Metformin prescription status and abdominal aortic aneurysm disease progression in the U.S. veteran population

Itoga, Nathan K.; Rothenberg, Kara A.; Suárez, Paola; Ho, Vy T.; Mell, Matthew W.; Xu, Baohui; Curtin, Catherine; Dalman, Ronald L.

doi:10.1016/j.jvs.2018.06.194

Cited by 92 publications

(70 citation statements)

References 29 publications

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“…33 Development of medical therapies for slowing AAA growth, such as the ongoing work in doxycycline and metformin, also has the potential to produce a paradigm shift in our management of AAAs, especially for frail patients. 34,35 Age and comorbidities are associated with poor outcomes but are not useful as tools for determining candidacy for surgery given the heterogeneity of outcomes. 36,37 Frailty, however, has consistently been shown to predict poor outcomes, and more evidence continues to accumulate that frailty is multidimensional and goes beyond merely comorbidities and functional status.…”

Section: Discussionmentioning

confidence: 99%

Variation in center-level frailty burden and the impact of frailty on long-term survival in patients undergoing elective repair for abdominal aortic aneurysms

George

Chen

Trickey

et al. 2020

Journal of Vascular Surgery

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Objective: Frailty is increasingly recognized as a key determinant in predicting postoperative outcomes. Centers that see more frail patients may not be captured in risk adjustment, potentially accounting for poorer outcomes in hospital comparisons. We aimed to (1) determine the effect of frailty on long-term mortality in patients undergoing elective abdominal aortic aneurysm (AAA) repair and (2) evaluate the variability in frailty burden among centers in the Vascular Quality Initiative (VQI) database. Methods:Patients undergoing elective open and endovascular AAA repair (2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017) were identified, and those with complete data on component variables of the VQI-derived Risk Analysis Index (VQI-RAI) and centers with $10 AAA repairs were included. VQI-RAI characteristics are sex, age, body mass index, renal failure, congestive heart failure, dyspnea, preoperative ambulation, and functional status. Frailty was defined as VQI-RAI $35 based on prior work in surgical patients using other quality improvement databases. This corresponds to the top 12% of patients at risk in the VQI. Center-level VQI-RAI differences were assessed by analysis of variance test. Relationships between frailty and survival were compared by Kaplan-Meier analysis and the log-rank test for open and endovascular procedures. Multivariable hierarchical Cox proportional hazards regression models were calculated with random intercepts for center, controlling for frailty, race, insurance, AAA diameter, procedure type, AAA case mix, and year.Results: A total of 15,803 patients from 185 centers were included. Mean VQI-RAI scores were 27.6 (standard deviation, 5.9; range, 4-56) and varied significantly across centers (F ¼ 2.41, P < .001). The percentage of frail patients per center ranged from 0% to 40.0%. In multivariable analysis, frailty was independently associated with long-term mortality (hazard ratio, 2.88; 95% confidence interval, 2.6-3.2) after accounting for covariates and center-level variance. Open AAA repair was not associated with long-term mortality after adjusting for frailty (hazard ratio, 0.98; 95% confidence interval, 0.86-1.13). There was a statistically significant difference in the percentage of frail patients compared with nonfrail patients who were discharged to a rehabilitation facility or nursing home after both open (40.5% vs 17.8%; P < .0001) and endovascular repair (17.7% vs 4.6%; P < .0001). Conclusions:There is considerable variability of preoperative frailty among VQI centers performing elective AAA repair. Adjusting for center-level variation, frailty but not procedure type had a significant association with long-term mortality; however, frailty and procedure type were both associated with nonhome discharge. Routine measurement of frailty preoperatively by centers to identify high-risk patients may help mitigate procedural and long-term outcomes and improve shared decision-making regarding AAA repair. (J Vasc Surg 2020;71:46-55.)

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Section: Discussionmentioning

confidence: 99%

Variation in center-level frailty burden and the impact of frailty on long-term survival in patients undergoing elective repair for abdominal aortic aneurysms

George

Chen

Trickey

et al. 2020

Journal of Vascular Surgery

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“…Much evidence has confirmed that Janus kinase/signal transducers and activators of transcription (JAK/STAT) and nuclear factor (NF)-κB as key signal integrators controlling the process of vascular inflammation and AAA formation. For example, metformin has been reported to inhibit the angiotensin II (AngII) induced AAA progression in mice through decreased the activity of NF-κB and STAT3 signal pathway 8,9 . Embelin inhibits AAA formation through decreasing IL-6 induced STAT3 and NF-κB inactivation 10 .…”

Section: Introductionmentioning

confidence: 99%

A novel STAT3 inhibitor attenuates angiotensin II-induced abdominal aortic aneurysm progression in mice through modulating vascular inflammation and autophagy

Cheng

Zhao

et al. 2020

Cell Death Dis

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Abdominal Aortic aneurysm (AAA) is associated with chronic inflammation, cells apoptosis, and impairment of autophagy. BP-1-102, a novel potent STAT3 inhibitor, has been recently reported to significantly block inflammationrelated signaling pathways of JAK2/STAT3 and NF-κB, as well as regulate autophagy. However, its role in vascular inflammation and AAA progression remains to be elucidated. In the present study, the effect and potential mechanisms of BP-1-102 on angiotensin II (AngII) induced AAA in ApoE −/− mice were investigated. AAA was induced in ApoE −/− mice with infusion of AngII for 28 days. BP-1-102 was administrated orally to mice every other day. Mice were sacrificed on day 7, day 14, and day 28 to evaluate the treatment effects. BP-1-102 markedly decreased AAA incidence and aortic diameter, maintained elastin structure and volume, reduced the expression of pro-inflammatory cytokines and MMPs, and inhibited inflammatory cells infiltration. Moreover, BP-1-102 dramatically reduced the expression of JAK2, p-STAT3, p-NF-κB, and Bcl-xL but maintained the expression of LC3B and Beclin in AAA tissues. In vitro, vascular smooth muscle cells (VSMCs) were treated with AngII and/or BP-1-102 at indicated time and concentration. BP-1-102 inhibited AngII-induced JAK2/STAT3 and NF-κB signaling activation and maintained autophagy-related proteins expression in VSMCs. Taken together, our findings suggest that BP-1-102 inhibits vascular inflammation and AAA progression through decreasing JAK2/STAT3 and NF-κB activation and maintaining autophagy.

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“…While 1 study demonstrated metformin failed to have any effect on AAA rupture rates, a population-based study by Fujimura et al reported metformin reduces AAA growth rate and recent studies found similar results 14 17 28 29. Metformin was associated with a lower risk of developing aortic aneurysm within a nested case–control of 4468 diabetics with and without aortic diseases 16.…”

Section: Discussionmentioning

confidence: 99%

Association between Metformin and Abdominal Aortic Aneurysm in Diabetic and Non-Diabetic Us Veterans

Sutton¹,

Magagnoli²,

Cummings³

et al. 2020

Journal of Investigative Medicine

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We sought to examine the progression from abdominal aortic aneurysm (AAA) diagnosis to surgery and death among diabetics with and without exposure to metformin as well as non-diabetics. We conducted a retrospective cohort study (January 2000 to July 2019) comparing 3 transitions (AAA surgery, death, and death after AAA surgery) among propensity score-matched metformin-exposed and unexposed diabetic veterans and non-diabetic veterans using the VA Informatics and Computing Infrastructure database. We fit an adjusted Cox proportional hazards model with transition-specific effects. There were 43,073 metformin-unexposed diabetics, 24,361 metformin-exposed diabetics and 56,006 non-diabetics. Compared with the non-diabetic cohort, both diabetic cohorts have a lower risk of surgery (no metformin (HR=0.740, 95% CI 0.706 to 0.776); with metformin (HR=0.770, 95% CI 0.730 to 0.813)). However, the non-metformin diabetic cohort has a higher risk of death (HR=1.024, 95% CI 1.004 to 1.045) and death after surgery (HR=1.086, 95% CI 1.013 to 1.165). The metformin-exposed diabetic cohort has a lower risk of death in the first 10 years after AAA diagnosis (HR=0.877, 95% CI 0.855 to 0.899), yet a higher risk of death 10 years after AAA diagnosis (HR=1.177, 95% CI 1.092 to 1.270) compared with non-diabetic cohort. Non-diabetics have the highest rate of AAA surgery compared with both diabetic cohorts. However, diabetics without metformin have the highest risk of death prior to, and after surgery. This research provides novel findings for patients diagnosed with AAA. The use of metformin after both AAA diagnosis and surgery should be further investigated.

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Metformin prescription status and abdominal aortic aneurysm disease progression in the U.S. veteran population

Cited by 92 publications

References 29 publications

Variation in center-level frailty burden and the impact of frailty on long-term survival in patients undergoing elective repair for abdominal aortic aneurysms

Variation in center-level frailty burden and the impact of frailty on long-term survival in patients undergoing elective repair for abdominal aortic aneurysms

A novel STAT3 inhibitor attenuates angiotensin II-induced abdominal aortic aneurysm progression in mice through modulating vascular inflammation and autophagy

Association between Metformin and Abdominal Aortic Aneurysm in Diabetic and Non-Diabetic Us Veterans

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