acute coronary syndromes ( acs ) continue to be a major cause of morbidity and mortality . data from the united states and europe have reported a decrease in the incidence of stelevation myocardial infarction ( stemi ) with an increase in nonstelevation myocardial infarction ( nstemi ) in the past decade . current 2012 american college of cardiology / american heart association ( acc / aha ) guidelines recommend early invasive strategy ( eis ) for management of patients with nstemi and refractory angina or electrical or hemodynamic insufficiency ( class ib ) , initially stabilized patients with nstemi , and high risk of clinical events ( class ia ) . the early invasive approach ( within 12 to 24 hours of presentation ) to reduce ischemic complications is also recommended in initially stabilized highrisk patients with nstemi ( class iia ) . the optimal timing of eis has been debated and undergone a paradigm shift in the last decade . the transition from 48 hours to within 24 hours occurred after the publication of the timing of intervention in acute coronary syndromes ( timacs ) trial in 2009 . however , there is a paucity of information with regard to the secular trends in utilization of eis in patients with nstemi and how this may vary among different nstemi patient populations . using a large nationwide administrative database , the present study aimed to analyze and describe age , sex , and race / ethnicityspecific trends in the incidence , utilization of eis , and inhospital outcomes for nstemi in the united states from 2002 to 2011 . data were obtained from the 2002 to 2011 nationwide inpatient sample ( nis ) databases . the nis , sponsored by the agency for healthcare research and quality as a part of the healthcare cost and utilization project ( hcup ) , is the largest publicly available allpayer inpatient care database in the united states . it contains dischargelevel data from 8 million hospital stays from approximately 1000 hospitals designed to approximate a 20% stratified sample of all community hospitals in the united states . criteria used for stratified sampling of hospitals include hospital ownership , bed size , teaching status , urban or rural location , and geographic region . discharge weights are provided for each patient discharge record , which were used to obtain national estimates . discharge weights are calculated for nis data by first stratifying the nis hospitals on the same variables used for creating the sample . a weight is then calculated for each stratum by dividing the number of universe discharges in that stratum ( obtained from american hospital association data ) by the number of nis discharges in the stratum . weighted estimates are calculated by uniformly applying stratum weights to the discharges according to the stratum from which the discharge was drawn . weights are assigned to each discharge and are stored in each record in the data element , discwt . when the discharge weights are applied to the unweighted nis data , the result is an estimate of the number of discharges for all inpatient discharges from community hospitals in the united states . this study was deemed exempt by the new york medical college institutional review board ( valhalla , ny ) because hcupnis is a public database with no personal identifying information . we used the international classification of diseases , ninth edition , clinical modification ( icd9cm ) , codes 410.xx to identify all patients 40 years of age with the principal diagnosis of acute myocardial infarction ( ami ; n=6 512 372 ) . patients with the principal diagnosis of nstemi were then identified using icd9cm codes 410.7x ( n=3 981 119 ) . we chose the principal diagnosis because it is considered the primary reason for hospital admission . eis was defined as coronary angiography ( icd9cm procedure codes 88.55 , 88.66 , 37.22 , or 37.23 ) with or without revascularization ( ie , percutaneous coronary intervention ( pci ; icd9cm procedure codes 00.66 , 36.01 , 36.02 , 36.05 , 36.06 and 36.07 ) or coronary artery bypass graft surgery ( cabg ; icd9cm procedure code 36.1x ) on day 0 ( considered within 24 hours of admission ) or on days 0 or 1 ( considered within 48 hours of admission ) . we initially studied the overall age , sex , and race / ethnicityspecific trends in the incidence of nstemi . our primary outcome of interest was allcause , inhospital mortality , defined as death during the hospitalization encounter in the nis database . we analyzed the overall age , sex , and race / ethnicityspecific trends in utilization of the eis , riskadjusted inhospital mortality , average length of stay , and total hospital cost in patients with nstemi . the nis provides total charges , which reflect the amount a hospital billed for services , rather than actual costs or the amount a hospital received in payment . in this study , we used the hcup costtocharge ratio file developed by the agency for healthcare research and quality ( ahrq ) to translate total charges into costs . each file contains hospitalspecific costtocharge ratios based on allpayer inpatient cost for nearly every hospital in the nis databases . cost information is obtained from the hospital accounting reports collected by the centers for medicare and medicaid services . baseline patient characteristics used included demographics ( age , sex , race / ethnicity , primary expected payer , weekday versus weekend admission ) , 29 elixhauser comorbidities as defined by the ahrq and other clinically relevant comorbidities ( smoking , dyslipidemia , known coronary artery disease [ cad ] , family history of cad , previous myocardial infarction [ mi ] , previous transient ischemic attack or stroke , previous pci , previous cabg , carotid artery disease , dementia , and atrial fibrillation ) . a list of icd9cm and clinical classifications software codes used to identify comorbidities and inhospital procedures is provided in table 1 . hospital characteristics , such as hospital region ( northeast , midwest , south , and west ) , bed size ( small , medium , and large ) , location ( rural or urban ) , and teaching status were also included . international classification of diseases , ninth edition , clinical modification ( icd9cm ) and clinical classifications software ( ccs ) codes used to identify comorbidities weighted data were used for all statistical analyses . for trend analysis , we used mantelhaenszel 's chisquare (  ) test of linear association for categorical variables and linear regression for continuous variables . to assess whether the incidence of nstemi , utilization of eis , or inhospital mortality has changed over time , unadjusted and multivariable adjusted logistic regression models were constructed . our independent variable , calendar year , was initially entered as a continuous variable in the regression models to obtain unadjusted and adjusted odds ratios ( ors ; per year ) for the temporal trends . to determine whether there was a temporal variability from year to year in the incidence of nstemi , utilization of eis , or inhospital mortality , we also evaluated calendar year as a categorical variable , with 2002 as the reference year . the regression models adjusted for all demographics ( except sex and race / ethnicity for sex and race / ethnicityspecific trends , respectively ) , hospital characteristics , and all elixhauser and other clinically relevant comorbidities . we graphically displayed the unadjusted and adjusted ors and 95% confidence intervals ( cis ) for incidence of nstemi , utilization of eis for nstemi , or inhospital mortality over time . statistical analysis was performed using ibm spss statistics 20.0 ( ibm corp . , armonk , ny ) . all p values were 2 sided with a significance threshold of p<0.001 ( a lowerthanusual pvalue threshold was selected to correct for the effects of a large sample size as well as inflation of type i error because of repeated testing using a large number of variables ) . categorical variables are expressed as percentage and continuous variables as mean sem . or , and data were obtained from the 2002 to 2011 nationwide inpatient sample ( nis ) databases . the nis , sponsored by the agency for healthcare research and quality as a part of the healthcare cost and utilization project ( hcup ) , is the largest publicly available allpayer inpatient care database in the united states . it contains dischargelevel data from 8 million hospital stays from approximately 1000 hospitals designed to approximate a 20% stratified sample of all community hospitals in the united states . criteria used for stratified sampling of hospitals include hospital ownership , bed size , teaching status , urban or rural location , and geographic region . discharge weights are provided for each patient discharge record , which were used to obtain national estimates . discharge weights are calculated for nis data by first stratifying the nis hospitals on the same variables used for creating the sample . a weight is then calculated for each stratum by dividing the number of universe discharges in that stratum ( obtained from american hospital association data ) by the number of nis discharges in the stratum . weighted estimates are calculated by uniformly applying stratum weights to the discharges according to the stratum from which the discharge was drawn . weights are assigned to each discharge and are stored in each record in the data element , discwt . when the discharge weights are applied to the unweighted nis data , the result is an estimate of the number of discharges for all inpatient discharges from community hospitals in the united states . this study was deemed exempt by the new york medical college institutional review board ( valhalla , ny ) because hcupnis is a public database with no personal identifying information . we used the international classification of diseases , ninth edition , clinical modification ( icd9cm ) , codes 410.xx to identify all patients 40 years of age with the principal diagnosis of acute myocardial infarction ( ami ; n=6 512 372 ) . patients with the principal diagnosis of nstemi were then identified using icd9cm codes 410.7x ( n=3 981 119 ) . we chose the principal diagnosis because it is considered the primary reason for hospital admission . eis was defined as coronary angiography ( icd9cm procedure codes 88.55 , 88.66 , 37.22 , or 37.23 ) with or without revascularization ( ie , percutaneous coronary intervention ( pci ; icd9cm procedure codes 00.66 , 36.01 , 36.02 , 36.05 , 36.06 and 36.07 ) or coronary artery bypass graft surgery ( cabg ; icd9cm procedure code 36.1x ) on day 0 ( considered within 24 hours of admission ) or on days 0 or 1 ( considered within 48 hours of admission ) . we initially studied the overall age , sex , and race / ethnicityspecific trends in the incidence of nstemi . our primary outcome of interest was allcause , inhospital mortality , defined as death during the hospitalization encounter in the nis database . we analyzed the overall age , sex , and race / ethnicityspecific trends in utilization of the eis , riskadjusted inhospital mortality , average length of stay , and total hospital cost in patients with nstemi . the nis provides total charges , which reflect the amount a hospital billed for services , rather than actual costs or the amount a hospital received in payment . in this study , we used the hcup costtocharge ratio file developed by the agency for healthcare research and quality ( ahrq ) to translate total charges into costs . each file contains hospitalspecific costtocharge ratios based on allpayer inpatient cost for nearly every hospital in the nis databases . cost information is obtained from the hospital accounting reports collected by the centers for medicare and medicaid services . baseline patient characteristics used included demographics ( age , sex , race / ethnicity , primary expected payer , weekday versus weekend admission ) , 29 elixhauser comorbidities as defined by the ahrq and other clinically relevant comorbidities ( smoking , dyslipidemia , known coronary artery disease [ cad ] , family history of cad , previous myocardial infarction [ mi ] , previous transient ischemic attack or stroke , previous pci , previous cabg , carotid artery disease , dementia , and atrial fibrillation ) . a list of icd9cm and clinical classifications software codes used to identify comorbidities and inhospital procedures is provided in table 1 . hospital characteristics , such as hospital region ( northeast , midwest , south , and west ) , bed size ( small , medium , and large ) , location ( rural or urban ) , and teaching status were also included . international classification of diseases , ninth edition , clinical modification ( icd9cm ) and clinical classifications software ( ccs ) codes used to identify comorbidities weighted data were used for all statistical analyses . for trend analysis , we used mantelhaenszel 's chisquare (  ) test of linear association for categorical variables and linear regression for continuous variables . to assess whether the incidence of nstemi , utilization of eis , or inhospital mortality has changed over time , unadjusted and multivariable adjusted logistic regression models were constructed . our independent variable , calendar year , was initially entered as a continuous variable in the regression models to obtain unadjusted and adjusted odds ratios ( ors ; per year ) for the temporal trends . to determine whether there was a temporal variability from year to year in the incidence of nstemi , utilization of eis , or inhospital mortality , we also evaluated calendar year as a categorical variable , with 2002 as the reference year . the regression models adjusted for all demographics ( except sex and race / ethnicity for sex and race / ethnicityspecific trends , respectively ) , hospital characteristics , and all elixhauser and other clinically relevant comorbidities . we graphically displayed the unadjusted and adjusted ors and 95% confidence intervals ( cis ) for incidence of nstemi , utilization of eis for nstemi , or inhospital mortality over time . statistical analysis was performed using ibm spss statistics 20.0 ( ibm corp . , armonk , ny ) . all p values were 2 sided with a significance threshold of p<0.001 ( a lowerthanusual pvalue threshold was selected to correct for the effects of a large sample size as well as inflation of type i error because of repeated testing using a large number of variables ) . categorical variables are expressed as percentage and continuous variables as mean sem . or , and from 2002 to 2011 , we identified 6 512 372 patients 40 years of age admitted with ami . of these , 3 981 119 ( 61.1% ) had nstemi . among patients with ami , the proportion of those presenting with nstemi increased from 52.8% in 2002 to 68.6% in 2011 ( ptrend<0.001 ) . after adjusting for baseline demographics , hospital characteristics , and comorbidities , we observed an increasing trend in the proportion of patients hospitalized with nstemi from 2002 to 2011 ( adjusted or [ per year ] , 1.055 ; 95% ci , 1.054 to 1.056 ; p<0.001 ; figure 1 ; table 2 ) . adjusted temporal trends of proportion of nonstelevation myocardial infarction : overall cohort , age , sex , and race / ethnicity stratified multivariable adjustment for baseline demographics , hospital characteristics , and 29 elixhauser and other clinically relevant comorbidities as outlined in the methodology . adjusted odds ratios ( or ; per year ) for trend were determined using logistic regression models evaluating calendar year as a continuous variable . numbers in parenthesis represent 95% confidence interval . a , nstemi ( % ) was calculated as the number of patients with nstemi divided by the number of patients with acute myocardial infarction ( ami ) per year100 ; ptrend<0.001 . b , trends in nstemi presented as unadjusted and adjusted odds ratio and 95% confidence interval ( ci ) for each year relative to 2002 ( reference year ) . regression model adjusted for demographics , hospital characteristics , and 29 elixhauser and other clinically relevant comorbidities . 95% cis are depicted , but are too narrow to be visualized outside the marker width . the increase in proportion of nstemi , it increased from 45.4% to 60.2% in those 40 to 64 years of age ( adjusted or [ per year ] , 1.045 ; 95% ci , 1.044 to 1.046 ; p<0.001 ) , from 54.5% to 70.7% in those 65 to 74 ( adjusted or [ per year ] , 1.056 ; 95% ci , 1.055 to 1.058 ; p<0.001 ) , and from 59% to 77.1% in patients 75 ( adjusted or [ per year ] , 1.066 ; 95% ci , 1.065 to 1.068 ; p<0.001 ) . when stratified according to sex , women ( 56.1% to 73.6% ; adjusted or [ per year ] , 1.070 ; 95% ci , 1.069 to 1.071 ; p<0.001 ) had a steeper proportional increase , compared to men ( 50.4% to 65.3% ; adjusted or [ per year ] , 1.046 ; 95% ci , 1.045 to 1.047 ; p<0.001 ) . age , sex , and race / ethnicity specific trends in incidence rates of nonstelevation myocardial infarction . a , age stratified ; ptrend<0.001 , ( b ) sex stratified ; ptrend<0.001 , and ( c ) race / ethnicity stratified ; ptrend<0.001 . table 3 depicts the baseline demographic , hospital , and clinical characteristics of patients admitted with nstemi from 2002 to 2011 . there was a slight decrease in mean age at admission during the study period ( 70.3613.11 years in 2002 versus 69.8713.53 in 2011 ; p<0.001 ) . more specifically , there was an increase in the proportion of nstemi patients aged 40 to 64 years and decrease in those aged 75 years from 2002 to 2011 ( ptrend<0.001 ) . similarly , there was a small , but statistically significant , increase in the proportion of men ( 56% in 2002 to 57.5% in 2011 ; ptrend<0.001 ) and a consequent decrease in the proportion of women ( 44.0% in 2002 to 42.5% in 2011 ; ptrend<0.001 ) with nstemi during the study period . the prevalence of smoking , dyslipidemia , cad , previous mi , carotid artery disease , diabetes mellitus , hypertension , obesity , peripheral vascular disease , chronic renal failure , alcohol abuse , deficiency anemias , coagulopathy , fluid / electrolyte disorders , and previous pci increased from 2002 to 2011 ( ptrend<0.001 for all ) . the prevalence of heart failure and chronic pulmonary diseases remained relatively constant throughout the study period . baseline demographics , hospital characteristics , comorbidities , utilization of early invasive strategy , and overall inhospital mortality in patients with nonstelevation myocardial infarction aids indicates acquired immunodeficiency syndrome ; cabg , coronary artery bypass graft surgery ; cad , coronary artery disease ; h / o , history of ; pci , percutaneous coronary intervention ; ra , rheumatoid arthritis ; tia , transient ischemic attack . utilization of eis on day 0 of presentation increased from 14.9% in 2002 to 21.8% in 2011 ( adjusted or [ per year ] , 1.065 ; 95% ci , 1.064 to 1.066 ; p<0.001 ) . the adjusted temporal trends for utilization of eis were similar across all age , sex , and racial / ethnic groups . patients 75 years of age had the highest proportional increase in utilization of eis ( adjusted or [ per year ] , 1.072 ; 95% ci , 1.069 to 1.074 ; p<0.001 ; figures 3 and 4 ; table 4 ) . adjusted temporal trends of nonstelevation myocardial infarction with utilization of the early invasive strategy at day 0 : overall cohort , age , sex , and race / ethnicity stratified multivariable adjustment for baseline demographics , hospital characteristics , and 29 elixhauser and other clinically relevant comorbidities as outlined in the methodology . adjusted odds ratios ( or ; per year ) for trend were determined using logistic regression models evaluating calendar year as a continuous variable . numbers in parenthesis represent 95% confidence interval . trends in utilization of early invasive strategy for nonstelevation b , trends in early invasive strategy at day 0 presented as unadjusted and adjusted odds ratio and 95% confidence interval ( ci ) for each year relative to 2002 ( reference year ) . regression model adjusted for demographics , hospital characteristics , and 29 elixhauser and other clinically relevant comorbidities . d , trends in early invasive strategy at day 0 or 1 presented as unadjusted and adjusted odds ratio and 95% confidence interval ( ci ) for each year relative to 2002 ( reference year ) . regression model adjusted for demographics , hospital characteristics , and 29 elixhauser and other clinically relevant comorbidities . 95% cis are depicted , but are too narrow to be visualized outside the marker width . age , sex , and race / ethnicity specific trends in utilization of early invasive strategy ( eis ) for nonstelevation myocardial infarction . a , age stratified , eis day 0 ; ptrend<0.001 , ( b ) sex stratified , eis day 0 ; ptrend<0.001 , ( c ) race / ethnicity stratified , eis day 0 ; ptrend<0.001 , ( d ) age stratified , eis day 0 or 1 ; ptrend<0.001 , ( e ) sex stratified , eis day 0 or 1 ; ptrend<0.001 , and ( f ) race / ethnicity stratified , eis day 0 or 1 ; ptrend<0.001 . results showed a temporal increase in the overall as well as the age , race / ethnicity , and sexstratified cohorts ( figures 3 and 4 ; table 5 ) . adjusted temporal trends of nonstelevation myocardial infarction with utilization of the early invasive strategy at day 0 to 1 : overall cohort , age , sex , and race / ethnicity stratified multivariable adjustment for baseline demographics , hospital characteristics , and 29 elixhauser and other clinically relevant comorbidities as outlined in the methodology . adjusted odds ratios ( or ; per year ) for trend were determined using logistic regression models evaluating calendar year as a continuous variable . inhospital mortality decreased from 5.5% in 2002 to 3.9% in 2011 in all patients with nstemi ( adjusted or [ per year ] , 0.976 ; 95% ci , 0.974 to 0.978 ; p<0.001 ) . on agestratified analysis , those 75 years of age had the greatest decrease in inhospital mortality ( adjusted or [ per year ] , 0.968 ; 95% ci , 0.966 to 0.971 ; p<0.001 ) . women had a steeper temporal decline in inhospital mortality , compared to men , from 2002 to 2011 ( adjusted or [ per year ] , 0.965 ; 95% ci , 0.962 to 0.968 ; p<0.001 in women and adjusted or [ per year ] , 0.986 ; 95% ci , 0.984 to 0.989 ; p<0.001 in men ) . statistically significant decline in mortality was also observed in all racial / ethnic groups . in patients receiving eis on day 0 of presentation , however , the overall trend in this decrease was not statistically significant ( adjusted or [ per year ] , 0.998 ; 95% ci , 0.991 to 1.004 ; p=0.471 ) . a temporal decline in inhospital mortality was observed in patients treated with invasive strategy on day 0 or 1 ( 2.4% in 2002 to 1.8% in 2011 ; adjusted or [ per year ] , 0.988 ; 95% ci , 0.983 to 0.993 ; p<0.001 ; figures 5 and 6 ; table 6 ) . in patients not receiving eis , inhospital mortality decreased from 6.7% in 2002 to 5.4% in 2011 ( adjusted or [ per year ] , 0.977 ; 95% ci , 0.975 to 0.979 ; p<0.001 ; figure 6 ; table 6 ) . adjusted temporal trends of riskadjusted inhospital mortality in patients with nonstelevation myocardial infarction : overall cohort , age , sex , race / ethnicity , and early invasive strategy stratified multivariable adjustment for baseline demographics , hospital characteristics , and 29 elixhauser and other clinically relevant comorbidities as outlined in the methodology . adjusted odds ratios ( or ; per year ) for trend a , inhospital mortality ( % ) was calculated as the number of patients who died during the hospitalization divided by the number of patients with nstemi per year100 ; ptrend<0.001 . b , trends in inhospital mortality presented as unadjusted and adjusted odds ratio ( or ) and 95% confidence interval ( ci ) for each year relative to 2002 ( reference year ) . regression model adjusted for demographics , hospital characteristics , and 29 elixhauser and other clinically relevant comorbidities . age , sex , race / ethnicity , and utilization of invasive strategyspecific trends in inhospital mortality in patients with nonstelevation myocardial infarction . a , age stratified , ( b ) sex stratified , ( c ) race / ethnicity stratified , and ( d ) stratified according to utilization of invasive strategy ( ptrend<0.001 for all ) . no eis was defined as patients who did not receive coronary angiography with intent to revascularize within day 0 or 1 . detailed results of the length and cost of stay temporal trends stratified by age , sex , and race / ethnicity are shown in tables 7 and 8 , respectively . the mean ( sem , in days ) length of stay decreased in the overall cohort of patients during the study period ( 5.70.01 in 2002 to 4.80.01 in 2011 ; ptrend<0.001 ) . patients with nstemi undergoing eis within day 0 had the shortest length of stay , and the length of stay declined in all patients undergoing eis , irrespective of timing ( from 4.40.03 in 2002 to 3.90.02 in 2011 for those with eis at day 0 and from 4.80.02 in 2002 to 4.10.01 in 2011 for those with eis within day 0 or 1 ; ptrend<0.001 for all ; figure 7 ; table 7 ) . temporal trends in length of stay ( meanse ) in days temporal trends in total hospital cost ( meanse ) in u.s . a , overall , ( b ) age , ( c ) sex , ( d ) race / ethnicity , and ( e ) timing of invasive strategy ( ptrend<0.001 for all ) . mean ( sem , in dollars ) cost of stay in the overall patient population admitted with nstemi increased from $ 14 77430 from 2002 to $ 20 26935 in 2011 ( ptrend<0.001 ) . the mean ( sem , in dollars ) costs accrued by those undergoing eis were higher and showed a similar increasing trend ( from $ 17 38580 in 2002 to $ 24 34576 in 2011 for those with eis at day 0 and from $ 17 53459 in 2002 to $ 23 97155 in 2011 for those with eis within day 0 or 1 ; ptrend<0.001 for all ; figure 8 ; table 8) . ( a ) overall , ( b ) age , ( c ) sex , ( d ) race / ethnicity , and ( e ) timing of invasive strategy ( ptrend<0.001 for all ) . from 2002 to 2011 , we identified 6 512 372 patients 40 years of age admitted with ami . of these , 3 981 119 ( 61.1% ) had nstemi . among patients with ami , the proportion of those presenting with nstemi increased from 52.8% in 2002 to 68.6% in 2011 ( ptrend<0.001 ) . after adjusting for baseline demographics , hospital characteristics , and comorbidities , we observed an increasing trend in the proportion of patients hospitalized with nstemi from 2002 to 2011 ( adjusted or [ per year ] , 1.055 ; 95% ci , 1.054 to 1.056 ; p<0.001 ; figure 1 ; table 2 ) . adjusted temporal trends of proportion of nonstelevation myocardial infarction : overall cohort , age , sex , and race / ethnicity stratified multivariable adjustment for baseline demographics , hospital characteristics , and 29 elixhauser and other clinically relevant comorbidities as outlined in the methodology . adjusted odds ratios ( or ; per year ) for trend were determined using logistic regression models evaluating calendar year as a continuous variable . numbers in parenthesis represent 95% confidence interval . a , nstemi ( % ) was calculated as the number of patients with nstemi divided by the number of patients with acute myocardial infarction ( ami ) per year100 ; ptrend<0.001 . b , trends in nstemi presented as unadjusted and adjusted odds ratio and 95% confidence interval ( ci ) for each year relative to 2002 ( reference year ) . regression model adjusted for demographics , hospital characteristics , and 29 elixhauser and other clinically relevant comorbidities . 95% cis are depicted , but are too narrow to be visualized outside the marker width . the increase in proportion of nstemi , it increased from 45.4% to 60.2% in those 40 to 64 years of age ( adjusted or [ per year ] , 1.045 ; 95% ci , 1.044 to 1.046 ; p<0.001 ) , from 54.5% to 70.7% in those 65 to 74 ( adjusted or [ per year ] , 1.056 ; 95% ci , 1.055 to 1.058 ; p<0.001 ) , and from 59% to 77.1% in patients 75 ( adjusted or [ per year ] , 1.066 ; 95% ci , 1.065 to 1.068 ; p<0.001 ) . when stratified according to sex , women ( 56.1% to 73.6% ; adjusted or [ per year ] , 1.070 ; 95% ci , 1.069 to 1.071 ; p<0.001 ) had a steeper proportional increase , compared to men ( 50.4% to 65.3% ; adjusted or [ per year ] , 1.046 ; 95% ci , 1.045 to 1.047 ; p<0.001 ) . age , sex , and race / ethnicity specific trends in incidence rates of nonstelevation myocardial infarction . a , age stratified ; ptrend<0.001 , ( b ) sex stratified ; ptrend<0.001 , and ( c ) race / ethnicity stratified ; ptrend<0.001 . table 3 depicts the baseline demographic , hospital , and clinical characteristics of patients admitted with nstemi from 2002 to 2011 . there was a slight decrease in mean age at admission during the study period ( 70.3613.11 years in 2002 versus 69.8713.53 in 2011 ; p<0.001 ) . more specifically , there was an increase in the proportion of nstemi patients aged 40 to 64 years and decrease in those aged 75 years from 2002 to 2011 ( ptrend<0.001 ) . similarly , there was a small , but statistically significant , increase in the proportion of men ( 56% in 2002 to 57.5% in 2011 ; ptrend<0.001 ) and a consequent decrease in the proportion of women ( 44.0% in 2002 to 42.5% in 2011 ; ptrend<0.001 ) with nstemi during the study period . the prevalence of smoking , dyslipidemia , cad , previous mi , carotid artery disease , diabetes mellitus , hypertension , obesity , peripheral vascular disease , chronic renal failure , alcohol abuse , deficiency anemias , coagulopathy , fluid / electrolyte disorders , and previous pci increased from 2002 to 2011 ( ptrend<0.001 for all ) . the prevalence of heart failure and chronic pulmonary diseases remained relatively constant throughout the study period . baseline demographics , hospital characteristics , comorbidities , utilization of early invasive strategy , and overall inhospital mortality in patients with nonstelevation myocardial infarction aids indicates acquired immunodeficiency syndrome ; cabg , coronary artery bypass graft surgery ; cad , coronary artery disease ; h / o , history of ; pci , percutaneous coronary intervention ; ra , rheumatoid arthritis ; tia , transient ischemic attack . utilization of eis on day 0 of presentation increased from 14.9% in 2002 to 21.8% in 2011 ( adjusted or [ per year ] , 1.065 ; 95% ci , 1.064 to 1.066 ; p<0.001 ) . the adjusted temporal trends for utilization of eis were similar across all age , sex , and racial / ethnic groups . patients 75 years of age had the highest proportional increase in utilization of eis ( adjusted or [ per year ] , 1.072 ; 95% ci , 1.069 to 1.074 ; p<0.001 ; figures 3 and 4 ; table 4 ) . adjusted temporal trends of nonstelevation myocardial infarction with utilization of the early invasive strategy at day 0 : overall cohort , age , sex , and race / ethnicity stratified multivariable adjustment for baseline demographics , hospital characteristics , and 29 elixhauser and other clinically relevant comorbidities as outlined in the methodology . adjusted odds ratios ( or ; per year ) for trend numbers in parenthesis represent 95% confidence interval . trends in utilization of early invasive strategy for nonstelevation myocardial infarction . b , trends in early invasive strategy at day 0 presented as unadjusted and adjusted odds ratio and 95% confidence interval ( ci ) for each year relative to 2002 ( reference year ) . regression model adjusted for demographics , hospital characteristics , and 29 elixhauser and other clinically relevant comorbidities . d , trends in early invasive strategy at day 0 or 1 presented as unadjusted and adjusted odds ratio and 95% confidence interval ( ci ) for each year relative to 2002 ( reference year ) . regression model adjusted for demographics , hospital characteristics , and 29 elixhauser and other clinically relevant comorbidities . 95% cis are depicted , but are too narrow to be visualized outside the marker width . age , sex , and race / ethnicity specific trends in utilization of early invasive strategy ( eis ) for nonstelevation myocardial infarction . a , age stratified , eis day 0 ; ptrend<0.001 , ( b ) sex stratified , eis day 0 ; ptrend<0.001 , ( c ) race / ethnicity stratified , eis day 0 ; ptrend<0.001 , ( d ) age stratified , eis day 0 or 1 ; ptrend<0.001 , ( e ) sex stratified , eis day 0 or 1 ; ptrend<0.001 , and ( f ) race / ethnicity stratified , eis day 0 or 1 ; ptrend<0.001 . results showed a temporal increase in the overall as well as the age , race / ethnicity , and sexstratified cohorts ( figures 3 and 4 ; table 5 ) . adjusted temporal trends of nonstelevation myocardial infarction with utilization of the early invasive strategy at day 0 to 1 : overall cohort , age , sex , and race / ethnicity stratified multivariable adjustment for baseline demographics , hospital characteristics , and 29 elixhauser and other clinically relevant comorbidities as outlined in the methodology . adjusted odds ratios ( or ; per year ) for trend were determined using logistic regression models evaluating calendar year as a continuous variable . inhospital mortality decreased from 5.5% in 2002 to 3.9% in 2011 in all patients with nstemi ( adjusted or [ per year ] , 0.976 ; 95% ci , 0.974 to 0.978 ; p<0.001 ) . on agestratified analysis , those 75 years of age had the greatest decrease in inhospital mortality ( adjusted or [ per year ] , 0.968 ; 95% ci , 0.966 to 0.971 ; p<0.001 ) . women had a steeper temporal decline in inhospital mortality , compared to men , from 2002 to 2011 ( adjusted or [ per year ] , 0.965 ; 95% ci , 0.962 to 0.968 ; p<0.001 in women and adjusted or [ per year ] , 0.986 ; 95% ci , 0.984 to 0.989 ; p<0.001 in men ) . statistically significant decline in mortality was also observed in all racial / ethnic groups . in patients receiving eis on day 0 of presentation , however , the overall trend in this decrease was not statistically significant ( adjusted or [ per year ] , 0.998 ; 95% ci , 0.991 to 1.004 ; p=0.471 ) . a temporal decline in inhospital mortality was observed in patients treated with invasive strategy on day 0 or 1 ( 2.4% in 2002 to 1.8% in 2011 ; adjusted or [ per year ] , 0.988 ; 95% ci , 0.983 to 0.993 ; p<0.001 ; figures 5 and 6 ; table 6 ) . in patients not receiving eis , inhospital mortality decreased from 6.7% in 2002 to 5.4% in 2011 ( adjusted or [ per year ] , 0.977 ; 95% ci , 0.975 to 0.979 ; p<0.001 ; figure 6 ; table 6 ) . adjusted temporal trends of riskadjusted inhospital mortality in patients with nonstelevation myocardial infarction : overall cohort , age , sex , race / ethnicity , and early invasive strategy stratified multivariable adjustment for baseline demographics , hospital characteristics , and 29 elixhauser and other clinically relevant comorbidities as outlined in the methodology . adjusted odds ratios ( or ; per year ) for trend were determined using logistic regression models evaluating calendar year as a continuous variable . a , inhospital mortality ( % ) was calculated as the number of patients who died during the hospitalization divided by the number of patients with nstemi per year100 ; ptrend<0.001 . b , trends in inhospital mortality presented as unadjusted and adjusted odds ratio ( or ) and 95% confidence interval ( ci ) for each year relative to 2002 ( reference year ) . regression model adjusted for demographics , hospital characteristics , and 29 elixhauser and other clinically relevant comorbidities . age , sex , race / ethnicity , and utilization of invasive strategyspecific trends in inhospital mortality in patients with nonstelevation myocardial infarction . a , age stratified , ( b ) sex stratified , ( c ) race / ethnicity stratified , and ( d ) stratified according to utilization of invasive strategy ( ptrend<0.001 for all ) . no eis was defined as patients who did not receive coronary angiography with intent to revascularize within day 0 or 1 . for secondary outcome analysis , we studied the temporal trends in cost and length of stay . detailed results of the length and cost of stay temporal trends stratified by age , sex , and race / ethnicity are shown in tables 7 and 8 , respectively . the mean ( sem , in days ) length of stay decreased in the overall cohort of patients during the study period ( 5.70.01 in 2002 to 4.80.01 in 2011 ; ptrend<0.001 ) . patients with nstemi undergoing eis within day 0 had the shortest length of stay , and the length of stay declined in all patients undergoing eis , irrespective of timing ( from 4.40.03 in 2002 to 3.90.02 in 2011 for those with eis at day 0 and from 4.80.02 in 2002 to 4.10.01 in 2011 for those with eis within day 0 or 1 ; ptrend<0.001 for all ; figure 7 ; table 7 ) . temporal trends in length of stay ( meanse ) in days temporal trends in total hospital cost ( meanse ) in u.s . dollars temporal trends in length of stay , in days . a , overall , ( b ) age , ( c ) sex , ( d ) race / ethnicity , and ( e ) timing of invasive strategy ( ptrend<0.001 for all ) . mean ( sem , in dollars ) cost of stay in the overall patient population admitted with nstemi increased from $ 14 77430 from 2002 to $ 20 26935 in 2011 ( ptrend<0.001 ) . the mean ( sem , in dollars ) costs accrued by those undergoing eis were higher and showed a similar increasing trend ( from $ 17 38580 in 2002 to $ 24 34576 in 2011 for those with eis at day 0 and from $ 17 53459 in 2002 to $ 23 97155 in 2011 for those with eis within day 0 or 1 ; ptrend<0.001 for all ; figure 8 ; table 8) . ( a ) overall , ( b ) age , ( c ) sex , ( d ) race / ethnicity , and ( e ) timing of invasive strategy ( ptrend<0.001 for all ) . we report an increasing trend in the proportion of nstemi admissions for the overall cohort and in the age , sex , and race / ethnicitystratified subgroups from 2002 to 2011 . this is associated with an increase in utilization of eis , decreased inhospital mortality , and decreased length of stay during the same period . analysis of the national registry of myocardial infarction from 1990 to 2006 reported an increase in the proportion of nstemi from 14.2% in 1990 to 59.1% in 2006 ( p<0.001 ) . the proportional increase in nstemi may be the result of an aging population , increasing chronic comorbidities , and reduction in smoking . part of the increase in the proportion of nstemi in our study may be attributable to increased utilization and higher sensitivity of cardiac biomarkers ( troponins ) . in the age and sexstratified analysis older patients are more likely to be women and have significant comorbidities that predispose them to nstemi . on trend analysis of baseline characteristics , we report an increase in the proportion of patients in the 40 to 64 years of age group . this is in concordance with the analysis of get with the guidelines coronary artery disease registry from 2003 to 2008 , with that age group representing the fastestgrowing segment of our population over the years . importantly , there was a temporal increase in utilization of the eis in the nstemi patient population . metaanalysis of randomized , control trials has consistently shown a benefit of eis in the setting of nstemi , especially in the highrisk patient population . definition of optimal timing of invasive management has undergone a paradigm shift in the last decade . the 2002 acc / aha guidelines for management of nstemi and the 2007 acc / aha guidelines for management of nstemi in the elderly patient population defined the eis as routine cardiac catheterization within 48 hours of presentation . the more recent timacs trial compared the routine early intervention ( 24 hours of presentation ; median time , 14 hours ) to delayed intervention ( 36 hours after presentation ; median time , 50 hours ) . there was no significant difference in the primary endpoint , other than in the prespecified subgroup with high global registry of acute coronary events scores . after 6 months , they reported a 28% relative reduction in secondary outcome of death , mi , and refractory ischemia in the early intervention group ( or , 0.72 ; 95% ci , 0.58 to 0.89 ; p=0.003 ) . the results of the crusade ( can rapid risk stratification of unstable angina patients suppress adverse outcomes with early implementation of the acc / aha guidelines ) quality improvement initiative from 2000 to 2002 indicated that the eis ( within 48 hours ) was not utilized in a majority of highrisk patients with nstemi . they reported male sex , ischemic electrocardiographic changes , younger age , positive biomarkers , lack of congestive heart failure , lack of renal insufficiency , and white race as predictors of early invasive management . we analyzed the trends in both day 0 and day 0 or 1 of presentation . utilization of eis at day 0 increased from 14.9% in 2002 to 21.8% in 2011 ( p<0.001 ) , and utilization of eis at day 0 or 1 increased from 27.8% in 2002 to 41.4% in 2011 ( p<0.001 ) . the increase in utilization was consistent among all age , race / ethnicity , and sexstratified subgroups after multivariable adjustment . men had a higher proportional increase in eis at both day 0 and day 0 or 1 of presentation . previous studies have discussed the sex differences in the invasive management of acs , with women being managed less aggressively than men . interestingly , patients 75 years of age had a higher proportional increase in eis at day 0 and patients 40 to 64 years of age had an overall higher proportional increase at day 0 or 1 . using the linked crusade registry and medicare and medicaid claims data , reported an increased utilization of evidence based nstemi care and decline in inhospital mortality in 2006 , compared with 2003 ( or , 0.82 ; 95% ci , 0.67 to 1.00 ; p=0.045 ) in patients 65 years of age with nstemi . recent trend analysis from denmark also reported an increase in initiation of coronary angiography for firsttime nstemi admissions at 3 days from 18.2% in 2001 to 55.7% to 2009 . we also report a decrease in riskadjusted inhospital mortality and length of stay for patients admitted with nstemi . the decline in inhospital mortality was observed in patients receiving eis as well as those not receiving eis . this observation is consistent with improvement in , or better adherence to , medical therapy , independent of eis utilization . the lower inhospital mortality observed in the eismanaged patients is likely the result of patient selection bias , as previously demonstrated by analysis of the crusade registry , and no causal association between eis and inhospital mortality can be inferred from the results of our study . the decline in overall inhospital mortality was most prominent in those 75 years of age . we have previously reported a 24% relative reduction of inhospital mortality in octogenarians treated with the early invasive approach versus the initial conservative strategy ( or , 0.76 ; 95% ci , 0.74 to 0.78 ; p<0.001 ) . however , it is not possible to conclusively establish a causal relationship between increasing utilization of eis and decreasing inhospital mortality from this study . the possibility of selection bias and residual measured and unmeasured confounding can not be completely eliminated . nis is an administrative database ; there is the potential for unrecognized miscoding of diagnostic and procedure codes . there is a possibility that widespread troponin utilization in the last decade may have contributed to the increase in nstemi diagnosis and also potentially decreased case severity of those classified as nstemi . also , conditions other than acs may have led to troponin elevations and hence miscoding of nstemi exists . clinical presentation and it is our assumption that day 0 corresponds to 24 hours and days 0 or 1 corresponds to 48 hours , because the database does not provide the timing of procedure in hours . for trends in total hospital costs the nis databases do not include nstemi hospitalizations for veterans hospitalized in veterans affairs hospitals . last , outcomes in the nis database are limited to inhospital events and causes of death are not differentiated . however , these potential limitations may be partially compensated by the large size of the database and the ability to obtain nationwide estimates using the discharge weights provided . the possibility of selection bias and residual measured and unmeasured confounding can not be completely eliminated . nis is an administrative database ; there is the potential for unrecognized miscoding of diagnostic and procedure codes . there is a possibility that widespread troponin utilization in the last decade may have contributed to the increase in nstemi diagnosis and also potentially decreased case severity of those classified as nstemi . also , conditions other than acs may have led to troponin elevations and hence miscoding of nstemi exists . clinical presentation and it is our assumption that day 0 corresponds to 24 hours and days 0 or 1 corresponds to 48 hours , because the database does not provide the timing of procedure in hours . for trends in total hospital costs the nis databases do not include nstemi hospitalizations for veterans hospitalized in veterans affairs hospitals . last , outcomes in the nis database are limited to inhospital events and causes of death are not differentiated . however , these potential limitations may be partially compensated by the large size of the database and the ability to obtain nationwide estimates using the discharge weights provided . in this large , nationwide analysis of patients with mi , we report an increase in proportion of nstemi with increasing utilization of eis in the united states . we also report a decrease in inhospital mortality and decrease in length of stay during the study period . nevertheless , age , sex , and race / ethnicityspecific differences in the management and outcomes of nstemi were observed , and further studies are needed to develop strategies to ensure more equitable care for nstemi .