Circulating biomarkers of cardiovascular disease are related to aneurysm volume in abdominal aortic aneurysm

Background: Surveillance programs in abdominal aortic aneurysms (AAA) are mainly based on imaging and leave room for improvement to timely identify patients at risk for AAA growth. Many biomarkers are dysregulated in patients with AAA, which fuels interest in biomarkers as indicators of disease progression. We examined associations of 92 cardiovascular disease (CVD)-related circulating biomarkers with AAA and sac volume. Methods: In a cross-sectional analysis, we separately investigated (1) 110 watchful waiting (WW) patients (undergoing periodic surveillance imaging without planned intervention) and (2) 203 patients after endovascular aneurysm repair (EVAR). The Cardiovascular Panel III (Olink Proteomics AB, Sweden) was used to measure 92 CVD-related circulating biomarkers. We used cluster analyses to investigate protein-based subphenotypes, and linear regression to examine associations of biomarkers with AAA and sac volume on CT scans. Results: Cluster analyses revealed two biomarker-based subgroups in both WW and EVAR patients, with higher levels of 76 and 74 proteins, respectively, in one subgroup versus the other. In WW patients, uPA showed a borderline significant association with AAA volume. Adjusting for clinical characteristics, there was a difference of −0.092 (−0.148, −0.036) loge mL in AAA volume per SD uPA. In EVAR patients, after multivariable adjustment, four biomarkers remained significantly associated with sac volume. The mean effects on sac volume per SD difference were: LDLR: −0.128 (−0.212, −0.044), TFPI: 0.139 (0.049, 0.229), TIMP4: 0.110 (0.023, 0.197), IGFBP-2: 0.103 (0.012, 0.194). Conclusion: LDLR, TFPI, TIMP4, and IGFBP-2 were independently associated with sac volume after EVAR. Subgroups of patients with high levels of the majority of CVD-related biomarkers emphasize the intertwined relationship between AAA and CVD. ClinicalTrials.gov Identifier: NCT03703947.</p

Targeted proteomics and metabolomics for biomarker discovery in abdominal aortic aneurysm and post-EVAR sac volume

BACKGROUND AND AIMS: Abdominal aortic aneurysm (AAA) patients undergo uniform surveillance programs both leading up to, and following surgery. Circulating biomarkers could play a pivotal role in individualizing surveillance. We applied a multi-omics approach to identify relevant biomarkers and gain pathophysiological insights. MATERIALS AND METHODS: In this cross-sectional study, 108 AAA patients and 200 post-endovascular aneurysm repair (post-EVAR) patients were separately investigated. We performed partial least squares regression and ingenuity pathway analysis on circulating concentrations of 96 proteins (92 Olink Cardiovascular-III panel, 4 ELISA-assays) and 199 metabolites (measured by LC-TQMS), and their associations with CT-based AAA/sac volume. RESULTS: The median (25th-75th percentile) maximal diameter was 50.0 mm (46.0, 53.0) in the AAA group, and 55.4 mm (45.0, 64.2) in the post-EVAR group. Correcting for clinical characteristics in AAA patients, the aneurysm volume Z-score differed 0.068 (95 %CI: (0.042, 0.093)), 0.066 (0.047, 0.085) and -0.051 (-0.064, -0.038) per Z-score valine, leucine and uPA, respectively. After correcting for clinical characteristics and orthogonalization in the post-EVAR group, the sac volume Z-score differed 0.049 (0.034, 0.063) per Z-score TIMP-4, -0.050 (-0.064, -0.037) per Z-score LDL-receptor, -0.051 (-0.062, -0.040) per Z-score 1-OG/2-OG and -0.056 (-0.066, -0.045) per Z-score 1-LG/2-LG. CONCLUSIONS: The branched-chain amino acids and uPA were related to AAA volume. For post-EVAR patients, LDL-receptor, monoacylglycerols and TIMP-4 are potential biomarkers for sac volume. Additionally, distinct markers for sac change were identified.</p

Targeted proteomics and metabolomics for biomarker discovery in abdominal aortic aneurysm and post-EVAR sac volume

BACKGROUND AND AIMS: Abdominal aortic aneurysm (AAA) patients undergo uniform surveillance programs both leading up to, and following surgery. Circulating biomarkers could play a pivotal role in individualizing surveillance. We applied a multi-omics approach to identify relevant biomarkers and gain pathophysiological insights. MATERIALS AND METHODS: In this cross-sectional study, 108 AAA patients and 200 post-endovascular aneurysm repair (post-EVAR) patients were separately investigated. We performed partial least squares regression and ingenuity pathway analysis on circulating concentrations of 96 proteins (92 Olink Cardiovascular-III panel, 4 ELISA-assays) and 199 metabolites (measured by LC-TQMS), and their associations with CT-based AAA/sac volume. RESULTS: The median (25th-75th percentile) maximal diameter was 50.0 mm (46.0, 53.0) in the AAA group, and 55.4 mm (45.0, 64.2) in the post-EVAR group. Correcting for clinical characteristics in AAA patients, the aneurysm volume Z-score differed 0.068 (95 %CI: (0.042, 0.093)), 0.066 (0.047, 0.085) and -0.051 (-0.064, -0.038) per Z-score valine, leucine and uPA, respectively. After correcting for clinical characteristics and orthogonalization in the post-EVAR group, the sac volume Z-score differed 0.049 (0.034, 0.063) per Z-score TIMP-4, -0.050 (-0.064, -0.037) per Z-score LDL-receptor, -0.051 (-0.062, -0.040) per Z-score 1-OG/2-OG and -0.056 (-0.066, -0.045) per Z-score 1-LG/2-LG. CONCLUSIONS: The branched-chain amino acids and uPA were related to AAA volume. For post-EVAR patients, LDL-receptor, monoacylglycerols and TIMP-4 are potential biomarkers for sac volume. Additionally, distinct markers for sac change were identified.</p

Survival After Uncomplicated EVAR in Octogenarians is Similar to the General Population of Octogenarians Without an Abdominal Aortic Aneurysm

Objective: Long term survival after endovascular aortic aneurysm repair (EVAR) in octogenarians remains unclear. This was evaluated by comparing octogenarians after EVAR with a matched group of octogenarians without an abdominal aortic aneurysm (AAA) from the Rotterdam Study (RS). The influence of complications after EVAR on survival was also studied with the aim of identifying risk factors for the development of complications in octogenarians. Methods: Using propensity score matching (PSM), 83 EVAR octogenarians were matched for comorbidities with 83 octogenarians from the RS, and survival was compared between these two groups using Cox proportional hazard analysis. Then, complications were studied, defined as cardiac or pulmonary, renal deterioration, access site bleeding, acute limb ischaemia or bowel ischaemia, within 30 days of surgery between 83 EVAR octogenarians and 475 EVAR non-octogenarians. Also, the difference in baseline characteristics between the octogenarians with and without complications after EVAR were studied, and survival was compared between the RS controls and the complicated and uncomplicated EVAR octogenarians separately. Results: The total EVAR octogenarian population did not show an increased mortality risk compared with RS octogenarian controls (hazard ratio [HR] 1.28, 95% confidence interval [CI] 0.84–1.97). Post-operative complications occurred in 22 octogenarians (27%) and 59 non-octogenarians (12.4%, p < .001), mainly cardiac, pulmonary, and bleeding complications. All baseline characteristics were similar in the complicated EVAR octogenarians compared with the uncomplicated EVAR octogenarians. After uncomplicated EVAR, octogenarians had a similar survival compared with the RS controls (HR 1.

Clinical outcome and morphologic determinants of mural thrombus in abdominal aortic endografts

Objective Endograft mural thrombus has been associated with stent graft or limb thrombosis after endovascular aneurysm repair (EVAR). This study aimed to identify clinical and morphologic determinants of endograft mural thrombus accumulation and its influence on thromboembolic events after EVAR. Methods A prospectively maintained database of patients treated by EVAR at a tertiary institution from 2000 to 2012 was analyzed. Patients treated for degenerative infrarenal abdominal aortic aneurysms and with available imaging for thrombus analysis were considered. All measurements were performed on three-dimensional center-lumen line computed tomography angiography (CTA) reconstructions. Patients with thrombus accumulation within the endograft's main body with a thickness >2 mm and an extension >25% of the main body's circumference were included in the study group and compared with a control group that included all remaining patients. Clinical and morphologic variables were assessed for association with significant thrombus accumulation within the endograft's main body by multivariate regression analysis. Estimates for freedom from thromboembolic events were obtained by Kaplan-Meier plots. Results Sixty-eight patients (16.4%) presented with endograft mural thrombus. Median follow-up time was 3.54 years (interquartile range, 1.99-5.47 years). In-graft mural thrombus was identified on 30-day CTA in 22 patients (32.4% of the study group), on 6-month CTA in 8 patients (11.8%), and on 1-year CTA in 17 patients (25%). Intraprosthetic thrombus progressively accumulated during the study period in 40 patients of the study group (55.8%). Overall, 17 patients (4.1%) presented with endograft or limb occlusions, 3 (4.4%) in the thrombus group and 14 (4.1%) in the control group (P =.89). Thirty-one patients (7.5%) received an aortouni-iliac (AUI) endograft. Two endograft occlusions were identified among AUI devices (6.5%; overall, 0.5%). None of these patients showed thrombotic deposits in the main body, nor were any outflow abnormalities identified on the immediately preceding CTA. Estimated freedom from thromboembolic events at 5 years was 95% in both groups (P =.97). Endograft thrombus accumulation was associated with >25% proximal aneurysm neck thrombus coverage at baseline (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1-3.3), neck length ≤15 mm (OR, 2.4; 95% CI, 1.3-4.2), proximal neck diameter ≥30 mm (OR, 2.4; 95% CI, 1.3-4.6), AUI (OR, 2.2; 95% CI, 1.8-5.5), or polyester-covered stent grafts (OR, 4.0; 95% CI, 2.2-7.3) and with main component "barrel-like" configuration (OR, 6.9; 95% CI, 1.7-28.3). Conclusions Mural thrombus formation within the main body of the endograft is related to different endograft configurations, main body geometry, and device fabric but appears to have no association with the occurrence of thromboembolic events over time

Iliac Seal Zone Dynamics and Clinical Consequences After Endovascular Aneurysm Repair

__Objective:__ To evaluate the dynamics of the iliac attachment zone after EVAR, and the association with clinical events. __Methods:__ A tertiary institution's prospective EVAR database was searched to identify common iliac arteries at risk. Internally validated measurements were made, using centre lumen line reconstructions. Iliac dilatation and endograft limb retraction were the main endpoints. Associations between dilatation, retraction, oversizing, and distal seal length were investigated. Association with clinical events (sealing or occlusion) was also explored. __Results:__ Of 452 primary EVAR patients treated from 2004 to 2012, 341 were included (mean age 72 years, 12% female, 597 common iliac arteries). Median follow-up was 4.7 years. At 30 days, the mean iliac diameter increased from 14 mm to 15 mm (p < .001). Over follow-up, it increased to 18 mm (p < .001). Iliac dilatation ≥20% occurred in 295 cases (49.4%) and exceeded the implanted endograft diameter in 170 (28.7%). Limb retraction ≥5 mm was identified in 54 patients (9.1%) and was associated with iliac seal complications (p < 0.001). Iliac endograft extension diameter ≥24 mm (OR 3.3, 95% CI 1.7-6.4) and iliac artery dilatation beyond the endograft (OR 2.1, 95% CI 1.2-3.8) were independent risk factors. Overall, there were 34 (5.7%) iliac seal complications. Retraction of the iliac endograft (OR 1.17 per mm, 95% CI 1.10-1.24) and baseline AAA diameter (1.04 per mm, 95% CI 1.01-1.07) were independent risk factors for seal related complications. Greater initial post-operative iliac seal length was protective (OR 0.94 per mm, 95% CI 0.90-0.97). __Conclusions:__ Iliac dilatation and endograft retraction are common findings during follow-up, potentially leading to adverse clinical events. Optimisation of the iliac seal zone providing a long distal seal length and added attention to patients with large aneurysms or receiving ≥24 mm diameter iliac extensions are recommended. Also, long-term surveillance including CTA is advised to reveal and correct loss of seal at the iliac attachment

Differences in mortality, risk factors, and complications after open and endovascular repair of ruptured abdominal aortic aneurysms

Objective/background Endovascular aneurysm repair (EVAR) for ruptured abdominal aortic aneurysm (rAAA) has faced resistance owing to the marginal evidence of benefit over open surgical repair (OSR). This study aims to determine the impact of treatment modality on early mortality after rAAA, and to assess differences in postoperative complications and long-term survival. Methods Patients treated between January 2000 and June 2013 were identified. The primary endpoint was early mortality. Secondary endpoints were postoperative complications and long-term survival. Independent risk factors for early mortality were calculated using multivariate logistic regression. Survival estimates were obtained by means of Kaplan-Meier curves. Results Two hundred and twenty-one patients were treated (age 72 ± 8 years, 90% male), 83 (38%) by EVAR and 138 (62%) by OSR. There were no differences between groups at the time of admission. Early mortality was significantly lower for EVAR compared with OSR (odds ratio [OR]: 0.45, 95% confidence interval [CI]: 0.21-0.97). Similarly, EVAR was associated with a threefold risk reduction in major complications (OR: 0.33, 95%CI: 0.15-0.71). Hemoglobin level <11 mg/dL was predictive of early death for patients in both groups. Age greater than 75 years and the presence of shock were significant risk factors for early death after OSR, but not after EVAR. The early survival benefit of EVAR over OSR persisted for up to 3 years. Conclusion This study shows an early mortality benefit after EVAR, which persists over the mid-term. It also suggests different prognostic significance for preoperative variables according to the type of repair. Age and the presence of shock were risk factors for early death after OSR, while hemoglobin level on admission was a risk factor for both groups. This information may contribute to repair-specific risk prediction and improved patient selection