You will be presented with a collection of medical randomized controlled trial (RCT) reports addressing a shared clinical question -- for instance, the efficacy of a medical intervention on a disease or condition. Given the titles and abstracts of these reports, your task is to generate the conclusion of the systematic review article synthesizing the key findings. Your conclusion should be a few sentences long. In your response, include only the conclusion and no other text. The RCT reports are below.



Title 1:
Is hypovitaminosis D associated with abdominal aortic aneurysm, and is there a dose-response relationship?
Abstract 1:
OBJECTIVE This study aims to investigate the association between plasma 25-hydroxyvitamin D ( 25(OH)D ) concentrations with the presence of abdominal aortic aneurysm ( AAA ) and aortic diameter . DESIGN An observational study of 4233 community-dwelling men aged 70 - 88 years , who participated in a r and omised controlled trial of screening for AAA . METHODS Infrarenal aortic diameter measured by ultrasound and  25(OH)D by immunoassay . RESULTS A total of 311 men ( 7.4 % ) with AAA ( defined as aortic diameter ≥ 30 mm ) comprised the study . Multivariable models were adjusted for age , smoking , cardiovascular disease , hypertension , diabetes , dyslipidaemia , body mass index and serum creatinine concentration . Amongst men with the lowest 25(OH)D quartile of values compared with the highest quartile , the adjusted odds ratio of having an AAA increased in a grade d fashion from 1.23 ( 95 % confidence interval ( CI ) 0.87 - 1.73 ) for AAA ≥ 30 mm to 5.42 ( 95 % CI 1.85 - 15.88 ) for AAA ≥ 40 mm . Similarly , there was a dose-response relationship between 25(OH)D concentrations and the size of the AAA : every 10-nmol l(-1 ) decrease in 25(OH)D levels was associated with 0.49 mm ( 95 % CI 0.11 - 0.87 ) increase in mean aortic diameter . CONCLUSIONS Low vitamin D status is associated with the presence of larger AAA  in older men , and there is a grade d inverse relationship between 25(OH)D concentrations and AAA diameter . Further research is needed to clarify the mechanisms underlying these associations


Title 2:
Biomarkers for abdominal aortic aneurysms from a sex perspective.
Abstract 2:
BACKGROUND Abdominal aortic aneurysms ( AAAs ) differ in men and women . Women are older at diagnosis , have a higher risk of rupture , and worse outcome after surgery compared with men . The higher occurrence of AAAs in men accounts for the dominance of men in biomarker analyses . OBJECTIVE The primary aim of this study was to investigate levels of established biomarkers for AAA in men and women , and the secondary aim was to compare biomarker levels in women with and without AAAs . METHODS In this prospect i ve case-control study , blood sample s were collected from 16 women and 18 men with AAAs ≥5.5 cm , from 20 women with AAAs < 5.5 cm , and from 18 women with peripheral artery disease ( PAD ) .  Plasma concentrations of matrix metalloproteinase ( MMP ) -2 , -9 , and -13 ; tissue inhibitor of MMP-1 ( TIMP-1 ) ; plasminogen activator inhibitor 1 ( PAI-1 ) ; high-sensitivity C-reactive protein ( hsCRP ) ; and estradiol levels were analyzed by ELISA . An ultrasound examination was performed in women with PAD to exclude an AAA . RESULTS Age and other comorbid conditions were similar between men and women with AAAs . Women with AAAs had higher levels of MMP-9 compared with men with equally large AAAs ( 42.8 ng/mL vs 36.2 ng/mL , P = 0.036 ) and lower levels of estradiol ( 30.0 pmoL vs 86.5 pmol/L , P < 0.001 ) . Women with AAAs had lower levels of MMP-9 compared with women without ( 59.5 ng/mL vs 132.6 ng/mL , P = 0.010 ) . There was no significant difference in the plasma levels of MMP-2 , MMP-13 , hsCRP , PAI-1 , TIMP-1 , and estradiol between women with and without AAAs . CONCLUSION The higher levels of MMP-9 in women compared with men with equally large AAAs could suggest that MMP-9 is a biomarker related to the sex differences in aneurysm development . The lower levels of estradiol in women with AAAs compared with men suggest that the possible protective effect of endogenous estrogen can not be explained by a difference in circulating levels of estradiol


Title 3:
Prevalence of abdominal aortic aneurysms and its relation with cardiovascular risk stratification: protocol of the Risk of Cardiovascular diseases and abdominal aortic Aneurysm in Varese (RoCAV) population based study
Abstract 3:
Background Recent meta-analyses suggested that screening program for abdominal aortic aneurysms ( AAA ) in 65-year old males is cost-effective at prevalence of about 1 % . Since some events occur also in females and among the youngers , screening could be feasible among those at higher risk , such as smokers or individuals with a family history of AAA . The RoCAV ( Risk of Cardiovascular diseases and abdominal aortic Aneurysms in Varese ) Project is a population -based study aim ed to evaluate AAA prevalence in Northern Italy in males over-65 years as well as among females and younger males , and to identify new markers for risk stratification by collecting a large set of CVD risk factors . The aims of the project are : ( i ) cross-sectional evaluation of AAA prevalence ( ii ) ; evaluation of st and ard CVD risk score as criteria for selecting subgroup at higher risk to be included in a screening program ; ( iii ) identification of new risk markers and risk score algorithm for AAA and CVD risk stratification ; ( iv ) cost-effective evaluation during the follow-up . Methods Males aged 50–75 years and females aged 60–75 years , resident in the city of Varese ( Lombardy Region ) , were r and omly selected from the civil registry . Among 5198 successfully invited , 3777 subjects accepted to participate and were finally recruited ( participation rate 63.8 % ) from June 2013 to May 2016 . Trained operators administered a computerized anamnestic question naire , measured anthropometric parameters ( BMI , body circumferences , skinfolds ) , blood pressure , ankle-brachial index , pulse wave velocity and performed abdominal aortic ultrasound scan , ECG and spirometry .  All methods were internationally vali date d. A blood sample was collected and stored in biobank . A follow-up will be carried out through linkage with electronic records . Discussion Participation rate and data quality assessment were as expected and will reasonably allow to reach the project aims . The expected impact in public health of the RoCAV project will be the potential implementation of a AAA screening program to the whole region as well as the formulation of new criteria for risk assessment of AAA and CVD


Title 4:
Analysis of in hospital mortality and long-term survival excluding in hospital mortality after open surgical repair of ruptured abdominal aortic aneurysm
Abstract 4:
Purpose The aim of this study was to confirm the factors that affect the mortality associated with the open surgical repair of ruptured abdominal aortic aneurysm ( rAAA ) and to analyze the long-term survival rates . Methods A retrospective review was performed on a prospect ively collected data base that included 455 consecutive patients who underwent open surgical repair for AAA between January 2001 and December 2012 . We divided our analysis into in-hospital and postdischarge periods and analyzed the risk factors that affected the long-term survival of rAAA patients . Results Of the 455 patients who were initially screened , 103 were rAAA patients , and 352 were non-rAAA ( nAAA ) patients . In the rAAA group , 25 patients ( 24.2 % ) died in the hospital and 78 were discharged . Long-term survival was significantly better in the nAAA group ( P = 0.001 ) . The 2- , 5- , and 10-year survival rates of the rAAA patients were 87 % , 73.4 % , and 54.1 % , respectively . Age ( hazard ratio [ HR ] , 1.05 ; 95 % confidence interval [ CI ] , 1.02–.08 ; P < 0.001 ) and aneurysm rupture ( HR , 1.96 ; 95 % CI , 1.12–.44 ; P = 0.01 ) significantly affected long-term survival . Conclusion Preoperative circulatory failure is the most common cause of death for in-hospital mortality of rAAA patients . After excluding patients who have died during the perioperative period , age is the only factor that affects the survival of rAAA patients


Title 5:
Cystatin C deficiency is associated with the progression of small abdominal aortic aneurysms
Abstract 5:
The cysteine protease inhibitor cystatin C may play a role in the development and progression of abdominal aortic aneurysms ( AAAs )


Title 6:
Circulating biomarkers and abdominal aortic aneurysm size.
Abstract 6:
BACKGROUND Abdominal aortic aneurysm ( AAA ) is a degenerative disease of the abdominal aorta leading to progressive dilatation , intra-luminal thrombus ( ILT ) formation , and rupture . Underst and ing the natural history of AAA is essential , because different processes and , therefore , different biomarkers , could be involved at each stage of disease progression . The purpose of the present study was to investigate the relationship between systemic expression of biomarkers of inflammation and extracellular matrix remodeling and aneurysm size in AAA patients . METHODS AND RESULTS All consecutive patients admitted to the ( out- ) patient clinic of the surgical department of two large community centers were prospect ively included . Patients were divided into three groups based on their aneurysm diameter : small ( 30 - 44 mm ; n = 59 ) , medium-sized ( 45 - 54 mm ; n = 64 ) or large ( ≥ 55 mm ; n = 95 ) AAA . Linear regression modeling showed that age and serum hsCRP concentration were positively associated , whereas serum HDL and IgG concentrations were negatively associated with aneurysm size . This regression model was corrected for possible bias due to statin use and center of inclusion ; and also indicated that in general men have larger aneurysms compared with women . CONCLUSIONS Different aneurysm sizes showed different expression pattern of HDL , IgG , and hsCRP . These biomarkers may be useful in predicting AAA progression


Title 7:
Screening for Abdominal Aortic Aneurysm: US Preventive Services Task Force Recommendation Statement.
Abstract 7:
Importance An abdominal aortic aneurysm ( AAA ) is typically defined as aortic enlargement with a diameter of 3.0 cm or larger . The prevalence of AAA has declined over the past 2 decades among screened men 65 years or older in various European countries . The current prevalence of AAA in the United States is unclear because of the low uptake of screening . Most AAAs are asymptomatic until they rupture . Although the risk for rupture varies greatly by aneurysm size , the associated risk for death with rupture is as high as 81 % . Objective To up date its 2014 recommendation , the USPSTF commissioned a review of the evidence on the effectiveness of 1-time and repeated screening for AAA , the associated harms of screening , and the benefits and harms of available treatments for small AAAs ( 3.0 - 5.4 cm in diameter ) identified through screening . Population This recommendation applies to asymptomatic adults 50 years or older . However , the r and omized trial evidence focuses almost entirely on men aged 65 to 75 years . Evidence Assessment Based on a review of the evidence , the USPSTF concludes with moderate certainty that screening for AAA in men aged 65 to 75 years who have ever smoked is of moderate net benefit . The USPSTF concludes with moderate certainty that screening for AAA in men aged 65 to 75 years who have never smoked is of small net benefit . The USPSTF concludes that the evidence is insufficient to determine the net benefit of screening for AAA in women aged 65 to 75 years who have ever smoked or have a family history of AAA . The USPSTF concludes with moderate certainty that the harms of screening for AAA in women aged 65 to 75 years who have never smoked and have no family history of AAA outweigh the benefits . Recommendations The USPSTF recommends 1-time screening for AAA with ultrasonography in men aged 65 to 75 years who have ever smoked . ( B recommendation ) The USPSTF recommends that clinicians selectively offer screening for AAA with ultrasonography in men aged 65 to 75 years who have never smoked rather than routinely screening all men in this group . ( C recommendation ) The USPSTF recommends against routine screening for  AAA  with ultrasonography in women who have never smoked and have no family history of AAA . ( D recommendation ) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for AAA with ultrasonography in women aged 65 to 75 years who have ever smoked or have a family history of AAA . ( I statement )
Multi-regression analysis found the difference in means of hsCRP plasma levels between AAA and control groups decreased as aortic diameter increased ( slope = -0.04 , p < .001 ) , suggesting that hsCRP levels may be inversely associated with increasing aneurysm size .
Our findings suggest that hsCRP levels may possibly be used as a diagnostic biomarker for AAA patients with medium or small aortic diameter but not for AAA patients with large aortic diameter .
The correlation between serum hsCRP  level and AAA aneurysm is not conclusive due to the small number of included articles and between- study heterogeneity