Cardiovascular risk in patients with small abdominal aortic aneurysms

Background: Abdominal aortic aneurysm (AAA) is a cardiovascular health problem. Ultrasound screening has been shown to reduce the risk of AAA-related, but not all-cause, mortality. The recent introduction of screening in several countries has meant that thousands of patients with a small AAA (<5·5cm) that does not require immediate treatment are diagnosed annually. We sought to investigate the cardiovascular profiles of patients with ectatic aortas and assess whether participation in screening reduces cardiovascular risk. Methods: We used three sets of data: from the National Health Service AAA Screening Programme (NAAASP) during the 2013–14 round that were linked with Health Episode Statistics (HES) (235 409 individuals); a subset of the Framingham Study population who had an abdominal CT scan in 2004–05 and were followed up for 10 years (1383 individuals); and data for patients with a small AAA who had been in surveillance for at least 1 year in the UK Aneurysm Growth Study (UKAGS) (384 individuals) or from a national UK audit (1538 individuals), to assess cardiovascular risk and events. Findings: In the linked NAAASP–HES cohort, cardiovascular mortality was 0·30% (95% CI 0·28–0·32) for individuals with an abdominal aortic diameter of less than 2·5 cm; 0·81% (0·51–1·11) for those between 2·5 and 2·9 cm; and 1·30% (0·90–1·71) for those less than 3·0 cm. Death from a cardiovascular event was more likely for individuals with a small AAA than for those without AAA (risk ratio 4·33, 95% CI 3·15–5·97). In the Framingham cohort, abdominal aortic diameter was independently associated with cardiovascular events (hazard ratio [HR] 1·1, 95% CI 1·02–1·18; p<0·0001). An abdominal aortic diameter of more than 2·5 cm was also associated with cardiovascular events (HR 7·6, 95% CI 5·1–11·3; p<0·0001). In the UKAGS and audit populations, patients were not more likely to take antiplatelet agents or statins after entering screening surveillance; cholesterol concentrations and blood pressure also increased. Interpretation: In these contemporary large cohorts of patients with small AAA, cardiovascular events and death were common and were the leading cause of death. The implication is that patients are not more likely to receive cardiovascular protection if they enter screening or surveillance with existing protocols. Cardiovascular risk reduction interventions should be implemented in screening programmes in the future

Sex-related trends in mortality after elective abdominal aortic aneurysm surgery between 2002 and 2013 at National Health Service hospitals in England: less benefit for women compared with men

Aims: To quantify the difference in long-term survival and cardiovascular morbidity between women and men undergoing elective abdominal aortic aneurysm (AAA) repair at National Health Service hospitals in England. Methods and results: Patients having elective repair of AAA were reviewed using the Hospital Episode Statistics and Office for National Statistics (ONS) datasets. The primary outcome measure was 30-day mortality and the secondary outcomes were 1-year, 5-year, and aortic-related mortality and post-operative complication rates. We used logistic regression and survival models to assess risk factors on the primary and secondary outcomes. Between 1 April 2002 and 31 March 2013, a total of 31 090 patients (4795 women and 26 295 men) underwent open AAA repair. Between 1 January 2006 and 31 March 2013, a total of 16 777 patients (2036 women and 14 741 men) underwent endovascular aneurysm repair (EVAR). All-cause and aortic-related mortalities at 30 days, 1 year, and 5 years were all higher in women, despite a lower prevalence of pre-operative cardiovascular risk factors. Female sex was a significant independent risk factor for 30-day mortality in both open repair [odds ratio (OR) 1.39; 95% confidence interval (CI) 1.25–1.56; P < 0.001] and EVAR (OR 1.57; 95% CI 1.23–2.00; P < 0.001) groups. Based on an all-cause long-term survival model, conditional on 30-day survival, the estimated hazard for women in the open repair group was significantly (P = 0.006) higher than men, but the sex difference was not significant in the EVAR group (P = 0.356). In the open repair group, women had significantly (P < 0.001) higher cumulative incidence probabilities for both aortic-related mortality and other-cause mortality. In the EVAR group, women had significantly (P < 0.001) higher mean cumulative incidence probabilities for the aortic-related mortality compared with men, but not for the other-cause mortality (P = 0.235). Conclusion: Women undergoing elective AAA repair at National Health Service hospitals in England had increased short- and long-term mortality and post-operative morbidity compared with men. These findings can be used to improve pre-operative counselling for women undergoing AAA repair, and highlight the need for female-specific pre-, peri-, and post-operative management strategies

Renal Function is the Main Predictor of Acute Kidney Injury after Endovascular Abdominal Aortic Aneurysm Repair.

BACKGROUND: Postoperative acute kidney injury (AKI) may occur in up to 18% of elective endovascular abdominal aortic aneurysm repair (EVAR) and has been associated with poor outcome; however, it is not clear which patients are at highest risk, to target renoprotection effectively. We sought to determine the predictive factors of AKI after elective EVAR. METHODS: Overall, 947 patients undergoing elective EVAR between January 2004 and December 2014 were analyzed, using prospectively collected data. Postoperative AKI was defined by serum creatinine change within 48 hr, as per the Kidney Disease Improving Global Outcomes guidelines. Cardiovascular and kidney-disease risk factors were entered in univariate and multivariate analyses to assess influence on AKI development. RESULTS: Overall, 167 (17.6%) patients developed AKI but only 2 patients required dialysis perioperatively. At multivariate analysis, adjusted for established AKI-risk factors and parameters that differed between groups at baseline, preoperative estimated glomerular filtration rate (eGFR; as per the chronic kidney disease epidemiology [CKD] formula); odds ratio (OR): 1.02 (per unit decrease); 95% confidence interval (CI): 1.003-1.041; P = 0.025; and chronic kidney disease (CKD) stage > 2 (OR: 1.28; 95% CI: 1.249-2.531, P = 0.001) were associated with development of AKI. CONCLUSIONS: AKI was common after elective infrarenal EVAR and preoperative renal function appears to be the main factor associated with AKI. Patients with a low eGFR need to be targeted with more aggressive renal protection

Investigation of the effect of genetic polymorphisms on aortic growth in patients with abdominal aortic aneurysm (AAA)

Investigation of the effect of genetic polymorphisms on aortic growth in patients with abdominal aortic aneurysm (AAA

Cardiovascular risk profile and management of risk factors in patients with small abdominal aortic aneurysm

Cardiovascular risk profile and management of risk factors in patients with small abdominal aortic aneurys

Type II endoleaks: challenges and solutions.

Type II endoleaks are the most common endovascular complications of endovascular abdominal aortic aneurysm repair (EVAR); however, there has been a divided opinion regarding their significance in EVAR. Some advocate a conservative approach unless there is clear evidence of sac expansion, while others maintain early intervention is best to prevent adverse late outcomes such as rupture. There is a lack of level-one evidence in this challenging group of patients, and due to a low event rate of complications, large numbers of patients would be required in well-designed trials to fully understand the natural history of type II endoleak. This review will discuss the imaging, management, and outcome of patients with isolated type II endoleaks following infra-renal EVAR

SMYD2 promoter DNA methylation is associated with abdominal aortic aneurysm (AAA) and SMYD2 expression in vascular smooth muscle cells

Background: Abdominal aortic aneurysm (AAA) is a deadly cardiovascular disease characterised by the gradual, irreversible dilation of the abdominal aorta. AAA is a complex genetic disease but little is known about the role of epigenetics. Our objective was to determine if global DNA methylation and CpG-specific methylation at known AAA risk loci is associated with AAA, and the functional effects of methylation changes. Results: We assessed global methylation in peripheral blood mononuclear cell DNA from 92 individuals with AAA and 93 controls using enzyme-linked immunosorbent assays, identifying hyper-methylation in those with large AAA and a positive linear association with AAA diameter (P < 0.0001,R2 = 0.3175).We then determined CpG methylation status of regulatory regions in genes located at AAA risk loci identified in genome-wide association studies, using bisulphite next-generation sequencing (NGS) in vascular smooth muscle cells (VSMCs) taken from aortic tissues of 44 individuals (24 AAAs and 20 controls). InIL6R, 2 CpGs were hyper-methylated (P = 0.0145); inERG, 13 CpGs were hyper-methylated (P = 0.0005); inSERPINB9, 6 CpGs were hypo-methylated (P = 0.0037) and 1 CpG was hyper-methylated (P = 0.0098); and inSMYD2, 4 CpGs were hypo-methylated (P = 0.0012).RT-qPCR was performed for each differentially methylated gene on mRNA from the same VSMCs and compared with methylation. This analysis revealed downregulation ofSMYD2andSERPINB9in AAA, and a direct linear relationship betweenSMYD2promoter methylation andSMYD2expression (P = 0.038). Furthermore, downregulation ofSMYD2at the site of aneurysm in the aortic wall was further corroborated in 6 of the same samples used for methylation and gene expression analysis with immunohistochemistry. Conclusions: This study is the first to assess DNA methylation in VSMCs from individuals with AAA using NGS, and provides further evidence there is an epigenetic basis to AAA. Our study shows that methylation status of theSMYD2promoter may be linked with decreasedSMYD2expression in disease pathobiology. In support of our work, downregulatedSMYD2has previously been associated with adverse cardiovascular physiology and inflammation, which are both hallmarks of AAA. The identification of such adverse epigenetic modifications could potentially contribute towards the development of epigenetic treatment strategies in the future

Impact of hospital volume on outcomes following treatment of thoracic aortic aneurysms and type-B dissections

Previous research suggests an association between hospital volume and outcomes in high-risk surgical pathologies. The association between hospital volume and outcomes in patients with isolated descending thoracic aortic aneurysms (DTAAs) and type-B thoracic aortic dissections (TBADs) is conflicting. We aimed to investigate this in a literature review and meta-analysis. A systematic review of the literature was performed to identify studies reporting mortality and morbidity following repair (elective or emergency) of DTAA and/or TBAD using the Medline and Embase Databases (2000-2015). Hospital volume was assessed based on the number of patients treated per institution: low volume (1-5 cases per year), medium volume (6-10) and high volume (>10). The primary outcome of interest was all-cause mortality during inpatient stay and at 30 days. Eighty-four series of non-dissecting DTAA or TBAD were included in data synthesis (4219 patients; mean age: 62 years; males: 73.5%). For all patients (emergency and elective) undergoing DTAA repair, in-hospital mortality was 8% [95% confidence interval (CI): 6-8%]. Results were not superior in high-volume centres (8 vs 6 vs 11% for high-, medium- and low-volume, respectively). Sub-analyses for emergency and elective repairs showed no significant differences. For TBAD repairs, in the combined population (emergency and elective), results reached borderline significance (P = 0.0475), favouring high-volume centres (6 vs 11 vs 14%), but this association disappeared when emergency and elective repairs were analysed separately. Nine series reported outcomes at 1 year and 5 series followed DTAA and 18 TBAD treatment. No meaningful long-term comparisons were possible due to the lack of data. No significant associations were detected between hospital volume and subsequent mortality following DTAA or TBAD treatment. Data were heterogeneous and long-term results were scarcely reported. A well-designed longitudinal study of sufficient size is required to inform future strategies in this area

Intervention Associated Acute Kidney Injury and Long-Term Cardiovascular Outcomes

BACKGROUND: Acute kidney injury (AKI) has been associated with all-cause short- and long-term mortality. However, its association with cardiovascular (CV) events remains unclear. We sought to investigate this in patients undergoing open (OAR) or endovascular (EVAR) abdominal aortic aneurysm repair, as they are likely to develop both AKI and CV morbidity. A meta-analysis was subsequently performed to confirm this in other CV-interventions. METHODS: AKI-incidence was assessed in a multicentre-cohort of 1,068 patients undergoing EVAR (947 individuals) or OAR electively using the 'Acute Kidney Injury Network' criteria. A composite-endpoint was used, consisting of non-fatal myocardial infarction (MI), stroke, vascular event, hospitalisation due to heart failure and CV death. A systematic literature review identified studies reporting AKI-incidence and CV events. Risk ratios (RRs) at 1 and 5 years were combined using meta-analysis. RESULTS: During a median follow-up of 62 months (range 11-121), AKI was associated with CV events on adjusted (for CV risk-factors) analyses (Incidence 36% of EVAR, 32% of OAR patients; hazard ratio 1.73, 95% CI 1.06-3.39, p=0.03) for the overall population. In the meta-analysis, 7 studies reported incidence of MI on 23,936 patients 1-year after coronary intervention (PCI) with a pooled RR of 1.76 (95% CI 1.45-2.83, p<0.001); at 2 years, 3 studies reported MI incidence on 17,773 patients after PCI with a pooled RR of 1.34 (95% CI 1.10-1.63, p=0.003). MI-incidence was reported 5 years after cardiac surgery by 3 studies (33,701 patients) with a pooled RR of 1.60 (95% CI 1.43-1.81). CONCLUSION: AKI is associated with long-term CV events after surgery or endovascular intervention

HYDration and Bicarbonate to Prevent Acute Renal Injury After Endovascular Aneurysm Repair With Suprarenal Fixation: Pilot/Feasibility Randomised Controlled Study (HYDRA Pilot Trial).

OBJECTIVE/BACKGROUND: Up to 25% of patients undergoing elective endovascular aneurysm repair (EVAR) develop acute kidney injury (AKI), which is associated with short and long-term morbidity and mortality. There is no high quality randomised evidence regarding prevention of EVAR related AKI. METHODS: A novel AKI prevention strategy for EVAR was devised, based on best evidence and an expert consensus group. This included a bolus of high dose sodium bicarbonate (NaHCO3) immediately before EVAR (1 mL/kg of 8.4% NaHCO3) and standardised crystalloid based hydration pre- and post-EVAR. A pilot/feasibility randomised controlled trial (RCT) was performed in two centres to assess the safety of the intervention, potential impact on AKI prevention, and feasibility of a national RCT; the primary end point was the proportion of eligible patients recruited into the study. AKI was defined using "Kidney Disease Improving Global Outcomes" and "Acute Kidney Injury Network" criteria based on National Institute for Health and Clinical Excellence AKI recommendations, using serum creatinine and hourly urine output. RESULTS: Fifty-eight patients (84% of those screened; median age 75 years [range 57-89 years], 10% female) were randomised to receive the standardised intravenous hydration with (intervention) or without (control) NaHCO3. Groups were comparable in terms of AKI risk factors; 56 of 58 participants had a device with suprarenal fixation. Overall, 33% of patients in the control arm developed AKI versus 7% in the intervention arm (as treated analysis). None of the patients receiving NaHCO3developed a serious intervention related adverse event; five patients did not attend their 30 day follow-up. CONCLUSION: Bolus high dose NaHCO3and hydration is a promising EVAR related AKI prevention method. This trial has confirmed the feasibility of delivering a definitive large RCT to confirm the efficacy of this novel intervention, in preventing EVAR related AKI