***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background Abdominal aortic aneurysm is a multifactorial disorder in which inflammation is an important pathophysiological feature . In explant culture , aneurysm biopsies secrete large amounts of interleukin-6 ( IL-6 ) , and among aneurysm patients , the circulating concentration of IL-6 appears to be increased . Methods and Results We investigated , in 19 patients , whether aneurysm wall was an important source of circulating IL-6 . We also tested the hypotheses , in 466 patients with a small aneurysm , that ( 1 ) high concentrations of circulating IL-6 signaled rapid aneurysm growth and ( 2 ) the −174 G→C polymorphism in the IL-6 promoter predicted survival . For 19 patients with large or inflammatory aneurysms , the concentration of IL-6 was higher in the iliac arteries than the brachial arteries ( median difference 26.5 pg/mL , this difference increasing with aneurysm diameter , P = 0.01 ) . In 466 patients with small aneurysms , the frequency of the −174 C allele ( 0.40 ) was similar to that in a normal healthy population . Patients of GG genotype had lower plasma concentrations of IL-6 than patients of GC and CC genotypes ( medians 1.9 , 4.8 , and 15.6 pg/mL , respectively , Kruskal-Wallis P = 0.047 ) . Cardiovascular and all-cause mortalities were lower for patients of GG genotype than for patients of GC and CC genotype : hazard ratios 0.32 ( 95 % CI 0.12 to 0.93 ) , P = 0.036 , and 0.51 ( 95 % CI 0.25 to 1.00 ) , P = 0.05 , respectively . There was no association between plasma IL-6 or IL-6 genotype and aneurysm growth . Conclusions Aortic aneurysms appear to be an important source of circulating IL-6 , the concentration being influenced by genotype . For patients with small aneurysms , the −174 G→C IL-6 genotype predicts future cardiovascular mortality CONTEXT Among patients with abdominal aortic aneurysm ( AAA ) who have high operative risk , repair is usually deferred until the AAA reaches a diameter at which rupture risk is thought to outweigh operative risk , but few data exist on rupture risk of large AAA . OBJECTIVE To determine the incidence of rupture in patients with large AAA . DESIGN AND SETTING Prospect i ve cohort study in 47 Veterans Affairs medical centers . PATIENTS Veterans ( n = 198 ) with AAA of at least 5.5 cm for whom elective AAA repair was not planned because of medical contraindication or patient refusal . Patients were enrolled between April 1995 and April 2000 and followed up through July 2000 ( mean , 1.52 years ) . MAIN OUTCOME MEASURE Incidence of AAA rupture by strata of initial and attained diameter . RESULTS Outcome ascertainment was complete for all patients . There were 112 deaths ( 57 % ) and the autopsy rate was 46 % . Forty-five patients had probable AAA rupture . The 1-year incidence of probable rupture by initial AAA diameter was 9.4 % for AAA of 5.5 to 5.9 cm , 10.2 % for AAA of 6.0 to 6.9 cm ( 19.1 % for the subgroup of 6.5 - 6.9 cm ) , and 32.5 % for AAA of 7.0 cm or more . Much of the increased risk of rupture associated with initial AAA diameters of 6.5 - 7.9 cm was related to the likelihood that the AAA diameter would reach 8.0 cm during follow-up , after which 25.7 % ruptured within 6 months . CONCLUSION The rupture rate is substantial in high-operative-risk patients with AAA of at least 5.5 cm in diameter and increases with larger diameter PURPOSE Chlamydia Pneumoniae has been shown to be associated with atherosclerosis , myocardial infa rct ion , and abdominal aortic aneurysms ( AAAs ) . The possible association between AAA expansion and C pneumoniae infection was therefore assessed . METHODS Blood sample s were taken from patients with an AAA that was considered for surgical repair after having been diagnosed by means of the Chichester aneurysm screening program ( UK ) as having an initially infrarenal aortic diameter of 3.0 to 5.9 cm . The patients were examined prospect ively for as long as 11.5 years ( mean , 4.1 years ) with ultrasound scanning .  Of 110 patients considered for surgery , 90 men and 10 women had blood sample s taken . Their IgG and IgA antibodies against C pneumoniae were measured by means of a microimmunofluorescence test . Unpaired t tests , multiple linear regression analyses , and logistic regression analyses were used for statistical analysis . RESULTS A total of 44 % ( 95 % CI , 31%-55 % ) of the men with an AAA had an IgA titer of 64 or more , an IgG titer of 128 or more , or both , compared with 10 % of the women with an AAA ( OR = 7.2 ; 95 % CI , 1.05 - 160.8 ) . A titer of IgG of 128 or more was significantly associated with higher expansion ( 5.3 vs 2.6 mm per year ) , even after adjustment for initial AAA size and age . A significant positive correlation between both IgA and IgG titers and mean annual expansion was observed ( r = 0.28 ; 95 % CI , 0.05 - 0.49 ; and r = 0.45 ; 95 % CI , 0.24 - 0.62 , respectively ) , persisting after adjusting for initial AAA size and age . An IgG titer of 128 or more was present significantly more often in cases with an expansion greater than 1 cm annually ( adjusted OR = 12.6 ; 95 % CI , 1.37 - 293 ) . CONCLUSION A high proportion of men with an AAA has signs of infection with C pneumoniae . The progression of their AAAs was positively correlated with the presence of indicators of C pneumoniae infection OBJECTIVES endothelin 1,2 plays a significant role in the process of atherogenesis and vascular wall injury . The aim of this study was to assess whether plasma endothelin 1,2 levels were elevated in patients with large or symptomatic abdominal aortic aneurysms ( AAAs ) . DESIGN a prospect i ve open study . MATERIAL S AND METHODS  plasma endothelin 1,2 levels  were measured in 65 consecutive patients with infrarenal aortic aneurysms and compared with the levels in 44 healthy volunteer controls . The data for abdominal aneurysm patients was analysed in four subgroups : ( i ) small aneurysms ( < 5 cm ) , ( ii ) large aneurysms ( > /=5 cm ) , ( iii ) asymptomatic aneurysms and ( iv ) symptomatic aneurysms . Comparisons were made between endothelin 1,2 levels in aneurysm patients and controls and between the different aneurysm subgroups . RESULTS a highly significant difference ( p<0.0001 ) was found between aneurysm patients and controls . Patients with large aneurysms had significantly higher levels than patients with small aneurysms ( p<0.01 ) . There was no statistical difference in endothelin 1,2 levels between symptomatic and asymptomatic patients ; however , the highest levels were found in large , symptomatic aneurysms and the lowest in small , asymptomatic aneurysms . CONCLUSIONS plasma endothelin 1,2 is an endogenous marker of aneurysm diameter . Further studies are required to determine whether it relates to the rate of growth of aneurysms Abstract The pathogenesis of abdominal aortic aneurysms ( AAA ) is a complex process in which atherosclerosis and inflammation play a leading role . Cytokines are important mediators of both processes . The aim of our study was to determine whether plasma levels of cytokines which are most involved in AAA pathogenesis can be used as endogenous markers of AAA development , and thus to facilitate the decision on surgical intervention in cases when this is clinical ly unclear ( e.g. small AAA ) . In the prospect i ve study a total of 90 patients with AAA were examined . These patients were divided into the following groups according to symptoms and AAA diameter : symptomatic AAAs , including ruptures ( n=16 ) ; asymptomatic AAAs ( n=74 ) ; AAAs with a diameter of up to 5 cm ( n=30 ) , AAAs of 5–8 cm ( n=38 ) , and AAAs with a diameter over 8 cm ( n=22 ) . The average age of the patients was 70.7 ( 56–82 ) years . The male to female ratio was 4:1 ( 71:19 ) . A control group consisted of 30 healthy individuals of similar age and sex presentation with no manifestation of atherosclerosis .  Plasma levels of cytokines  were assessed in venous blood by means of radio- or enzymo-immunoassay . Statistical processing of the results was conducted with ANOVA and Wilcoxon tests with Spearman correlation , where p<0.05 was considered to be statistically significant . Plasma concentrations of cytokines were significantly higher in AAA patients than in healthy individuals . In AAA patients the tumour necrosis factor-α ( TNF-α ) and interleukin ( IL-8 ) levels were low in large and in symptomatic AAAs . IL-6 levels were increased with increasing AAA diameter and symptoms . IL-8 levels ( p<0.05 ) showed a statistically significant correlation with the diameter , and TNF-α ( p<0.05 ) with the symptoms of AAA . IL-1β , IL-2 and IL-6 did not show any significant changes with different AAA diameter or symptomatology . In Conclusion : IL-8 and TNF-α can be used as endogenous markers of the process of AAA development , in deciding for either surgical or endovascular treatment of patients when the clinical indication is not entirely clear BACKGROUND Serum C-reactive protein ( CRP ) has proven to be an independent marker of the extent of atherosclerosis in patients with coronary , cerebrovascular , and peripheral arterial disease . In this prospect i ve observational study , we wanted to assess the relationship between serum CRP and extent of disease transversely and longitudinally in time , as well as future cardiovascular complications in patients with peripheral arterial disease ( PAD ) . Hypothesizing that CRP not only is a marker of but also actively participates in atherogenesis , we explored the possibility of CRP production by femoral atherosclerotic plaques . METHODS  Serum CRP  was measured as highly sensitive ( hsCRP ) in 387 patients with PAD attending the vascular clinic of a university and 2 affiliated teaching hospitals .  Serum hsCRP  was related to the ankle-brachial pressure index ( ABPI ) as an indication of severity of disease at inclusion and at 12 months ' follow-up and to future events ( death and coronary , cerebral , and peripheral arterial events ) . In femoral plaques , the production of CRP was analyzed with reverse transcription-polymerase chain reaction , and CRP plaque localization was assessed with immunostaining on serial tissue sections with antibodies toward CRP , smooth muscle cells , T cells , and macrophages . RESULTS The hsCRP ( average + /- SD ) was 3.26 + /- 2.41 mg/L. Serum hsCRP showed a correlation with baseline and 12-month follow-up ABPI ( Spearman rank correlation ; P < .05 for both correlations ) . When the patients were divided into three equally sized groups according to baseline serum hsCRP , the ABPI at baseline and at 12 months decreased significantly from the low- to the high-hsCRP group ( baseline ABPI : 0.70 , 0.65 , and 0.57 , P < .01 ; 12-month follow-up ABPI : 0.78 , 0.70 , and 0.65 , P < .01 ) . These associations persisted after correction for conventional risk factors . Furthermore , serum hsCRP was related to the combined end point " death and /or any cardiovascular event " ( log-rank test ; P = .04 ) during a median 24-month follow-up period . Reverse transcription-polymerase chain reaction analysis showed CRP production in 4 of 14 femoral plaques . CRP was detected in all femoral plaques , but not in healthy brachial arteries . Immunoreactivity for CRP was observed in smooth muscle cells , macrophages , and T cells . CONCLUSIONS Serum hsCRP was related to the severity of PAD , showing a relation to future hemodynamic function and cardiovascular events in PAD patients . In addition to coronary plaques , aneurysmal aortas , and failed venous coronary bypasses , femoral plaques also produce CRP , thus illustrating that the production of CRP may represent a universal response to vascular injury and suggesting that vascular CRP may contribute to plaque development OBJECTIVE plasmin is a common activator of the known proteolytic systems involved in the aneurysmal degradation , and is reported to be associated with the expansion of abdominal aortic aneurysms ( AAA ) . The aim of this study was to 
    Output:
    
Several potential biomarkers were identified .
The strongest association with AAA was obtained with serum elastin peptides ( SEP ) and plasmin-antiplasmin ( PAP ) complexes .
Matrix-degrading metalloproteinase 9 ( MMP9 ) and interferon-gamma ( IFN-gamma ) could have clinical potential while many putative biomarkers showed poor association .
Several circulating agents in peripheral blood may predict AAA size , expansion rate or rupture .