***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 sought to investigate whether pregnancy-associated plasma protein-A ( PAPP-A ) is useful for risk assessment in non-ST-segment elevation acute coronary syndrome ( NSTE-ACS ) . BACKGROUND PAPP-A is a high molecular weight , zinc-binding metalloproteinase that is associated with vulnerable plaque and may be a predictor of cardiovascular disease and mortality . METHODS We measured PAPP-A at baseline in 3,782 patients with non NSTE-ACS r and omized to ranolazine or placebo in the MERLIN-TIMI 36 ( Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes ) trial and followed for an average of 1 year . A cut point of 6.0 μIU/ml was chosen from pilot work in this cohort . RESULTS PAPP-A > 6.0 μIU/ml at presentation was associated with higher rates of cardiovascular death ( CVD ) or myocardial infa rct ion ( MI ) at 30 days ( 7.4 % vs. 3.7 % , hazard ratio [ HR ] : 2.01 ; 95 % confidence interval [ CI ] : 1.43 to 2.82 ; p < 0.001 ) and at 1 year ( 14.9 % vs. 9.7 % , HR : 1.63 ; 95 % CI : 1.29 to 2.05 ; p < 0.001 ) . PAPP-A was also associated with higher rates of CVD ( HR : 1.94 ; 95 % CI : 1.07 to 3.52 , p = 0.027 ) and myocardial infa rct ion ( HR : 1.82 ; 95 % CI : 1.22 to 2.71 , p = 0.003 ) individually at 30 days . There was no difference in the risk associated with PAPP-A stratified by baseline cardiac troponin I [ Accu-TnI > 0.04 μg/l ] , p interaction = 0.87 ) . After adjustment for cardiac troponin I , ST-segment deviation , age , sex , diabetes , smoking , hypertension , and coronary artery disease , PAPP-A was independently associated with CVD/myocardial infa rct ion at 30 days ( adjusted HR : 1.62 , 95 % CI : 1.15 to 2.29 ; p = 0.006 ) and 1 year ( adjusted HR : 1.35 , 95 % CI : 1.07 to 1.71 ; p = 0.012 ) . PAPP-A also improved the net reclassification for CVD/MI ( p = 0.003 ) . There was no significant interaction with ranolazine . CONCLUSIONS PAPP-A was independently associated with recurrent cardiovascular events in patients with NSTE-ACS . This finding supports PAPP-A as a c and i date prognostic marker in patients with ACS and supports investigation of its therapeutic implication 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 To investigate whether pregnancy-associated plasma protein-A ( PAPP-A ) is a prognostic marker in patients admitted with high-risk acute coronary syndrome . In patients admitted with high-risk non-ST-segment elevation acute coronary syndrome ( NSTE-ACS ) and ST-segment elevation myocardial infa rct ion ( STEMI ) , risk stratification is primarily determined by the markers of myocardial necrosis and known demographic risk profiles . However , it has recently been proposed that the presence and extent of vulnerable plaques might influence the prognosis significantly . A marker for the vulnerable plaque could identify patients at high risk who would potentially benefit from intensive treatment and surveillance . Two population s of consecutive patients admitted with high-risk NSTE-ACS ( n = 123 ) and STEMI ( n = 314 ) were evaluated with serial measurements of PAPP-A. The incidence of mortality and nonfatal myocardial infa rct ion was prospect ively registered for 2.66 to 3.47 years . In the patients with high-risk NSTE-ACS , PAPP-A was related to the risk of nonfatal myocardial infa rct ion ( p = 0.02 ) and death ( p = 0.03 ) . This result was consistent on multivariate analysis of the combination of mortality or nonfatal myocardial infa rct ion ( odds ratio 2.65 , 95 % confidence interval 1.40 to 5.03 ) but not for mortality alone ( p = NS ) . In patients with STEMI , PAPP-A was related to the risk of death ( p = 0.01 ) but not the composite outcome of myocardial infa rct ion and death . This was also true after adjustment for other univariate predictors of death ( odds ratio 2.19 , 95 % confidence interval 1.16 to 4.16 ) . In conclusion , PAPP-A seems to be valuable in predicting the outcomes of patients admitted with high-risk NSTE-ACS or STEMI OBJECTIVES Long-term risk stratification in patients presenting with acute coronary syndromes ( ACS ) is possible by measuring cardiac troponin ( cTn ) . The present study examined whether PAPP-A measured in an emergency department ( ED ) chest pain population in association with conventional and novel high sensitivity cTn ( hs-cTnI ) assays can predict long-term mortality . METHODS In 320 patients with cTn measurements the earliest heparinized plasma PAPP-A concentration after presentation was used for risk stratification for death by Kaplan-Meier and Cox analyses . Subgroup analyses using the earliest PAPP-A concentrations were also performed in a cohort of subjects with presentation cTnI < or = 99th percentile but with significantly changing cardiac troponin concentrations as measured by the AccuTnI assay and the hs-cTnI assay ( n=45 and 120 subjects , respectively ) . RESULTS Subjects with PAPP-A concentrations in the highest tertile were at higher risk for death ( HR > 2.00 ; p < or = 0.05 at 2 years ) even after adjusting for cTnI at presentation . In the cohort with cTnI < or = 99th percentile but with changing hs-cTnI concentrations , subjects in the top PAPP-A tertile had a higher probability for death ( p=0.02 ) . CONCLUSION Early measurement of PAPP-A may identify chest pain patients at higher risk for long-term death . Additional prospect i ve ACS studies are required to fully eluci date PAPP-A 's role OBJECTIVE Pregnancy associated plasma protein-A ( PAPP-A ) is a potential new marker for vulnerable plaques in the coronary arteries only examined in stable coronary disease ( CAD ) in patients undergoing coronary angiography . Here we address the prognostic value of serum PAPP-A in unselected stable CAD patients . METHOD Blood sample s were drawn at study entry . Serum PAPP-A values ≥4mIU/L were considered elevated . Mortality and non-fatal myocardial infa rct ion was prospect ively registered . The primary outcome was the composite outcome of myocardial infa rct ion and all-cause mortality , secondary outcomes were all-cause mortality and myocardial infa rct ion . RESULTS Patients ( n=4243 ) were followed for a median of 2.8 years . In a Cox analysis , elevated PAPP-A was significantly related to the composite outcome of myocardial infa rct ion and death ( HR 1.99 , 95 % CI 1.62 - 2.45 , p<0.0005 ) , all-cause mortality ( HR 2.42 , 1.92 - 3.06 , p<0.0005 ) , and myocardial infa rct ion ( HR 1.40 , 1.01 - 1.94 , p=0.046 ) . After Holm 's correction , the latter significance disappeared . After adjustment for risk factors and medication at entry , elevated PAPP-A remained significantly related to the composite outcome ( HR 1.51 , 1.22 - 1.86 , p<0.0005 ) and all-cause mortality ( HR 1.68 , 1.32 - 2.13 , p<0.0005 ) . CONCLUSION In patients with stable CAD elevated serum PAPP-A seems promising as aid in identifying patients at high risk for death 
    Output:
    
Elevated serum PAPP-A level is associated with adverse vascular outcomes in patients with CHD