early risk stratification is essential in the management of patients with suspected or confirmed acute coronary syndrome . traditionally , risk stratification involves an evaluation of medical history , a physical examination , and electrocardiography ( ecg ) upon admission . in recent years , additional variables for early risk stratification in patients with st elevation myocardial infarction ( stemi ) have been identified , and include the elevation of cardiac biochemical markers . for example , the myocardial release of troponin i ( tni ) and n - terminal pro - b - type natriuretic peptide ( nt - probnp ) represent sensitive serum markers for minimal myocardial injury . when present , these markers are associated with an increased likelihood of a cardiac event.1 ) the elevation of another marker , high - sensitivity c - reactive protein ( hscrp ) , upon admission with stemi is associated with an increased risk of complications both during hospitalization and after discharge.2 ) these biochemical markers are noninvasive indicators of the risk of first or recurrent cardiovascular events and also predict the success of therapeutic and preventive interventions.1 ) thus , several studies have demonstrated the independent prognostic value of elevated tni , nt - probnp , or hscrp at admission in patients with stemi.3 - 9 ) additionally , in patients treated for stemi , early st - segment resolution has been associated with a better outcome based on improved early infarct - related artery patency , smaller infarct size , and less impairment of left ventricular function.10 - 12 ) however , the combination of these two early available tools for predicting risk soon after a patient 's presentation has not been evaluated . to address these issues , we retrospectively assessed the clinical characteristics and follow - up outcomes of consecutive patients who received primary percutaneous coronary intervention ( pci ) after stemi . the aim of this study was to evaluate the combined effect of using multiple biochemical markers and st - segment resolution assessments for early risk stratification in patients with stemi and treated by pci . between january 2006 and june 2008 , 178 consecutive patients who presented with their first stemi and were subsequently treated with primary pci were enrolled in the study , which took place at two coronary care units at the kyung hee university hospital , seoul , korea . all patients were treated according to the standard of care for stemi and underwent primary pci . the diagnostic work - up in all patients consisted of history , 12-lead ecg , blood chemistries , and a two - dimensional ( 2d ) echocardiography . the inclusion criteria were as follows : 1 ) presentation within 12 hours of symptom onset ; 2 ) chest pain lasting 30 minutes and resistant to nitrates ; and 3 ) 0.2 mv st - segment elevation in at least two contiguous leads on 12-lead ecg . the exclusion criteria were as follows : 1 ) prior myocardial infarction , defined by pre - existing pathologic q - wave ; 2 ) non - st elevation myocardial infarction ; and 3 ) thrombolytic therapy taken instead of pci . patents with infectious disease , collagen disease , malignant disease , or severe hepatic or renal failure were also excluded . initial clinical demographic data , including killip classification , symptom - to - balloon times , door - to - balloon times , and pre- and post - thrombolysis in myocardial infarction ( timi ) flow grades were evaluated . all patients included in the study sample provided written informed consent for all procedures and our institutional review board approved this research . for all 178 patients , a standard 12-lead ecg was obtained at initial presentation and at 60 minutes after pci , and was obtained by investigators blinded to the clinical characteristics and coronary angiography findings of the patients . using calipers , the sum of the st - segment elevation 20 ms after the j point was calculated and compared with the baseline ecg . the percent resolution of the st - segment on ecg was categorized as complete ( 70% ) , partial ( 30% to 70% ) , or incomplete ( 30% ) , as originally described by schroder et al.10 ) in all patients , standard echocardiography was performed within one hour after coronary intervention . blood samples used to obtain serum levels of tni , nt - probnp , and hscrp were taken on presentation at the emergency department of each center . creatine phosphokinase ( ck ) , ck - mb isoenzyme , and tni levels were measured quantitatively at admission , six hours later , and then twice daily over the first 48 hours . levels were detected routinely in the laboratory using commercially available assays ( abbott immunoassay , abbott laboratories , abbott park , il , usa ) . the normal value of tni in our institution is 0.5 ng / ml . tni levels 0.5 ng / ml on admission was used as a serum marker for myocardial ischemia . nt - probnp was quantified using a one - step enzyme immunoassay based on electrochemiluminescence technology ( elecsys 2010 , roche diagnostics ) . the choice of the specific type of des { i.e. , sirolimus - eluting ( cypher , cordis , johnson & johnson , miami lakes , fl , usa ) or paclitaxel - eluting ( taxus , boston scientific , natick , ma , usa ) stents } was left to the surgeon 's discretion . patients were prescribed aspirin and clopidogrel for at least six months , regardless of des type . the outcome events in this study were all cause mortality , repeated myocardial infarction , and readmission for worsening of heart failure up to six months after pci . continuous variables are presented as a meana standard deviation or median , as appropriate , and categorical variables as a percentage . continuous data were compared using one - way analysis of variance among st - segment resolution groups . a multivariate analysis using forward stepwise logistic regression was performed to check for independent variables related to major adverse cardiac events ( mace ) reported up to six months of follow - up . the overall mace - free survival rates were calculated using the kaplan - meier method , and the differences were determined using the log - rank test . the independent effects of variables on prognosis were calculated using a cox proportional hazards regression model . additionally , we performed a univariate and multivariate analysis using a cox proportional hazards regression model , in which we explored the effects of different combinations of biomarkers on patient prognosis . between january 2006 and june 2008 , 178 consecutive patients who presented with their first stemi and were subsequently treated with primary pci were enrolled in the study , which took place at two coronary care units at the kyung hee university hospital , seoul , korea . all patients were treated according to the standard of care for stemi and underwent primary pci . the diagnostic work - up in all patients consisted of history , 12-lead ecg , blood chemistries , and a two - dimensional ( 2d ) echocardiography . the inclusion criteria were as follows : 1 ) presentation within 12 hours of symptom onset ; 2 ) chest pain lasting 30 minutes and resistant to nitrates ; and 3 ) 0.2 mv st - segment elevation in at least two contiguous leads on 12-lead ecg . the exclusion criteria were as follows : 1 ) prior myocardial infarction , defined by pre - existing pathologic q - wave ; 2 ) non - st elevation myocardial infarction ; and 3 ) thrombolytic therapy taken instead of pci . patents with infectious disease , collagen disease , malignant disease , or severe hepatic or renal failure were also excluded . initial clinical demographic data , including killip classification , symptom - to - balloon times , door - to - balloon times , and pre- and post - thrombolysis in myocardial infarction ( timi ) flow grades were evaluated . all patients included in the study sample provided written informed consent for all procedures and our institutional review board approved this research . for all 178 patients , a standard 12-lead ecg was obtained at initial presentation and at 60 minutes after pci , and was obtained by investigators blinded to the clinical characteristics and coronary angiography findings of the patients . using calipers , the sum of the st - segment elevation 20 ms after the j point was calculated and compared with the baseline ecg . the percent resolution of the st - segment on ecg was categorized as complete ( 70% ) , partial ( 30% to 70% ) , or incomplete ( 30% ) , as originally described by schroder et al.10 ) in all patients , standard echocardiography was performed within one hour after coronary intervention . blood samples used to obtain serum levels of tni , nt - probnp , and hscrp were taken on presentation at the emergency department of each center . creatine phosphokinase ( ck ) , ck - mb isoenzyme , and tni levels were measured quantitatively at admission , six hours later , and then twice daily over the first 48 hours . levels were detected routinely in the laboratory using commercially available assays ( abbott immunoassay , abbott laboratories , abbott park , il , usa ) . the normal value of tni in our institution is 0.5 ng / ml . tni levels 0.5 ng / ml on admission was used as a serum marker for myocardial ischemia . nt - probnp was quantified using a one - step enzyme immunoassay based on electrochemiluminescence technology ( elecsys 2010 , roche diagnostics ) . the choice of the specific type of des { i.e. , sirolimus - eluting ( cypher , cordis , johnson & johnson , miami lakes , fl , usa ) or paclitaxel - eluting ( taxus , boston scientific , natick , ma , usa ) stents } was left to the surgeon 's discretion . patients were prescribed aspirin and clopidogrel for at least six months , regardless of des type . the outcome events in this study were all cause mortality , repeated myocardial infarction , and readmission for worsening of heart failure up to six months after pci . continuous variables are presented as a meana standard deviation or median , as appropriate , and categorical variables as a percentage . continuous data were compared using one - way analysis of variance among st - segment resolution groups . a multivariate analysis using forward stepwise logistic regression was performed to check for independent variables related to major adverse cardiac events ( mace ) reported up to six months of follow - up . the overall mace - free survival rates were calculated using the kaplan - meier method , and the differences were determined using the log - rank test . the independent effects of variables on prognosis were calculated using a cox proportional hazards regression model . additionally , we performed a univariate and multivariate analysis using a cox proportional hazards regression model , in which we explored the effects of different combinations of biomarkers on patient prognosis . the 178 patients treated with primary pci were divided into the following three groups according to st - segment resolution : complete ( n=63 , 59.912.3 years , male 81% ) , partial ( n=90 , 63.910.9 years , male 68% ) , and incomplete ( n=25 , 67.613.3 years , male 76% ) . baseline characteristics , risk factors , lv ef , and biochemical markers at admission are listed in table 1 . patients in the incomplete resolution group were older , had worse killip classifications , and had significantly prolonged symptom - to - door times and door - to - balloon times . risk factors such as diabetes , hypertension , dyslipidemia , smoking history , and ischemic heart disease history were not different among the three groups . there were no significant differences among the groups regarding use of medications , such as aspirin , clopidogrel , beta - blockers , angiotensin converting enzyme inhibitors , angiotensin receptor blockers , and statins either during admission or after discharge ( data not shown ) . the lv ef was significantly lower in patients with incomplete resolution ( table 1 ) . biochemical markers , such as tni , nt - probnp , and hscrp at admission were significantly higher among patients in the incomplete resolution group , and were well correlated with the percent of st - segment resolution ( r=-0.38 , p<0.01 ; r=-0.41 , p<0.01 ; r=-0.43 , p<0.01 , respectively ) . however , the maximal values of ck - mb and tni after pci were not significantly different among the three groups ( data not shown ) . as shown in table 2 , there were no differences among the 3 groups in the number of diseased vessels , location of the culprit artery , type of lesion , or target lesion . pre- and post - timi flow grade 0 or 1 was more commonly observed in the incomplete group , but this finding was not statistically significant . the duration of coronary care unit admission in days was significantly prolonged in the incomplete group ( 2.31.4 , 3.22.3 and 4.72.9 , respectively ; p<0.05 ) . three ( 1.7% ) patients died before discharge , and another four ( 2.2% ) patients died during the follow - up period . the all - cause mortality rate increased stepwise according to st - segment resolution status ( 0% , 1% , and 24% , respectively ; p<0.01 ) . three patients were retreated due to repeated infarction , as shown in table 2 . during follow - up , 17 patients were readmitted for worsening congestive heart failure . the readmission rate was 3% ( 2/63 ) , 10% ( 9/90 ) , and 24% ( 6/25 ) in complete , partial , and incomplete st resolution groups , respectively ( p<0.01 ) . using median values , the study sample was divided into two groups according to the initial tni ( median=0.38 ng / ml ) , hscrp ( median=2.45 mg / l ) , and nt - probnp ( median=456 pg / ml ) levels . kaplan - meier curves showing mace - free - survival based on the biochemical levels and st - segment resolutions are presented in fig . 1 . there was a significant increased risk of six - month mace with increasing baseline circulating levels of either tni ( 6% , and 23% for lower and higher levels , respectively ; p<0.01 ) , hscrp ( 6% , and 23% for lower and higher levels , respectively ; p<0.01 ) , or nt - probnp ( 10% , and 24% for lower and higher levels , respectively ; p<0.05 ) . there was also a significant , gradually increased risk of six - month mace according to the st resolution status ( 5% , 12% , and 48% for complete , partial and incomplete st resolution , respectively ; p<0.01 ) . to evaluate the independent contribution of st - segment resolution to the prediction of clinical outcomes after stemi , variables used for this analysis were age , killip classification , symptom - to - balloon time , door - to - balloon time , lv ef , tni , hs - crp , nt - probnp , and the degree of st - segment resolution . for multiple regression analysis , the most important predictors of clinical outcomes after stemi were the lv ef { hazards ratio ( hr ) : 0.83 ( 0.76 - 0.91 ) , p<0.01 } , hscrp { hr : 1.15 ( 1.05 - 1.26 ) , p<0.05 } , and the degree of st - segment resolution { hr : 0.96 ( 0.93 - 0.09 ) , p<0.05}. the additional benefit of using st - segment resolution to predict cardiac events is shown in fig . with regard to the incremental value , st - segment resolution is a good parameter to predict mace after stemi . however , the addition of biochemical markers markedly improved the prognostic utility of the model containing st - segment resolution . the 178 patients treated with primary pci were divided into the following three groups according to st - segment resolution : complete ( n=63 , 59.912.3 years , male 81% ) , partial ( n=90 , 63.910.9 years , male 68% ) , and incomplete ( n=25 , 67.613.3 years , male 76% ) . baseline characteristics , risk factors , lv ef , and biochemical markers at admission are listed in table 1 . patients in the incomplete resolution group were older , had worse killip classifications , and had significantly prolonged symptom - to - door times and door - to - balloon times . risk factors such as diabetes , hypertension , dyslipidemia , smoking history , and ischemic heart disease history were not different among the three groups . there were no significant differences among the groups regarding use of medications , such as aspirin , clopidogrel , beta - blockers , angiotensin converting enzyme inhibitors , angiotensin receptor blockers , and statins either during admission or after discharge ( data not shown ) . the lv ef was significantly lower in patients with incomplete resolution ( table 1 ) . biochemical markers , such as tni , nt - probnp , and hscrp at admission were significantly higher among patients in the incomplete resolution group , and were well correlated with the percent of st - segment resolution ( r=-0.38 , p<0.01 ; r=-0.41 , p<0.01 ; r=-0.43 , p<0.01 , respectively ) . however , the maximal values of ck - mb and tni after pci were not significantly different among the three groups ( data not shown ) . as shown in table 2 , there were no differences among the 3 groups in the number of diseased vessels , location of the culprit artery , type of lesion , or target lesion . pre- and post - timi flow grade 0 or 1 was more commonly observed in the incomplete group , but this finding was not statistically significant . the duration of coronary care unit admission in days was significantly prolonged in the incomplete group ( 2.31.4 , 3.22.3 and 4.72.9 , respectively ; p<0.05 ) . three ( 1.7% ) patients died before discharge , and another four ( 2.2% ) patients died during the follow - up period . the all - cause mortality rate increased stepwise according to st - segment resolution status ( 0% , 1% , and 24% , respectively ; p<0.01 ) . three patients were retreated due to repeated infarction , as shown in table 2 . during follow - up , 17 patients were readmitted for worsening congestive heart failure . the readmission rate was 3% ( 2/63 ) , 10% ( 9/90 ) , and 24% ( 6/25 ) in complete , partial , and incomplete st resolution groups , respectively ( p<0.01 ) . using median values , the study sample was divided into two groups according to the initial tni ( median=0.38 ng / ml ) , hscrp ( median=2.45 mg / l ) , and nt - probnp ( median=456 pg / ml ) levels . kaplan - meier curves showing mace - free - survival based on the biochemical levels and st - segment resolutions are presented in fig . 1 . there was a significant increased risk of six - month mace with increasing baseline circulating levels of either tni ( 6% , and 23% for lower and higher levels , respectively ; p<0.01 ) , hscrp ( 6% , and 23% for lower and higher levels , respectively ; p<0.01 ) , or nt - probnp ( 10% , and 24% for lower and higher levels , respectively ; p<0.05 ) . there was also a significant , gradually increased risk of six - month mace according to the st resolution status ( 5% , 12% , and 48% for complete , partial and incomplete st resolution , respectively ; p<0.01 ) . to evaluate the independent contribution of st - segment resolution to the prediction of clinical outcomes after stemi , variables used for this analysis were age , killip classification , symptom - to - balloon time , door - to - balloon time , lv ef , tni , hs - crp , nt - probnp , and the degree of st - segment resolution . the most important predictors of clinical outcomes after stemi were the lv ef { hazards ratio ( hr ) : 0.83 ( 0.76 - 0.91 ) , p<0.01 } , hscrp { hr : 1.15 ( 1.05 - 1.26 ) , p<0.05 } , and the degree of st - segment resolution { hr : 0.96 ( 0.93 - 0.09 ) , p<0.05}. the additional benefit of using st - segment resolution to predict cardiac events is shown in fig . however , the addition of biochemical markers markedly improved the prognostic utility of the model containing st - segment resolution . in this study , initial tni , nt - probnp , and hscrp plasma levels were higher in the incomplete st - segment resolution group than in the st - segment resolution groups , and these elevated biomarkers on admission predicted an adverse prognosis over the following six months , especially among patients who presented with two or three elevated biomarkers . furthermore , biochemical markers , such as tni , nt - probnp , and hscrp at admission were well correlated with the percent of st - segment resolution . the combination of these tools improved risk stratification in stemi . in agreement with previous studies,13 - 15 ) elevated levels of tni , nt - probnp , and hscrp were each associated with higher rates of mace . among them , only the hscrp at initial presentation was significantly and independently associated with an adverse prognosis over the next six months . this finding suggests that the inflammatory process associated with myocardial necrosis may be still ongoing when the degree of inflammation in the acute phase increases , as several lines of studies have suggested.16 - 18 ) by contrast , tni and nt - probnp were not independent predictors of clinical outcomes . this discrepancy with previous studies is probably explained by the relatively small sample size . however , despite the small sample size , the combination of several these markers allowed for a very good prediction of clinical outcomes in patients with stemi treated with pci as shown in fig . 2 . these incremental effects could be explained by the different pathophysiological mechanisms assessed by these three biomarkers in myocardial ischemia , i.e. , elevations in troponins indicate myocardial necrosis,3)13 ) nt - probnp is elevated in response to left ventricular overload,8)9 ) and hscrp is a marker of inflammation.1)2 ) multi - marker approaches to rapidly stratify patients and identify those at risk for adverse cardiac outcomes may help in the selection of more intense interventional or pharmacological treatment strategies . in the present study , st - segment resolution at 60 minutes was independently associated with six - month mace , which agrees with the findings of previous studies.3)10 ) another strong finding was a positive correlation between st - segment resolution and the three biochemical makers . we evaluated the association between the initial biochemical makers and partial or incomplete st - segment resolution . in a multivariate analysis , elevated hscrp { hr : 6.29 ( 2.43 - 16.30 ) , p<0.01 } and elevated nt - probnp { hr : 3.32 ( 1.29 - 8.52 ) , p<0.01 } were independently associated with partial or incomplete st - segment resolution , but not elevated tni { hr : 2.47 ( 0.99 - 6.20 ) , p=0.053}. this finding suggests that high burdens of inflammation and ventricular loads may be associated with a lower likelihood of successful epicardial reperfusion . for this reason , the combination of biomarkers and early st - segment resolution improved risk prediction . biomarkers at admission and st - segment resolution at 60 minutes are strong predictors of clinical outcomes , and the combination of them gives additive early information concerning patient prognosis , and further improves risk stratification in stemi . the possibility of selection bias and low statistical power must therefore be considered when interpreting our findings . however , we demonstrated that elevated levels of biochemical markers were each associated with higher rates of clinical outcomes , as has been demonstrated by previous studies.1)7)11)15 ) we also showed the powerful prognostic value of the combination of biomarkers at admission and st - segment resolution at 60 minutes . another weak point of this study is that it was a retrospective study and we therefore could not control medications use . in this study , medications were chosen by each physician according to each patient 's status . we also achieved the purpose of this study by demonstrating improved predictions of clinical outcomes using the two different systems for patients with first stemi . our study suggests an association among high plasma levels of tni , nt - probnp , and hscrp at admission , incomplete st segment resolution in patients with stemi after pci , and unfavorable clinical outcomes . multi - directional approaches to risk stratification and treatment of patients with st - emi may improve the outcomes of adverse cardiac events . our study suggests an association among high plasma levels of tni , nt - probnp , and hscrp at admission , incomplete st segment resolution in patients with stemi after pci , and unfavorable clinical outcomes . multi - directional approaches to risk stratification and treatment of patients with st - emi may improve the outcomes of adverse cardiac events .