Inflammation and TGF-ß Signaling Differ between Abdominal Aneurysms and Occlusive Disease.

Abdominal aortic aneurysms (AAA), are usually asymptomatic until rupture causes fatal bleeding, posing a major vascular health problem. AAAs are associated with advanced age, male gender, and cardiovascular risk factors (e.g. hypertension and smoking). Strikingly, AAA and AOD (arterial occlusive disease) patients have a similar atherosclerotic burden, yet develop either arterial dilatation or occlusion, respectively. The molecular mechanisms underlying this diversion are yet unknown. As this knowledge could improve AAA treatment strategies, we aimed to identify genes and signaling pathways involved. We compared RNA expression profiles of abdominal aortic AAA and AOD patient samples. Based on differential gene expression profiles, we selected a gene set that could serve as blood biomarker or as pharmacological intervention target for AAA. In this AAA gene list we identified previously AAA-associated genes COL11A1, ADIPOQ, and LPL, thus validating our approach as well as novel genes; CXCL13, SLC7A5, FDC-SP not previously linked to aneurysmal disease. Pathway analysis revealed overrepresentation of significantly altered immune-related pathways between AAA and AOD. Additionally, we found bone morphogenetic protein (BMP) signaling inhibition simultaneous with activation of transforming growth factor ß (TGF-ß) signaling associated with AAA. Concluding our gene expression profiling approach identifies novel genes and an interplay between BMP and TGF-ß signaling regulation specifically for AAA.

Higher 30 Day Mortality in Patients with Familial Abdominal Aortic Aneurysm after EVAR.

OBJECTIVES: To determine the influence of a positive family history for aneurysms on clinical success and mortality after endovascular aneurysm repair (EVAR). METHODS: From 2009 to 2011, 1262 patients with abdominal aortic aneurysms (AAA) treated by EVAR were enrolled in a prospective, industry sponsored clinical registry ENGAGE. Patients were classified into familial and sporadic AAA patients according to baseline clinical reports. Clinical characteristics, aneurysm morphology, and follow-up were registered. The primary endpoint was clinical success after EVAR, a composite of technical success and freedom from the following complications: AAA increase >5 mm, type I and III endoleak, rupture, conversion, secondary procedures, migration, and occlusion. Secondary endpoints were the individual components of clinical success, 30 day mortality, and aneurysm related and all cause mortality. RESULTS: Of the 1262 AAA patients (89.5% male and mean age 73.1 years), 86 patients (6.8%) reported a positive family history and were classified as familial AAA. Duration of follow-up was 4.4 ± 1.7 years. Patients with familial AAA were more often female (18.6% vs. 9.9%, p = .012). No difference was observed in aneurysm morphology. There was no significant difference in clinical success between patients with familial and sporadic AAA (72.1% vs. 79.3%, p=.116). Familial AAA patients had a higher 30 day mortality after EVAR (4.7% vs. 1.0%, adjusted HR 5.7, 1.8-17.9, p = .003) as well as aneurysm related mortality (5.8% vs. 1.3%, adjusted HR 5.4, 1.9-14.9, p = .001), while no difference was observed in all cause mortality (19.8% vs. 24.3%, adjusted HR 0.8, 0.5-1.4, p = .501). CONCLUSIONS: The current study shows a higher 30 day mortality after EVAR in familial AAA patients. Future studies should determine the role of family history in AAA treatment, suitability for endovascular or open repair, and on adaptation of post-operative surveillance. For the time being, patients with familial forms of AAA should be considered at higher risk for EVAR and warrant extra vigilance.

Type 2 diabetes mellitus, independent of insulin use, is associated with an increased risk of cardiac complications after vascular surgery.

Previous reports on the prognostic value of diabetes mellitus for cardiac complications after vascular surgery show divergent results, especially in regards to the role of type 2 diabetes as a cardiac risk factor, which remains unclear. The aim of this study was to assess the impact of type 2 diabetes on 30-day cardiac complications after vascular surgery. Patients undergoing elective vascular surgery between 2002 and 2011 were included in this retrospective cohort study. Previous diagnosis of type 1 and 2 diabetes and use of oral glucose-lowering medications and insulin were recorded. Patients with type 1 diabetes were excluded from the analysis. The main outcome parameter was cardiac complications, a composite of cardiovascular death, non-fatal myocardial infarction, congestive heart failure, severe arrhythmia and asymptomatic troponin release within 30 days of surgery. In multivariate analysis, corrections were made for comorbidities, demographics, medication use and surgical risk. Of 1462 patients, 329 (22.5%) patients had type 2 diabetes. Cardiac complications occurred in 155 (13.7%) patients without diabetes and in 68 (20.7%) with type 2 diabetes. In multivariate analysis, type 2 diabetes was associated with a significantly increased risk of 30-day cardiac complications (odds ratio 1.80; 95% confidence interval 1.25 to 2.60). Results were similar for type 2 diabetes patients managed with (odds ratio 1.84; 95% confidence interval 1.01 to 3.37) and without (odds ratio 1.79; 95% confidence interval 1.19 to 2.70) insulin. Type 2 diabetes is an independent risk factor for cardiac complications after vascular surgery and should be treated as such in preoperative cardiac risk stratification.

ABO blood type does not influence the risk of cardiovascular complications and mortality after vascular surgery.

OBJECTIVES: Thrombotic complications are common in vascular surgery patients. Non-O blood types are associated with an increased risk of thrombo-embolic diseases. The aim of this study is to assess the prognostic implications of non-O vs. O blood type regarding 30-day cardiovascular events and long-term mortality after vascular surgery. METHODS: The population of this retrospective cohort study consisted of 4679 patients undergoing elective major vascular surgery between the years 1990 and 2011. Baseline characteristics, ABO blood type and follow-up were obtained. Multivariable regression analyses, adjusted for age, gender, medical history, medication and smoking were used to evaluate the impact of non-O blood type on 30-day cardiovascular events (cardiovascular death, myocardial infarction and stroke) and long-term mortality. RESULTS: Non-O blood type was present in 2627 (56%) patients. Within 30 days after surgery, 129 (4.9%) non-O and 112 (5.5%) O patients suffered a cardiovascular event (P = 0.42). Non-O blood type was not associated with increased mortality during long-term follow-up (adjusted hazard ratio (aHR) 0.96; 95% confidence interval (CI) 0.88-1.04, with a median follow-up of 4 years). Anti-platelet and anticoagulant drugs did not interact with the relationship between ABO blood type and long-term outcome. CONCLUSION: Non-O blood type is not associated with either 30-day cardiovascular complications or long-term mortality in vascular surgery patients.

Vitamin D deficiency may be an independent risk factor for arterial disease.

OBJECTIVES: The aim of this study was to assess the vitamin D status in patients with occlusive or aneurysmatic arterial disease in relation to clinical cardiovascular risk profiles and markers of atherosclerotic disease. METHODS: We included 490 patients with symptomatic peripheral arterial disease (PAD, n = 254) or aortic aneurysm (n = 236). Cardiovascular risk factors and comorbidities carotid intima-media thickness (CIMT), ankle-brachial index (ABI), serum high-sensitive C-reactive protein (hs-CRP) and vitamin D were assessed. Patients were categorised into severely (≤25 nmol l(-1)) or moderately (26-50 nmol l(-1)) vitamin D deficient, vitamin D insufficient (51-75 nmol l(-1)) or vitamin D sufficient (>75 nmol l(-1)). RESULTS: Overall, 45% of patients suffered from moderate or severe vitamin D deficiency. The prevalence of vitamin D deficiency was similar in patients with PAD and those with an aortic aneurysm. Low levels of vitamin D were associated with congestive heart failure and cerebrovascular disease. Adjusting for clinical cardiovascular risk factors, multivariable regression analyses showed that low vitamin D status was associated with higher CIMT (P = 0.001), lower ABI (P < 0.001) and higher hs-CRP (P = 0.022). CONCLUSIONS: The current study shows a strong association between low vitamin D status and arterial disease, independent of traditional cardiovascular risk factors and irrespective of the type of vascular disease, that is, occlusive or aneurysmatic disease.

General anaesthesia is associated with adverse cardiac outcome after endovascular aneurysm repair.

OBJECTIVES: Endovascular aneurysm repair (EVAR) is associated with reduced cardiac stress compared with open repair and is an attractive therapeutic option, especially in cardiac fragile patients. General and locoregional anaesthesia differ regarding the stress response evoked by surgery. The aim of the study is to compare the incidence of cardiac events after EVAR under general or locoregional anaesthesia. METHODS: A total of 302 consecutive patients undergoing infrarenal EVAR between 2002 and 2011 were analysed in this retrospective cohort study. Selection of anaesthesia type was at the discretion of the treating physicians. Medical history, medication use, anaesthesia technique and follow-up were obtained. The study end point was 30-day cardiac complications, including cardiac death, non-fatal myocardial infarction, heart failure, ventricular arrhythmia and troponin T release. Multivariable analysis, adjusted for the propensity of receiving a locoregional technique and cardiac risk factors according to the Revised Cardiac Risk Index, was used to assess the association between cardiac events and anaesthesia type. RESULTS: A total of 173 patients underwent general anaesthesia and 129 locoregional anaesthesia. Obesity, aspirin use and therapeutic anticoagulation were more common in patients receiving general anaesthesia. Cardiac events were observed in 13.3% of patients receiving general anaesthesia and in 4.7% of patients receiving locoregional anaesthesia (P = 0.02), or 6.4% versus .8% (P = 0.02) when asymptomatic troponin release is excluded from the end point. In the general anaesthesia group, two cardiac deaths, six non-fatal myocardial infarctions, two cases of non-fatal heart failure, one non-fatal cardiac arrest and 12 cases of troponin T release were observed, compared with one myocardial infarction and five cases of troponin T release in the locoregional anaesthesia group. In multivariable analysis, general anaesthesia was associated with adverse cardiac events (odds ratio (OR) 3.8; 95%-confidence interval (CI) 1.1-12.9). Non-cardiac complications occurred in 11.6% of patients in both groups (P = 1.00). CONCLUSION: General anaesthesia was associated with an increased risk of cardiac events in EVAR, compared with locoregional anaesthesia.