Statins Reduce Abdominal Aortic Aneurysm Growth, Rupture, and Perioperative Mortality: A Systematic Review and Meta‐Analysis

Salata, Konrad; Syed, Muzammil H.; Hussain, Mohamad A.; Mestral, Charles de; Greco, Elisa; Mamdani, Muhammad; Tu, Jack V.; Forbes, Thomas L.; Bhatt, Deepak L.; Verma, Subodh; Al‐Omran, Mohammed

doi:10.1161/jaha.118.008657

Cited by 109 publications

(81 citation statements)

References 83 publications

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“…40 In a clinical setting, a recent meta-analysis has stated that statin therapy may be associated with reduction in AAA progression, rupture, and lower rates of peri-operative mortality following elective AAA repair. 2 Also, in postdeployment of EVAR, it has been documented that statin therapy can be predictive of AAA sac diameter reduction. 41 Although optimisation with best medical treatment is recommended, evidence of the effect of single drugs has been conflicting 42 and further research is required.…”

Section: Discussionmentioning

confidence: 99%

“…Later results, however, have shown that prophylactic treatment with statins should be included because of the effect on reduction in growth progression, rupture, and lower rates of peri-operative mortality. 2 Statins have also been shown to be independent predictors of decreased long term mortality after AAA. 3e7 The aim of the study was to search the literature to study the long term effects of statins after open surgical repair (OSR) and endovascular aneurysm repair (EVAR) in general and to search for possible trends in the choice of treatment.…”

Section: Introductionmentioning

confidence: 99%

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Editor's Choice – Effect of Statins on Total Mortality in Abdominal Aortic Aneurysm Repair: A Systematic Review and Meta-analysis

Risum

Sandven

Sundhagen

et al. 2021

European Journal of Vascular and Endovascular Surgery

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WHAT THIS PAPER ADDS The beneficial effect of statins on long term survival after operative treatment, both open surgery and endovascular aneurysm repair (EVAR) has been confirmed. Statin therapy after abdominal aneurysm repair should be included in the guidelines. Objective: The aim was to summarise the evidence from published epidemiological studies investigating the efficacy of statin therapy on long term survival in patients after abdominal aortic aneurysm (AAA) repair. Data sources: This study was a systematic review with critical appraisal and meta-analysis of observational studies. Review methods: A systematic literature search was carried out throughout February 2020, revealing 14 eligible cohort studies of which 11 were judged to be of high quality. A random effects model was used to synthesise results, and heterogeneity between studies examined by subgroup and meta-regression analyses considering patient and study related variables. Small study effect was evaluated. Results: The pooled estimate showed that statin treatment among 69 790 AAA patients with a median follow up of 3.1 years was associated with a 35% relative reduction in total mortality (rate ratio 0.65, 95% confidence interval 0.57e0.73) with moderate heterogeneity (I 2 ¼ 68%) and no small study effect. Conclusion: Evidence from this systematic review indicates a beneficial effect of statins on long term survival in patients treated by AAA repair.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Editor's Choice – Effect of Statins on Total Mortality in Abdominal Aortic Aneurysm Repair: A Systematic Review and Meta-analysis

Risum

Sandven

Sundhagen

et al. 2021

European Journal of Vascular and Endovascular Surgery

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“…Although recommended to reduce cardiovascular events (4), antiplatelet medications and antihypertensive agents have not been shown to influence AAA growth or rupture risk. Although a large systematic review found a possible association of statins with a reduction in AAA growth and rupture (114), similar effects have not been shown for other medication classes including angiotensin converting enzyme inhibitors, beta blockers, and doxycycline (41,58). Accordingly, screening for AAA in populations at risk (23), surveillance of small AAAs, and pre-emptive surgical repair at the point when risk of rupture outweighs the surgical risks are crucial.…”

Section: Introductionmentioning

confidence: 99%

Involvement of Myeloid Cells and Noncoding RNA in Abdominal Aortic Aneurysm Disease

Knappich

Spin

Eckstein

et al. 2020

Antioxidants & Redox Signaling

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Significance: Abdominal aortic aneurysm (AAA) is a potentially fatal condition, featuring the possibility of high-mortality rupture. To date, prophylactic surgery by means of open surgical repair or endovascular aortic repair at specific thresholds is considered standard therapy. Both surgical options hold different risk profiles of short-and long-term morbidity and mortality. Targeting early stages of AAA development to decelerate disease progression is desirable. Recent Advances: Understanding the pathomechanisms that initiate formation, maintain growth, and promote rupture of AAA is crucial to developing new medical therapeutic options. Inflammatory cells, in particular macrophages, have been investigated for their contribution to AAA disease for decades, whereas evidence on lymphocytes, mast cells, and neutrophils is sparse. Recently, there has been increasing interest in noncoding RNAs (ncRNAs) and their involvement in disease development, including AAA. Critical Issues: The current evidence on myeloid cells and ncRNAs in AAA largely originates from small animal models, making clinical extrapolation difficult. Although it is feasible to collect surgical human AAA samples, these tissues reflect end-stage disease, preventing examination of critical mechanisms behind early AAA formation. Future Directions: Gaining more insight into how myeloid cells and ncRNAs contribute to AAA disease, particularly in early stages, might suggest nonsurgical AAA treatment options. The utilization of large animal models might be helpful in this context to help bridge translational results to humans. Antioxid. Redox Signal. 00, 000-000.

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“…However, recent genetic studies suggest that lipids could play a role in the etiology of AAA [[7], [8], [9], [10]]. Similarly, the effect of statins on AAA displayed contradictory results, although more recent studies support a protective role of these drugs in preventing AAA growth and rupture [[11], [12], [13]]. Regardless of the potential contribution of lipids on AAA progression, it is well accepted that low levels of high-density lipoprotein (HDL) cholesterol are associated to both AAA presence and evolution [14,15].…”

Section: Introductionmentioning

confidence: 99%

APOA1 oxidation is associated to dysfunctional high-density lipoproteins in human abdominal aortic aneurysm

et al. 2019

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Background High-density lipoproteins (HDL) are a complex mixture of lipids and proteins with vasculoprotective properties. However, HDL components could suffer post-translational modifications (PTMs) under pathological conditions, leading to dysfunctional HDL. We studied whether HDL are modified in abdominal aortic aneurysm (AAA) and the effect on HDL functionality. Methods HDL were isolated by ultracentrifugation from AAA tissue (HDL-T) and from plasma of healthy volunteers and then incubated with AAA tissue-conditioned medium (HDL-AAA CM). PTMs from these particles were characterized using Comet-PTM. The ability of HDL-AAA CM for promoting cholesterol efflux was determined ex vivo and in vivo by using J774A.1 [ 3 H]cholesterol-labeled mouse macrophages and after injecting [ 3 H]cholesterol-labeled mouse macrophages and HDL into the peritoneal cavity of wild-type C57BL/6 mice, respectively. Trp50 and Trp108 oxidized forms of APOA1 in HDL incubated with conditioned-medium of activated neutrophils and in plasma of AAA patients and controls were measured by targeted parallel reaction monitoring. Findings Oxidation was the most prevalent PTM in apolipoproteins, particularly in APOA1. Trp50 and Trp108 in APOA1 were the residues most clearly affected by oxidation in HDL-T and in HDL-AAA CM, when compared to their controls. In addition, cholesterol efflux was decreased in macrophages incubated with HDL-AAA CM in vitro and a decreased macrophage-to-serum reverse cholesterol transport was also observed in mice injected with HDL-AAA CM. Finally, both oxidized Trp50 and Trp108 forms of APOA1 were increased in HDL incubated with conditioned-medium of activated neutrophils and in plasma of AAA patients in relation to controls. Interpretation Oxidative modifications of HDL present in AAA tissue and plasma were closely associated with the loss of vasculoprotective properties of HDL in AAA. Fund MINECO, ISCiii-FEDER, CIBERDEM, CIBERCV and LA CAIXA.

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Statins Reduce Abdominal Aortic Aneurysm Growth, Rupture, and Perioperative Mortality: A Systematic Review and Meta‐Analysis

Cited by 109 publications

References 83 publications

Editor's Choice – Effect of Statins on Total Mortality in Abdominal Aortic Aneurysm Repair: A Systematic Review and Meta-analysis

Editor's Choice – Effect of Statins on Total Mortality in Abdominal Aortic Aneurysm Repair: A Systematic Review and Meta-analysis

Involvement of Myeloid Cells and Noncoding RNA in Abdominal Aortic Aneurysm Disease

APOA1 oxidation is associated to dysfunctional high-density lipoproteins in human abdominal aortic aneurysm

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