***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: OBJECTIVES This study was design ed to evaluate B-type natriuretic peptide ( BNP ) for risk assessment and clinical decision making over a range of cut points , alone and with cardiac troponin I ( cTnI ) , in patients with non-ST-elevation acute coronary syndromes ( ACS ) . BACKGROUND B-type natriuretic peptide holds promise for risk stratification . Additional evidence regarding optimal decision limits , use in combination with troponin , and use in targeting therapy is needed before acceptance into clinical use for ACS . METHODS We evaluated BNP at baseline in 1,676 patients with non-ST-elevation ACS r and omized to early invasive versus conservative management . RESULTS Patients with elevated BNP ( > 80 pg/ml ; n = 320 ) were at higher risk of death at seven days ( 2.5 % vs. 0.7 % , p = 0.006 ) and six months ( 8.4 % vs. 1.8 % , p < 0.0001 ) . The association between BNP and mortality at six months ( adjusted odds ratio [ OR ] 3.3 ; 95 % confidence interval [ CI ] 1.7 to 6.3 ) was independent of important clinical predictors , including cTnI and congestive heart failure ( CHF ) . Patients with elevated BNP had a fivefold higher risk of developing new CHF by 30 days ( 5.9 % vs. 1.0 % , p < 0.0001 ) . B-type natriuretic peptide added prognostic information to cTnI , discriminating patients at higher mortality risk among those with negative ( OR 6.9 ; 95 % CI 1.9 to 25.8 ) and positive ( OR 4.1 ; 95 % CI 1.9 to 9.0 ) baseline cTnI results . No difference was observed in the effect of invasive versus conservative management when stratified by baseline levels of BNP ( p(interaction ) > or = 0.6 ) . CONCLUSIONS Elevated BNP ( > 80 pg/ml ) at presentation identifies patients with non-ST-elevation ACS who are at higher risk of death and CHF and adds incremental information to cTnI. Additional work is needed to identify therapies that may reduce the risk associated with increased BNP OBJECTIVES The goal of this study was to determine the predictive value of pregnancy-associated plasma protein-A ( PAPP-A ) in patients with acute coronary syndromes ( ACS ) . BACKGROUND Pregnancy-associated plasma protein-A is a zinc-binding matrix metalloproteinase abundantly expressed in eroded and ruptured plaques and may serve as a marker of plaque destabilization . METHODS In 547 patients with angiographically vali date d ACS and in a heterogeneous emergency room population of 644 patients with acute chest pain , respectively , PAPP-A as well as markers of myocardial necrosis ( troponin T [ TnT ] ) , ischemia ( vascular endothelial growth factor [ VEGF ] ) , inflammation ( high-sensitivity C-reactive protein [ hsCRP ] ) , anti-inflammatory activity ( interleukin [IL]-10 ) , and platelet activation ( soluble CD40 lig and [ sCD40L ] ) were determined . Patients were followed for the occurrence of death or myocardial infa rct ion . RESULTS In patients with ACS , elevated PAPP-A levels ( > 12.6 mIU/l ) indicated an increased risk ( odds ratio 2.44 [ 95 % confidence interval ( CI ) 1.43 to 4.15 ] ; p = 0.001 ) . When the analysis was restricted to TnT-negative patients , PAPP-A still identified a subgroup of high-risk patients ( odds ratio [ OR ] 2.72 [ 95 % confidence interval ( CI ) 1.25 to 5.89 ] ; p = 0.009 ) . In a multivariable model , PAPP-A ( OR 2.01 ; p = 0.015 ) , sCD40L ( OR 2.37 ; p = 0.003 ) , IL-10 ( OR 0.43 ; p = 0.003 ) , and VEGF ( OR 2.19 ; p = 0.018 ) were independent predictors . Prospect i ve validation in patients with chest pain confirmed that  PAPP-A levels reliably identify high-risk patients ( adjusted OR 2.32 [ 95 % CI 1.32 to 4.26 ] ; p = 0.008 ) . Patients negative for all three markers ( TnT , sCD40L , and PAPP-A ) were at very low cardiac risk ( 30 days : 3.0 % event rate ; no death ) . CONCLUSIONS The PAPP-A level as a marker of plaque instability is a strong independent predictor of cardiovascular events in patients with ACS . Simultaneous determination of biomarkers with distinct pathophysiological profiles appears to remarkably improve risk stratification in patients with ACS BACKGROUND Although previous investigations have suggested that 24 hours is required to exclude acute myocardial infa rct ion in patients who are admitted to a coronary care unit for the evaluation of acute chest pain , we hypothesized that a 12-hour period might be adequate for patients with a low probability of infa rct ion at the time of admission . METHODS Using a Bayesian model , we developed a strategy to identify c and i date s for a shorter period of observation from an analysis of a derivation set of 976 patients with acute chest pain who were admitted to three teaching and four community hospitals . In the derivation set , patients whose clinical characteristics in the emergency room predicted a low ( less than or equal to 7 percent ) probability of myocardial infa rct ion had only a 0.4 percent risk of infa rct ion if they had neither abnormal levels of cardiac enzymes nor recurrent ischemic pain during the first 12 hours of hospitalization . In an independent testing set of 2684 patients from the seven hospitals , 957 admitted patients ( 36 percent ) were classified as c and i date s for this 12-hour period of observation according to a previously published multivariate algorithm . Few of these patients were actually transferred from a monitored setting at 12 hours . RESULTS Of the 771 c and i date s for a 12-hour period of observation who did not have enzyme abnormalities or recurrent pain during the first 12 hours , 4 ( 0.5 percent ) were subsequently found to have acute myocardial infa rct ion , and only 3 ( 0.4 percent ) died after primary cardiac arrests , all of which occurred three to five days after admission . Rates of other major cardiovascular complications were low in the patients who might have been transferred from the coronary care unit after 12 hours with this strategy . In patients with a higher initial risk of infa rct ion , the st and ard strategy of 24-hour observation identified all but 11 of 739 acute myocardial infa rct ions ( 1 percent ) . CONCLUSIONS Emergency room clinical data can be used to identify a large subgroup of patients for whom a 12-hour period of observation is normally sufficient to exclude acute myocardial infa rct ion . Patient-specific evaluation and treatment can then proceed without the restrictions imposed by " rule-out " protocol s for myocardial infa rct ion Background —Monocyte chemoattractant protein-1 ( MCP-1 ) is a chemokine responsible for the recruitment of monocytes to sites of inflammation . MCP-1 appears to play a critical role at multiple stages in atherosclerosis , including the initiation of the fatty streak , promotion of plaque instability , and remodeling after myocardial infa rct ion . Methods and Results —MCP-1 was measured from frozen plasma specimens in 279 healthy volunteers and 2270 patients with acute coronary syndromes enrolled in the Oral Glycoprotein IIb/IIIa Inhibition with Orbofiban in Patients with Unstable Coronary Syndromes ( OPUS-TIMI ) 16 trial . Median [ 25th , 75th percentiles ] MCP-1 levels were 157 [ 124 , 196 ] pg/mL in healthy volunteers and 178 [ 128 , 238 ] pg/mL in the OPUS-TIMI 16 population ( P < 0.001 ) . In OPUS-TIMI 16 , baseline MCP-1 levels were associated with older age , female sex , hypertension , diabetes , prior coronary disease , and renal insufficiency ( P < 0.01 for each ) but not with smoking status , body mass index , ejection fraction , troponin I or C-reactive protein . After adjustment for differences in baseline characteristics , ECG changes , troponin I , and C-reactive protein , an MCP-1 level > 75th percentile ( corresponding to the 90th percentile in the healthy volunteers ) was associated with an increased risk of death or myocardial infa rct ion through 10 months of follow-up ( adjusted hazard ratio , 1.53 ; 95 % CI , 1.09 to 2.14;P = 0.01 ) . Conclusions —In a large cohort of patients with acute coronary syndromes , an elevated baseline level of MCP-1 was associated both with traditional risk factors for atherosclerosis as well as an increased risk for death or myocardial infa rct ion , independent of baseline variables . Because it appears to play a crucial role at multiple stages of atherosclerosis , MCP-1 is attractive as a surrogate biomarker and merits further study as a potential therapeutic target Proinflammatory state may contribute to the excessive prevalence of type 2 diabetes and cardiovascular disease observed in population s originating from the Indian subcontinent ( Asian Indians ) . This study was conducted to evaluate whether nondiabetic Asian Indian men living in the United States manifest a proinflammatory state when compared with Caucasians of similar age and body fat content . We also compared the relationships between plasma high-sensitivity C-reactive protein ( hs-CRP ) , a marker of low- grade inflammation , and various parameters of body composition and fat distribution and insulin sensitivity in Asian Indians and Caucasians . For this purpose ,  plasma hs-CRP , oral glucose tolerance test , and anthropometric measurements  were conducted in 82 Asian Indian men and 55 Caucasian men of similar age . The two groups had similar body fat content and truncal skinfolds thickness . Asian Indians had higher insulin areas under the curve during oral glucose tolerance tests , indicating a greater insulin resistance . Asian Indians also manifested a significant elevation of plasma hs-CRP . We conclude that young , overtly healthy Asian Indian men have both greater insulin resistance and higher hs-CRP levels than do Caucasians . This difference can not be explained by greater adiposity in Asian Indians and suggests that many Asian Indians have an underlying proinflammatory state that may contribute to their increased risk for both type 2 diabetes and cardiovascular disease To achieve more appropriate triage to the coronary care unit of patients presenting with acute chest pain , we used clinical data on 1379 patients at two hospitals to construct a simple computer protocol to predict the presence of myocardial infa rct ion . When we tested this protocol prospect ively in 4770 patients at two university hospitals and four community hospitals , the computer-derived protocol had a significantly higher specificity ( 74 vs. 71 percent ) in predicting the absence of infa rct ion than physicians deciding whether to admit patients to the coronary care unit , and it had a similar sensitivity in detecting the presence of infa rct ion ( 88.0 vs. 87.8 percent ) . Decisions based solely on the computer protocol would have reduced the admission of patients without infa rct ion to the coronary care unit by 11.5 percent without adversely affecting the admission of patients in whom emergent complications developed that required intensive care . Although this protocol should not be used to override careful clinical judgment in individual cases , the computer protocol for the most part yields accurate estimates of the probability of myocardial infa rct ion . Decisions about admission to the coronary care unit based on the protocol would have been as effective as those actually made by the unaided physicians who cared for the patients , and less costly . Whether physicians who are aided by the protocol perform better than unaided physicians can not be determined without further study BACKGROUND In patients with unstable coronary artery disease , there is a relation between the short-term risk of death and blood levels of troponin  T ( a marker of myocardial damage ) and C-reactive protein and fibrinogen ( markers of inflammation ) . Using information obtained during an extension of the follow-up period in the Fragmin during Instability in Coronary Artery Disease trial , we evaluated the usefulness of troponin T , C-reactive protein , and fibrinogen levels and other indicators of risk as predictors of the long-term risk of death from cardiac causes . METHODS Levels of C-reactive protein and fibrinogen at enrollment and the maximal level of troponin T during the first 24 hours after enrollment were analyzed in 917 patients included in a clinical trial of low-molecular-weight heparin in unstable coronary artery disease . The patients were followed for a mean of 37.0 months ( range , 1.6 to 50.6 ) . RESULTS During follow-up , 1.2 percent of the 173 patients with maximal blood troponin T levels of less than 0.06 microg per liter died of cardiac causes , as compared with 8.7 percent of the 367 patients with levels 
    Output:
    
Published evidence is not sufficient to support the routine use of new protein markers in screening for ACS in the emergency department setting