***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: Abstract — Plasma levels of C-reactive protein ( CRP , a marker of the reactant plasma protein component of the inflammatory response ) and of fibrin D-dimer ( a marker of cross-linked fibrin turnover ) have each been associated in recent studies with the risk of future ischemic heart disease ( IHD ) . Previous experimental studies have shown that fibrin degradation products , including D-dimer , have effects on inflammatory processes and acute-phase protein responses . In the Speedwell Prospect i ve Study , we therefore measured  CRP and D-dimer levels  in stored plasma sample s from 1690 men aged 49 to 67 years who were followed-up for incident IHD for an average of 75±4 months ( mean±SD ) and studied their associations with each other , with baseline and incident IHD , and with IHD risk factors . CRP and D-dimer levels were each associated with age , plasma fibrinogen , smoking habit , and baseline evidence of IHD . CRP was associated with D-dimer ( r = 0.21 , P < 0.00001 ) . On univariate analyses , both CRP and D-dimer were associated with incident IHD . The incidence of IHD increased with CRP independently of the level of D-dimer ( P = 0.0002 ) and also increased with D-dimer independently of the level of CRP ( P = 0.048 ) . In multivariate analyses , inclusion of D-dimer and conventional risk factors reduced the strength of the association between CRP and incident IHD ; likewise , inclusion of CRP and conventional risk factors reduced the strength of the association between D-dimer and incident IHD . We conclude that although these respective markers of inflammation and fibrin turnover show modest association with each other in middle-aged men , they may have additive associations with risk of incident IHD . Further larger studies are required to test this hypothesis BACKGROUND Epidemiologic studies have shown that C-reactive protein ( CRP ) is a risk factor for coronary heart disease . Whether routine measurement of CRP has a role in the prediction of future coronary disease in everyday clinical practice has not yet been investigated . METHODS Within the Rotterdam Study , a population -based cohort study of 7983 men and women 55 years and older , we conducted a nested case-control study to investigate the value of CRP in coronary disease prediction . Data are based on 157 participants who experienced a myocardial infa rct ion during follow-up and 500 r and omly selected controls .  High-sensitivity CRP and traditional cardiovascular risk factors were measured at baseline . RESULTS The age- and sex-adjusted relative risk of myocardial infa rct ion for subjects in the highest quartile of the population distribution of CRP compared with the lowest quartile was 2.0 ( 95 % confidence interval , 1.1 - 3.4 ) . After additional adjustment for traditional cardiovascular risk factors , the increase in risk largely disappeared ( odds ratio , 1.2 ; 95 % confidence interval , 0.6 - 2.2 ) . Adding CRP to a coronary disease risk function based on risk factors that are routinely assessed in clinical practice or to the Framingham risk function did not improve the area under the receiver operating characteristic curve of these risk functions . Sensitivity and specificity of both risk functions , computed after dichotomizing the estimated disease probabilities using prespecified cutoff points , hardly improved when CRP was added . CONCLUSION Measurement of  CRP in elderly people has no additional value in coronary disease risk prediction when traditional cardiovascular risk factors are known 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 Objective —This study was undertaken to examine the association of plasma inflammatory markers such as C-reactive protein ( CRP ) , interleukin-6 , and fibrinogen with the incidence of coronary heart disease within the prospect i ve cohort study on myocardial infa rct ion ( PRIME study ) . Methods and Results —Multiple risk factors were recorded at baseline in 9758 men aged 50 to 59 years who were free of coronary heart disease ( CHD ) on entry . Nested case-control comparisons were carried out on 317 participants who suffered myocardial infa rct ion (MI)-coronary death ( n=163 ) or angina ( n=158 ) as an initial CHD event during a follow-up for 5 years . After adjustment for traditional risk factors , incident MI-coronary death , but not angina , was significantly associated with CRP , interleukin-6 , and fibrinogen , but only interleukin-6 remained significantly associated with MI-coronary death when the 3 inflammatory markers were included in the model . The different interleukin-6 levels in Northern Irel and and France partly explained the difference in risk between these countries . Interleukin-6 appeared as a risk marker of MI-coronary death , and it improved the definition of CHD risk beyond LDL cholesterol . Conclusions —This association may reflect the underlying inflammatory reaction located in the atherosclerotic plaque or a genetic susceptibility on the part of CHD subjects to answer a proinflammatory stimulus and subsequent increase in hepatic CRP gene expression C-reactive protein ( CRP ) was proposed as a stronger predictor of cardiovascular events than low-density lipoprotein cholesterol ( LDL-C ) ; however , these associations may differ between myocardial infa rct ion ( MI ) and stroke . We compared statistically the associations of CRP and LDL-C levels with risk of MI versus stroke and examined to what extent consideration of CRP or LDL-C increases the population attributable fractions ( PAFs ) of MI and stroke beyond traditional risk factors among 27,548 subjects from the European Prospect i ve Investigation into Cancer and Nutrition-Potsdam Study in a case-cohort design . Among subjects without prior MI or stroke , 156 developed MI and 132 stroke during 6.0 years of follow-up . In adjusted competing risk analyses CRP was positively related to MI and stroke ( P difference between endpoints = 0.55 ) , whereas LDL-C was related to MI but not stroke ( P difference between endpoints = 0.003 ) . The PAF for smoking , diabetes , and hypertension combined was 0.76 for MI , and 0.58 for stroke . With additional consideration of CRP the PAFs were 0.80 and 0.68 , while with addition of LDL-C the PAFs were 0.88 and 0.55 . We conclude that CRP is equally strongly related to risk of MI and stroke , whereas LDL-C is related to risk of MI but not stroke . Consideration of LDL-C beyond smoking , diabetes and hypertension may increase the PAF of MI slightly more than CRP . In contrast , consideration of CRP but not of  LDL-C  may increase the PAF of stroke beyond these factors BACKGROUND Since inflammation is believed to have a role in the pathogenesis of cardiovascular events , measurement of markers of inflammation has been proposed as a method to improve the prediction of the risk of these events . METHODS We conducted a prospect i ve , nested case-control study among 28,263 apparently healthy postmenopausal women over a mean follow-up period of three years to assess the risk of cardiovascular events associated with base-line levels of markers of inflammation . The markers included high-sensitivity C-reactive protein ( hs-CRP ) , serum amyloid A , interleukin-6 , and soluble intercellular adhesion molecule type 1 ( sICAM-1 ) . We also studied homocysteine and a variety of lipid and lipoprotein measurements .  Cardiovascular events were defined as death from coronary heart disease , nonfatal myocardial infa rct ion or stroke , or the need for coronary-revascularization procedures . RESULTS Of the 12 markers measured , hs-CRP was the strongest univariate predictor of the risk of cardiovascular events ; the relative risk of events for women in the highest as compared with the lowest quartile for this marker was 4.4 ( 95 percent confidence interval , 2.2 to 8.9 ) . Other markers significantly associated with the risk of cardiovascular events were serum amyloid A ( relative risk for the highest as compared with the lowest quartile , 3.0 ) , sICAM-1 ( 2.6 ) , interleukin-6 ( 2.2 ) , homocysteine ( 2.0 ) , total cholesterol ( 2.4 ) , LDL cholesterol ( 2.4 ) , apolipoprotein B-100 ( 3.4 ) , HDL cholesterol ( 0.3 ) , and the ratio of total cholesterol to HDL cholesterol ( 3.4 ) . Prediction models that incorporated markers of inflammation in addition to lipids were significantly better at predicting risk than models based on lipid levels alone ( P<0.001 ) . The levels of hs-CRP and serum amyloid A were significant predictors of risk even in the subgroup of women with LDL cholesterol levels below 130 mg per deciliter ( 3.4 mmol per liter ) , the target for primary prevention established by the National Cholesterol Education Program . In multivariate analyses , the only plasma markers that independently predicted risk were hs-CRP ( relative risk for the highest as compared with the lowest quartile , 1.5 ; 95 percent confidence interval , 1.1 to 2.1 ) and the ratio of total cholesterol to HDL cholesterol ( relative risk , 1.4 ; 95 percent confidence interval , 1.1 to 1.9 ) . CONCLUSIONS The addition of the measurement of C-reactive protein to screening based on lipid levels may provide an improved method of identifying persons at risk for cardiovascular events BACKGROUND Statins lower the levels of low-density lipoprotein ( LDL ) cholesterol and C-reactive protein ( CRP ) . Whether this latter property affects clinical outcomes is unknown . METHODS We evaluated relationships between the LDL cholesterol and CRP levels achieved after treatment with 80 mg of atorvastatin or 40 mg of pravastatin per day and the risk of recurrent myocardial infa rct ion or death from coronary causes among 3745 patients with acute coronary syndromes . RESULTS Patients in whom statin therapy result ed in LDL cholesterol levels  of less than 70 mg per deciliter ( 1.8 mmol per liter ) had lower event rates than those with higher levels ( 2.7 vs. 4.0 events per 100 person-years , P=0.008 ) . However , a virtually identical difference was observed between those who had CRP levels of less than 2 mg per liter after statin therapy and those who had higher levels ( 2.8 vs. 3.9 events per 100 person-years , P=0.006 ) , an effect present at all levels of LDL cholesterol achieved . For patients with post-treatment LDL cholesterol levels  of more than 70 mg per deciliter , the rates of recurrent events were 4.6 per 100 person-years among those with CRP levels of more than 2 mg per liter and 3.2 events per 100 person-years among those with CRP levels of less than 2 mg per liter ; the respective rates among those with LDL cholesterol levels of less than 70 mg per deciliter were 3.1 and 2.4 events per 100 person-years ( P<0.001 ) . Although atorvastatin was more likely than pravastatin to result in low levels of LDL cholesterol and CRP , meeting these targets was more important in determining the outcomes than was the specific choice of therapy . Patients who had LDL cholesterol levels of less than 70 mg per deciliter and CRP levels of less than 1 mg per liter after statin therapy had the lowest rate of recurrent events ( 1.9 per 100 person-years ) . CONCLUSIONS Patients who have low CRP levels after statin therapy  have better clinical outcomes than those with higher CRP levels , regardless of the result ant 
    Output:
    
The potential clinical benefit of new risk factors for refining global risk assessment is thought to be greatest for persons who are classified as intermediate-risk when stratified by using conventional risk factors ( 15 ) .
Most studies provided an overall estimate of the risk associated with high CRP levels , after adjustment for other risk factors , but did not provide specific evidence about the intermediate-risk group .