The Protective Effect of Metformin on Abdominal Aortic Aneurysm: A Systematic Review and Meta-Analysis.
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ABSTRACT: Background
Type 2 diabetes mellitus (T2DM) patients have a lower risk of abdominal aortic aneurysm (AAA) and its comorbidities, which might be associated with the usage of metformin. The objective of the study was to evaluate the role of metformin in the process of AAA development.Method
PubMed, Embase and Cochrane Library were searched up to May 15th, 2021. We implemented several methods including the risk of bias graph, GRADE system and funnel plot to assess the quality and possible bias of this study. Subgroup analysis and sensitivity analysis were applied to address quality differences and validate the robustness of the final results.Result
Ten articles were enrolled after screening 151 articles searched from databases. The pooled results showed that, compared with T2DM patients without metformin, metformin prescription was associated with a slower annual growth rate of the aneurysm (mean difference (MD) -0.67 cm [95% confidence interval (CI) -1.20 ~ -0.15 cm]). Besides, metformin exposure was associated with a lower frequency of AAA events (odds ratio (OR) 0.61 [95% CI 0.41-0.92]).Conclusion
Metformin alleviated both annual expansion rate and aneurysm rupture frequency in AAA patients with T2DM.Systematic review registration
PROSPERO, identifier https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=217859 (CRD42020217859).
SUBMITTER: Yuan Z
PROVIDER: S-EPMC8355809 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background There are no recognized pharmacological treatments for abdominal aortic aneurysms ( AAA ), although statins are suggested to be beneficial. We sought to summarize the literature regarding the effects of statins on human AAA growth, rupture, and 30-day mortality. Methods and Results We conducted a systematic review and meta-analysis of randomized and observational studies using the Cochrane CENTRAL database, MEDLINE , and EMBASE up to June 15, 2018. Review, abstraction, and quality assessment were conducted by 2 independent reviewers, and a third author resolved discrepancies. Pooled mean differences and odds ratios with 95% confidence intervals were calculated using random effects models. Heterogeneity was quantified using the I2 statistic, and publication bias was assessed using funnel plots. Our search yielded 911 articles. One case-control and 21 cohort studies involving 80 428 patients were included. The risk of bias was low to moderate. Statin use was associated with a mean AAA growth rate reduction of 0.82 mm/y (95% confidence interval 0.33, 1.32, P=0.001, I2=86%). Statins were also associated with a lower rupture risk (odds ratio 0.63, 95% confidence interval 0.51, 0.78, P<0.0001, I2=27%), and preoperative statin use was associated with a lower 30-day mortality following elective AAA repair (odds ratio 0.55, 95% confidence interval 0.36, 0.83, P=0.005, I2=57%). Conclusions Statin therapy may be associated with reduction in AAA progression, rupture, and lower rates of perioperative mortality following elective AAA repair. These data argue for widespread statin use in AAA patients. Clinical Trial Registration URL : www.crd.york.ac.uk . Unique identifier: CRD 42017056480.
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Project description:In population-based studies performed on multiple continents during the past two decades, diabetes mellitus has been negatively associated with the prevalence and progression of abdominal aortic aneurysm (AAA) disease. We investigated the possibility that metformin, the primary oral hypoglycemic agent in use worldwide, may influence the progression of AAA disease.Preoperative AAA patients with diabetes were identified from an institutional database. After tabulation of individual cardiovascular and demographic risk factors and prescription drug regimens, odds ratios for categorical influences on annual AAA enlargement were calculated through nominal logistical regression. Experimental AAA modeling experiments were subsequently performed in normoglycemic mice to validate the database-derived observations as well as to suggest potential mechanisms of metformin-mediated aneurysm suppression.Fifty-eight patients met criteria for study inclusion. Of 11 distinct classes of medication considered, only metformin use was negatively associated with AAA enlargement. This association remained significant after controlling for gender, age, cigarette smoking status, and obesity. The median enlargement rate in AAA patients not taking oral diabetic medication was 1.5 mm/y; by nominal logistic regression, metformin, hyperlipidemia, and age ?70 years were associated with below-median enlargement, whereas sulfonylurea therapy, initial aortic diameter ?40 mm, and statin use were associated with above-median enlargement. In experimental modeling, metformin dramatically suppressed the formation and progression, with medial elastin and smooth muscle preservation and reduced aortic mural macrophage, CD8 T cell, and neovessel density.Epidemiologic evidence of AAA suppression in diabetes may be attributable to concurrent therapy with the oral hypoglycemic agent metformin.
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Project description:Several studies have found that smoking increases the risk of abdominal aortic aneurysm, however, the strength of the association has differed between studies and data from cohort studies have not yet been summarized. A systematic review and meta-analysis was therefore conducted to clarify this association. We searched PubMed and Embase databases up to May 2nd 2018. A random effects model was used to estimate summary relative risks (RRs) and 95% confidence intervals (CIs). Twenty three prospective studies were included. Comparing current, former and ever smokers with never smokers the summary RRs were 4.87 (95% CI: 3.93-6.02, I2?=?92%, n?=?20), 2.10 (95% CI: 1.76-2.50, I2?=?71%, n?=?15) and 3.28 (95% CI: 2.60-4.15, I2?=?96%, n?=?18), respectively. The summary RR was 1.87 (95% CI: 1.45-2.40, I2?=?97%) per 10 cigarettes per day, 1.78 (95% CI: 1.54-2.06, I2?=?83%) per 10 pack-years was and 0.45 (95% CI: 0.32-0.63, I2?=?92.3%) per 10 years of smoking cessation. There was evidence of nonlinearity for cigarettes per day and pack-years (pnonlinearity?<?0.0001 and pnonlinearity?=?0.02, respectively), but not for smoking cessation, pnonlinearity?=?0.85. Among smokers who quit, the RR was similar to that of never smokers by 25 years of smoking cessation. These findings confirm a strong association between smoking and the risk of developing abdominal aortic aneurysms.
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Project description:The association between physical activity and risk of abdominal aortic aneurysm has been inconsistent with some studies reporting a reduced risk while others have found no association. We conducted a systematic review and meta-analysis of prospective studies to quantify the association. PubMed and Embase databases were searched up to 3 October 2020. Prospective studies were included if they reported adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) of abdominal aortic aneurysm associated with physical activity. Summary RRs (95% CIs) were estimated using a random effects model. Nine prospective studies (2073 cases, 409,732 participants) were included. The summary RR for high vs. low physical activity was 0.70 (95% CI: 0.56-0.87, I2 = 58%) and per 20 metabolic equivalent task (MET)-hours/week increase of activity was 0.84 (95% CI: 0.74-0.95, I2 = 59%, n = 6). Although the test for nonlinearity was not significant (p = 0.09) the association appeared to be stronger when increasing the physical activity level from 0 to around 20-25 MET-hours/week than at higher levels. The current meta-analysis suggest that higher physical activity may reduce the risk of abdominal aortic aneurysm, however, further studies are needed to clarify the dose-response relationship between different subtypes and intensities of activity and abdominal aortic aneurysm risk.
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Project description:ObjectivesPrevious studies have reported inconsistent findings regarding the association between elevated plasma homocysteine (Hcy) levels and abdominal aortic aneurysm (AAA). We investigated this association between Hcy levels in patients with AAA and unaffected controls by conducting a meta-analysis and systematic review.MethodsWe conducted a systematic literature search (up to August 2013) of the PubMed database and Embase. We selected observational studies that evaluated Hcy levels in subjects with AAA compared to unaffected controls. Criteria for inclusion were the assessment of baseline Hcy and risk of AAA as an outcome. The results were presented as odd ratio (OR) and corresponding 95% confidence intervals (CI) comparing AAA patients to the control subjects.Results7 studies with 6,445 participants were identified and analyzed. Overall, elevated plasma Hcy was associated with an increased risk of AAA (3.29; 95% CI 1.66-6.51). The pooled adjusted OR from a random effect model of only men participants in the AAA compared with the control group was 2.36 (95% CI 0.63-8.82).ConclusionThis meta-analysis and systematic review suggested that Hcy significantly increased the risk of AAA.
| S-EPMC3897527 | biostudies-literature
Project description:OBJECTIVES:Emergency endovascular aneurysm repair (eEVAR) may improve outcomes for patients with ruptured abdominal aortic aneurysm (RAAA). The study aim was to compare the outcomes for eEVAR with conventional open surgical repair for the treatment of RAAA. SETTING:A systematic review of relevant publications was performed. Randomised controlled trials (RCTs) comparing eEVAR with open surgical repair for RAAA were included. PARTICIPANTS:3 RCTs were included, with a total of 761 patients with RAAA. INTERVENTIONS:Meta-analysis was performed with fixed-effects models with ORs and 95% CIs for dichotomous data and mean differences with 95% CIs for continuous data. PRIMARY AND SECONDARY OUTCOME MEASURES:Primary outcome was short-term mortality. Secondary outcome measures included aneurysm-specific and general complication rates, quality of life and economic analysis. RESULTS:Overall risk of bias was low. There was no difference between the 2 interventions on 30-day (or in-hospital) mortality, OR 0.91 (95% CI 0.67 to 1.22; p=0.52). 30-day complications included myocardial infarction, stroke, composite cardiac complications, renal complications, severe bowel ischaemia, spinal cord ischaemia, reoperation, amputation and respiratory failure. Reporting was incomplete, and no robust conclusion was drawn. For complication outcomes that did include at least 2 studies in the meta-analysis, there was no clear evidence to support a difference between eEVAR and open repair. Longer term outcomes and cost per patient were evaluated in only a single study, thus precluding definite conclusions. CONCLUSIONS:Outcomes between eEVAR and open repair, specifically 30-day mortality, are similar. However, further high-quality trials are required, as the paucity of data currently limits the conclusions.
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Project description:IntroductionMendelian randomisation (MR) has been suggested to be able to overcome biases of observational studies, but no meta-analysis is available on MR studies on abdominal aortic aneurysm (AAA). This systematic review and Meta-analysis examined the evidence of causal risk factors for AAA identified in MR studies.MethodsPublicly available databases were systematically searched for MR studies that reported any causal risk factors for AAA diagnosis. Meta-analyses were performed using random effect models and reported as odds ratio (OR) and 95% confidence intervals (CI). Study quality was assessed using a modified version of Strengthening the Reporting of Mendelian Randomisation Studies (STROBE-MR) guidelines.ResultsSixteen MR studies involving 34,050 patients with AAA and 2,205,894 controls were included. Meta-analyses suggested that one standard deviation increase in high density lipoprotein (HDL) significantly reduced (OR: 0.66, 95% CI: 0.61, 0.72) and one standard deviation increase in low density lipoprotein (LDL) significantly increased the risk (OR: 1.68, 95%, CI: 1.55, 1.82) of AAA. One standard deviation increase in triglycerides did not significantly increase the risk of AAA (OR: 1.21, 95% CI: 0.86, 1.71). Quality assessment suggested that ten and five studies were of low and moderate risk of bias respectively, with one study considered as high risk of bias.ConclusionThis meta-analysis suggests LDL and HDL are positive and negative casual risk factors for AAA.
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| S-EPMC6324275 | biostudies-literature
Project description:BackgroundThe 'weekend effect' describes the phenomenon where patient outcomes appear worse for those admitted at the weekend. It has been used recently to justify significant changes in UK health policy. Recent evidence has suggested that the effect may be due to a combination of inadequate correction for confounding factors and inaccurate coding. The effects of these factors were investigated in patients with acute abdominal aortic aneurysm (AAA).MethodsPatients undergoing non-elective AAA repair entered into the UK National Vascular Registry from January 2013 until December 2015 were included in a case-control study. The patients were divided according to whether they were treated during the week (Monday 08.00 hours to Friday 17.00 hours) or at the weekend. Data extracted included demographics, co-morbidities, preoperative medications and baseline blood test results, as well as outcomes. Coding issues were investigated by looking at patients treated for ruptured, symptomatic or asymptomatic AAA within the non-elective cohort. The primary outcome was in-hospital mortality. Secondary outcomes included length of inpatient stay, and cardiac, respiratory and renal complications.ResultsThe mortality rate appeared to be higher at the weekend (odds ratio (OR) 1·69, 95 per cent c.i. 1·47 to 1·94; P < 0·001), but this effect disappeared when confounding factors and coding issues were corrected for (corrected OR for ruptured AAA 1·09, 0·92 to 1·29; P = 0·330). Differences in outcomes were similar for prolonged length of hospital stay (uncorrected OR 1·21, 95 per cent c.i. 1·06 to 1·37, P = 0·005; corrected OR for ruptured AAA 1·06, 0·91 to 1·10, P = 0·478), and morbidity outcomes.ConclusionAfter appropriate correction for confounding factors and coding effects, there was no evidence of a significant weekend effect in the treatment of non-elective AAA in the UK.
| S-EPMC5989979 | biostudies-literature
Project description:BACKGROUND:Several studies on the growth rates of abdominal aortic aneurysm (AAA) in Chinese population have been conducted; however, this issue remains unclear. The aim of this study is to systematically review published data of the AAA growth rates among people in China. METHODS:We conducted a comprehensive search of multiple databases to identify all studies of AAA growth in the Chinese population from inception until June 2017. AAA growth rates were combined to yield the growth rates at specified aneurysm diameter ranges, with using a random-effects model or fixed-effects model according to heterogeneity. RESULTS:A total of 8257 studies were initially identified and only 4 studies were eventually included. A random-effects analysis showed that the growth rates of AAA in Chinses population is ranging from 0.18 cm/year to 0.75 cm/year. The pooled mean growth rates among individuals with aneurysm measuring 3.0-3.9 cm, 4.0-5.9 cm and ≧ 6.0 cm in diameter were 0.21 cm/year (95% CI: 0.19 cm/year to 0.23 cm/year), 0.38 cm/year (95% CI: 0.33 cm/year to 0.43 cm/year), and 0.71 cm/year (95% CI: 0.64 cm/year to 0.77 cm/year) respectively. Further analysis found that the pooled mean growth rates for individuals with small AAA (diameters measuring 3.0-4.9 cm) was 0.28 cm/year (95% CI: - 0.06 cm/year to 0.61 cm/year)`and for individuals with large AAA (diameters ≥5.0 cm) was 0.75 cm/year (95% CI: 0.20 cm/year to 1.3 cm/year). Finally, meta-regression showed a strong trend of linear relationship between AAA growth rate and aneurysm diameter. CONCLUSIONS:The growth rates of AAA in the Chinese population increase with AAA enlargement and appear to range from 0.18 cm/year in the smallest AAAs to 0.75 cm/year when the diameter exceeds 6 cm. However, based on current studies, it is difficult to estimate the accurate average AAA growth rate in Chinese patients. More large-scale, high-quality studies are required to achieve that. Overall, AAA growth rate increase with increased aneurysm diameter.
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