the association of increased serum levels of acute - phase proteins with the progression of atherosclerosis and with the occurrence of atherosclerosis - related adverse events , such as coronary heart disease and myocardial infarction ( mi ) , has been well documented in several epidemiological studies.1 - 6 ) currently , the pentraxin protein family is divided into two subfamilies based on size : the classical " short " pentraxin ( 25 kda ) and the " long " pentraxin ( 40 - 50 kda ) . pentraxin 3 ( ptx3 ) is a " long " pentraxin that is highly expressed in the heart , whereas c - reactive protein ( crp ) is a " short " pentraxin and is produced from the liver.7 ) in several recent studies,8)9 ) ptx3 appeared to be not only an early indicator of irreversible myocyte injury , but also a prognostic marker in patients with acute myocardial infarction ( ami ) . the global registry of acute coronary events ( grace ) risk score,10)11 ) designed in 94 hospitals and 14 countries , has been used as a tool to predict death in - hospital12 ) and death after discharge13 ) in patients with acute coronary syndrome ( acs ) . the grace risk score is represented by the following three categories ; st segment elevation mi ( stemi ) , non - st segment elevation mi ( nstemi ) , and unstable angina pectoris ( uap ) . acs represents a broad spectrum of ischemic myocardial events including ua , nstemi , and stemi that are associated with high morbidity and mortality despite early diagnosis , medical intervention and management.14 ) our hypothesis is that ptx3 is a prognostic biomarker in patients with acs . we estimated the all - cause mortality or death / mi , in - hospital and to 6 months , using the grace risk scores and compared these estimates to serum ptx3 concentrations . the aim of this study was to prove whether the value of ptx3 could be a prognostic marker , with the use of the grace risk assessment tool , in acs patients . mary 's hospital , 137 patient subjects with acs , with or without st segment elevation , underwent percutaneous coronary intervention ( pci ) ; those who had no prior pci and/or follow - up coronary angiography were enrolled . there were 108 male and 29 female patients enrolled , with a mean age of 6112 years . patients were informed of the investigative nature of the study , and written informed consent was obtained before enrollment . patients with acs were classified into the following standard subtypes : stemi , nstemi and uap . the grace diagnostic criteria of inclusion for ami , according to the rationale and design of the grace investigators , was met if patients had a cardiac ischemic symptom and at least one of the following increases in cardiac enzymes : 1 ) creatine kinase mb fraction ( ck - mb ) > 2 times upper limit of the hospital 's normal range , and/or 2 ) positive troponin t result.10 ) nstemi was defined as occurrence of acute mi with positive cardiac enzyme results , with or without accompanying electrocardiographic changes other than st segment elevation . stemi was defined as persistent st segment elevation of 1 mm in 2 contiguous electrocardiographic leads or the presence of a new left bundle branch block with positive cardiac enzyme results.10 ) the diagnostic inclusion criteria for uap , according to the rationale and design of the grace investigators , was met if patients had a cardiac ischemic symptom with serial enzymes and st segment elevation negative for mi.10 ) patients were excluded if they had 1 ) prior pci and/or follow - up coronary angiogram , or 2 ) prior coronary artery bypass graft ( cabg ) . each patient 's individual grace risk score , including the parameters of age , heart rate , systolic blood pressure , serum creatinine level , killip class , presence of cardiac arrest at admission , st segment deviation , and elevated cardiac enzymes for all - cause mortality , in - hospital and to 6 months , was calculated using the published risk score calculator from the grace registry . full details of the grace risk assessment tool have been previously published.10 ) we estimated the all - cause mortality or death / mi , in - hospital and to 6 months , using the grace risk scores and compared it with serum ptx3 concentrations . a coronary angiogram was performed using the judkins ' method , following the puncture of the femoral artery or via a radial artery approach according to current guidelines from the american college of cardiology / american heart association / society for cardiovascular angiography and intervention ( acc / aha / scai ) 2005 guideline update for pci.15 ) significant stenosis was defined as a diameter stenosis of 50% or greater . a standard antiplatelet therapy and other medications for acs were provided according to current guidelines from the acc / aha16)17 ) and the european society of cardiology ( esc).18 ) in all patients , aspirin ( 300 mg / day ) and clopidogrel ( 600 mg / day ) were loaded before procedure . an intravenous bolus of 100 u / kg weight of unfractionated heparin was given , and then additional heparin boluses were given to maintain an activated clotting time of 250 - 300 seconds during the procedure.19)20 ) during the procedure , blood was drawn into ethylenediaminetetraacetic acid vacuum containers . ptx3 was assayed with a noncommercial enzyme linked immuno sorbent assay ( elisa ) , based on the monoclonal antibody mnb10 and rabbit anti - serum . group comparisons for continuous variables of baseline clinical characteristics were performed using the analysis of variance test , and analysis for categorical data was performed using the  test . comparisons between the groups for serum ptx3 concentration were analyzed using an independent t - test , which was conducted using the sas statistical software , version 9.1 ( sas institute , cary , nc , usa ) . in multivariate logistic regression analysis , the value for median serum ptx3 concentration was used as a cut - off point to determine an independent parameter for all - cause mortality in - hospital and to 6 months . mary 's hospital , 137 patient subjects with acs , with or without st segment elevation , underwent percutaneous coronary intervention ( pci ) ; those who had no prior pci and/or follow - up coronary angiography were enrolled . there were 108 male and 29 female patients enrolled , with a mean age of 6112 years . patients were informed of the investigative nature of the study , and written informed consent was obtained before enrollment . patients with acs were classified into the following standard subtypes : stemi , nstemi and uap . the grace diagnostic criteria of inclusion for ami , according to the rationale and design of the grace investigators , was met if patients had a cardiac ischemic symptom and at least one of the following increases in cardiac enzymes : 1 ) creatine kinase mb fraction ( ck - mb ) > 2 times upper limit of the hospital 's normal range , and/or 2 ) positive troponin t result.10 ) nstemi was defined as occurrence of acute mi with positive cardiac enzyme results , with or without accompanying electrocardiographic changes other than st segment elevation . stemi was defined as persistent st segment elevation of 1 mm in 2 contiguous electrocardiographic leads or the presence of a new left bundle branch block with positive cardiac enzyme results.10 ) the diagnostic inclusion criteria for uap , according to the rationale and design of the grace investigators , was met if patients had a cardiac ischemic symptom with serial enzymes and st segment elevation negative for mi.10 ) patients were excluded if they had 1 ) prior pci and/or follow - up coronary angiogram , or 2 ) prior coronary artery bypass graft ( cabg ) . each patient 's individual grace risk score , including the parameters of age , heart rate , systolic blood pressure , serum creatinine level , killip class , presence of cardiac arrest at admission , st segment deviation , and elevated cardiac enzymes for all - cause mortality , in - hospital and to 6 months , was calculated using the published risk score calculator from the grace registry . full details of the grace risk assessment tool have been previously published.10 ) we estimated the all - cause mortality or death / mi , in - hospital and to 6 months , using the grace risk scores and compared it with serum ptx3 concentrations . a coronary angiogram was performed using the judkins ' method , following the puncture of the femoral artery or via a radial artery approach according to current guidelines from the american college of cardiology / american heart association / society for cardiovascular angiography and intervention ( acc / aha / scai ) 2005 guideline update for pci.15 ) significant stenosis was defined as a diameter stenosis of 50% or greater . a standard antiplatelet therapy and other medications for acs were provided according to current guidelines from the acc / aha16)17 ) and the european society of cardiology ( esc).18 ) in all patients , aspirin ( 300 mg / day ) and clopidogrel ( 600 mg / day ) were loaded before procedure . an intravenous bolus of 100 u / kg weight of unfractionated heparin was given , and then additional heparin boluses were given to maintain an activated clotting time of 250 - 300 seconds during the procedure.19)20 ) ptx3 was assayed with a noncommercial enzyme linked immuno sorbent assay ( elisa ) , based on the monoclonal antibody mnb10 and rabbit anti - serum . group comparisons for continuous variables of baseline clinical characteristics were performed using the analysis of variance test , and analysis for categorical data was performed using the  test . comparisons between the groups for serum ptx3 concentration were analyzed using an independent t - test , which was conducted using the sas statistical software , version 9.1 ( sas institute , cary , nc , usa ) . in multivariate logistic regression analysis , the value for median serum ptx3 concentration was used as a cut - off point to determine an independent parameter for all - cause mortality in - hospital and to 6 months . a total of 137 consecutive patients with acs ( mean age , 6112 years , m : f ratio 108 : 29 ) , including 76 ( 55.5% ) with stemi , 38 ( 27.7% ) with nstemi , and 23 ( 16.6% ) with uap , were studied . the baseline clinical and laboratory findings of the three groups were summarized in table 1 . the serum ptx3 concentration was not correlated with crp ( r=0.199 , p=0.058 ) , ck - mb ( r=0.022 , p=0.830 ) , ischemia modified albumin ( r=-0.103 , p=0.375 ) , brain natriuretic peptide albumin ( r=0.159 , p=0.296 ) and pro - brain natriuretic peptide ( r=0.260 , p=0.074 ) . the serum ptx3 concentration was significantly correlated with troponin t ( r=0.332 , p=0.001 ) ( fig . the serum ptx3 concentration was significantly correlated to death / mi in - hospital ( r=0.242 , p=0.015 ) and death / mi to 6 months ( r=0.227 , p=0.023 ) . the serum ptx3 concentration was not correlated to all - cause mortality in - hospital ( r=0.112 , p=0.269 ) and to 6 months ( r=0.132 , p=0.191 ) ( table 2 ) . the serum ptx3 concentration exhibited a significant increase in stemi ( 2.42.1 ng / ml ) as compared to the uap group ( 1.30.9 ng / ml ) with a p=0.017 . but there was no significant difference between the nstemi and uap groups ( 1.91.4 ng / ml vs. 1.30.9 ng / ml , p=0.083 , respectively ) , as well as between the stemi and nstemi groups ( 2.42.1 ng / ml vs. 1.91.4 ng / ml , p=0.185 , respectively ) ( fig . 2 ) . among the parameters determining the grace risk scores , the degree of killip class in congestive heart failure ( chf ) was independently associated with the supramedian ptx3 concentration [ odds ratio : 4.221 ( 95% confidence interval : 1.038 - 4.787 ) , p=0.040 ] ( table 3 ) . the cut - off value of serum ptx3 concentration ( 0.88 ng / ml ) shows a sensitivity ( 87.5% ) and a specificity ( 69.1% ) for predicting the probability of all - cause mortality in - hospital ( > 3% ) , as the highest tertile of grace risk assessment , and the cut - off value of serum ptx3 concentration ( 0.92 ng / ml ) shows a sensitivity ( 78.2% ) and a specificity ( 50.0% ) for predicting the probability of death / mi in - hospital ( > 5% ) ( fig . a total of 137 consecutive patients with acs ( mean age , 6112 years , m : f ratio 108 : 29 ) , including 76 ( 55.5% ) with stemi , 38 ( 27.7% ) with nstemi , and 23 ( 16.6% ) with uap , were studied . the baseline clinical and laboratory findings of the three groups were summarized in table 1 . the serum ptx3 concentration was not correlated with crp ( r=0.199 , p=0.058 ) , ck - mb ( r=0.022 , p=0.830 ) , ischemia modified albumin ( r=-0.103 , p=0.375 ) , brain natriuretic peptide albumin ( r=0.159 , p=0.296 ) and pro - brain natriuretic peptide ( r=0.260 , p=0.074 ) . the serum ptx3 concentration was significantly correlated with troponin t ( r=0.332 , p=0.001 ) ( fig . the serum ptx3 concentration was significantly correlated to death / mi in - hospital ( r=0.242 , p=0.015 ) and death / mi to 6 months ( r=0.227 , p=0.023 ) . the serum ptx3 concentration was not correlated to all - cause mortality in - hospital ( r=0.112 , p=0.269 ) and to 6 months ( r=0.132 , p=0.191 ) ( table 2 ) . the serum ptx3 concentration exhibited a significant increase in stemi ( 2.42.1 ng / ml ) as compared to the uap group ( 1.30.9 ng / ml ) with a p=0.017 . but there was no significant difference between the nstemi and uap groups ( 1.91.4 ng / ml vs. 1.30.9 ng / ml , p=0.083 , respectively ) , as well as between the stemi and nstemi groups ( 2.42.1 ng / ml vs. 1.91.4 ng / ml , p=0.185 , respectively ) ( fig . 2 ) . among the parameters determining the grace risk scores , the degree of killip class in congestive heart failure ( chf ) was independently associated with the supramedian ptx3 concentration [ odds ratio : 4.221 ( 95% confidence interval : 1.038 - 4.787 ) , p=0.040 ] ( table 3 ) . the cut - off value of serum ptx3 concentration ( 0.88 ng / ml ) shows a sensitivity ( 87.5% ) and a specificity ( 69.1% ) for predicting the probability of all - cause mortality in - hospital ( > 3% ) , as the highest tertile of grace risk assessment , and the cut - off value of serum ptx3 concentration ( 0.92 ng / ml ) shows a sensitivity ( 78.2% ) and a specificity ( 50.0% ) for predicting the probability of death / mi in - hospital ( > 5% ) ( fig . although crp has been used as a worldwide diagnostic biomarker in ischemic heart diseases , the increased serum crp levels in the acute conditions such as acs have been considered a nonspecific response to myocardial injury,21 ) and the actual role of crp in the pathogenesis of heart damage is still debated.22)23 ) peri et al.8 ) reported serum ptx3 as an early indicator of ami in humans and with no correlation between serum concentrations of ptx3 and crp . the grace risk scoring system , a multinational registry involving all subsets of acs including stemi , nstemi and uap , derived from clinical parameters at the time of hospitalization , was found to accurately predict mortality at 6 months.10 ) parameters in this grace scoring system are age , history of chf , history of mi , elevated resting heart rate , low systolic blood pressure on arrival , st - segment depression , elevated initial serum creatinine , and elevated cardiac enzymes in - hospital.10 ) recently , latini et al.9 ) reported the acute - phase protein ptx3 as a predictor of 3-month mortality after adjustment for major risk factors and other acute - phase prognostic markers . in our results , the role of ptx3 as a prognostic biomarker was shown by an increased serum ptx3 that was closely related to death due to mi , in - hospital or to 6 months , in acs patients , including stemi , nstemi , and uap groups . recently , several studies have mentioned that the plasma ptx3 level had increased in patients with heart failure and was independently associated with an increased risk for cardiac events.24)25 ) suzuki et al.24 ) demonstrated that the concentration of plasma ptx3 levels was significantly higher in patients with heart failure than in control subjects and increased with advancing new york heat association ( nyha ) functional class , especially in severe patients with heart failure and nyha class iii or iv . in this study , the serum ptx3 concentration was significantly correlated to troponin t and the degree of killip class , in chf , among the parameters determining the grace risk scores , and the degree of killip class was independently associated with an incremental change in the serum ptx3 level . to establish the role of ptx3 in the pathophysiology of chf , further investigations are required in larger populations via multicenter trials . inflammatory mediators are intimately associated with the cascade of events leading to atherosclerotic plaque initiation , development , and rupture . a study by inoue et al.26 ) compared 52 patients with stable angina pectoris ( sap ) to 16 patients with uap and reported that ptx3 was not associated with coronary risk factors including hypertension , diabetes mellitus and hyperlipidemia ; the value of ptx3 was significantly higher in the uap than in the sap group . they suggested that the levels of plasma ptx3 had increased in patients with arterial inflammation , especially uap , and that the detection of ptx3 was due to ptx3 having originated from the atherosclerotic plaque itself , thereby reflecting active atherosclerosis . therefore , ' ptx3 ' will be useful for the prediction of uap . in contrast , salio et al.27 ) reported , in a mouse model , that ptx3 plays a nonredundant , regulatory , cardioprotective role in ami and suggested that modulation of the complement cascade contributes to the cardioprotective function of ptx3 . although our data found much evidence converging to support inoue 's report , we need to conduct further research in a larger population . kotooka et al.28 ) reported that pci also induces a significant inflammatory reaction in the injured vessel wall and enhances plasma ptx3 concentration that leads to the development of neointimal thickening and restenosis after coronary stenting . however , to elucidate the mechanism of in - stent restenosis after pci , more analysis of ptx3 is warranted . first , there is the limitation of " time gap " between the sampling of ptx3 during the procedure and the calculation of grace risk score at admission , including the difference of " door to balloon time " ( stemi : nstemi : uap ; 2.62.4 : 8.99.7 : 17.27.2 , respectively , p=0.001 ) . second , despite several studies indicating ptx3 as a prognostic biomarker of acs , a normal range for ptx3 levels has not been established . last , our investigators suggest that the actual long - term outcomes in acs patient subjects could be confirmed via future follow - up coronary angiography or telephone interview . the killip class that reflects chf is an independent factor associated with an incremental change in the serum ptx3 level . our investigators suggest that the serum ptx3 level provides important information for risk stratification of chf diagnosis , among the parameters determining grace risk scores of acs subjects , including subtypes stemi , nstemi and uap . first , there is the limitation of " time gap " between the sampling of ptx3 during the procedure and the calculation of grace risk score at admission , including the difference of " door to balloon time " ( stemi : nstemi : uap ; 2.62.4 : 8.99.7 : 17.27.2 , respectively , p=0.001 ) . second , despite several studies indicating ptx3 as a prognostic biomarker of acs , a normal range for ptx3 levels has not been established . last , our investigators suggest that the actual long - term outcomes in acs patient subjects could be confirmed via future follow - up coronary angiography or telephone interview . the killip class that reflects chf is an independent factor associated with an incremental change in the serum ptx3 level . our investigators suggest that the serum ptx3 level provides important information for risk stratification of chf diagnosis , among the parameters determining grace risk scores of acs subjects , including subtypes stemi , nstemi and uap .