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

Nathan K. Itoga, Kara A. Rothenberg, Paola Suarez, Thuy Vy Ho, Matthew Mell, Baohui Xu, Catherine M. Curtin, Ronald L. Dalman

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Identification of a safe and effective medical therapy for abdominal aortic aneurysm (AAA) disease remains a significant unmet medical need. Recent small cohort studies indicate that metformin, the world's most commonly prescribed oral hypoglycemic agent, may limit AAA enlargement. We sought to validate these preliminary observations in a larger cohort. Methods: All patients with asymptomatic AAA disease managed in the Veterans Affairs Health Care System between 2003 and 2013 were identified by International Classification of Diseases, Ninth Revision codes. Those with a concomitant diagnosis of diabetes mellitus who also received two or more abdominal imaging studies (computed tomography, magnetic resonance imaging, or ultrasound) documenting the presence and size of an AAA, separated by at least 1 year, were included for review. Maximal AAA diameters were determined from radiologic reports. Further data acquisition was censored after surgical AAA repair, when performed. Comorbidities, active smoking status, and outpatient medication records (within 6 months of AAA diagnosis) were also queried. Yearly AAA enlargement rates, as a function of metformin treatment status, were compared using two statistical models expressed in millimeters per year: a multivariate linear regression (model 1) and a multivariate mixed-effects model with random intercept and random slope (model 2). Results: A total of 13,834 patients with 58,833 radiographic records were included in the analysis, with radiology imaging follow-up of 4.2 ± 2.6 years (mean ± standard deviation). The average age of the patients at AAA diagnosis was 69.8 ± 7.8 years, and 39.7% had a metformin prescription within ±6 months of AAA. The mean growth rate for AAAs in the entire cohort was 1.4 ± 2.0 mm/y by model 1 analysis and 1.3 ± 1.6 mm/y by model 2 analysis. The unadjusted mean rate of AAA growth was 1.2 ± 1.9 mm/y for patients prescribed metformin compared with 1.5 ± 2.2 mm/y for those without (P <.001), a 20% decrease. This effect remained significant when adjusted for variables relevant on AAA progression: metformin prescription was associated with a reduction in yearly AAA growth rate of −0.23 mm (95% confidence interval, −0.35 to −0.16; P <.001) by model 1 analysis and 0.20 mm/y (95% confidence interval, −0.26 to −0.14; P <.001) by model 2 analysis. A subset analysis of 7462 patients with baseline AAA size of 35 to 49 mm showed a similar inhibitory effect (1.4 ± 2.0 mm/y to 1.7 ± 2.2 mm/y; P <.001). Patients' factors associated with an increased yearly AAA growth rate were baseline AAA size, metastatic solid tumors, active smoking, chronic obstructive pulmonary disease, and chronic renal disease. Factors associated with decreased yearly AAA growth rates included prescriptions for angiotensin II type 1 receptor blockers or sulfonylureas and the presence of diabetes-related complications. Conclusions: In a nationwide analysis of diabetic Veterans Affairs patients, prescription for metformin was associated with decreased AAA enlargement. These findings provide further support for the conduct of prospective clinical trials to test the ability of metformin to limit progression of early AAA disease.

Original languageEnglish (US)
JournalJournal of Vascular Surgery
DOIs
StateAccepted/In press - Jan 1 2018
Externally publishedYes

Fingerprint

Aortic Diseases
Metformin
Abdominal Aortic Aneurysm
Veterans
Prescriptions
Disease Progression
Population
Growth
Linear Models
Smoking
Confidence Intervals
Veterans Health
Angiotensin II Type 1 Receptor Blockers
Aptitude

Keywords

  • Abdominal aortic aneurysm
  • Metformin
  • Veterans Affairs

ASJC Scopus subject areas

  • Surgery
  • Cardiology and Cardiovascular Medicine

Cite this

Metformin prescription status and abdominal aortic aneurysm disease progression in the U.S. veteran population. / Itoga, Nathan K.; Rothenberg, Kara A.; Suarez, Paola; Ho, Thuy Vy; Mell, Matthew; Xu, Baohui; Curtin, Catherine M.; Dalman, Ronald L.

In: Journal of Vascular Surgery, 01.01.2018.

Research output: Contribution to journalArticle

Itoga, Nathan K. ; Rothenberg, Kara A. ; Suarez, Paola ; Ho, Thuy Vy ; Mell, Matthew ; Xu, Baohui ; Curtin, Catherine M. ; Dalman, Ronald L. / Metformin prescription status and abdominal aortic aneurysm disease progression in the U.S. veteran population. In: Journal of Vascular Surgery. 2018.
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abstract = "Background: Identification of a safe and effective medical therapy for abdominal aortic aneurysm (AAA) disease remains a significant unmet medical need. Recent small cohort studies indicate that metformin, the world's most commonly prescribed oral hypoglycemic agent, may limit AAA enlargement. We sought to validate these preliminary observations in a larger cohort. Methods: All patients with asymptomatic AAA disease managed in the Veterans Affairs Health Care System between 2003 and 2013 were identified by International Classification of Diseases, Ninth Revision codes. Those with a concomitant diagnosis of diabetes mellitus who also received two or more abdominal imaging studies (computed tomography, magnetic resonance imaging, or ultrasound) documenting the presence and size of an AAA, separated by at least 1 year, were included for review. Maximal AAA diameters were determined from radiologic reports. Further data acquisition was censored after surgical AAA repair, when performed. Comorbidities, active smoking status, and outpatient medication records (within 6 months of AAA diagnosis) were also queried. Yearly AAA enlargement rates, as a function of metformin treatment status, were compared using two statistical models expressed in millimeters per year: a multivariate linear regression (model 1) and a multivariate mixed-effects model with random intercept and random slope (model 2). Results: A total of 13,834 patients with 58,833 radiographic records were included in the analysis, with radiology imaging follow-up of 4.2 ± 2.6 years (mean ± standard deviation). The average age of the patients at AAA diagnosis was 69.8 ± 7.8 years, and 39.7{\%} had a metformin prescription within ±6 months of AAA. The mean growth rate for AAAs in the entire cohort was 1.4 ± 2.0 mm/y by model 1 analysis and 1.3 ± 1.6 mm/y by model 2 analysis. The unadjusted mean rate of AAA growth was 1.2 ± 1.9 mm/y for patients prescribed metformin compared with 1.5 ± 2.2 mm/y for those without (P <.001), a 20{\%} decrease. This effect remained significant when adjusted for variables relevant on AAA progression: metformin prescription was associated with a reduction in yearly AAA growth rate of −0.23 mm (95{\%} confidence interval, −0.35 to −0.16; P <.001) by model 1 analysis and 0.20 mm/y (95{\%} confidence interval, −0.26 to −0.14; P <.001) by model 2 analysis. A subset analysis of 7462 patients with baseline AAA size of 35 to 49 mm showed a similar inhibitory effect (1.4 ± 2.0 mm/y to 1.7 ± 2.2 mm/y; P <.001). Patients' factors associated with an increased yearly AAA growth rate were baseline AAA size, metastatic solid tumors, active smoking, chronic obstructive pulmonary disease, and chronic renal disease. Factors associated with decreased yearly AAA growth rates included prescriptions for angiotensin II type 1 receptor blockers or sulfonylureas and the presence of diabetes-related complications. Conclusions: In a nationwide analysis of diabetic Veterans Affairs patients, prescription for metformin was associated with decreased AAA enlargement. These findings provide further support for the conduct of prospective clinical trials to test the ability of metformin to limit progression of early AAA disease.",
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TY - JOUR

T1 - Metformin prescription status and abdominal aortic aneurysm disease progression in the U.S. veteran population

AU - Itoga, Nathan K.

AU - Rothenberg, Kara A.

AU - Suarez, Paola

AU - Ho, Thuy Vy

AU - Mell, Matthew

AU - Xu, Baohui

AU - Curtin, Catherine M.

AU - Dalman, Ronald L.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: Identification of a safe and effective medical therapy for abdominal aortic aneurysm (AAA) disease remains a significant unmet medical need. Recent small cohort studies indicate that metformin, the world's most commonly prescribed oral hypoglycemic agent, may limit AAA enlargement. We sought to validate these preliminary observations in a larger cohort. Methods: All patients with asymptomatic AAA disease managed in the Veterans Affairs Health Care System between 2003 and 2013 were identified by International Classification of Diseases, Ninth Revision codes. Those with a concomitant diagnosis of diabetes mellitus who also received two or more abdominal imaging studies (computed tomography, magnetic resonance imaging, or ultrasound) documenting the presence and size of an AAA, separated by at least 1 year, were included for review. Maximal AAA diameters were determined from radiologic reports. Further data acquisition was censored after surgical AAA repair, when performed. Comorbidities, active smoking status, and outpatient medication records (within 6 months of AAA diagnosis) were also queried. Yearly AAA enlargement rates, as a function of metformin treatment status, were compared using two statistical models expressed in millimeters per year: a multivariate linear regression (model 1) and a multivariate mixed-effects model with random intercept and random slope (model 2). Results: A total of 13,834 patients with 58,833 radiographic records were included in the analysis, with radiology imaging follow-up of 4.2 ± 2.6 years (mean ± standard deviation). The average age of the patients at AAA diagnosis was 69.8 ± 7.8 years, and 39.7% had a metformin prescription within ±6 months of AAA. The mean growth rate for AAAs in the entire cohort was 1.4 ± 2.0 mm/y by model 1 analysis and 1.3 ± 1.6 mm/y by model 2 analysis. The unadjusted mean rate of AAA growth was 1.2 ± 1.9 mm/y for patients prescribed metformin compared with 1.5 ± 2.2 mm/y for those without (P <.001), a 20% decrease. This effect remained significant when adjusted for variables relevant on AAA progression: metformin prescription was associated with a reduction in yearly AAA growth rate of −0.23 mm (95% confidence interval, −0.35 to −0.16; P <.001) by model 1 analysis and 0.20 mm/y (95% confidence interval, −0.26 to −0.14; P <.001) by model 2 analysis. A subset analysis of 7462 patients with baseline AAA size of 35 to 49 mm showed a similar inhibitory effect (1.4 ± 2.0 mm/y to 1.7 ± 2.2 mm/y; P <.001). Patients' factors associated with an increased yearly AAA growth rate were baseline AAA size, metastatic solid tumors, active smoking, chronic obstructive pulmonary disease, and chronic renal disease. Factors associated with decreased yearly AAA growth rates included prescriptions for angiotensin II type 1 receptor blockers or sulfonylureas and the presence of diabetes-related complications. Conclusions: In a nationwide analysis of diabetic Veterans Affairs patients, prescription for metformin was associated with decreased AAA enlargement. These findings provide further support for the conduct of prospective clinical trials to test the ability of metformin to limit progression of early AAA disease.

AB - Background: Identification of a safe and effective medical therapy for abdominal aortic aneurysm (AAA) disease remains a significant unmet medical need. Recent small cohort studies indicate that metformin, the world's most commonly prescribed oral hypoglycemic agent, may limit AAA enlargement. We sought to validate these preliminary observations in a larger cohort. Methods: All patients with asymptomatic AAA disease managed in the Veterans Affairs Health Care System between 2003 and 2013 were identified by International Classification of Diseases, Ninth Revision codes. Those with a concomitant diagnosis of diabetes mellitus who also received two or more abdominal imaging studies (computed tomography, magnetic resonance imaging, or ultrasound) documenting the presence and size of an AAA, separated by at least 1 year, were included for review. Maximal AAA diameters were determined from radiologic reports. Further data acquisition was censored after surgical AAA repair, when performed. Comorbidities, active smoking status, and outpatient medication records (within 6 months of AAA diagnosis) were also queried. Yearly AAA enlargement rates, as a function of metformin treatment status, were compared using two statistical models expressed in millimeters per year: a multivariate linear regression (model 1) and a multivariate mixed-effects model with random intercept and random slope (model 2). Results: A total of 13,834 patients with 58,833 radiographic records were included in the analysis, with radiology imaging follow-up of 4.2 ± 2.6 years (mean ± standard deviation). The average age of the patients at AAA diagnosis was 69.8 ± 7.8 years, and 39.7% had a metformin prescription within ±6 months of AAA. The mean growth rate for AAAs in the entire cohort was 1.4 ± 2.0 mm/y by model 1 analysis and 1.3 ± 1.6 mm/y by model 2 analysis. The unadjusted mean rate of AAA growth was 1.2 ± 1.9 mm/y for patients prescribed metformin compared with 1.5 ± 2.2 mm/y for those without (P <.001), a 20% decrease. This effect remained significant when adjusted for variables relevant on AAA progression: metformin prescription was associated with a reduction in yearly AAA growth rate of −0.23 mm (95% confidence interval, −0.35 to −0.16; P <.001) by model 1 analysis and 0.20 mm/y (95% confidence interval, −0.26 to −0.14; P <.001) by model 2 analysis. A subset analysis of 7462 patients with baseline AAA size of 35 to 49 mm showed a similar inhibitory effect (1.4 ± 2.0 mm/y to 1.7 ± 2.2 mm/y; P <.001). Patients' factors associated with an increased yearly AAA growth rate were baseline AAA size, metastatic solid tumors, active smoking, chronic obstructive pulmonary disease, and chronic renal disease. Factors associated with decreased yearly AAA growth rates included prescriptions for angiotensin II type 1 receptor blockers or sulfonylureas and the presence of diabetes-related complications. Conclusions: In a nationwide analysis of diabetic Veterans Affairs patients, prescription for metformin was associated with decreased AAA enlargement. These findings provide further support for the conduct of prospective clinical trials to test the ability of metformin to limit progression of early AAA disease.

KW - Abdominal aortic aneurysm

KW - Metformin

KW - Veterans Affairs

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