ABSTRACT
OBJECTIVE: Experimental studies suggest that fenofibrate prevents abdominal aortic aneurysm (AAA) development by lowering aortic osteopontin (OPN) concentration and reducing the number of macrophages infiltrating the aortic wall. The current study examined the effects of a short course of fenofibrate on AAA pathology in people with large AAAs awaiting aortic repair. METHODS: This randomised double blind parallel trial included male and female participants aged ≥ 60 years who had an asymptomatic AAA measuring ≥ 50 mm and were scheduled to undergo open AAA repair. Participants were allocated to fenofibrate (145 mg/day) or matching placebo for at least two weeks before elective AAA repair. Blood samples were collected at recruitment and immediately prior to surgery. AAA biopsies were obtained during aortic surgery. The primary outcomes were (1) AAA OPN concentration; (2) serum OPN concentration; and (3) number of AAA macrophages. Exploratory outcomes included circulating and aortic concentrations of other proteins previously associated with AAA. Outcomes assessed at a single time point were compared using logistic regression. Longitudinal outcomes were compared using linear mixed effects models. RESULTS: Forty-three participants were randomised. After three withdrawals, 40 were followed until the time of surgery (21 allocated fenofibrate and 19 allocated placebo). As expected, serum triglycerides reduced significantly from recruitment to the time of surgery in participants allocated fenofibrate. No differences in any of the primary and exploratory outcomes were observed between groups. CONCLUSION: A short course of 145 mg of fenofibrate/day did not lower concentrations of OPN or aortic macrophage density in people with large AAAs.
Subject(s)
Aorta, Abdominal/drug effects , Aorta, Abdominal/surgery , Aortic Aneurysm, Abdominal/therapy , Fenofibrate/administration & dosage , Vascular Surgical Procedures , Aged , Aorta, Abdominal/metabolism , Aorta, Abdominal/pathology , Aortic Aneurysm, Abdominal/blood , Aortic Aneurysm, Abdominal/pathology , Biomarkers/blood , Disease Progression , Double-Blind Method , Drug Administration Schedule , Female , Fenofibrate/adverse effects , Humans , Macrophages/pathology , Male , Middle Aged , Osteopontin/blood , Queensland , Time Factors , Treatment Outcome , Triglycerides/blood , Vascular Remodeling/drug effects , Vascular Surgical Procedures/adverse effectsABSTRACT
OBJECTIVE: Endoleak is a common complication of endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA) but can be detected only through prolonged follow-up with repeated aortic imaging. This study examined the potential for circulating matrix metalloproteinase 9 (MMP9), osteoprotegerin (OPG), D-dimer, homocysteine (HCY), and C-reactive protein (CRP) to act as diagnostic markers for endoleak in AAA patients undergoing elective EVAR. METHODS: Linear mixed-effects models were constructed to assess differences in AAA diameter after EVAR between groups of patients who did and did not develop endoleak during follow-up, adjusting for potential confounders. Circulating MMP9, OPG, D-dimer, HCY, and CRP concentrations were measured in preoperative and postoperative plasma samples. The association of these markers with endoleak diagnosis was assessed using linear mixed effects adjusted as before. The potential for each marker to diagnose endoleak was assessed using receiver operating characteristic curves. RESULTS: Seventy-five patients were included in the study, 24 of whom developed an endoleak during follow-up. Patients with an endoleak had significantly larger AAA sac diameters than those who did not have an endoleak. None of the assessed markers showed a significant association with endoleak. This was confirmed through receiver operating characteristic curve analyses indicating poor diagnostic ability for all markers. CONCLUSIONS: Circulating concentrations of MMP9, OPG, D-dimer, HCY, and CRP were not associated with endoleak in patients undergoing EVAR in this study.
Subject(s)
Aortic Aneurysm, Abdominal/surgery , Blood Vessel Prosthesis Implantation/adverse effects , C-Reactive Protein/metabolism , Endoleak/blood , Endovascular Procedures/adverse effects , Fibrin Fibrinogen Degradation Products/metabolism , Homocysteine/blood , Matrix Metalloproteinase 9/blood , Osteoprotegerin/blood , Aged , Aged, 80 and over , Aortic Aneurysm, Abdominal/blood , Aortic Aneurysm, Abdominal/diagnostic imaging , Aortography/methods , Area Under Curve , Australia , Biomarkers/blood , Computed Tomography Angiography , Endoleak/diagnostic imaging , Endoleak/etiology , Female , Humans , Linear Models , Male , Predictive Value of Tests , Prospective Studies , ROC Curve , Registries , Risk Factors , Treatment OutcomeABSTRACT
Cell-mediated immunity to Burkholderia pseudomallei, the causative agent of melioidosis, provides protection from disease progression. An indirect haemagglutination assay was used to detect antibodies to B. pseudomallei in 1500 healthy donors in an endemic region of Australia. Lymphocyte proliferation, activation and cytokine expression to B. pseudomallei antigen were determined in eight donors who were seropositive and in eight age- and sex-matched controls. In North Queensland, 2.5% of the population was seropositive for B. pseudomallei, which is less than half that which was previously described. Of clinical significance was the observation that while 75% of the seropositive individuals had increased lymphocyte proliferation to B. pseudomallei antigens, there were no significant differences observed in lymphocyte activation or production of cytokines.
