the symptoms that patients are experiencing during acute coronary events are a key component in health care providers ' decision to initiate medical treatment and in further evaluation . in addition , patients ' earlier recognition of symptoms will facilitate the need for treatment seeking.1 ) a study reported that chest pain was the sole symptom in only 35% of cases and chest pain was accompanied by other symptoms in 57% of cases.2 ) overall , patients experienced a mean of 4.75 symptoms as part of the acute event of acute myocardial infarction ( ami).3 ) the absence of chest pain and the vagueness of symptoms might not be recognized as an indication of a cardiac problem , resulting in a delay in seeking medical care . in addition , this atypical presentation predicted lower use of thrombolytic therapy and was associated with hospital complications compared with the typical presentation.4)5 ) symptom clusters can be defined as multiple symptoms that are related to each other and are experienced concurrently.6)7 ) the clusters share a common etiology and a measurement of frequency , and severity of symptoms within clusters typically correlate with each other.8 ) they may also be useful in formulating criteria and evaluating patterns of symptoms . it is worthwhile to know how individual symptoms cluster by demographic and clinical characteristics of the subgroups in order to provide key information for early detection and diagnosis.9)10 ) identification of symptom clusters can be a clinically relevant way to detect specific demographic groups that are most likely to experience similar symptoms with readily identifiable characteristics.11)12 ) previous cluster studies on prehospital symptoms provided a useful grouping of acute coronary syndrome ( acs ) patients based on their experienced symptoms.9)-12 ) the clarification of prospective clinical outcomes for major adverse cardiac events ( mace ) should be helpful to health care providers in planning treatment strategies depending on the clusters . therefore , this study examined symptom clusters during acute events and clinical outcomes at 1-year follow - up by symptom cluster in patients with first - time ami . this clinical trial should enable health care providers to educate , more efficiently , individuals in the target populations at risk for cardiovascular disease ( cvd ) , to reduce prehospital delay time in korea , and to provide a useful treatment strategy for different symptomatic groups . the data for this study were obtained from first - time ami patients who were hospitalized for revascularization . subjects were recruited from the pool of patients hospitalized in chonnam national university hospital ( cnuh ) between 2007 and 2009 . inclusion criteria were : 1 ) patients who had undergone a first attack of st - elevation myocardial infarction ( stemi ) or non - st - elevation myocardial infarction ( nstemi ) , 2 ) verbally communicable , and 3 ) those who agreed to participate in the study . after obtaining approval of the institutional review board of the hospital , the principal investigator ( pi ) contacted eligible patients who were hospitalized in a cardiovascular care unit to ask them to participate in the study . this study was approved by the clinical ethics committee at cnuh before data collection was carried out . the pi interviewed the patients who had undergone a percutaneous coronary intervention using a semi - structured questionnaire . the interview was done in the education room with a research assistant ( ra ) . electronic medical records ( emr ) were also reviewed to collect medical treatment histories and laboratory data . each patient was asked about his chief complaints and associated symptoms that he experienced during the acute phase of an ami . if needed , figured descriptors were given for patients to choose and the pi or the ras checked their symptoms . patients ' pain or discomfort anywhere in the chest was coded as a chest pain . severity of chest pain or discomfort during the acute phase was asked and recoded on a 1 - 10 scale . patients were also asked about risk factors , their chronic disease , and past / family history questions . data for clinical outcomes including mace and mortality were also obtained at the 1-year follow - up period . all clinical events were verified through the emr or telephone follow - up calls by a research nurse . all acute symptoms of patients were coded as a categorical variable ; 1 point was given for ' present ' and 0 points for ' none ' . the coded symptoms in the statistical package for the social sciences ( spss , spss inc . , chicago , il , usa ) data set were analyzed by latent class ( lc ) cluster analysis using latent gold software , version 3.0.13 ) cluster analysis is defined as the classification of similar objects into the form of groups , which refers to the parameters of cluster ; that is , to its cluster - specific means , variances , and covariances that have a geometrical interpretation.13 ) lc cluster analysis is a statistical model - based clustering technique and can include covariates to predict class membership . an individual 's posterior class - membership probabilities are computed from the estimated model parameters and his observed scores using the maximum likelihood method . the most popular set of model selection tools in lc cluster analysis are information criteria such as akaike information criterion ( aic ) and the bayesian information criterion ( bic).14 ) in this study , decreases in the values of bic and aic were minimal between the three- and four - cluster models . the cluster membership of 3 clusters was conversed to an spss data set to identify the membership and associated factors . bivariate analyses using -tests , t - tests , and analysis of variance were conducted to identify the relationship between cluster assignment and patients ' characteristics . cox proportional hazards regression analysis was used to test a cluster membership as an independent predictor of 1-year mortality and maces . age was included and controlled for in the multivariate models of mortality and maces due to aging 's known prognostic importance . the data for this study were obtained from first - time ami patients who were hospitalized for revascularization . subjects were recruited from the pool of patients hospitalized in chonnam national university hospital ( cnuh ) between 2007 and 2009 . inclusion criteria were : 1 ) patients who had undergone a first attack of st - elevation myocardial infarction ( stemi ) or non - st - elevation myocardial infarction ( nstemi ) , 2 ) verbally communicable , and 3 ) those who agreed to participate in the study . after obtaining approval of the institutional review board of the hospital , the principal investigator ( pi ) contacted eligible patients who were hospitalized in a cardiovascular care unit to ask them to participate in the study . this study was approved by the clinical ethics committee at cnuh before data collection was carried out . the pi interviewed the patients who had undergone a percutaneous coronary intervention using a semi - structured questionnaire . the interview was done in the education room with a research assistant ( ra ) . electronic medical records ( emr ) were also reviewed to collect medical treatment histories and laboratory data . each patient was asked about his chief complaints and associated symptoms that he experienced during the acute phase of an ami . if needed , figured descriptors were given for patients to choose and the pi or the ras checked their symptoms . patients ' pain or discomfort anywhere in the chest was coded as a chest pain . severity of chest pain or discomfort during the acute phase was asked and recoded on a 1 - 10 scale . patients were also asked about risk factors , their chronic disease , and past / family history questions . data for clinical outcomes including mace and mortality were also obtained at the 1-year follow - up period . all clinical events were verified through the emr or telephone follow - up calls by a research nurse . all acute symptoms of patients were coded as a categorical variable ; 1 point was given for ' present ' and 0 points for ' none ' . the coded symptoms in the statistical package for the social sciences ( spss , spss inc . , chicago , il , usa ) data set were analyzed by latent class ( lc ) cluster analysis using latent gold software , version 3.0.13 ) cluster analysis is defined as the classification of similar objects into the form of groups , which refers to the parameters of cluster ; that is , to its cluster - specific means , variances , and covariances that have a geometrical interpretation.13 ) lc cluster analysis is a statistical model - based clustering technique and can include covariates to predict class membership . an individual 's posterior class - membership probabilities are computed from the estimated model parameters and his observed scores using the maximum likelihood method . the most popular set of model selection tools in lc cluster analysis are information criteria such as akaike information criterion ( aic ) and the bayesian information criterion ( bic).14 ) in this study , decreases in the values of bic and aic were minimal between the three- and four - cluster models . the cluster membership of 3 clusters was conversed to an spss data set to identify the membership and associated factors . bivariate analyses using -tests , t - tests , and analysis of variance were conducted to identify the relationship between cluster assignment and patients ' characteristics . cox proportional hazards regression analysis was used to test a cluster membership as an independent predictor of 1-year mortality and maces . age was included and controlled for in the multivariate models of mortality and maces due to aging 's known prognostic importance . the majority of patients ( 71.1% ) were men and the average age was 63.810.3 years ( range 26 - 89 ) . about 52% of the patients 49.1% had hypertension and 32.2% had diabetes ( average lengths of periods 8.47.3 and 11.89.7 years ) . about one third of patients ( 35.3% ) had a dyslipidemia and 38.6% were current smokers . about 12% of the patients had a past history of angina or stroke , and 19.7% had a family history of cvd including hypertension , stroke or ischemic heart disease ( table 1 ) . the size of cluster 1 was the biggest ( n=223 , 57.0% ) , followed by cluster 2 ( n=109 , 27.9% ) and cluster 3 ( n=59 , 15.1% ) . all cluster membership within each symptom cluster was significantly different ( p<0.01 ) except palpitation ( p=0.527 ) . the patients in cluster 1 and cluster 2 experienced a high frequency of chest pain / discomfort ( 100% and 94.5% , respectively ) and a moderate cold sweating . among the three groups , cluster 3 had the least chest pain and moderate frequencies of shortness of breath and weakness or fatigue . we named cluster 1 , 2 , and 3 as typical chest pain , multiple symptoms , and atypical symptom clusters , respectively . bivariate analyses showed that patients of cluster 2 were the youngest ( 58.112.8 years ) and those of cluster 3 were the oldest ( 69.312.3 years ) among the three clusters ( p<0.001 ) . as for cvd risk factors , the patients of cluster 2 were more likely to be overweight bmi > 25 kg / m ( p=0.002 ) and current smokers ( p=0.031 ) , and the patients of cluster 3 were more likely to have diabetes ( p<0.001 ) . 94.3% of cluster 3 reported that they did not perceive their symptoms as cardiac in origin and they had the fewest complaints of acute symptoms and the lowest self - reported intensity score of chest pain among the three groups ( p<0.001 ) . the patients of cluster 3 had the highest value for high sensitivity c - reactive protein ( hs - crp ) and the lowest in left ventricular ejection fraction ( lvef ) , which were checked immediately after hospital admission ; they had the longest stay at hospital among the three groups ( p<0.001 ) ( table 2 ) . bivariate analysis revealed that there was no significant difference among clustered groups in the prevalence of maces including an ami re - attack and total vessel or lesion revascularization . however , the prevalence of cardiac or non - cardiac deaths turned out to be significantly different by clusters ( p=0.022 ) ( table 3 ) . multivariate cox proportional hazards regression analysis demonstrated that when age , marital status and monthly income were adjusted for , patients in cluster 3 predicted a significantly higher risk of 1-year mortality compared to those in cluster 1 , a typical chest pain cluster ( hazard ratio 3.288 , 95% confidence interval 1.087 - 9.943 , p=0.035 ) ( table 4 ) . the majority of patients ( 71.1% ) were men and the average age was 63.810.3 years ( range 26 - 89 ) . about 52% of the patients 49.1% had hypertension and 32.2% had diabetes ( average lengths of periods 8.47.3 and 11.89.7 years ) . about one third of patients ( 35.3% ) had a dyslipidemia and 38.6% were current smokers . about 12% of the patients had a past history of angina or stroke , and 19.7% had a family history of cvd including hypertension , stroke or ischemic heart disease ( table 1 ) . the size of cluster 1 was the biggest ( n=223 , 57.0% ) , followed by cluster 2 ( n=109 , 27.9% ) and cluster 3 ( n=59 , 15.1% ) . all cluster membership within each symptom cluster was significantly different ( p<0.01 ) except palpitation ( p=0.527 ) . the patients in cluster 1 and cluster 2 experienced a high frequency of chest pain / discomfort ( 100% and 94.5% , respectively ) and a moderate cold sweating . among the three groups , cluster 3 had the least chest pain and moderate frequencies of shortness of breath and weakness or fatigue . we named cluster 1 , 2 , and 3 as typical chest pain , multiple symptoms , and atypical symptom clusters , respectively . bivariate analyses showed that patients of cluster 2 were the youngest ( 58.112.8 years ) and those of cluster 3 were the oldest ( 69.312.3 years ) among the three clusters ( p<0.001 ) . as for cvd risk factors , the patients of cluster 2 were more likely to be overweight bmi > 25 kg / m ( p=0.002 ) and current smokers ( p=0.031 ) , and the patients of cluster 3 were more likely to have diabetes ( p<0.001 ) . 94.3% of cluster 3 reported that they did not perceive their symptoms as cardiac in origin and they had the fewest complaints of acute symptoms and the lowest self - reported intensity score of chest pain among the three groups ( p<0.001 ) . the patients of cluster 3 had the highest value for high sensitivity c - reactive protein ( hs - crp ) and the lowest in left ventricular ejection fraction ( lvef ) , which were checked immediately after hospital admission ; they had the longest stay at hospital among the three groups ( p<0.001 ) ( table 2 ) . bivariate analysis revealed that there was no significant difference among clustered groups in the prevalence of maces including an ami re - attack and total vessel or lesion revascularization . however , the prevalence of cardiac or non - cardiac deaths turned out to be significantly different by clusters ( p=0.022 ) ( table 3 ) . multivariate cox proportional hazards regression analysis demonstrated that when age , marital status and monthly income were adjusted for , patients in cluster 3 predicted a significantly higher risk of 1-year mortality compared to those in cluster 1 , a typical chest pain cluster ( hazard ratio 3.288 , 95% confidence interval 1.087 - 9.943 , p=0.035 ) ( table 4 ) . three clusters of acute symptoms in this study were consistent with previous studies of 1 ) 1270 ami women that was made up of older / silent asymptomatic , diverse / mildly symptomatic , and younger / multiple distressing symptom groups,10 ) and of 2 ) 247 acs elderly people that had classic , weary ( severe fatigue and shortness of breath ) , and diffuse symptoms.11 ) however , four or five groupings were also reported and this grouping differed by a target population , number of examined symptoms , or statistical methods.9)15 ) about 97% ( 56/57 ) of patients in cluster 3 , the atypical symptom cluster , did not experience any pain or discomfort anywhere but the chest . in addition , they reported the least pain intensity among the three clusters , and instead were more likely to have gastrointestinal symptoms , weakness and syncope compared to the other two clusters . it was also challenging for clinicians in triage to decide on a cardiac diagnosis.4)5 ) this delayed decision to seek care in this study was supported by the fact that the majority of the patients in cluster 3 did not attribute their symptoms to a cardiac origin until they went to the hospital . failure to recognize the symptoms correctly as cardiac problems was consistently recognized as a significant predicting factor for prehospital delay by lots of nursing researchers.16)-18 ) in this study , 16.1% of the sample had no chest pain , while previous studies showed that about 9 - 20% of an international sample9)19 ) and 9% of a korean sample experienced no chest pain.20 ) atypical symptoms at the hospital presentation were found in many clinical studies as a significant factor predicting lower use of thrombolytic therapy and adverse hospital outcomes.4)5 ) the present study also supports the view that the rate of all - causes of death ( 7/59 , 12.3% ) in cluster 3 is significantly higher than that of the other clusters ( < 6% ) . the patients who belonged to cluster 3 were significantly older than those of the other two clusters . only 5% of them referred to chest pain as a chief complaint at hospital presentation . this was consistent with a previous study that older ami patients were less likely to report classic pain and used fewer words to describe their discomfort compared with younger patients.4 ) this result was also supported by a recent study on older adults ( > 65 years ) based on symptoms they had experienced for a week prior to an acute event showing that fatigue emerged in all three clusters with an overall prevalence of 76.1% , while chest pain was experienced by only 56% of patients.11 ) the characteristics represented in cluster 3 were similar to the diffuse symptom cluster that was identified among 331 patients with acs by riegel and her colleagues.15 ) they reported that the diffuse symptom group with a low frequency of symptoms tended to be older than other groups . this finding supports the need for an increased index of supervision for patients with an atypical symptom presentation . the 10.3% ( 21/203 ) of patients with st - elevation myocardial infarction ( stemi ) belonged to cluster 3 , the atypical symptom group , in this study . we should have greater concern for these stemi patients with atypical presentation to increase their awareness of the benefit of rapid reperfusion therapy . further research would then be needed to examine the associations between symptom clusters and characteristics especially for stemi patients , to provide a useful guideline for early recognition of the symptoms during an acute coronary event . about 51% of the patients in cluster 3 had a history of diabetes and this was significantly higher compared to the other two clusters . this finding was supported by previous studies demonstrating that ami patients with atypical symptoms were more likely to be older , female , and diabetic.1)5)21 ) therefore , older adults at high risk for cvd , especially those who have diabetes , should pay more attention to their risks of developing ami and should engage in health - seeking behaviors when unusual symptoms occur . the values of hs - crp , lvef , and killip class were significantly increased and total length of hospital stay was significantly longer in those in the atypical symptom cluster . when age and socio - economic status were adjusted for , although the prevalence of maces was not different , the atypical symptom cluster predicted a 3.3 times higher risk of 1-year mortality compared with the typical chest pain cluster . this is consistent with a previous cluster study showing that the patients in the diffuse symptom group had significantly higher mortality at 2 years than those with the other three cluster groups in acs patients ( 17% vs. 2 - 5%).15 ) these findings support the view that intensive medical treatments are needed for ami patients with atypical presentations , especially for those who are old and diabetic . however , riegel 's study used a secondary data set , which was obtained from 5 multi - centers during a 2-year follow - up period for known cvd patients including history of ami and care of a cardiologist.15 ) this limits direct comparisons with our study , which was conducted in first - time ami patients through a direct interview at one hospital . further longitudinal research is needed to replicate and verify the differences in clinical outcome among symptom cluster groups . classic symptoms characterized by chest pain and associated symptoms were presented dominantly by clusters 1 and 2 , and the patients of cluster 2 who were the youngest complained of the largest number of acute symptoms . this finding was consistent with previous observational and cluster studies showing that classic chest symptom was a predictive factor of acs in younger patients < 70 years.1)9)21 ) they were more likely to be obese , current smokers , and to have dyslipidemia compared to other cluster groups . this supports the conclusion that it is essential to manage individuals with those risk factors to prevent cvd in younger adults . therefore , the study population can not be considered as representative of all ami patients in korea . other limitations include the retrospective nature of the study and the fact that patient information involved personal recollections . we have identified three distinct clusters among 14 acute symptoms ; typical chest pain , multiple symptom , and atypical symptom clusters . the patients with the atypical symptom cluster , which contained older and more diabetic patients , had worse clinical markers at hospital presentation and significantly higher mortality rates within the 1-year of follow - up compared to those in the other two clusters . this study poses a challenge to healthcare providers : how to utilize the symptom cluster to identify common symptom patterns and to develop educational strategies that may facilitate rapid identification of ami . also , we recommend that clinicians treat more intensively older ami patients who have vague or atypical symptoms at hospital presentation . therefore , the study population can not be considered as representative of all ami patients in korea . other limitations include the retrospective nature of the study and the fact that patient information involved personal recollections . we have identified three distinct clusters among 14 acute symptoms ; typical chest pain , multiple symptom , and atypical symptom clusters . the patients with the atypical symptom cluster , which contained older and more diabetic patients , had worse clinical markers at hospital presentation and significantly higher mortality rates within the 1-year of follow - up compared to those in the other two clusters . this study poses a challenge to healthcare providers : how to utilize the symptom cluster to identify common symptom patterns and to develop educational strategies that may facilitate rapid identification of ami . also , we recommend that clinicians treat more intensively older ami patients who have vague or atypical symptoms at hospital presentation .
background and objectivesidentifying symptom clusters of acute myocardial infarction ( ami ) and their clinical significance may be useful in guiding treatment seeking behaviors and in planning treatment strategy . 
 the aim of this study was to identify clusters of acute symptoms and their associated factors that manifested in patients with first - time ami , and to compare clinical outcomes among cluster groups within 1-year of follow-up.subjects and methodsa total of 391 ami patients were interviewed individually using a structured questionnaire for acute and associated symptoms between march 2008 and june 2009 in korea.resultsamong 14 acute symptoms , three distinct clusters were identified by latent class cluster analysis : typical chest symptom ( 57.0% ) , multiple symptom ( 27.9% ) , and atypical symptom ( 15.1% ) clusters . 
 the cluster with atypical symptoms was characterized by the least chest pain ( 3.4% ) and moderate frequencies ( 31 - 61% ) of gastrointestinal symptoms , weakness or fatigue , and shortness of breath ; they were more likely to be older , diabetic and to have worse clinical markers at hospital presentation compared with those with other clusters . 
 cox proportional hazards regression analysis showed that , when age and gender were adjusted for , the atypical symptom cluster significantly predicted a higher risk of 1-year mortality compared to the typical chest pain cluster ( hazard ratio 3.288 , 95% confidence interval 1.087 - 9.943 , p=0.035).conclusionclusters of symptoms can be utilized in guiding a rapid identification of symptom patterns and in detecting higher risk patients . 
 intensive treatment should be considered for older and diabetic patients with atypical presentation .