PMID- 32619497 OWN - NLM STAT- MEDLINE DCOM- 20210118 LR - 20210712 IS - 1615-5947 (Electronic) IS - 0890-5096 (Linking) VI - 70 DP - 2021 Jan TI - Metformin Prescription Associated with Reduced Abdominal Aortic Aneurysm Growth Rate and Reduced Chemokine Expression in a Swedish Cohort. PG - 425-433 LID - S0890-5096(20)30540-9 [pii] LID - 10.1016/j.avsg.2020.06.039 [doi] AB - BACKGROUND: Recent reports suggest that the negative association between diabetes mellitus and abdominal aortic aneurysm (AAA) may be driven by metformin, the world's most common antidiabetic drug rather than diabetes per se. We sought to investigate the association among AAA growth rate, chemokine profile, and metformin prescription in a contemporary Swedish cohort. METHODS: Patients under surveillance for small AAA were identified at 4 Swedish vascular centers with active AAA screening programs. Annual AAA growth rate, medical history, and prescribed medications were recorded for linear regression analysis. In a subset of patients with AAA and control subjects without AAA or diabetes, plasma samples were available and analyzed for 40 inflammatory chemokines. RESULTS: A total of 526 patients were included for AAA growth analysis: 428 without type 2 diabetes mellitus (T2DM), 65 with T2DM and metformin prescription, and 33 with T2DM but without metformin prescription. Patients were included from 2005 to 2017 with mean follow-up of 3.2 (1.7) years and median annual AAA growth rate 1.6 mm, range -4.8 to 15.4 mm. Mean (standard deviation) annual AAA growth rates were 2.3 (2.2) mm in non-T2DM patients versus 1.1 (1.1) mm in patients with T2DM with metformin prescription and 1.6 (1.4) mm among those with T2DM without metformin prescription. With non-T2DM patients as reference in an unadjusted and 2 adjusted models, metformin prescription was significantly associated with reduced AAA growth rate (P < 0.001, P = 0.005, and P = 0.024, respectively), but not T2DM without metformin prescription (P = 0.137, P = 0.331, and P = 0.479, respectively). Among 240 patients with AAA (152 without T2DM, 51 with T2DM and metformin, and 37 with T2DM without metformin) and 59 without AAA or T2DM, metformin prescription was associated with reduced expression of chemokines representing all classes of leukocytes. CONCLUSIONS: Metformin prescription is associated with reduced AAA growth rate, possibly mediated by broad anti-inflammatory effects. A randomized controlled trial is needed to determine what role metformin may play in AAA disease, particularly in the absence of T2DM. CI - Copyright (c) 2020 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Unosson, Jon AU - Unosson J AD - Department of Surgical Sciences, Vascular Surgery, Uppsala University, Uppsala, Sweden. Electronic address: jon.unosson@surgsci.uu.se. FAU - Wagsater, Dick AU - Wagsater D AD - Department of Surgical Sciences, Vascular Surgery, Uppsala University, Uppsala, Sweden; Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linkoping University Linkoping, Sweden. FAU - Bjarnegard, Niclas AU - Bjarnegard N AD - Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linkoping University Linkoping, Sweden. FAU - De Basso, Rachel AU - De Basso R AD - Department of Natural Science and Biomedicine, School of Health and Welfare, Jonkoping University, Jonkoping, Sweden. FAU - Welander, Martin AU - Welander M AD - Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linkoping University Linkoping, Sweden. FAU - Mani, Kevin AU - Mani K AD - Department of Surgical Sciences, Vascular Surgery, Uppsala University, Uppsala, Sweden. FAU - Gottsater, Anders AU - Gottsater A AD - Department of Vascular Diseases, Skane University Hospital, Lund University, Malmo, Sweden. FAU - Wanhainen, Anders AU - Wanhainen A AD - Department of Surgical Sciences, Vascular Surgery, Uppsala University, Uppsala, Sweden. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20200630 PL - Netherlands TA - Ann Vasc Surg JT - Annals of vascular surgery JID - 8703941 RN - 0 (Biomarkers) RN - 0 (Chemokines) RN - 0 (Hypoglycemic Agents) RN - 9100L32L2N (Metformin) SB - IM CIN - Ann Vasc Surg. 2021 Jan;70:e1-e2. PMID: 32736029 MH - Aged MH - Aortic Aneurysm, Abdominal/blood/diagnostic imaging/epidemiology/*prevention & control MH - Biomarkers/blood MH - Case-Control Studies MH - Chemokines/*blood MH - Diabetes Mellitus, Type 2/blood/diagnosis/*drug therapy/epidemiology MH - Down-Regulation MH - Drug Prescriptions MH - Female MH - Humans MH - Hypoglycemic Agents/*therapeutic use MH - Male MH - Metformin/*therapeutic use MH - Middle Aged MH - Protective Factors MH - Risk Factors MH - Sweden/epidemiology EDAT- 2020/07/04 06:00 MHDA- 2021/01/20 06:00 CRDT- 2020/07/04 06:00 PHST- 2020/04/14 00:00 [received] PHST- 2020/06/04 00:00 [revised] PHST- 2020/06/12 00:00 [accepted] PHST- 2020/07/04 06:00 [pubmed] PHST- 2021/01/20 06:00 [medline] PHST- 2020/07/04 06:00 [entrez] AID - S0890-5096(20)30540-9 [pii] AID - 10.1016/j.avsg.2020.06.039 [doi] PST - ppublish SO - Ann Vasc Surg. 2021 Jan;70:425-433. doi: 10.1016/j.avsg.2020.06.039. Epub 2020 Jun 30.