Editor's Choice - Dual Antiplatelet Therapy Improves Outcome in Diabetic Patients Undergoing Endovascular Femoropopliteal Stenting for Critical Limb Ischaemia.

OBJECTIVE: The purpose of this study was to analyse the effect of dual antiplatelet therapy (DAPT) compared to aspirin on outcome after endovascular interventions in patients with CLI. METHODS: This was a population based retrospective nationwide cohort analysis. Several linked national databases in Sweden: Swedish National Vascular Registry, Prescribed Drug Registry and National Discharge Registry. A total of 1941 patients (median age 79; range 43-103 years; women 58%) were identified with CLI who had undergone primary femoropopliteal endovascular intervention between 2006 and 2012. Of these, 599 (31%) patients were treated after the intervention with DAPT (aspirin and clopidogrel) and 1342 (69%) patients were treated with aspirin only. Percutaneous transluminal angioplasty (PTA) was performed in 1131 patients (58%), stenting in 633 patients (33%), and subintimal angioplasty (SAP) in 177 patients (9%). RESULTS: DAPT was given after PTA, stenting, and SAP to 17% (n = 188), 53% (n = 334), and 44% (n = 77) of the patients, respectively. During the study period, 77 patients (13%) with DAPT and 228 patients (17%) with aspirin underwent a major amputation. Patients receiving DAPT after stenting had a lower rate of amputation (HR 0.56; 95% CI 0.36-0.86) than patients receiving aspirin alone. In the subgroup analysis, the protective effect of DAPT on amputation seemed to be confined to patients with diabetes mellitus receiving a stent (HR 0.26; 95% CI 0.13-0.52; p < .001). DAPT after PTA or SAP did not influence limb salvage, and there was no overall difference in mortality. There was no significant difference in bleeding complications between DAPT and aspirin. CONCLUSION: DAPT with aspirin and clopidogrel compared to aspirin alone was associated with a lower amputation rate but not a higher bleeding rate in patients with diabetes and CLI after endovascular femoropopliteal stenting.

Massive Blood Transfusion in Patients with Ruptured Abdominal Aortic Aneurysm.

OBJECTIVES: The aim was to study blood transfusions and blood product ratios in massively transfused patients treated for ruptured abdominal aortic aneurysms (rAAAs). METHODS: This was a registry based cohort study of rAAA patients repaired at three major vascular centres between 2008 and 2013. Data were collected from the Swedish Vascular Registry, hospitals medical records, and local transfusion registries. The transfusion data were analysed for the first 24 h of treatment. Massive transfusion (MT) was defined as 4 or more units of red blood cell (RBC) transfused within 1 h, or 10 or more RBC units within 24 h. Logistic regression was used to calculate the odds ratio of 30 day mortality associated with the ratios of blood products and timing of first units of platelets (PLTs) and fresh frozen plasma (FFP) transfused. RESULTS: Three hundred sixty nine rAAA patients were included: 80% men; 173 endovascular aneurysm repairs (EVARs) and 196 open repairs (ORs) with median RBC transfusion 8 units (Q1-Q3, 4-14) and 14 units (Q1-Q3, 8-28), respectively. A total of 261 (71%) patients required MT. EVAR patients with MT (n = 96) required less transfusion than OR patients (n = 165): median RBC 10 units (Q1-Q3, 6-16.5) vs. 15 units (Q1-Q3, 9-26) (p = .002), FFP 6 units (Q1-Q3, 2-14.5) vs. 13 units (Q1-Q3, 7-24) (p < .001), and PLT 0 units (Q1-Q3, 0-2) vs. 2 units (Q1-Q3, 0-4) (p = .01). Median blood product ratios in MT patients were FFP/RBC (EVAR group 0.59 [0.33-0.86], OR group 0.84 [0.67-1.2]; p < .001], and PLT/RBC (EVAR 0 [0-0.17], OR 0.12 (0-0.18); p < .001]. In patients repaired by OR a FFP/RBC ratio close to 1 was associated with reduced 30 day mortality (p = .003). The median PLT/RBC ratio was higher during the later part of the study period (p < .001, median test), whereas there was no significant difference in median FFP/RBC ratio (p = .101, median test). CONCLUSION: The majority of rAAA patients undergoing EVAR required MT. EVAR patients treated with MT had lower FFP/RBC and PLT/RBC ratios than OR patients with MT. The mortality risk was lower with FFP/RBC ratio close to 1:1 in open repaired patients requiring MT. The 24 h PLT/RBC ratio increased over the study period.

The Receptor for Advanced Glycation End Products (Rage) and Its Ligands in Plasma and Infrainguinal Bypass Vein.

OBJECTIVE: The aim was to investigate whether RAGE and its ligands are associated with infrainguinal bypass outcome in patients with and without diabetes. METHODS: This was a prospective observational cohort. Patients (n = 68) with (n = 38) and without (n = 30) diabetes undergoing infrainguinal vein bypass for peripheral arterial disease were followed for 3 years. Endosecretory RAGE (esRAGE), S100A12, advanced glycation end products, and carboxymethyl-lysine (CML) were determined in plasma using ELISA. The influence of plasma levels on the main outcome (amputation free survival) was evaluated using Cox proportional hazard analysis. Plasma esRAGE, CML, and S100A12 in healthy controls (n = 30) without cardiovascular disease matched for sex and age were compared with patients, using the Mann-Whitney U test. Veins from bypass surgery procedures were stained and S100A12, RAGE, AGE, and CML were determined using immunohistochemistry. RESULTS: Forty-six patients survived with an intact leg during follow up. Seventeen died (median survival time 702 days, IQR 188-899 day), and six had amputations. High plasma S100A12 was associated with reduced amputation free survival (hazard ratio [HR] 2.99; 95% CI 1.24-7.24) when comparing levels above the 75th percentile with levels below. The increased risk was unchanged adjusting for age, sex, and diabetes. Diabetic patients had higher plasma S100A12 (11.75 ng/mL; 95% CI 8.12-15.38 ng/mL) than non-diabetic patients (5.0141 ng/mL; 95% CI 3.62-6.41 ng/mL), whereas plasma CML, esRAGE, and AGE were similar. Plasma CML and S100A12 were higher in patients than in controls (1.25 µg/mL, 95% CI 1.18-1.32 µg/mL vs. 0.8925 µg/mL, 95% CI 0.82-0.96 µg/mL; and 8.7 µg/mL, 95% CI 6.52-10.95 µg/mL vs. 3.47 µg/mL, 95% CI 2.95-3.99 µg/mL, respectively). The proportion of vein tissue stained for AGE (21%), RAGE (5%), CML (9%) and S100A12 (3%), were similar in patients with and without diabetes. CONCLUSIONS: Plasma S100A12 and CML are elevated in peripheral arterial disease and markers of RAGE and its ligands are found in vein used for bypass. This indicates a role for S100A12, CML, and RAGE in peripheral arterial disease complications by activation of the RAGE system.

External validation of the Swedvasc registry: a first-time individual cross-matching with the unique personal identity number.

OBJECTIVE: To study external validity of the Swedvasc registry concerning numbers of procedures and mortality. MATERIALS AND METHODS: Vascular registry data for carotid, infrainguinal bypass and aortic aneurysm (AAA) procedures were compared to the Swedish Hospital Discharge Register (SHDR) data, and the National Population Registry (for mortality) by matching every individual patient using the unique personal identity numbers (PINs). The time-period studied was 2000-2004 (5 years) for carotid and infrainguinal procedures. A separate analysis was performed for AAA-surgery in 2006. RESULTS: The external validity for carotid, infrainguinal bypass and AAA repair was 93.4%, 93.0% and 93.1%, respectively. The 30-day mortality was 0.86% after carotid and 2.9% after infrainguinal bypass procedures. Mortality was 2.6% after planned and 25.9% after unplanned AAA repair. Although there was a general trend towards inferior outcomes after procedures not registered in the Swedvasc, those procedures were so few that in none of the analyses did the inclusion of non-registered procedures affect general outcomes significantly. Combining data from both registries, the incidence for carotid, infrainguinal bypass and AAA procedures was 7.8, 15.2 and 13.6 per 100,000 person-years, respectively. In the hospital-specific analysis for 2006 it was shown that the non-registered procedures for AAA were localized to one non-compliant county hospital, and small district hospitals not performing elective AAA-surgery but only rare emergency operations. CONCLUSION: The external and internal validity of the Swedvasc registry allows to confidently assess volumes of, and mortality after, vascular surgery in Sweden.

Influence of perioperative blood glucose levels on outcome after infrainguinal bypass surgery in patients with diabetes.

BACKGROUND: High glucose levels are associated with increased morbidity and mortality after coronary surgery and in intensive care. The influence of perioperative hyperglycaemia on the outcome after infrainguinal bypass surgery among diabetic patients is largely unknown. The aim was to determine whether high perioperative glucose levels were associated with increased morbidity after infrainguinal bypass surgery. METHODS: Ninety-one consecutive diabetic patients undergoing primary infrainguinal bypass surgery were identified from a prospective vascular registry. Risk factors, indication for surgery, operative details and outcome data were extracted from the medical records. Exposure to perioperative hyperglycaemia was measured using the area under the curve (AUC) method; the AUC was calculated using all blood glucose readings during the first 48 h after surgery. RESULTS: Multivariable analysis showed that the AUC for glucose (odds ratio (OR) 13.35, first versus fourth quartile), renal insufficiency (OR 4.77) and infected foot ulcer (OR 3.38) was significantly associated with poor outcome (death, major amputation or graft occlusion at 90 days). Similarly, the AUC for glucose (OR 14.45, first versus fourth quartile), female sex (OR 3.49) and tissue loss as indication (OR 3.30) was associated with surgical wound complications at 30 days. CONCLUSION: Poor perioperative glycaemic control was associated with an unfavourable outcome after infrainguinal bypass surgery in diabetic patients.

A randomized prospective study of valvulotome efficacy in in situ reconstructions.

OBJECTIVES: To compare the efficacy of valvulotomes during in situ bypass surgery. DESIGN: A randomized prospective blinded study. MATERIALS AND METHODS: Thirty PAD patients scheduled for infrainguinal greater saphenous vein bypass were randomized to use of adjustable or fixed valvulotomes for valve destruction. Valvulotomy was performed after construction of the proximal anastomosis. The efficacy of valve destruction was determined by angioscopy after completion of the distal anastomosis by a separate blinded examiner. RESULTS: A total of 123 valves were evaluated, 61 after use of an adjustable and 62 with a fixed valvulotome. There was no difference ( p = .88) in number of retained valves between the two groups ( n = 16, 17, respectively). The majority of incompletely destroyed valves were found in the proximal parts of the graft (46%, 13 out of 28). The primary patency at 30 days was 100 and 79%, respectively, p = .09). CONCLUSIONS: No significant difference in efficacy between valvulotomes was found. Both types tend to miss a large proportion of proximal valves.

Plasma levels of cyclic GMP and endothelin in postmenopausal women with unstable coronary artery disease.

Many women with typical anginal chest pain have normal coronary angiograms, which may be due to altered endothelial function. We evaluated the endothelial markers cyclic GMP (cGMP) and immunoreactive endothelin (ir-ET) regarding presence of coronary atherosclerosis in women with clinical signs of unstable coronary artery disease (CAD). Plasma levels of cGMP and ir-ET were determined in 118 patients and 84 controls. Ischaemia was evaluated at an exercise test. Of the patients 20% had normal vessels, 14% insignificant CAD and 66%, significant stenosis at coronary angiography. Mean (95% CI) concentration of cGMP (nmol/l) was higher in patients than in controls (5.05 (4.53; 5.58) vs. 3.79 (3.34; 4.23)). Separating patients according to daily intake of nitroglycerin, only patients with this medication had significantly higher cGMP level (5.73 (4.88; 6.58)), whereas the difference between those without (4.35 (3.76; 4.94)) and controls disappeared. Patients with ischaemia at exercise test had higher cGMP level than those without (6.01 (5.13; 6.88) vs. 4.30 (3.66; 4.94)), even after adjusting for nitroglycerin treatment. ir-ET (pmol/l) was lower in patients with normal vessels than patients with coronary atherosclerosis (0.83 (0.78; 0.88) vs. 0.98 (0.92; 1.04)) and than the control group (0.91 (0.87; 0.94)). The difference between the control group and patients with atherosclerosis was also significant. Patients with unstable CAD and long-term nitroglycerin treatment have increased cGMP level. Patients with exercise-induced ischaemia have higher cGMP level than those without, irrespective of nitroglycerin treatment, which may reflect a general compensatory mechanism. Patients with normal vessels have low level of ir-ET, indicating different mechanisms for ischaemia/angina in these patients compared with patients with atherosclerosis.