that can be modified.77 Pharmacological mecha-nisms to reduce AAA rupture risk have been explored. Case–control data have shown that patients taking angiotensin- converting-enzyme inhibitors are less likely to present with AAA rupture (OR 0.82, 95% CI 0.74–0.9).102 This finding has yet to be reproduced in a prospective, randomized controlled trial.
Treatment and outcomes of AAAPatients with an AAA have higher all-cause mortality than healthy age-matched and sex-matched controls.103 This finding could be a consequence of the heavy burden of atherosclerosis in the coronary and renal circulation of this group of patients. All patients with cardio vascular disease, especially those with an AAA, should have aggressive pharmacological risk factor optimization. The amelioration of risk factors may not prevent the progress of the aneurysm, but it should have a considerable impact on overall survival.55
Once an aneurysm becomes established, the natural history is one of gradual growth. A clearer understand-ing of the pathophysiology of AAA has led to trials of pharmacological strategies to limit aneurysm expansion. studies of β-blockers104 and antibiotics105 have failed to translate findings in animal studies to therapies in clinical
practice.26 At present, the only proven management strat-egy to reduce rupture risk is surgical inter vention. This procedure is an effective and durable solution, yet despite technical improvements in perioperative care, the mean 30-day mortality remains >5% in many countries.106 The relatively high mortality from open repair led to the concept that a fabric-covered stent might be delivered endoluminally to exclude the aneurysm from the cir-culation and prevent rupture (endovascular aneurysm repair; evAR).
Factors influencing surgical outcomesModality of treatmentThe initial evidence of benefit with evAR over open surgery was provided by single-center and registry data. These registries described 2.9–5.8% mortality for elective evAR and led to randomized controlled trials comparing established open surgery with endo vascular techniques.107,108 Three randomized controlled trials have compared evAR with open surgery in fit patients for elective surgery. The evAR1,109 DReAM,110 and OveR111 trials have reported medium-term and long-term outcomes. All studies have demonstrated an early perioperative mortality benefit for evAR versus open surgery (evAR1: 1.7% versus 4.7%, P = 0.009;109 DReAM: 1.2% versus 4.6%, P = 0.1;110 OveR: 0.5% versus 3.0%, P = 0.004111). In addition, patients assigned to evAR had less blood loss, required fewer blood transfusions, and had reduced intensive-care stay than patients assigned to open surgery. However, no difference between the two treatment options was demonstrated for long-term (>2 years) total mortality or AAA-related mortality (Figure 3).
The uptake of evAR for elective surgical management of AAA is now approaching 80% in many centers.112 In the context of surgical management of a ruptured AAA, a substantial body of evidence demonstrates improved survival with an evAR-first approach.113 This result is currently the subject of a series of prospective, random-ized controlled trials, such as the IMPROve trial (nCT00746122), AJAX trial (IsRCTn66212637),114 and eCAR trial (nCT00577616).115
no currently used scoring systems can accurately predict patient outcomes following open surgery or evAR for AAA.116 Risks of mortality, organ failure, and infec-tion can be estimated from national databases, but these tools lack the refinement to provide objective patient specificity. scoring systems, including the Physiological and Operative severity score for the enumera tion of Mortality and Morbidity (POssUM)117 and the Glasgow Aneurysm score (GAs),118 have low positive predictive values for death and major morbidity following open repair. They also have limited value in clinical decision making for individual patients at high-risk and are not used to benchmark performance.
The physiological insult and patient-specific risks vary between open surgery and evAR. An increasing body of evidence shows that aortic morphology can substan-tially affect outcome in endovascular surgery.119 Risk stratification will likely be performed in the future using
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patient-specific morphological assessment, which will identify rupture risk and predict likely surgical outcome following evAR.
Unit caseload and outcomeA strong relationship exists between high annual case-load and low elective mortality for both open surgery and evAR. A pooled effect estimate from a meta-analysis of >110,000 cases demonstrated that the RR of mortality in high-volume versus low-volume treatment centers was 0.57 (95% CI 0.53–0.62), with a mean threshold between groups of 32 AAA cases per year.120 This mortality benefit also translates to emergent repairs (OR 0.531, 95% CI 0.42–0.68) and ruptured AAA repairs (OR 0.53, 95% CI 0.42–0.67). These findings reflect the multifaceted care of patients with high-risk vascular disease.121 Data indi-cate that mortality is low with high-volume surgeons and high-volume centers. Transfer of low-volume surgeons to high-volume centers that offer optimal infrastructure with expert vascular anesthetists, intensive-care physi-cians, and effective multidisciplinary teams improves out-comes.122 As a consequence, vascular surgical services in many countries are undergoing a process of centralization to ensure optimal service provision to all patients.
AgeMortality after elective AAA repair is age-related, for both open surgery and evAR.123 Following evAR, the 30-day mortality risk increases in relation to age, with patients aged ≥85 years being twice as likely to die as those patients aged 75–79 years (3.2% mortality versus 1.6%, P <0.0001).124 Age-specific outcomes of open and endovascular repairs highlight the advantage of
endo vascular surgery in the elderly. The in-hospital mor-tality following elective open AAA surgery in the over 85s is six times greater than following evAR.125 In the same elderly population, 85% of evAR patients were discharged home compared with 50% of patients after open surgery, with the remainder requiring care-home placement.125
sexFemale sex is independently associated with higher 28-day and 1-year mortality than male sex in patients undergoing elective AAA repair (28-day OR 1.33, 95% CI 1.02–1.70; 1-year OR 1.25, 95% CI 1.01–1.53).123 specifically, women have a higher risk of mortality after elective evAR than men (OR 1.68, 95% CI 1.42–1.99).124 They also have a significantly higher rate of aborted procedures, lower rates of procedural success, and an increased risk of access-site-related complications than men.124 All these issues could be a consequence of ana-tomical characteristics that increase the technical chal-lenge of the procedure, as women have shorter infrarenal aneurysm necks, smaller proximal neck diameters, and smaller access (iliac) arteries than do men.126
Despite female sex being a poor prognostic indicator, early surgery in women is still justified. In a scandinavian series, 24% of women with rupture had an AAA of <5.5 cm.127 An AAA with a diameter of 5 cm in a woman might carry a similar rupture risk to an AAA with a 6 cm diameter in a man.128 Women are also less likely to survive repair (evAR and open surgery) of a ruptured AAA than men (OR 1.53, 95% CI 1.47–1.57), and women are 9.8% less likely to be discharged home from hospital after repair of a ruptured AAA.129
obesityRetrospective analyses of case series have identified high BMI (>30 kg/m2) as a significant risk factor for poor outcome after surgery for AAA.130 Patients with increased BMI are more likely to sustain wound infections than their counterparts of ‘normal’ weight (BMI 18.5–24.9 kg/m2).130 short-term outcomes among obese patients with AAA are improved after evAR compared with open surgery.131 This finding could be a product of the less-invasive nature of evAR and the reduced amount of time that the patient spends under anesthetic. Percutaneous endo-vascular techniques could have a particular advantage in patients with obesity, because these procedures involve smaller incisions and less dissection and trauma, which are all factors likely to reduce morbidity.132
other systemic factorsMedical comorbidities that are independent predictors of perioperative mortality after open AAA repair include congestive cardiac failure, chronic renal impairment, coro nary artery disease, and COPD.133 Major heart and lung disease is less relevant as a risk factor for evAR than for open repair.124 Factors that impact on outcome follow-ing evAR are more related to complex arterial anatomy than to complex patient physiology. The patients at highest risk in both groups are those with renal failure,134 which is likely to be a consequence of the multifocal
atherosclerosis in the coronary and cerebrovascular circulations of these patients. A clear understanding of the risks associated with organ-system dysfunction has led to a large number of risk scores being developed for AAA surgery. These scores are generally based on pre-operative physiological derangement and evaluation of the patient’s health status. Widely used scores include the POssUM,117 GAs,118 and Acute Physiology And Chronic Health evaluation (APACHe II).135 The key limitation of these scoring systems is their lack of disease specificity and failure to assess physiological reserve.136
Metabolic fitness is a modern metric of patient well-being and likely tolerance to a surgical insult.136 Cardiopulmonary exercise testing measures how effi-ciently patients meet increased metabolic demand and can identify patients unlikely to survive in the mid-term, following successful surgery.137 Optimal models of risk will eventually incorporate physiological and anatomi-cal data. Appropriate case selection that accounts for all variables likely to impact on surgical outcome is the most ethical way of identifying which patients will truly benefit from elective AAA repair.
ConclusionsAAA is a local representation of a systemic disease of the vasculature. AAAs continue to be an important sur-gical problem, particularly in elderly men in whom the prevalence is as high as 8%. The risk factors for develop-ing an AAA are similar to those for athero sclerosis, including advancing age, male sex, smoking, and hyper-cholesterolemia, although the disease processes are dif-ferent. A genetic component to the pathogenesis of AAA
is likely, yet the disease phenotype seems to be dictated by environment. elective treatment of AAA aims to eradi-cate the risk of rupture. An ideal test to calculate the risk of AAA rupture is yet to be described. The only effective treatment is surgery, which carries its own risks of mortal-ity. A large volume of research has, therefore, explored factors that are likely to reduce the risks of treatment and broaden the applicability of surgery to more-infirm patients. Minimally invasive evAR, performed in high-volume treatment centers, offers the lowest risk therapy to patients with AAA, and could offer a survival advan-tage to patients at high risk with cardiac and respiratory comorbidities. Although evAR has proven advantages in the short-term, a subset of patients will continue to be best served by an open AAA repair. Research should con-centrate on identification of patient-specific factors that will determine the optimal treatment modality. Future prospective epidemiological studies should be aligned to large molecular biological studies to establish patterns of risk factors or molecular markers of AAA rupture to aid clinical decision making.
Review criteria
A systematic literature search of articles published in the english language between 1990 and 2010 was carried out using the PubMed and embase databases. MeSH search terms were “epidemiology”, “abdominal aortic aneurysm”, “ruptured aortic aneurysm”, “aortic aneurysms, abdominal”, “risk factors”, and “outcome assessment”. Additional papers were identified by manually searching the reference lists of retrieved articles.
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Author contributionsAll the authors contributed to discussion of content for the article. I. M. Nordon researched data to include in the manuscript, wrote the manuscript, and revised the manuscript in response to the peer-reviewers’ comments. R. J. Hinchliffe and I. M. Loftus wrote the manuscript and reviewed and edited the manuscript before submission. M. M. Thompson reviewed and edited the manuscript before submission.
