Håkan Pärsson

The effect of azithromycin and Chlamydophilia pneumonia infection on expansion of small abdominal aortic aneurysms - A prospective randomized double-blind trial

OBJECTIVE The aim of the study was to evaluate the effect of azithromycin on the expansion rate of small abdominal aortic aneurysms (AAAs), and to determine whether or not a correlation exists between serological markers for Chlamydophilia pneumonia (Cpn) infection and AAA expansion. METHODS Nine vascular centers were included and 259 patients were invited to participate. Ten patients declined and 2 patients had chronic kidney failure, leaving a total of 247 patients. Inclusion criteria were: AAA 35-49 mm and age <80 years. Patients were randomized to receive either azithromycin (Azithromax, Pfizer Inc, New York, NY) 600 mg once daily for 3 days and then 600 mg once weekly for 15 weeks, or placebo in identical tablets. The ultrasound scans were performed in a standardized way within a month before inclusion and every 6 months for a minimum follow-up time of 18 months. Cpn serology was analyzed in blood samples taken at inclusion and 6 months later. Serum was analyzed for Cpn IgA and IgG antibodies by microimmunofluorescence (MIF). Computed tomography (CT) scans were done in 66 patients at inclusion and at 1 year for volume calculations. RESULTS Thirty-four patients were excluded, ie, could not be followed for 18 months, 20 in the placebo group and 16 in the active treatment group. A total of 211 patients had at least two measurements and all were analyzed in an intention-to-treat analysis. Detectable IgA against Cpn was found in 115 patients and detectable IgG against Cpn in 160 patients. No statistically significant differences were found between the groups regarding median expansion rate measured by ultrasound scan (0.22 cm/year, interquartile range [IQR]: 0.09 to 0.34 in the placebo group vs 0.22, IQR: 0.12 to 0.36 in the treatment group, P = .85). Volume calculation did not change that outcome (10.4 cm(3)/year in the placebo group vs 15.9 cm(3)/year in the treatment group, P = .61). No correlation was found between serological markers for Cpn infection and the expansion rate. Patients taking statins in combination with acetylsalicylic acid (ASA) had significantly reduced expansion rate compared to patients who did not take statins or ASA, 0.14 cm/year vs 0.27 cm/year, P < .001. CONCLUSION Azithromycin did not have any effect on AAA expansion. No correlation was found between serological markers for Cpn and AAA expansion, indicating no clinical relevance for Cpn testing in AAA surveillance. However, a significant reduction in AAA expansion rate was found in patients treated with a combination of ASA and statins.

Long-Term Survival After Carotid Endarterectomy for Asymptomatic Stenosis

Background and Purpose— Large randomized trials have demonstrated a net benefit of carotid endarterectomy (CEA) for asymptomatic carotid artery stenosis compared with best medical treatment. However, it takes years to overcome the perioperative risk and gain the reduction in stroke or death risk. Long-term survival after CEA for asymptomatic stenosis may be an important consideration in deciding on this prophylactic procedure, but is not well documented. The aim was to analyze long-term survival after CEA for asymptomatic stenosis and the impact of risk factors in a population-based study. Methods— The Swedish vascular registry (Swedvasc) covers all centers performing CEA. Data on all registered CEAs during 1994 to 2003 were retrieved. All patients were cross-matched with the Population-Registry for accurate data on mortality (date of death). Analyses with Kaplan-Meier curves for survival and relative odds ratio (OR) for predictors of survival were performed. Results— A total of 6169 CEAs in 5808 patients were registered, with a median time at risk of 5.1 (range, 0.1 to 11.8) years. The indication for CEA was asymptomatic stenosis in 10.8% of the patients. Survival after CEA for asymptomatic stenosis was 78.2% after 5 and 45.5% after 10 years. Previous vascular surgery (OR, 1.8; 1.1 to 3.0), cardiac disease (OR, 1.7; 1.0 to 2.8), diabetes mellitus (OR, 2.3; 1.3 to 4.1), and age (OR, 1.5; 1.1 to 2.1 per 10 years) were predictors of decreased 5-year survival. Conclusions— In this population-based study of patients operated on for asymptomatic stenosis, a substantial reduction in long-term survival was observed. Predictors of decreased longevity were age at operation, diabetes, cardiac disease, and previous vascular surgery.

Expansion of Small-diameter Abdominal Aortic Aneurysms is Not Reflected by the Release of Inflammatory Mediators IL-6, MMP-9 and CRP in Plasma

OBJECTIVES The aim of this study was to evaluate a possible correlation between plasma levels of interleukin-6 (IL-6), metalloproteinase-9 (MMP-9) and C-reactive protein (CRP) and the expansion of small abdominal aortic aneurysms (AAAs). DESIGN Patients were selected from a prospective randomised clinical trial and categorised in two groups, in which one group received active treatment (azithromycin) and the other received placebo. No statistical difference in the expansion rate of AAAs between the groups was found and the two groups were considered as one cohort in the present study. MATERIAL AND METHODS In this study, 213 patients with AAAs between 35 and 49 mm were followed-up with ultrasound examination every 6th month. Blood samples were taken on two occasions (6 months apart). IL-6 and MMP-9 were analysed on one occasion using Quantikine analysing kits (R&D Systems, Inc., USA). CRP was analysed using sensitive-CRP method. RESULTS Levels of IL-6, MMP-9 and CRP did not correlate with AAA expansion. Neither was there any correlation between statin medication and changes in MMP-9 levels over the 6-month period. Patients on statins had a lower expansion rate than those not taking statins: 0.16 versus 0.25 cm per year. CONCLUSION No correlation was found between levels of circulating IL-6, MMP-9, CRP and the expansion of small-diameter AAAs, indicating no clinical use of these markers in AAA surveillance.

The association between serological markers for chlamydophila pneumoniae and the development of abdominal aortic aneurysm

BACKGROUND To investigate the association between serological markers for Chlamydophila pneumoniae (Cpn) and the development of abdominal aortic aneurysm (AAA) in a population-based case-control study. METHODS A screening for AAA among 65-75-year-old men and women was performed in a population with high prevalence of disease. Most of the subjects had undergone previous testing at the age of 60, including blood sampling. A total of 42 patients with AAA were compared with 100 age- and gender-matched controls with normal aortas. Cpn immunoglobulin A (IgA) and immunoglobulin G (IgG) antibodies present in plasma samples obtained at the time of screening (current) and in the past 5-15 (mean, 12) years (historical) were analyzed. Cpn antibody titers (<1/64, 1/64, 1/264, and 1/1024) were analyzed using the microimmunofluorescence technique. RESULTS No differences in current Cpn immunoglobulin A and IgG antibodies titers (p = 0.111 and 0.659), historical titers (p = 0.449 and 0.228), or titer change (delta) (p = 0.794 and 0.172) were observed between patients with AAA and controls. In all, 82% of the patients with AAA had a current Cpn IgG titer of 1/1024 as compared with the 70% of the control group. All 11 patients who had an aortic diameter of >40 mm reported having high current Cpn IgG titers. The fact that such a large proportion of the healthy population demonstrated an immune response against Cpn made it difficult to demonstrate possible effects of Cpn infection on AAA formation in a case-control study. CONCLUSION No significant associations were found between AAA detected by screening and Cpn antibody titer levels at the time of screening or during past screening at the age of 60.

Carotid Endarterectomy Induces the Release of Inflammatory Markers and the Activation of Coagulation as Measured in the Jugular Bulb

BACKGROUND AND PURPOSE Transient cerebral hypoxia may induce neuronal injury through an ischemia-reperfusion (I/R) response, with a subsequent activation of inflammation and coagulation-fibrinolysis. During carotid endarterectomy (CEA), the artery is clamped, which might impair the regional cerebral perfusion and initiate a local I/R response. Data suggest that the CD40-CD40 ligand dyad acts as a modulator in the induced activation. The aim of this study was to locally measure soluble CD40 ligand (sCD40L), in conjunction with inflammation and coagulation activation markers, during CEA. SUBJECTS AND METHODS This is a prospective study of 18 patients undergoing CEA. Blood samples from the venous jugular bulb (JB) and the radial artery (RA) were drawn at baseline and during the procedure. Measurements of sCD40L, interleukin-6 (IL-6), fragment 1 + 2 (F1 + 2), plasminogen activator inhibitor-1 (PAI-1), and d-dimer were analyzed. Comparisons during CEA were made between levels: baselines versus JB, JB versus RA, and sequential JB measurements. Fifty cardiovascular healthy patients were the reference group for the sCD40L baseline comparison. RESULTS Increased cerebral IL-6 levels were demonstrated throughout the procedure, as well as the temporal influence in F1 + 2, PAI-1, and d-dimer values. sCD40L remained unchanged throughout the procedure . This indicates a local cerebral inflammatory reaction together with an activation of coagulation-fibrinolysis, but it does not appear to primarily involve the CD40-CD40 ligand dyad. CONCLUSIONS Signs of a local inflammatory reaction and activation of coagulation were observed during CEA, but levels of sCD40L remained stable, unaffected by carotid artery clamping and reperfusion.