***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 —Markers of systemic inflammation ( eg , C-reactive protein [ CRP ] and interleukin-6 [ IL-6 ] ) have been proposed to be “ nontraditional ” risk factors for cardiovascular disease in patients with type 2 diabetes mellitus . Matrix metalloproteinase-9 ( MMP-9 ) has been implicated in the pathogenesis of atherosclerotic plaque rupture , which raises the possibility of the use of MMP-9 levels as a marker for future myocardial infa rct ion or unstable angina . In vitro and animal studies suggest that thiazolidinediones can reduce the expression of these markers . The purpose of this analysis was to determine whether rosiglitazone alters serum concentrations of CRP , IL-6 , MMP-9 , and white blood cell count ( WBC ) and to examine the relationship of these effects with demographic and disease variables . Methods and Results —CRP , IL-6 , MMP-9 , and WBC were analyzed from stored frozen serum sample s obtained from patients with type 2 diabetes who completed a 26-week r and omized , double-blind , placebo-controlled study . After 26 weeks of rosiglitazone treatment , the percentage reductions in mean CRP , MMP-9 , and WBC levels were statistically significant compared with baseline and placebo ( P < 0.01 ) . The percentage reduction in mean IL-6 was small and similar in the rosiglitazone and placebo groups . The change in each inflammatory marker from baseline to week 26 was significantly correlated ( P < 0.05 ) with each of the other markers , as well as with the homeostasis model assessment estimate of insulin resistance . Conclusions —Rosiglitazone reduces serum levels of MMP-9 and the proinflammatory marker CRP in patients with type 2 diabetes , which indicates potentially beneficial effects on overall cardiovascular risk Ramipril improves cardiovascular outcome in patients with peripheral arterial disease ; however , the precise mechanisms of benefit remain to be eluci date d. The effect of ramipril on large-artery stiffness in patients with peripheral arterial disease was examined . In addition , we determined the effect of ramiprilat on extracellular matrix from human aortic smooth muscle cell culture . Forty patients with peripheral arterial disease were r and omized to receive ramipril , 10 mg once daily or placebo for 24 weeks . Arterial stiffness was assessed globally via systemic arterial compliance and augmentation index ( carotid tonometry and Doppler velocimetry ) , and regionally via carotid – femoral pulse wave velocity . Angiotensin-converting enzyme inhibition increased arterial compliance by 0.10±0.02 mL/mm Hg , ( P<0.001 , all probability values relative to placebo ) and reduced pulse wave velocity by 1.7±0.2 m/s ( P<0.001 ) , augmentation index by 4.1±0.3 % ( P<0.001 ) , and systolic blood pressure by 5±1 mm Hg ( P<0.001 ) . Ramipril did not reduce mean arterial pressure significantly compared with placebo ( P=0.59 ) . In cell culture , ramiprilat  decreased collagen deposition by > 50 % and increased elastin and fibrillin-1 deposition by > 3- and 4-fold respectively ( histochemistry and immunohistochemistry ) . Fibrillin-1 gene expression was increased 5-fold ( real-time reverse-transcriptase polymerase chain reaction ) . Ramiprilat also reduced gene and protein ( Western ) expression of both matrix metalloproteinase (MMP)-2 and MMP-3 . In conclusion , ramipril promoted an elastogenic matrix profile that may contribute to the observed clinical reduction in large-artery stiffness and carotid pressure augmentation , which occurred independently of mean arterial blood pressure reduction in patients with peripheral arterial disease PURPOSE Early repair of abdominal aortic aneurysms ( AAA ) is particularly appropriate for those that are most likely to exp and . Our aim was to define features on computed tomography ( CT ) scanning associated with subsequent rapid aneurysm expansion . METHODS We review ed CT scans of 80 patients with AAA ( > 3.0 cm ) who underwent CT scanning of the abdomen and pelvis two times , at least 6 months apart , between 1986 and 1992 . The aneurysms initially measured 4.4 + /- 0.6 cm , and the mean interval between obtaining scans was 22 + /- 12 months . Clinical variables assessed included age , sex , medical risk factors , underlying cardiovascular and pulmonary diseases , and administration of beta blockers and lipid-lowering agents . Computer-aided measurements on each CT scan section included the maximal and minimal diameters and area of the aneurysm . Dimensions of the luminal thrombus and the arc of aneurysm wall covered by thrombus ( TARC ) . Maximal aneurysm dimensions were related to juxtarenal aortic and second lumbar vertebral body dimensions . RESULTS Mean aneurysm expansion was 0.26 + /- 0.25 cm/yr . CT scanning variables that correlated significantly with rate of expansion included the mean TARC ( r = 0.43 , p < 0.001 ) , thrombus volume fraction ( r = 0.37 , p < 0.001 ) , TARC on the largest aneurysm cross section ( r = 0.34 , p < 0.01 ) , and thrombus area fraction ( r = 0.30 , p < 0.01 ) . Rapid expansion ( > 0.5 cm/yr ) occurred in 15 ( 19 % ) aneurysms . The two predictors for rapid expansion on logistic regression analysis were mean TARC ( p < 0.005 ) and the presence of carotid artery disease ( p < 0.05 ) . CONCLUSION An increased AAA thrombus load is associated with a higher likelihood of rapid expansion and should weigh in favor of early surgical repair BACKGROUND Angiotensin-converting enzyme ( ACE ) inhibitors prevent the expansion and rupture of aortic aneurysms in animals . We investigated the association between ACE inhibitors and rupture in patients with abdominal aortic aneurysms . METHODS We did a population -based case-control study of linked administrative data bases in Ontario , Canada . The sample included consecutive patients older than 65 ( n=15,326 ) admitted to hospital with a primary diagnosis of ruptured or intact abdominal aortic aneurysm between April 1 , 1992 , and April 1 , 2002 . FINDINGS Patients who received ACE inhibitors before admission were significantly less likely to present with ruptured aneurysm ( odds ratio [ OR ] 0.82 , 95 % CI 0.74 - 0.90 ) than those who did not receive ACE inhibitors . Adjustment for demographic characteristics , risk factors for rupture , comorbidities , contraindications to ACE inhibitors , measures of health-care use , and aneurysm screening yielded similar results ( 0.83 , 0.73 - 0.95 ) . Consistent findings were noted in subgroups at high risk of rupture , including patients older than 75 years and those with a history of hypertension . Conversely , such protective associations were not observed for beta blockers ( 1.02 , 0.89 - 1.17 ) , calcium channel blockers ( 1.01 , 0.89 - 1.14 ) , alpha blockers ( 1.15 , 0.86 - 1.54 ) , angiotensin receptor blockers ( 1.24 , 0.71 - 2.18 ) , or thiazide diuretics ( 0.91 , 0.78 - 1.07 ) . INTERPRETATION ACE inhibitors are associated with a reduced risk of ruptured abdominal aortic aneurysm , unlike other antihypertensive agents . R and omised trials of ACE inhibitors for prevention of aortic rupture might be warranted Aortic aneurysm is the 10th leading cause of death in older men [ 1 ] , but fundamental issues about the cause and epidemiology of this condition remain unresolved . A fourfold variation in the prevalence of abdominal aortic aneurysm ( AAA ) has been seen among participants in screening programs [ 2 ] , and the traditional view that AAA is a manifestation of atherosclerosis has been challenged by recent studies that suggest a role for specific genetic factors [ 3 ] . Most information on the epidemiology of AAA has come from screening studies [ 4 - 10 ] . However , the studies that have reported on potential risk factors have screened fewer than 5500 patients each , result ing in too few cases for multivariable analysis . Two nested casecontrol studies have reported multiple risk factor analyses for aortic aneurysms [ 11 , 12 ] , but these studies were also relatively small ( one contained 41 and one contained 165 aneurysms ) , did not attempt to identify all cases of AAA in their study population s , did not consider such important factors as family history of AAA , and disagreed about the significance of such factors as height and serum cholesterol levels . To identify factors that are independently associated with AAA and to determine the prevalence of previously unrecognized AAA in defined demographic and risk groups , we collected and analyzed self-reported information from a large cohort of veterans who participated in a multicenter ultrasonographic screening program . Methods Participants The Aneurysm Detection and Management ( ADAM ) study is an ongoing r and omized clinical trial comparing two strategies for the management of AAA ( immediate surgery and surgery reserved for aneurysms that enlarge to 5.5 cm , enlarge rapidly , or cause symptoms ) in patients 50 to 79 years of age with asymptomatic AAAs 4.0 to 5.4 cm in diameter [ 13 ] . Ultrasonography screening clinics were established at the 15 participating Department of Veterans Affairs medical centers to support recruitment into the trial . Active patients at these centers ( that is , patients treated during the current or previous fiscal year and those who had future appointments ) who met the age criteria for the study were invited by mail to attend the clinic . Throughout the screening period , the letters were mailed in batches according to patient social security number using the continuously up date d administrative patient data at each participating center . A second mailing that was done at some centers excluded persons who had previously been seen in the screening clinic . Active patients at the participating centers were also accepted for screening on a walk-in basis ; patients 50 to 79 years of age were included in the analysis because they were members of the target population and eventually would have been invited to participate . Inadvertent repeated screenings were identified by patient social security number , and results of second screenings were excluded . Patients who reported previously having been told that they had an AAA were also excluded . We include data from patients who were screened from the beginning of the program in October 1992 through March 1995 . The study was approved by the human rights committee at the Veterans Affairs Cooperative Studies Program coordinating center and by the institutional review boards at the 15 participating centers . Assessment of Associated Factors Before ultrasonographic examination , all patients completed a brief  question  naire that asked about demographic information and possible risk factors for AAA . Patients were asked whether they had ever been told by a physician that they had the condition in question ( for example , high blood pressure ) . The question naire was developed for the study , tested at the participating centers , and revised accordingly before the study began . The reliability of the data from the self-reported question naire was assessed by comparing this data with data collected in the subset of screened patients who had an AAA and who were later included in the clinical trial . These data were recorded by a study nurse after discussion with the patient and review of the patient 's medical records . Ascertainment of Abdominal Aortic Aneurysm The abdominal aorta was measured above and below the renal arteries using a 3.5-MHz real-time sector scanner . The ultrasonographers were instructed to 1 ) scan the aorta in the anteroposterior and lateral planes and 2 ) report the maximum external diameter at the widest point of any dilatation for the suprarenal and infrarenal segments . The ultrasonographers met twice during the study period to review techniques and compare measurement distributions . Patients found to have an AAA or another suspected abnormality were referred for evaluation , and discrepancies between the results of subsequent testing and the results of the initial screening were reported back to the study ultrasonographer . Screening appointments for patients whose examinations were inadequate because of insufficient fasting were rescheduled . An infrarenal aortic diameter of 4.0 cm or larger is generally agreed to constitute AAA , but no method for defining a smaller AAA has gained wide acceptance [ 14 ] . Most investigators have used unadjusted aortic diameter ( with such cutoff points as 3.0 cm , which is known to be associated with risk for rupture [ 15 ] ) but this practice may exaggerate the prevalence of AAA in larger people . To avoid this problem , use of a ratio of infrarenal aortic diameter to suprarenal aortic diameter of 1.5 or greater has been proposed [ 14 ] . However , this method labels some small aortas as having an AAA and fails to account for aneurysmal dilatation of the suprarenal aorta . The latter problem has , in turn , been addressed by a proposal to define AAA as an aortic diameter more than 1.5 times the diameter that would be expected on the basis of age , sex , body size , and other factors . However , values for the expected diameter have not been well defined [ 14 ] . Therefore , we considered several definitions of AAA , including an 
    Output:
    
Studies so far suggest a protective role for diabetes on the development of AAA .