Metformin Prescription Associated with Reduced Abdominal Aortic Aneurysm Growth Rate and Reduced Chemokine Expression in a Swedish Cohort.

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.

Plasma D-dimer as a predictor of intraluminal thrombus burden and progression of abdominal aortic aneurysm.

AIM: Intraluminal thrombus (ILT) is presented in most abdominal aortic aneurysms (AAAs) and is suggested to promote AAA expansion. D-dimer, a breakdown product in the thrombus remodeling, may have prognostic value for AAA. This study investigated the interrelation between plasma D-dimer level, ILT volume, AAA size and progression. MAIN METHODS: This was a retrospective observational study that involved 181 patients with infra-renal AAA. They were divided into small and large AAA groups according to AAA diameter. 24 of them had repeated abdominal computed tomography angiography (CTA) scan and were divided into slow-growing and fast-growing AAA groups according to the median value of AAA growth rate. Baseline and follow-up plasma D-dimer level, maximum diameter of AAA, total infra-renal aortic volume and ILT volume were analyzed. KEY FINDINGS: Plasma D-dimer level was positively correlated with ILT volume (R = 0.382, P < 0.001) and maximum diameter of AAA (R = 0.442, P < 0.001). Increasing value of plasma D-dimer was positively associated with the accelerated growth rate of AAA (R = 0.720, P < 0.01). ILT volume showed positive correlation with maximum diameter (R = 0.859, P < 0.001) and growth rate of AAA (R = 0.490, P < 0.05). After adjusting the baseline ILT volume, the positive correlations remained to be statistically significant between plasma D-dimer level and AAA size (R = 0.200, P < 0.05), as well as increasing value of plasma D-dimer and growth rate of AAA (R = 0.642, P < 0.05). SIGNIFICANCE: Plasma D-dimer level reflected ILT burden in AAAs. Plasma D-dimer level and ILT volume were positively correlated with AAA size. Increasing value of plasma D-dimer and baseline ILT volume could be predictors of AAA progression.

A preoperative risk score for transfusion in infrarenal endovascular aneurysm repair to avoid type and cross.

OBJECTIVE: Preoperative type and cross are often routinely ordered before elective endovascular aneurysm repair (EVAR), but the cost of this practice is high, and transfusion is rare. We therefore aimed to stratify patients by their risk of transfusion to identify a cohort in whom a type and screen would be sufficient. METHODS: We queried the targeted vascular module of the National Surgical Quality Improvement Program (NSQIP) for all elective EVARs from 2011 to 2015. We included only infrarenal aneurysms and excluded ruptured aneurysms and patients transfused within 72 hours preoperatively. Two-thirds of the cases were randomly assigned to a model derivation cohort and one third to a validation cohort. We created and subsequently validated a risk model for transfusion within the first 24 hours of surgery (including intraoperatively), using logistic regression. RESULTS: Between 2011 and 2015, there were 4875 patients who underwent elective infrarenal EVAR, only 221 (4.5%) of whom received a transfusion within 24 hours of surgery. The frequency of transfusion during the study period declined monotonously from 6.5% in 2011 to 3.2% in 2015. The factors independently associated with transfusion were preoperative hematocrit <36% (odds ratio [OR], 3.4 [95% confidence interval, 2.1-5.4]; P < .001), aortic diameter (per centimeter increase: OR, 1.2 [1.03-1.4]; P = .02), preoperative dependent functional status (OR, 2.5 [1.1-5.5]; P = .03), and chronic obstructive pulmonary disease (OR, 1.7 [1.04-2.9]; P = .04). A risk prediction model based on these criteria produced a C statistic of 0.69 in the prediction cohort and 0.76 in the validation cohort and a Hosmer-Lemeshow goodness of fit of 0.62 and 0.14, respectively. A score of <3 of 9, corresponding to a <5% probability of transfusion, would avoid preoperative type and cross in 86% of patients. Of the 4203 patients (86%) with a hematocrit >36%, only 6 (0.1%) had a risk score of >3. CONCLUSIONS: Perioperative transfusion for EVAR is becoming increasingly uncommon and is predicted well by a transfusion risk score or simply a hematocrit of <36%. Application of this risk score would avoid unnecessary type and cross in the majority of patients, leading to significant savings in both time and cost.

Assessment of biomarkers and predictive model for short-term prospective abdominal aortic aneurysm growth-A pilot study.

BACKGROUND: Abdominal aortic aneurysms (AAAs) are currently followed with serial ultrasound or computed tomography scanning diameter measurements, but evidence shows that AAA expansion is mostly discontinuous and quite unpredictable in any given patient. A reliable predictive model of AAA growth and/or rupture risk could help individualize treatment, follow-up protocols, and cost-effectiveness. Our objective is to set a predictive model of short-term prospective AAA growth, after clinical, serologic, and anatomic data. METHODS: A prospective pilot cohort was designed. We recruited 96 consecutive, asymptomatic, infrarenal, atherosclerotic AAA patients. We registered clinical data (age, gender, cardiovascular risk factors, comorbidity, and statin intake), baseline aortic diameter, prospective 1-year AAA growth, and the concentration of metalloprotease-2, metalloprotease-9, cystatin C, α1-antitrypsin, myeloperoxidase, monocyte chemoattractant protein-1, homocysteine, D-dimer, plasmin-antiplasmin complex (PAP), and C-reactive protein in peripheral blood at the time of baseline assessment. With all these data, we elaborated predictive models for 1-year AAA growth assessed both as a continuous variable (mm/year) and a dichotomic one (defined as stability, if AAA growth rate was ≤2 mm/year, versus expansion, if AAA growth rate was >2 mm/year), using simple and multiple linear and logistic regression. RESULTS: The multivariate model confirmed the independent impact of D-dimer levels and chronic renal failure (CRF) on increasing AAA growth rates. Every increase by 1 ng/mL in the plasma concentration of D-dimer was related to a mean 1-year increase of 0.0062 mm in the AAA growth. Likewise, CRF increased the 1-year prospective AAA growth by a mean of 2.95 mm. When we assessed AAA growth as a dichotomic variable, the increase in the peripheral concentrations of PAP slightly increased the risk of AAA expansion (odds ratio [OR]: 1.01; 95% confidence interval [CI]: 1.00-1.02), but the presence of CRF increased the risk dramatically (OR: 14,523.62; 95% CI: 0-7.39E+40). CONCLUSIONS: Plasma D-dimer and PAP levels seem promising biomarkers of short-term AAA activity. CRF is an important independent prognostic factor of AAA expansion. The dichotomic classification of AAA growth, as stability versus progression, can be useful in the development of management models and their clinical application.

[Assessment of osteopontin and osteoprotegerin levels in abdominal aortic aneurysm patients]. / Ocena stezenia osteopontyny i osteoprotegryny u chorych z tetniakiem aorty brzusznej.

Abdominal Aortic Aneurysm (AAA) is multifactorial disease with unknown ethiology. Among the theories on the pathogenesis of AAA are some ge. netic factors, infections, disorders in connective tissue (collagenosis), arteriosclerosis, inflammation, incorrect immune response (autoimmunity). It was discovered that crucial for AAA development is intense inflammatory reaction combined with high proteolytic activity. Recent evidence confirmed the association between osteopontin (OPN) and osteoprotegerin (OPG) levels and cardiovascular diseases and arterio. sclerosis. The aim of this work was assessment of plasma levels of OPN and OPG in the group of the patients with AAA and correlation of results with clinical parameters, "classical" risk factors for development of AAA, arteriosclerosis and morbidity. The reference group consist of the patients with Leriche Syndrome (LS). The OPG level was assessed in plasma and OPN levels were assessed in plasma and urine. Plasma OPG levels were higher in AAA group than in LS group (difference not statistically significant, p = 0.0549). It was statistically significant positive correlation between plasma OPN levels and CRP levels in the groups of AAA and LS patients. It was not any association between plasma OPG and OPN levels and abdominal aortic diameter. Plasma OPG levels correlated positively with the existence of coronary artery disease in AAA patients. Insignificant, but higher levels of this protein were found also in a group of AAA patient with myocardial infarction. In LS group we found statistically significant positive association between plasma OPG levels and patient with stroke. However, in AAA patients with incidence of stroke, we found higher plasma levels of OPN. Interestingly, there was not any association between OPN levels in the urine and clinical parameters, risk factors and morbidity, including kidney diseases. inflammatory role of OPN and depicts better reflection of inflammatory reaction of OPN than OPG in both group of patients. Plasma OPG levels in AAA patients are more associated with coronary artery disease than with peripheral artery disease, what is characteristic for LS patients. Lack of association of urine OPN levels with above mentioned parameters suggest minor importance of this urine protein in clinical condition evaluation of patients with AAA and advanced arteriosclerosis.

Assessment of renal function by means of cystatin C following standard and fenestrated endovascular aneurysm repair.

BACKGROUND: Cystatin C (Cyst C) is more sensitive marker for early renal injury. However, serum creatinine (sCr) and estimated glomerular filtration rate (eGFR) are still used as the standard renal markers after endovascular aortic aneurysm repair (EVAR). The goal of this study was to compare the efficacy of Cyst C, sCr, and eGFR as markers of renal function after EVAR. PATIENTS AND METHODS: This study examined 29 patients (27 men) with a mean age of 76.9 years (range, 55-89 years) undergoing standard (n = 19) and fenestrated (n = 10) EVAR for abdominal aortic aneurysm (AAA) of mean diameter 6.9 cm (range, 5.5-10 cm). Cyst C and sCr were measured and eGFR calculated before and 1 day and 1, 6, and 12 months after EVAR. RESULTS: At 24 hours after procedure, a significant increase in Cyst C (P < 0.005) and sCr (P = 0.028) and significant decrease in eGFR (P = 0.04) were seen. Cyst C continued to increase and was significantly higher at 1 (P < 0.002), 6 (P < 0.005), and 12 (P < 0.005) months compared with baseline. By contrast, sCr and eGFR did not show any significant change at 1, 6, and 12 months from the baseline level. Cyst C increased significantly postoperatively regardless of the baseline renal function. None of the patients required renal replacement therapy. CONCLUSIONS: EVAR is associated with a significant increase in Cyst C starting 24 hours after the procedure and is maintained for 12 months. sCr and eGFR only show significant change at 24 hours and therefore may underestimate long-term renal damage after EVAR.

A global assessment of the inflammatory response elicited upon open abdominal aortic aneurysm repair.

The inflammatory response during elective open infrarenal abdominal aortic aneurysm repair and its impact on outcome is investigated. Twenty high-risk patients were enrolled, and blood samples were obtained at 8 perioperative time points. Endotoxin, cytokines (tumor necrosis factor-alpha and interleukin-1beta, and interleukin-6), CD11b expression, and nitric oxide were measured. Peak endotoxin levels occurred within 30 minutes of reperfusion and were higher among patients developing complications. Interleukin-6 levels increased during reperfusion, reaching a peak on the first postoperative day. Interleukin-6 increase correlated with aortic clamp time and morbidity. CD11b expression increased 30 minutes after reperfusion, and this effect was greater among patients who developed complications. Endotoxin may be important in the pathogenesis of multiple organ dysfunction syndrome. Activated neutrophils may have a central role in tissue injury after reperfusion. Intraoperative CD11b upregulation may be an early marker for postoperative complications after infrarenal abdominal aortic aneurysm repair.

Coated prostheses are associated with prolonged inflammation in aortic surgery: a cost analysis.

This prospective study was conducted to compare inflammatory responses between patients receiving coated and uncoated vascular prostheses, and to examine their effect on length of stay and cost of patients undergoing abdominal aortic aneurysmectomy. Patients undergoing elective vascular reconstruction of an abdominal aortic aneurysm were assigned randomly to coated-graft or uncoated-graft groups (n = 20, for each group). Interleukin (IL)-6, granulocyte elastase, white blood cell count, C-reactive protein (CRP), and body temperature (BT) were prospectively recorded preoperatively and on postoperative days (PODs) 1, 3, 7, and 14. In-hospital stay and hospitalized costs were also analyzed. IL-6 and CRP concentrations in the coated-graft group were higher than those in the uncoated-graft group (P = 0.01 and 0.05). BT was more frequently elevated >37 degrees C at POD 14 in the coated-graft group than in the uncoated-graft group (P =0.03). Discharge was delayed, and overall hospitalization cost was higher in the coated-graft group than in the uncoated group (17.6 vs. 13.5 days, and 2 010 000 vs. 1 780 000 yen, P = 0.006 and P = 0.002, respectively). Coated vascular prosthesis demonstrated more profound inflammatory reaction than noncoated prosthesis, postoperatively.

Intraoperative autotransfusion for repair of unruptured aneurysms of the infrarenal abdominal aorta. A multicenter study of 203 patients. Association Universitaire de Recherche en Chirurgie (AURC).

BACKGROUND: The goals of this study were to evaluate the costs and savings of intra- and postoperative blood transfusions as well as the potential biological modifications associated with the use of intraoperative blood salvage. METHODS: Intraoperative autotransfusion (IOAT) with wash-out was prospectively studied during the repair of unruptured aneurysms of infrarenal abdominal aorta in 203 patients operated on in 13 institutions. RESULTS: The mean quantity of blood retrieved was 688+/-468 mL The mean quantity of blood derivatives and intraoperative solutes used for repletion was 4,261 ml, ranging from 1,723 ml between days 0 to D2 to 562 ml from D3 to D8. Ninety-eight patients did not receive any blood derivatives at all. Thirty-five patients received plasma to correct coagulation factors. The quantity of autotransfused globular concentrate was less than 500 ml in 89 patients. CONCLUSIONS: IOAT precluded the need for transfusion of homologous globular concentrates, particularly in those patients who had bled most. On average, more than two globular concentrates were recuperated. Use of IOAT led to financial savings. Perioperative bleeding is not the only factor that intervenes in the decision to transfuse globular concentrates. Postoperative dilution is the most important factor as attested by the amount of protides and the hematocrit. Coagulation factors are modified but remain compatible with normal hematosis in 83% of patients undergoing operation.