Screening for and Optimal Management of Small Abdominal Aortic Aneurysms: The Quest Continues

Author(s): Kosmas I. Paraskevas*, Hans-Henning Eckstein, Andrew N. Nicolaides, George Geroulakos

Journal Name: Current Vascular Pharmacology

Volume 18 , Issue 6 , 2020

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Screening for and Optimal Management of Small Abdominal Aortic Aneurysms: The Quest Continues

Kosmas I. Paraskevas1, * , Hans-Henning Eckstein2 , Andrew N. Nicolaides3 and George Geroulakos1

1Department of Vascular Surgery, ‘Attikon’ University Hospital, National and Kapodistrian University of Athens, Athens, Greece;
2Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany;
3Vascular Screening and Diagnostic Center, Nicosia, Cyprus

Article Information

Identifiers and Pagination:

Year: 2020
Volume: 18
Issue: 6
First Page: 663
Last Page: 666
Publisher Id: CVP-18-6-663
DOI: 10.2174/1570161118999191126145824

Article History:





* Address correspondence to this author at the Department of Vascular Surgery, “Attikon” University Hospital, 1, Rimini Street, Chaidari 12463, Athens, Greece; E-mail: paraskevask@hotmail.com

A comprehensive review nearly 30 years ago outlined the dilemmas when considering the optimal management of a ≤5.0 cm abdominal aortic aneurysm (AAA), namely the balance between the risks and benefits of offering a procedure [1]. Two recent articles suggest that the management of such small AAAs is enduringly controversial [2, 3]. Another controversy is that of screening for small AAAs [4 - 7].

This Editorial will discuss these much debated issues.

1. IS IT WORTH SCREENING FOR SMALL AAAS?

Screening for AAAs was introduced during the 2000s in the UK, Sweden and the U.S.A. on the basis of reduced disease-specific mortality with AAA screening [4 - 6]. A U.S. Preventive Services Task Force review estimated a 50% relative risk reduction with AAA screening after 13-15 years’ follow-up [7]. The data from the 1980s-1990s therefore suggested that AAA screening is associated with significant reductions in AAA-related mortality.

The Western Australia screening study was the latest of the major AAA screening trials [8]. This study did not confirm the positive late results of earlier trials, such as the Multicentre Aneurysm Screening Study [4], which showed a 40% reduction in AAA-related mortality at final follow-up at 13 years.

Due to the decreasing prevalence of AAAs in many western countries, associated with reductions in smoking and improvement in primary cardiovascular disease prevention, population-based screening may eventually not be effective [9]. In some countries with a very low prevalence of AAAs (e.g. Belgium) there are already some reservations regarding mass AAA screening [10]. It was proposed that a more targeted approach to specific high-risk populations may be required [11, 12]. Such targeted screening for AAAs has also been proposed for high-risk females (e.g. those aged ≥76 years with a history of smoking, hypertension, stroke/transient ischaemic attack, carotid artery stenosis, atrial fibrillation and low ankle-brachial pressure index) [13]. In addition, very recent data from Germany showed, that >30% of all ruptured AAAs would have never been eligible for a screening programme including only males ≥65 years old [14].

The benefits of population screening for AAAs may vary by country. In the UK where the prevalence of AAA is falling in parallel with a reduction in smoking rates, AAA screening remains cost-effective down to a prevalence of 0.35% (current prevalence in 65-year-old men in England: 1.1%) [15].

An updated (2018) meta-analysis of the longest (≥13 years) follow-up results from 4 randomised controlled trials of AAA screening in ≥65-year-old men showed that invitation to screening significantly reduced all-cause mortality according to time-to-event data (hazard ratio: 0.98; 95% confidence interval [CI]: 0.96-0.99; p=0.003) [16]. Invitation to screening also significantly reduced AAA-related mortality (odds ratio [OR]: 0.66; 95%CI: 0.47-0.93; p=0.02) but not non-AAA-related mortality (OR: 1.00; 95%CI: 0.98-1.02; p=0.96) [16].

A recent article debating the benefits of AAA screening programmes reported that for every 10, 000 men invited to attend, 46 avoid dying from a ruptured AAA [17]. For every avoided death, however, 4 men are diagnosed with an AAA that would otherwise never have been detected or caused health problems in their lifetime. These “over diagnosed” patients may be at risk for physical and psychological harm [17].

Current evidence therefore suggests that the screening for small AAAs controversy is far from resolved.

2. OPTIMAL MANAGEMENT OF SMALL AAAS: IS THERE A ROLE FOR PHARMACOTHERAPY?

Patients with AAAs have a higher risk of concomitant diseases (e.g. coronary heart disease and chronic obstructive pulmonary disease) and vascular risk factors (e.g. smoking, hyperlipidaemia and hypertension) [18, 19]. Controlling these risk factors are essential prevention strategies. Several pharmacological agents have been proposed to limit AAA expansion and/or be beneficial for AAA patients. A detailed description of pharmacological treatment that may be beneficial for AAA patients is beyond the scope of this Editorial and is reviewed elsewhere [20, 21]. Briefly, macrolides (roxithromycin and azithromycin) appear to combat Chlamydia pneumoniae infections (which were reported to be associated with AAAs) [20]. Statins have anti-inflammatory and antioxidant effects, as well as a possible reduction of AAA progression rates [20, 21]. A recent systematic review and meta-analysis showed that statin use was associated with a reduction in AAA progression rates, a lower AAA rupture risk, as well as lower perioperative mortality rates following elective AAA repair [21]. Corticosteroids may be effective for inflammatory AAAs [20]. Antiplatelets may diminish AAA formation and decrease ruptured AAA-associated death [20]. These effects have not been firmly established and need verification from clinical trials.

An interesting finding is that diabetes mellitus may decrease the risk of developing an AAA [22]. The underlying mechanisms may include increased arterial wall matrix formation via advanced glycation end-products, suppression of plasmin and reduction of levels and activity of matrix metalloproteinases (MMP)-2 and 9, diminished aortic wall macrophage infiltration, elastolysis and neovascularisation [22]. Antidiabetic agents like metformin and thiazolidinediones may also protect against AAAs [23]. The diabetes pandemic (together with reduced smoking rates) may therefore be partly responsible for the fall in the prevalence of AAAs.

Circulating biomarkers reflecting the development and progression of AAAs, as well as effective pharmacological agents to prevent AAA growth are needed [24, 25]. Evidence from epidemiologic and experimental work suggest that the pathogenesis of AAA is often related to atherosclerosis risk factors, particularly smoking, genetic influence, and the development of inflammatory atherosclerotic plaque formation, which results in degradation of the structural integrity of the aorta [24, 25].

High plasma levels of lipoprotein (a) [Lp(a)] are associated with coronary artery disease, stroke and peripheral artery disease [26 - 29]. In a meta-analysis, patients with AAA had modest but significantly higher levels of Lp(a) compared with controls (Standardised Mean Difference: 0.87, 95% CI: 0.41-1.33, p<0.001) [30]. The conclusion was that circulating Lp(a) may be a useful biomarker in screening for AAAs [30]. If Lp(a) does indeed prove to be causal, antisense oligonucleotides have been shown to markedly lower Lp(a) levels (by up to 80%) [31]. Therefore, they may become an option to delay, or even obviate, the need for interventions.

3. OPTIMAL MANAGEMENT OF AAAS: PRESENT AND FUTURE

In 2018, both the American Society for Vascular Surgery (SVS) [32] and the European Society for Vascular Surgery (ESVS) [33] updated their guidelines for the management of AAAs. National Guidelines and Recommendations have also recently been released (e.g. the recommendations from the Spanish AAA Working Group [34]). According to the 2018 SVS Guidelines, elective repair is suggested for women with an AAA between 5.0 and 5.4 cm in diameter and those with a rapidly expanding small fusiform AAA (Level of Recommendation: 2 [Weak]; Quality of Evidence: B [Moderate]) [32]. A weak recommendation for elective repair below the 5.5 cm threshold is provided for specific subgroups of patients (e.g. younger patients at low surgical risk, patients with a positive family history, patients with saccular AAAs, etc) [32]. Similarly, the ESVS guidelines provide a weak recommendation for elective repair in women with AAAs ≥5.0 cm in diameter (Class IIb; Level of Recommendation: C) [33]. For the vast majority of patients with small AAAs the conclusions of the 4th Cochrane review on the management of these patients are still valid [35]. Summarising the evidence of 4 randomised controlled trials (3314 patients), it concluded that there is no advantage to immediate repair for small AAAs (4.0 to 5.5 cm), regardless of whether open or endovascular repair is used [35]. Finally, institutional and individual surgical experience matters with respect to short-term outcomes, patient selection and follow-up. Centralisation of aortic services should be strongly considered to optimise outcomes [36].

CONCLUSION

The debate about screening for, and management of, small AAAs has been on-going for 3 decades. Changes in the prevalence of AAAs and vascular disease prevention strategies, have not resolved this controversy. Future pharmacological developments may shift the balance towards a more conservative/medical management of AAAs. However, any promising results involving pharmacological agents must be verified in appropriately-designed trials. It is relevant to consider that identifying an AAA will classify a patient as having a “CHD equivalent status” that requires management [18].

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