***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 Among apparently healthy men , elevated levels of C-reactive protein ( CRP ) , a marker for systemic inflammation , predict risk of myocardial infa rct ion and thromboembolic stroke . Whether increased levels of CRP are also associated with the development of symptomatic peripheral arterial disease ( PAD ) is unknown . METHODS AND RESULTS Using a prospect i ve , nested , case-control design , we measured baseline levels of CRP in 144 apparently healthy men participating in the Physicians ' Health Study who subsequently developed symptomatic PAD ( intermittent claudication or need for revascularization ) and in an equal number of control subjects matched on the basis of age and smoking habit who remained free of vascular disease during a follow-up period of 60 months .  Median CRP levels at baseline were significantly higher among those who subsequently developed PAD ( 1.34 versus 0.99 mg/L ; P=.04 ) . Furthermore , the risks of developing PAD increased significantly with each increasing quartile of baseline CRP concentration such that relative risks of PAD from lowest ( referent ) to highest quartile of CRP were 1.0 , 1.3 , 2.0 , and 2.1 ( Ptrend=.02 ) . Compared with those with no clinical evidence of disease , the subgroup of case patients who required revascularization had the highest baseline CRP levels ( median= 1.75 mg/L ; P= .04 ) ; relative risks from lowest to highest quartile of CRP for this end point were 1.0 , 1.8 , 3.8 , and 4.1 ( Ptrend=.02 ) . Risk estimates were similar after additional control for body mass index , hypercholesterolemia , hypertension , diabetes , and a family history of premature atherosclerosis . CONCLUSIONS These prospect i ve data indicate that among apparently healthy men , baseline levels of CRP predict future risk of developing symptomatic PAD and thus provide further support for the hypothesis that chronic inflammation is important in the pathogenesis of atherothrombosis In 1998 , the American Heart Association convened Prevention Conference V to examine strategies for the identification of high-risk patients who need primary prevention . Among the strategies discussed was the measurement of markers of inflammation.1  The Conference concluded that “ many of these markers ( including inflammatory markers ) are not yet considered applicable for routine risk assessment because of : ( 1 ) lack of measurement st and ardization , ( 2 ) lack of consistency in epidemiological findings from prospect i ve studies with endpoints , and ( 3 ) lack of evidence that the novel marker adds to risk prediction over and above that already achievable through the use of established risk factors . ” The National Cholesterol Education Program Adult Treatment Panel III Guidelines identified these markers as emerging risk factors,1a which could be used as an optional risk factor measurement to adjust estimates of absolute risk obtained using st and ard risk factors . Since these publications , a large number of peer- review ed scientific reports have been published relating inflammatory markers to cardiovascular disease ( CVD ) . Several commercial assays for inflammatory markers have become available . As a consequence of the exp and ing research base and availability of assays , the number of inflammatory marker tests ordered by clinicians for CVD risk prediction has grown rapidly . Despite this , there has been no consensus from professional societies or governmental agencies as to how these assays of markers of inflammation should be used in clinical practice . On March 14 and 15 , 2002 , a workshop titled “ CDC/AHA Workshop on Inflammatory Markers and Cardiovascular Disease : Applications to Clinical and Public Health Practice ” was convened in Atlanta , Ga , to address these issues . The goals of this workshop were to determine which of the currently available tests should be used ; what results should be used to define high risk ; which patients should be tested ; and the indications for which the tests would be most useful . These BACKGROUND The objective of this study was to examine the association of Joint National Committee ( JNC-V ) blood pressure and National Cholesterol Education Program ( NCEP ) cholesterol categories with coronary heart disease ( CHD ) risk , to incorporate them into coronary prediction algorithms , and to compare the discrimination properties of this approach with other noncategorical prediction functions . METHODS AND RESULTS This work was design ed as a prospect i ve , single-center study in the setting of a community-based cohort . The patients were 2489 men and 2856 women 30 to 74 years old at baseline with 12 years of follow-up . During the 12 years of follow-up , a total of 383 men and 227 women developed  CHD , which was significantly associated with categories of blood pressure , total cholesterol , LDL cholesterol , and HDL cholesterol ( all P<.001 ) . Sex-specific prediction equations were formulated to predict CHD risk according to age , diabetes , smoking , JNC-V blood pressure categories , and NCEP total cholesterol and LDL cholesterol categories . The accuracy of this categorical approach was found to be comparable to CHD prediction when the continuous variables themselves were used . After adjustment for other factors , approximately 28 % of CHD events in men and 29 % in women were attributable to blood pressure levels that exceeded high normal ( > or = 130/85 ) . The corresponding multivariable-adjusted attributable risk percent associated with elevated total cholesterol ( > or = 200 mg/dL ) was 27 % in men and 34 % in women . CONCLUSIONS Recommended guidelines of blood pressure , total cholesterol , and LDL cholesterol effectively predict CHD risk in a middle-aged white population sample . A simple coronary disease prediction algorithm was developed using categorical variables , which allows physicians to predict multivariate CHD risk in patients without overt CHD AIMS Recently , markers of inflammation , haemostasis , and blood rheology have received much attention as risk factors for coronary heart disease and stroke . However , their role in peripheral arterial disease ( PAD ) is not well established and some of them , including the pro-inflammatory cytokine interleukin-6 ( IL-6 ) , have not been examined before in prospect i ve epidemiological studies . METHODS AND RESULTS In the Edinburgh Artery Study , we studied the development of PAD in the general population and evaluated 17 potential blood markers as predictors of incident PAD . At baseline ( 1987 ) , 1519 men and women free of PAD aged 55 - 74 were recruited . After 17 years , 208 subjects had developed symptomatic PAD . In analysis adjusted for cardiovascular risk factors and baseline cardiovascular disease ( CVD ) , only C-reactive protein , fibrinogen , lipoprotein ( a ) , and haematocrit [ hazard ratio ( 95 % CI ) corresponding to an increase equal to the inter-tertile range 1.30 ( 1.08 , 1.56 ) , 1.16 ( 1.05 , 1.17 ) , 1.22 ( 1.04 , 1.44 ) , 1.22 ( 1.08 , 1.38 ) ] were significantly ( P < 0.01 ) associated with PAD . However , these markers provided very little prognostic information for incident PAD to that obtained by cardiovascular risk factors and the ankle brachial index . Other markers including IL-6 , intracellular adhesion molecule 1 , d-dimer , tissue plasminogen activator antigen , and plasma and blood viscosities showed weak associations , which were considerably attenuated when CVD risk factors were accounted for . CONCLUSIONS Our prospect i ve data showed that several inflammatory , haemostatic , and rheological markers are associated with incident PAD ; however , their clinical utility is likely to be limited . Future research is necessary to vali date the importance of these biomarkers explicitly on PAD and to address the causality of the reported associations CONTEXT Despite improved underst and ing of atherothrombosis , cardiovascular prediction algorithms for women have largely relied on traditional risk factors . OBJECTIVE To develop and vali date cardiovascular risk algorithms for women based on a large panel of traditional and novel risk factors . DESIGN , SETTING , AND PARTICIPANTS Thirty-five factors were assessed among 24 558 initially healthy US women 45 years or older who were followed up for a median of 10.2 years ( through March 2004 ) for incident cardiovascular events ( an adjudicated composite of myocardial infa rct ion , ischemic stroke , coronary revascularization , and cardiovascular death ) . We used data among a r and om two thirds ( derivation cohort , n = 16 400 ) to develop new risk algorithms that were then tested to compare observed and predicted outcomes in the remaining one third of women ( validation cohort , n = 8158 ) . MAIN OUTCOME MEASURE Minimization of the Bayes Information Criterion was used in the derivation cohort to develop the best-fitting parsimonious prediction models . In the validation cohort , we compared predicted vs actual 10-year cardiovascular event rates when the new algorithms were compared with models based on covariates included in the Adult Treatment Panel III risk score . RESULTS In the derivation cohort , a best-fitting model ( model A ) and a clinical ly simplified model ( model B , the Reynolds Risk Score ) had lower Bayes Information Criterion scores than models based on covariates used in Adult Treatment Panel III . In the validation cohort , all measures of fit , discrimination , and calibration were improved when either model A or B was used . For example , among participants without diabetes with estimated 10-year risks according to the Adult Treatment Panel III of 5 % to less than 10 % ( n = 603 ) or 10 % to less than 20 % ( n = 156 ) , model A reclassified 379 ( 50 % ) into higher- or lower-risk categories that in each instance more accurately matched actual event rates . Similar effects were achieved for clinical ly simplified model B limited to age , systolic blood pressure , hemoglobin A(1c ) if diabetic , smoking , total and high-density lipoprotein cholesterol , high-sensitivity C-reactive protein , and parental history of myocardial infa rct ion before age 60 years . Neither new algorithm provided substantive information about women at very low risk based on the published Adult Treatment Panel III score . CONCLUSION We developed , vali date d , and demonstrated highly improved accuracy of 2 clinical algorithms for global cardiovascular risk prediction that reclassified 40 % to 50 % of women at intermediate risk into higher- or lower-risk categories CONTEXT Inflammation is hypothesized to play a role in development of type 2 diabetes mellitus ( DM ) ; however , clinical data addressing this issue are limited . OBJECTIVE To determine whether elevated levels of the inflammatory markers interleukin 6 ( IL-6 ) and  C-reactive protein ( CRP ) are associated with development of  type 2 DM in healthy middle-aged women . DESIGN Prospect i ve , nested case-control study . SETTING The Women 's Health Study , an ongoing US primary prevention , r and omized clinical trial initiated in 1992 . PARTICIPANTS From a nationwide cohort of 27 628 women free of diagnosed DM , cardiovascular disease , and cancer at baseline , 188 women who developed diagnosed DM over a 4-year follow-up period were defined as cases and matched by age and fasting status with 362 disease-free controls . MAIN OUTCOME MEASURES Incidence of confirmed clinical ly diagnosed type 2 DM by baseline levels of IL-6 and CRP . RESULTS Baseline levels of IL-6 ( P<.001 ) and CRP ( P<.001 ) were significantly higher among cases than among controls . The relative risks of future DM for women in the highest vs lowest quartile of these inflammatory markers were 7.5 for IL-6 ( 95 % confidence interval [ CI ] , 3.7 - 15.4 ) and 15.7 for CRP ( 95 % CI , 6.5 - 37.9 ) . Positive associations persisted after adjustment for body mass index , family history of diabetes , smoking , exercise , use of alcohol , and hormone replacement therapy ; multivariate relative risks for the highest vs lowest quartiles were 2.3 for IL-6 ( 95 % CI , 0.9 - 5.6 ; P for trend = .07 ) and 4.2 for CRP ( 95 % CI , 1.5 - 12.0 ; P for trend = .001 ) . Similar results were observed in analyses limited to women with a baseline hemoglobin A(1c ) of 6.0 % or less and after adjustment for fasting insulin level . CONCLUSIONS Elevated levels of CRP and IL-6 predict the development of type 2 DM . These data support a possible role for inflammation in diabetogenesis BACKGROUND C-reactive protein is an inflammatory marker believed to be of value in the prediction of coronary events . We report data from a large study of C-reactive protein and other circulating inflammatory markers , as well as up date d meta-analyses , to evaluate their relevance to the prediction of coronary heart disease . METHODS Measurements were made in sample s obtained at base line from up to 2459 patients who had a nonfatal myocardial infa rct ion or died of coronary heart disease during the study and from up to 3969 controls without a coronary heart disease event in the Reykjavik prospect i ve study of 18,569 participants .  Measurements were made in paired sample s obtained an average of 12 years apart from 379 of these participants in order to quantify within-person fluctuations in inflammatory marker levels 
    Output:
    
CRP does not perform better than the Framingham risk equation for discrimination .
The improvement in risk stratification or reclassification from addition of CRP to models based on established risk factors is small and inconsistent .