aDeparDenmark;Hospital, AImprovemeRigshospitUniversityAalborg UnGentofte HService, TMedical SEmergencykPrehospitalPrehospitaDenmark;nDepartmeUniversity,manuscript

0002-9149http://dx.do

Impact of Health Care System Delay in Patients WithST-Elevation Myocardial Infarction on Return to Labor

Market and Work Retirement

Kristina Grønborg Laut, MPH, PhDa,b,*, Jacob Hjort, MPHc, Thomas Engstrøm, DMScid,Lisette Okkels Jensen, DMScie, Hans-Henrik Tilsted Hansen, MDf, Jan Skov Jensen, MD, PhDg,

Frants Pedersen, PhDd, Erik Jørgensen, MDd, Lene Holmvang, DMScid,Alma Becic Pedersen, MD, PhDb, Erika Frischknecht Christensen, MDh, Freddy Lippert, MDi,

Torsten Lang-Jensen, MDj, Henning Jans, MDk, Poul Anders Hansen, MDl, Sven Trautner, MDm,Steen Dalby Kristensen, DMScia, Jens Flensted Lassen, MD, PhDa, Timothy L. Lash, MPH, DScb,n,

Peter Clemmensen, DMScid, and Christian Juhl Terkelsen, DMScia

System delay (delay from emergency medical service call to reperfusion with primary

tment ofbDepararhus,nt, Cealet, CoHospiiversityospital,he Centervice,Medi

l Emel EmermFalcknt of EAtlantreceive

/14/$ -i.org/1

percutaneous coronary intervention [PPCI]) is acknowledged as a performance measure inST-elevation myocardial infarction (STEMI), as shorter system delay is associated with lowermortality. It is unknown whether system delay also impacts ability to stay in the labor market.Therefore, the aim of the study was to evaluate whether system delay is associated withduration of absence from work or time to retirement from work among patients with STEMItreated with PPCI. We conducted a population-based cohort study including patients£67 years of age who were admitted with STEMI from January 1, 1999, to December 1, 2011and treated with PPCI. Data were derived from Danish population-based registries. Onlypatients who were full- or part-time employed before their STEMI admission were included.Association between system delay and time to return to the labor market was analyzed using acompeting-risk regression analysis. Association between system delay and time to retirementfromworkwas analyzed using a Cox regressionmodel. A total of 4,061 patients were included.Ninety-three percent returned to the labormarket during 4 years of follow-up, and 41% retiredduring 8 years of follow-up. After adjustment, system delay >120minutes was associated withreduced resumption of work (subhazard ratio 0.86, 95% confidence interval 0.81 to 0.92) andearlier retirement from work (hazard ratio 1.21, 95% confidence interval 1.08 to 1.36). Inconclusion, system delaywas associatedwith reducedwork resumption and earlier retirement.This highlights the value of system delay as a performance measure in treating patients withSTEMI. � 2014 Elsevier Inc. All rights reserved. (Am J Cardiol 2014;114:1810e1816)

There is ample evidence that time from first contact withthe health care system to initiation of reperfusion therapy(system delay) is associated with mortality in patients withST-elevation myocardial infarction (STEMI).1e3 Approxi-mately 45% of all patients admitted with acute myocardial

Cardiology, Aarhus University Hospital, Skejby, Aarhus,tment of Clinical Epidemiology, Aarhus UniversityDenmark; cDepartment of Public Health and Qualityntral Region Denmark; dDepartment of Cardiology,penhagen, Denmark; eDepartment of Cardiology, Odensetal, Odensen, Denmark; fDepartment of Cardiology,Hospital, Aalborg, Denmark; gDepartment of Cardiology,Copenhagen, Denmark; hPrehospital Emergency Medicalral Denmark Region, Denmark; iPrehospital EmergencyThe Capital Region of Denmark, Denmark; jPrehospitalcal Service, The South Denmark Region, Denmark;rgency Medical Service, Region Zealand, Denmark;gency Medical Service, The North Denmark Region,Emergency Medical Service, Copenhagen, Denmark; andpidemiology, Rollins School of Public Health, Emorya, Georgia. Manuscript received June 11, 2014; revisedd and accepted September 17, 2014.

see front matter � 2014 Elsevier Inc. All rights reserved.0.1016/j.amjcard.2014.09.018

infarction (AMI) are of the working age.4,5 In 2009, loss inproduction because of cardiovascular heart disease mortalityand morbidity was estimated to cost the European Unionaround V18 billion, of which about 9% is due to illnessamong patients of working age.6 Only few studies have

Drs. Laut, Lassen, and Terkelsen conceived the study idea. Dr. Laut,Dr. Terkelsen, and Mr. Lang-Jensen designed the study. All the authorscollected the data. Dr. Laut, Dr. Terkelsen, Mr. Hjort, Dr. Pedersen, andDr. Lash directed the analyses, which were carried out by Dr. Laut,Dr. Terkelsen, and Mr. Hjort. Dr. Lash and Dr. Kristensen revised theanalysis. All the authors participated in the discussion and interpretation ofthe results. Dr. Laut organized the writing and wrote the initial draft. All theauthors critically revised the manuscript for intellectual content andapproved the final version.

This work was financial supported by the Department of Cardiology,Aarhus University Hospital, Skejby, Aarhus, Denmark the Riisfort Foun-dation and the Arvid Nilssons Foundation. The funding sources had noinvolvement in carrying out the project.

See page 1815 for disclosure information.*Corresponding author: Tel: (þ45) 7845-2029; fax: (þ45) 8949-6009.E-mail address: kristina@laut.dk (K.G. Laut).

www.ajconline.org

Figure 1. Flow of patients into the study.

Coronary Artery Disease/Return to Labor Market and Work Retirement After STEMI 1811

evaluated return-to-work rates and retirement in patientswith STEMI treated with primary percutaneous coronaryintervention (PPCI), and these have been based on smallstudy samples.7,8 Shorter system delay is associated withlower risk of development of congestive heart failure afterSTEMI.9 Work outcome likely depends on left ventricularfunction (left ventricular ejection fraction), but it has notbeen evaluated whether shorter system delay affects theprobability of return to the labor market or retirement fromwork. The aim of the present nationwide study was toexamine the association between system delay and time towork resumption and time to retirement from work in pa-tients with STEMI treated with PPCI.

Methods

We conducted a population-based historical cohort studyincluding all patients �67 years who were admitted withSTEMI from January 1, 1999, to December 1, 2011. Onlypatients who were full-time or part-time employed, 3 weeksbefore STEMI were included, and for each patient only thefirst admission with STEMI during the study period wasincluded. Eligible patients were transported by the emer-gency medical services (EMS), treated with PPCI within12 hours of symptom onset at 1 of the 5 PCI-centers inDenmark (Aalborg, Gentofte, Odense, Rigshospitalet, andAarhus University Hospital in Skejby), and had a maximalsystem delay of 360 minutes (Figure 1). Patients withSTEMI were identified from the Western Denmark HeartRegistry (West Denmark) and the invasive cardiology(PATS) databases at Gentofte and Rigshospitalet (EasternDenmark). These registries collect baseline characteristicsand patient- and procedure-specific information on all an-giographies and coronary interventions performed in all

adult patients in Denmark since 1999. In 2008 the regis-tration was 98% complete for PPCI.10

The Danish health care system provides universal tax-supported healthcare, guaranteeing free access to generalpractitioners and hospitals, including EMS transportation forall inhabitants (5.5 million). The civil registration number, a10-digit unique personal identifier number is assigned to allDanish residents at birth or immigration and used in allDanish healthcare registries,11 enabling unambiguous link-age on individual level of data from Western Denmark HeartRegistry and PATS databases and other Danish registries.

The study was registered and approved by the DanishData Protection Agency (J # 2012-41-0043), the DanishHealth and Medicines Authority (j.nr.3-3013-81/1), and theNational Board of Health (J.nr. 6-8011-978/1).

System delay was defined as the time from first contact tothe EMS (112 call) to first catheterization with a guidingcatheter during PPCI.3,12 The Danish EMS system includingtime registration has been described in detail elsewhere.3

First catheterization with a guiding catheter during PPCIwas derived from the Western Denmark Heart Registry andPATS. System delay was categorized into 2 groups, namely�120 minutes and >120 minutes.

Outcomes were time to return to labor market, time towork retirement, and length of sick-leave period. All datawere derived from the Danish National Register on PublicTransfer Payments (DREAM). DREAM was founded in1991 and includes weekly registration on public transferpayments from any Danish authority given to all personswith a civil registration number.13 DREAM is maintained bythe Danish Ministry of Employment and updated monthly.By 2012, about 5 million Danes were registered. Those notincluded should not have received any transfer income fromany Danish authority during the last 20 years.13 Each

Table 1Characteristics of patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention and working three weeksbefore STEMI, stratified according to system delay (N¼4,061)

Characteristics System delay (minutes)* P Value

�120 (N 2,305)* >120 (N 1,756)*

Patients (%) Valid Cases Patients (%) Valid Cases

Median system delay (IQR†) (minutes) 89.3 (73.3-104.5) 2,305 157.9 (135.9-192.7) 1,756 <0.001Median age (IQR†) (years) 54 (48-59) 2,305 55(49-59) 1,756 0.04Women 334 (15%) 2,305 291 (17%) 1,756 0.07Non-married 626 (27%) 2,305 418 (24%) 1,756 0.02Comorbidity0 1,913 (83%) 2,305 1,446 (82%) 1,756 0.591þ 392 (17%) 310 (18%)

Treated hypertension 520 (24%) 2,173 357 (22%) 1,625 0.15Diabetes mellitus 139 (6%) 2,186 87 (5%) 1,641 0.18Familiar disposition IHDz 730 (46%) 1,586 606 (43%) 1,393 0.17Active or previous smoker 1,832 (89%) 2,056 1,273 (85%) 1,489 0.001Killip class 1,660 1,505 0.09I 1,572 (95%) 1,404 (93%)II-IV 88 (5%) 101 (7%)Median duration (IQR†) (weeks) of work

absenteeism during 4-years of follow-up10 (0-27) 2,305 12 (3-31) 1,756 <0.01

* System delay is the time from first contact with the 112 service system until Primary Percutaneous Coronary Intervention.† IQR ¼ Interquartile range.z Ischemic Heart Disease.

Figure 2. Cumulative incidence of return to labor market after ST-elevationmyocardial infarction (STEMI), stratified according to system delay (minutes).

1812 The American Journal of Cardiology (www.ajconline.org)

patient’s work situation was evaluated 1 year before and upto 8 years after the index PPCI procedure.

We recoded the original 104 different transfer-paymentcodes into 4 variables, namely (1) employment, (2) retire-ment from work, (3) sick leave, and (4) death(Supplementary Table 1). Work resumption was defined asreturn to full- or part-time work and required 4 fullconsecutive weeks with no registration in the DREAMdatabase or 1 of the transfer-payment codes predefined as“employment” (Supplementary Table 1).

Retirement included the following 3 categories: (1) per-sons who were granted disability pension, available for

those aged 18 to 59; (2) voluntary early retirement pension,available for those aged 60 to 65; and (3) public retirementpension, available for those aged 65þ. In Denmark, thegeneral retirement age is 65 to 67 years for both gendersdepending on birth year, but in the private sector and someoccupations a higher retirement age is applicable.

Sick leave was defined as 1 or more full weeks on sicknessallowance. In Denmark, sick leave extending beyond 3weeks must be sanctioned by the workers’ general practi-tioner. Workers are entitled to receive sickness allowance fora maximum period of 52 weeks within an 18 month periodwith full compensation.

We used the Danish National Registry of Patients toidentify co-morbid conditions before STEMI. This registryholds records of all nonpsychiatric hospitalizations inDenmark since 1977 and outpatient visits since 1995,including the dates of admission and discharge, and up to 20discharge diagnoses classified according to InternationalClassification of Diseases (eighth edition until the end of1993 and tenth edition thereafter).14 Based on the completehospitalization history of each patient, we computed theCharlson Co-morbidity Index. We classified co-morbidityinto 2 categories, namely no co-morbidity and 1 or moreco-morbidities.15

We obtained information on vital status until July 19,2012, from the Danish Civil Registration System. Thisregistry contains information on all Danish residents from1968 onward and includes daily updated information onvital status and migration.11

Follow-up ended on July 19, 2012, and median follow-up time was 239 weeks (interquartile range [IQR] 126 to358 weeks). When looking at return to labor market, follow-up began on the day of PPCI and ended on the date of returnto the labor market, work retirement, death, emigration, or

Table 2Multivariable analyses of covariates associated with return to the labor market, and retirement from work after ST-elevation myocardial infarction in patientstreated with primary percutaneous coronary intervention (PPCI) (N: 4,061)

Covariates included in the models Return to labor market (SHR)* (95% CI)(N¼ 4,061)

P-value Retirement from work(HR)† (95% CI)(N¼ 4,061)

P-value

System delay >120 minutesz 0.86 (0.81, 0.92) <0.001 1.21 (1.08, 1.36) 0.001Age (Years)<50 1.00 Reference <0.05 1.00 Reference <0.00150-<60 0.93 (0.88, 1.00) 5.10 (4.05, 6.42)60þ 0.91 (0.82, 1.00) 31.11 (24.51, 39.50)

Men 0.82 (0.76, 0.89) <0.001 1.17 (1.00, 1.36) 0.05Married 1.00 Reference 0.42 1.00 Reference <0.001Not married 1.03 (0.96, 1.11) 1.67 (1.45, 1.94)Comorbid conditions0 1.00 Reference 0.22 1.00 Reference 0.441þ 0.95 (0.87, 1.03) 1.06 (0.92, 1.22)

Smoker 0.37 0.07Never 1.00 Reference 1.00 ReferenceActive or previous 1.05 (0.94, 1.16) 0.85 (0.72, 1.01)

Year 0.07 0.48�2006 1.00 Reference 1.00 Reference>2006 0.94 (0.89, 1.00) 0.95 (0.83, 1.09)

* Return to labor marketeAnalysis based on competing-risk analysis with death and work retirement as competing risks. SHR ¼ Sub Hazard Ratios.Variables are mutual adjusted.

† Work retirementeAnalysis based on cox-regression modeling. HR ¼ Hazard Ratios. Variables are mutual adjusted.z System delay is the time from first contact with the 112 service system until PPCI.

Figure 3. Cumulative incidence of work retirement (weeks) after ST-elevationmyocardial infarction (STEMI), stratified according to system delay (minutes).

Coronary Artery Disease/Return to Labor Market and Work Retirement After STEMI 1813

after 208 weeks of follow-up (4 years, this to ensure that atleast 10% of the study population remained at risk),whichever came first. When looking at work retirement,follow-up began on the day of PPCI and ended at the date ofwork retirement, death, emigration, or after 416 weeks offollow-up (8 years, this to ensure at least 10% of the studypopulation remained at risk), whichever came first.

Continuous data are summarized as medians with IQR.Categorical variables are reported as frequencies and per-centages. The chi-square test andWilcoxon rank sum test wereused for comparisons of categorical variables and continuousvariables as appropriate. Missing values among covariates

were replaced with their conditional means, obtained frommultiple imputations by the Stata ICE (StataCorp, CollegeStation, Texas) command.16We imputed 10 data sets based onthe covariates listed in Table 1. However, Killip class andpredisposition of ischemic heart disease were missing in>20% of patients, so we chose not to impute them, and thesevariables were therefore not included in the final analysis.

We performed 2 different types of analyses. (1) The 4-yearprobability of returning to the labor market was assessed bythe cumulative incidence function with death and workretirement as competing risks.17 Cumulative incidence curveswere stratified according to intervals of system delay. Asso-ciations between system delay, selected clinical and de-mographic data, and work resumption were assessed usingmultivariate competing-risk analysis estimating subhazardratios with 95% confidence intervals. (2) We used Cox pro-portional hazards regression to compute adjusted incidencerates (hazard ratios) of work retirement during an 8-yearperiod with 95% confidence interval. Cumulative incidenceswere stratified according to intervals of system delay withdeath as a competing risk.

Comparisons of groups were performed by includingsystem delay as a categorical variable in both the competingrisk analysis and the Cox proportional hazards regression.We included year of index PPCI in the multivariate modelsto reveal a possible time trend.

In the Cox regression analysis, the assumption of propor-tional hazards was assessed graphically and found appropriate.In the competing-risk regression analyses, the proportionalhazards assumption was checked by evaluating whetherthe subhazard ratios for each covariate were time-varying.

A p value <0.05 was considered to indicate statisticalsignificance. All statistical analyses were carried out using

1814 The American Journal of Cardiology (www.ajconline.org)

Stata 11.0 statistical software (StataCorp, College Station,Texas).

Results

Our final analytic sample included 4,061 patients withSTEMI treated with PPCI and with a treatment delay of<12 hours. For a full description of patient flow andexclusion criteria see Figure 1.

Baseline patient characteristics stratified according tosystem delay are listed in Table 1. Compared with thosewith a system delay >120 minutes, patients with systemdelays of �120 minutes were more likely to be younger, notmarried, and active smokers (Table 1). There were no dif-ferences between groups regarding co-morbidity and gender(Table 1).

At 1 month, 29% (n¼ 673) of patients with a system delayof �120 minutes had returned to the labor market, 96% ofwhom to a full-time position (Figure 2). In patients with asystem delay of >120 minutes, 25% had returned to work at1 month (n ¼ 436) with 94% being employed full-time. At1 year the proportion of patients being employed hadincreased to 87% (n ¼ 2,017) and 83% (n ¼ 1,456) in the2 groups, respectively. During follow-up, 93% (n¼ 2,137) ofpatients with a system delay of�120 minutes had returned tothe labor market, whereas this was true for 89% (n¼ 1,557) ofpatients with a system delay of >120 minutes (Figure 2).Table 2 lists factors associated with return to the labor market.In this multivariate analysis, system delay of >120 minutesremained associated with a lower chance of returning to thelabor market. Moreover, men had a lower chance of returningto work compared with women. The association betweensystem delay and return to work did not change over years.

A total of 29% (n ¼ 1,192) of the study populationretired during follow-up. Proportions of people retired at 1year were 6.6% (n ¼ 152) in the group of patients with asystem delay of �120 minutes compared with 8.6%(n ¼ 151) in the group with a system delay of >120 minutes(Figure 3). At the end of follow-up, 26% (n ¼ 598) of pa-tients with a system delay of �120 minutes had retiredcompared with 34% (n ¼ 594) of patients with a systemdelay of >120 minutes. After adjustment for confoundingfactors, system delay was associated with work retirement(Table 2). The association between system delay andretirement did not change over years (Table 2).

A subgroup analysis including only patients <60 yearsrevealed the same tendency between system delay and re-turn to labor market and early retirement (results notshown).

Four weeks after STEMI, 61% (n ¼ 1,406) of patientswith a system delay of �120 minutes were receiving sick-ness allowance compared with 64% (n ¼ 1,124) of patientswith a system delay of >120 minutes. Mean duration ofwork absenteeism during 4 years of follow-up was 10 weeks(IQR 0 to 27) in patients with system delay of �120 minutesand 12 weeks (IQR 3 to 31) in patients with system delay of>120 minutes (p <0.01).

Discussion

This population-based follow-up study is the first toexamine the association between health care system delay

and work resumption or work retirement in patients withSTEMI treated with PPCI. The main findings were that asystem delay �120 minutes is associated with labor marketreintegration and retention. Our data thus extend findingsfrom 2 previous Danish studies, which demonstrated thatshort health care system delay is associated with lowermortality and a lower risk for readmission and outpatient’scontacts due to congestive heart failure.3,9 It is not surprisingthat timely reperfusion with PPCI for STEMI increasesmyocardial salvage, which results in improved left ventric-ular function and better health outcomes in general. Simi-larly, other studies report that the decision to return to workafter AMI is associated with heart failure and reduced leftventricular function.7,8,18 In addition, a Danish study from2004 showed that patients with AMI with an impaired leftventricular ejection fraction had a reduced rate of return-to-work during the first 6 months and increased risk ofretirement during a 4-year follow-up period.19

We found that most patients, including those with systemdelay >120 minutes, having an AMI returned to the labormarket after a brief period of convalescence. Previous studiesreport that 50% to 90% of men and women who are workingbefore AMI return to work after the acute event.7,8,18e21

Potential explanations for the high proportion returning tothe labor market in our study could be the greater degree ofaccessibility and follow-up of labor market data through theDREAM database, that our study population was fairlyyoung and with few co-morbid conditions (Table 1) and thatwe included only patients treated with PPCI, which isregarded as the optimal reperfusion treatment.

Adjusting for confounding factors, we found that menhad reduced probability of returning to the labor market,which is in contrast to 2 previous studies.7,19 These con-flicting results merit further research, because recent studiesindicate that long-term prognosis after PPCI is comparablein men and women.22 One explanation could be that theseprevious studies are based on other geographically selectedpopulations, include only small numbers of women, andhave been partly based on interview data, which is subject torecall bias. Moreover, it could be speculated that job de-mands among men are on average more physically chal-lenging than those of women.

Although a substantial proportion of our study populationreturned to the labor market, system delays of >120 minuteswas still associated with faster withdrawal from the labormarket. In addition, patients with coronary heart disease areknown to have impaired health-related quality of lifecompared with the general population.23 Recent studies haveshown a significant influence of health-related quality of lifeon long-term outcomes.23e25 Despite advances in treatment,many patients still have impaired physical, social, andemotional performance that could result in reduced jobretention. Further studies within the area are needed.

Health care costs are increasing and retaining people inthe labor market is as important as ever. Our study indicatesthat investing in infrastructure and systems to optimizeSTEMI strategies—including prehospital diagnosis ofSTEMI and field triage to reduce delays—may lead, on thelong term, to cost savings.

The Danish tax-supported health care system and greatnumber of highly reliable registries provide an optimal

Coronary Artery Disease/Return to Labor Market and Work Retirement After STEMI 1815

setting to conduct population-based studies. Still, as in anystudy design, there is a risk of bias. We were unable tocontrol for several potential confounding factors, such asdepression, left ventricular ejection fraction, infarct location,health-related quality of life, educational status, previouscategory of work, and socio-economic status documented toaffect work retention and resumption.7,26e29 We do not,however, believe that these factors have a great influence onsystem delay in our health care setting with equal access totreatment including free EMS transportation. Moreover, thedegree of coronary artery disease (number of diseased ves-sels) and Killip class were missing in up to 38% of the studypopulation. Both variables have shown to be associated withlong-term risk for readmission or outpatient contact becauseof congestive heart failure9; but again, there is no reason tobelieve that these factors affected system delay, and thus noreason to believe that they affected the overall findings ofthe study. Furthermore, data were collected prospectivelybefore we decided to perform the study, thus reducing therisk of information bias. However, sick listing of <3 weeksare not recoded in the DREAM database. In this period, noincome is transferred to employers, unless the employee hasa chronic disease, in which case the municipal authoritiespay the expenses from the very first day. Thus, we wereunable to register very short periods of sick leave for allpatients. We restricted our study to patients with STEMI inthe labor market 3 weeks before the STEMI and to people ofworking age, which included only 30% of the originalsource population. This restriction might hamper general-izability of the results to the larger population of all patientswith STEMI.

Disclosures

The authors have no conflict of interests to disclose.

Supplementary Data

Supplementary data associated with this article can befound, in the online version, at http://dx.doi.org/10.1016/j.amjcard.2014.09.018.

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