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Patients surviving an acute myocardial infarction (AMI) have an increased risk of stroke.1–3 The risk of stroke after

AMI is ≈0.9% to 1.4% during the hospital stay, 2.1% within 1 year,1,2,4,5 and 5.7% within 4 years.6 The most important risk factors for the occurrence of stroke are older age, diabetes mellitus, hypertension, prior stroke, heart failure, atrial fibril-lation, and coronary artery by-pass grafting.1,4,7

Stroke after AMI is associated with an increased risk of death. One study found that patients with AMI that have a stroke have an increased risk of dying during hospitaliza-tion with an odds ratio of 4.3.8 The short-term mortality rate (death in-hospital or during the 30-day follow-up) has been estimated to be 17.0% to 45.9%, whereas the long-term mor-tality rate (1.5–3.4 years after discharge) is estimated to be 16.9% to 27.9%.2,4,7–10 There are several limitations to these estimates. Most previous studies did not analyze ischemic and hemorrhagic stroke separately, probably because of small sample sizes; however, hemorrhagic stroke is associ-ated with higher mortality compared with ischemic stroke.11 One study found a 1-year mortality rate after hemorrhagic

stroke of 71.8% in a selected population of patients with AMI treated with thrombolysis.12 The risk of hemorrhagic stroke after AMI is closely related to the use of thrombolytic therapy, whereas ischemic stroke has other, partly unknown, mechanisms. It is, therefore, of interest to analyze ischemic stroke separately.

Most studies describe short-term mortality, often using the duration of the hospital stay as the follow-up duration. However, the hospitalization period has decreased over time making comparisons between studies rather difficult. Moreover, the treatment of AMI has changed markedly during the past decade resulting in decreased mortality. It is unknown whether mortality after an AMI-associated stroke has changed as well. Only 1 previous study has presented a time trend of mortality after AMI-associated stroke. The results of that study suggested that the mortality increased from 1986 to 2005. However, the calculations were based on a few stroke cases making the conclusion unreliable.2 Factors associated with increased or decreased mortality after an AMI-associated ischemic stroke remain unclear.

Background and Purpose—Acute myocardial infarction (AMI) increases the risk of ischemic stroke, and mortality among these patients is high. Here, we aimed to estimate the 1-year mortality reliably after AMI complicated by ischemic stroke. We also aimed to identify trends over time for mortality during 1998–2008, as well as factors that predicted increased or decreased mortality.

Methods—Data for 173 233 unselected patients with AMI were collected from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admissions registry for 1998–2008. Specifically, we analyzed 1-year follow-up and mortality data for patients with AMI with and without ischemic stroke. Kaplan–Meyer analysis was used to analyze mortality trends over time, and Cox regression analysis was used to identify uni- and multivariate predictors of mortality.

Results—The 1-year mortality was 36.5% for AMI complicated by ischemic stroke and 18.3% for AMI without stroke. Mortality decreased over time in patients with and without ischemic stroke. The absolute decreases in mortality were 9.4% and 7.5%, respectively. Reperfusion and secondary preventive therapies were associated with a decreased mortality rate.

Conclusions—Mortality after AMI complicated by an ischemic stroke is very high but decreased from 1998 to 2008. The increased use of evidence-based therapies explains the improved prognosis. (Stroke. 2013;44:3050-3055.)

Key Words: mortality ◼ myocardial infarction ◼ risk factors ◼ stroke ◼ trends

Mortality After Ischemic Stroke in Patients With Acute Myocardial Infarction

Predictors and Trends Over Time in Sweden

Anna Brammås; Stina Jakobsson; Anders Ulvenstam, MD; Thomas Mooe, MD, PhD

Received March 12, 2013; final revision received July 13, 2013; accepted July 15, 2013.From the Department of Public Health and Clinical Medicine, Umeå University, Sweden (A.B., S.J., T.M.); and Department of Internal Medicine,

Section of Cardiology, Östersund Hospital, Sweden (A.U., T.M.).The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.

113.001434/-/DC1.Correspondence to Thomas Mooe, MD, PhD, Department of Internal Medicine, Section of Cardiology, Östersund Hospital, Östersunds sjukhus, Hus 10,

Plan 5, 83183 Östersund, Sweden. E-mail thomas.mooe@medicin.umu.se© 2013 American Heart Association, Inc.

Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STROKEAHA.113.001434

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Brammås et al Mortality After MI-Associated Ischemic Stroke 3051

In the present study, our primary aim was to determine the mortality rate associated with ischemic stroke during the first year after an AMI. Second, we wished to identify trends in mortality during the 1998–2008 period and to identify fac-tors associated with increased or decreased risk of death after AMI-associated ischemic stroke.

Materials and MethodsPatient data were obtained from the Swedish Web-system for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) that includes Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA), a national quality register of all patients admitted to a coro-nary care unit in Swedish hospitals. Patient data are reported on case record forms that include >100 variables; information is recorded on hospital admission, while the patient is in-hospital and at dis-charge. These records include patient demographics, risk factors, medical history, biochemical markers, discharge diagnosis, and discharge medications. The validity of the entered data is examined annually and shows 93% to 97% conformity between the Register of Information and Knowledge about Swedish Heart Intensive Care Admissions data and patient records. In 2008, 74 of 74 hospitals with coronary care units participated, covering >95% of Swedish coronary care units admissions, when compared with the Swedish National Patient Register.13 We collected data from patients with the index AMI during 1998–2008 with follow-up until 2009; this included a total of 173 233 patients.

We combined data from Register of Information and Knowledge about Swedish Heart Intensive Care Admissions with data from the National Patient Register to identify patients with ischemic stroke and to identify all causes of death. The National Patient Register includes dates for admission and discharge as well as diagnoses at discharge for all hospital stays in Sweden. The International Classification of Diseases-Ninth Revision (433 and 434) and International

Classification of Diseases-Tenth Revision (I63 and I64) codes for ce-rebral infarction were used. The National Patient Register has been validated and a diagnosis of stroke or transient ischemic attack has a positive predictive value of 98.6%.14 Both registers are based on the entire population in Sweden. There were no criteria for exclusion.

Patients were registered from 1998 to 2008 at the time of their in-dex AMI. The follow-up time for the major outcomes ischemic stroke and death was 1 year from AMI admission.

All patients for whom data were entered into the Register of Information and Knowledge about Swedish Heart Intensive Care Admissions were informed of their participation in the registry (patients could request to be excluded from the registry) and the long-term follow-up. The registry was approved by the National Board of Health and Welfare and the Swedish Data Inspection Board. The merging of registries was approved by the local ethics committee.

The variable “heart failure during hospitalization” was defined as the occurrence of pulmonary rales or treatment with intravenous di-uretics during hospitalization. The variable “smoking” was defined as smoking within the past month. “Atrial fibrillation” includes patients with atrial fibrillation (all types) before or during hospitalization.

Statistical AnalysisThe study period was divided into 5 time periods (1998–2000, 2001–2002, 2003–2004, 2005–2006, and 2007–2008) to study changes over time. The results are presented as mean values for continuous variables and as percentages for categorical variables. Comparisons between patient groups were performed using the Mann–Whitney U test for continuous variables and the χ2 test for categorical variables.

Kaplan–Meyer curves were calculated for the occurrence of death during the 5 different time periods and compared between groups us-ing the log-rank test. Uni- and multivariable predictors of risks were assessed using Cox proportional hazards regression analysis. The end point was defined as death within 1 year from admission to hos-pital for AMI. For our multivariable model, we used previously es-tablished predictors of risk for death and added the factors from our

Table 1. Characteristics of Patients With AMI (N=173 233) With and Without Ischemic Stroke Stratified by Survival

Variable

Ischemic Stroke Ischemic Stroke and Death No Ischemic Stroke No Ischemic Stroke and Death

n=4561 n=2624 n=135 587 n=30 461

Women, % 41.4 48.2 34.8 43.7

Age (mean) 74.8 79.6 69.1 79.2

Comorbidities, %

Prior ischemic stroke 21.8 26.0 6.2 15.3

Prior AMI 18.2 23.4 13.4 25.4

Prior heart failure 13.3 22.1 8.3 27.1

Diabetes mellitus 24.5 27.8 17.7 25.1

Prior kidney failure 1.7 3.0 1.5 5.7

Atrial fibrillation 26.2 34.8 12.7 27.8

Smoking 17.7 13.6 23.8 14.0

Clinical characteristics

Systolic blood pressure (mean) 150.1n=1971

145.5n=997

147.3n=62042

132.4n=11580

STEMI, % 34.0 31.2 36.5 31.4

Heart failure during hospitalization, % 41.6 60.1 28.2 63.5

Treatment in-hospital, %

Acute CABG 0.4 0.2 0.2 0.2

PCI 10.3 6.3 16.0 5.7

Thrombolysis 13.8 11.7 16.0 13.8

AMI indicates acute myocardial infarction; CABG, coronary artery by-pass grafting; PCI, percutaneous coronary intervention; and STEMI, ST-segment–elevation myocardial infarction.

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3052 Stroke November 2013

univariable analysis. Patients who died during hospitalization were excluded from the analysis when variables on treatment at discharge were included. We excluded variables from the multivariable analy-ses that had <90% valid cases (body mass index, habitual smoking, heart rate, systolic blood pressure, diastolic blood pressure, plasma cholesterol, plasma low-density lipoprotein, plasma glucose, and the use of AT2-inhibitors at discharge). A P value <0.05 was considered significant. All statistical analyses were performed using SPSS ver-sion 20.0 software.

ResultsThis study included 173 233 patients with AMI from 1998 to 2008. The patients had a mean age of 71.2 years, and 36.8% were women. The patient characteristics are shown in Table 1. Of the 173 233 patients with AMI, 7185 (4.1%) had an isch-emic stroke within 1 year of AMI and 2624 (36.5%) of these patients died during that year. Of the patients that did not have ischemic stroke in the year after AMI, 30 461 (18.3%) died. Overall, patients with ischemic stroke were older and had more comorbidities; this was also true for the patients who died during the first year after AMI.

Time TrendsTable 2 and Table I in the online-only Data Supplement describe the variation in patient characteristics and comorbidi-ties over time for patients with and without ischemic stroke

stratified for survival. Prior AMI decreased in all patient groups, probably because of the selection criterion (only the first event of AMI in the registry was included in the analysis). Hypertension increased in all groups, probably because of improved diagnosis. The proportion of ST-segment–elevation myocardial infarction decreased in all groups. The use of thrombolysis decreased, whereas the use of percutaneous cor-onary intervention increased.

The changes in medication at discharge over time are shown in Figure 1 and Figure I in the online-only Data Supplement. The use of β-blockers, acetylsalicylic acid, P2Y12-inhibitors, and statins increased in all patient groups. Overall, the use of evidence-based medication was lower in patients with stroke, as well as in nonsurvivors.

The overall mortality decreased during 1998–2008. In patients with and without stroke, the absolute decreases were 9.4% and 7.5%, respectively, whereas the relative decreases were 23.8% and 34.6%, respectively. The Kaplan–Meyer survival curves for patients with and without ischemic stroke stratified by time period are shown in Figure 2. The decrease in mortality was similar for men and women. In men, the 1-year mortality was 36.2%, 37.4%, 34.8%, 30.3%, and 27.1% and in women 44.2%, 41.3%, 40.4%, 38.8%, and 33.8% during the time periods 1998–2000, 2001–2002, 2003–2004, 2005–2006, and 2007–2008, respectively.

Table 2. Characteristics of Patients With AMI With Ischemic Stroke Within 1 Year of AMI Stratified by Time Period and Survival

1998–2000 2001–2002 2003–2004 2005–2006 2007–2008

Stroke (n=1172)

Stroke and Death (n=774)

39.5%Stroke

(n=879)

Stroke and Death (n=568)

39.1%Stroke

(n=818)

Stroke and Death (n=496)

37.3%Stroke

(n=791)

Stroke and Death (n=419)

34.1%Stroke

(n=824)

Stroke and Death (n=367)

30.1%

Patient characteristics

Women, % 38.2 46.4 42.0 46.1 43.4 49.6 42.2 51.3 42.1 50.1

Age (mean) 74.3 78.3 74.8 79.8 75.4 79.6 74.5 80.5 74.9 81.0

Comorbidities, %

Prior stroke 27.3 31.4 26.1 30.1 26.2 29.6 26.3 32.9 24.5 29.4

Prior ischemic stroke

20.1 24.8 20.7 24.5 23.0 25.2 23.5 28.9 21.7 28.3

Prior AMI 23.3 27.4 20.7 23.9 18.8 24.2 14.3 18.9 11.8 18.3

Prior heart failure 13.1 25.8 15.2 27.5 14.5 26.6 11.0 21.7 12.0 22.1

Prior diabetes mellitus

25.2 29.3 28.6 24.3 22.2 29.2 21.4 28.6 24.0 27.2

Prior kidney failure 0.9 2.6 1.7 3.7 1.5 3.2 2.0 3.6 2.7 5.2

Hypertension 40.2 42.9 45.1 43.5 48.5 48.0 49.6 46.0 52.4 54.4

Atrial fibrillation 27.7 32.8 26.1 37.7 26.4 34.3 24.4 32.7 25.1 37.3

Smoking 17.5 12.6 16.2 14.3 16.8 11.6 18.7 11.0 19.0 7.4

Clinical characteristics, %

STEMI 40.5 32.8 33.7 31.0 33.5 30.3 30.7 28.1 29.1 24.9

Heart failure during hospitalization

46.9 64.2 46.3 61.3 39.2 61.5 39.6 56.0 34.4 52.6

Treatment in-hospital, %

Acute CABG 0.2 0.1 0.4 0.5 0.4 0.0 0.6 0.0 0.7 0.3

Acute PCI 2.6 2.1 4.2 2.4 10.1 4.5 18.9 12.6 19.1 15.8

Thrombolysis 25.9 18.2 18.0 14.2 13.3 12.2 3.6 5.5 2.9 0.8

AMI indicates acute myocardial infarction; CABG, coronary artery by-pass grafting; PCI, percutaneous coronary intervention; and STEMI, ST-segment–elevation myocardial infarction.

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Predictors of Mortality After Ischemic StrokeTable 3 shows the results of the Cox regression analy-ses in patients who had an ischemic stroke after AMI. Heart failure, renal disease, peripheral arterial disease, and diabetes mellitus had the strongest association with death. Evidence-based treatments were associated with a decreased risk of death. Diuretic use was associated with an increased risk of death. Table II in the online-only Data Supplement shows the corresponding analyses for patients without ischemic stroke.

DiscussionThis is the first study with an adequate size and duration of follow-up to assess trends over time and predictors of mor-tality after AMI-associated ischemic stroke reliably. The main findings were as follows: first, the mortality after AMI-associated ischemic stroke decreased during the 1998–2008 period. Second, patients with an AMI-associated ischemic

stroke have an absolute mortality rate during the first year after the AMI that is 16% to 19% higher than the mortal-ity rate of those without ischemic stroke. Third, evidence-based treatments are associated with decreased mortality in an adjusted analysis.

The large number of patients in this study allowed us to make a reliable estimate of the mortality in this fairly unselected population. The 1-year mortality of 36.5% was only slightly higher than in most previous studies of short-term mortality (in-hospital and 30 days).2,4,7,8 Most studies have not separated ischemic and hemorrhagic stroke, which causes a higher mor-tality estimate. The mortality, as well as the risk of stroke, rap-idly declines after an AMI, which can explain the rather low difference between 30-day and 1-year mortality.3,5 We did not subclassify stroke events because ischemic strokes occurring after AMI are generally classified as cardioembolic. This clas-sification can be questioned because other mechanisms may be more important than embolism.15

We found that mortality decreased during the 1998–2008 period, both in patients with and without an ischemic stroke after AMI. The relative risk reduction was larger in the popu-lation without ischemic stroke, whereas the absolute decrease was slightly greater for patients with stroke. There was a simi-lar decrease in mortality in men and in women with stroke, but the women had a higher mortality during the study period. There is only 1 previous study, by Saczynski et al,2 that reported results for a time trend of mortality after stroke fol-lowing an AMI. On the basis of 132 stroke cases and 43 deaths during 1986–2005, the authors suggested that the mortality after stroke has increased. However, a reliable time trend can-not be based on such a small patient population.

The present results are in agreement with earlier stud-ies of mortality after stroke without a previous AMI, which show a decreasing mortality even though time periods and populations differ.16–19 There are probably several explana-tions for the decrease in mortality. Some studies have shown that specific stroke units have improved the prognosis of patients with stroke,19,20 and the 30-day mortality is lower for patients admitted to a stroke unit.21 Other explanations include

Figure 1. Time trends for discharge medication use (%) for patients with acute myocardial infarction with ischemic stroke who have survived (solid line) or died (broken line). ACE indicates angiotensin-converting enzyme; and ASA, acetylsalicylic acid.

Figure 2. Cumulative survival for patients with (left) and without (right) ischemic stroke within 1 year after acute myocardial infarction stratified by time period.

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3054 Stroke November 2013

improved secondary preventive treatment and improvement of cardiovascular risk factors.22

During the study period, the use of recommended treat-ments according to guidelines increased, particularly the use of statins and P2Y12-inhibitors. Overall, the use of recom-mended therapies was lower among patients with ischemic stroke and even lower among patients who died. The patients in these groups are older, have more comorbidities, and may have a short expected survival time and contraindications for medications. However, they may also have received subopti-mal treatment.

Predictors of MortalityIn the multivariate Cox regression analysis, older age, heart failure, prior ischemic stroke, prior AMI, prior diabetes mel-litus, prior renal failure, prior peripheral arterial disease, and atrial fibrillation were predictors of death. All secondary pre-ventive medications lowered the risk, except for diuretics, which increased the risk for mortality. Although multivariate adjustments were made, a possible selection bias make it dif-ficult to estimate the true size of the risk reduction achieved by different treatments.

These results agree with those of previous studies of risk factors for mortality after AMI not complicated by ischemic stroke. In those studies, older age, history of heart failure or stroke, and heart failure during the hospital stay were shown to predict the 2-year mortality rate.23

Strengths and LimitationsThe strength of this study is the large number of included patients, which enabled precise estimates even in subsets of patients. In combination with the long study period, the large study population made it possible to analyze trends reliably over time. As for limitations, there were too many missing data for several variables, which could thus not be included in the multivariate Cox regression analysis. Furthermore, we did not have information about kidney function, which has prog-nostic importance. As always, there is the risk of confounders that are not taken into account because they were not recorded as variables in the database.

ConclusionsThe 1-year mortality after AMI complicated by ischemic stroke is very high. Notably, the 1-year mortality for AMI plus ischemic stroke is ≈50% higher than for patients with AMI without stroke. Mortality decreased during the 1998–2008 period in parallel with increased use of evidence-based sec-ondary preventive medications.

Sources of FundingThis study was supported by grants from the Research and Development Unit at Jamtland County Council.

DisclosuresNone.

Table 3. Uni- and Multivariate Predictors of Mortality for Patients With Ischemic Stroke Within 1 Year After Acute Myocardial Infarction

Variable Univariate Hazard Ratio P Value Multivariate Hazard Ratio P Value

Age (1 SD) 1.99 (1.86–2.13) <0.001 1.64 (1.52–1.77) <0.001

Sex (women) 1.26 (1.15–1.37) <0.001 1.03 (0.94–1.13) 0.53

Prior heart failure 1.90 (1.72–2.09) <0.001 1.33 (1.19–1.49) <0.001

Prior hemorrhagic stroke 0.96 (0.68–1.34) 0.804 0.93 (0.65–1.33) 0.704

Prior ischemic stroke 1.23 (1.12–1.36) <0.001 1.16 (1.04–1.28) 0.006

Prior AMI 1.36 (1.23–1.50) <0.001 1.12 (1.00–1.24) 0.050

Prior diabetes mellitus 1.18 (1.07–1.29) 0.001 1.21 (1.09–1.34) <0.001

Prior kidney failure 1.83 (1.46–2.29) <0.001 1.46 (1.15–1.86) 0.002

Prior peripheral arterial disease 1.49 (1.29–1.71) <0.001 1.27 (1.09–1.47) 0.002

Hypertension 0.98 (0.93–1.03) 0.395 … …

Atrial fibrillation 1.47 (1.34–1.61) <0.001 1.14 (1.03–1.25) 0.010

Smoking 0.66 (0.57–0.76) <0.001 … …

Heart failure during hospitalization 1.74 (1.60–1.90) <0.001 1.34 (1.22–1.47) <0.001

PCI 0.49 (0.43–0.56) <0.001 0.79 (0.68–0.91) 0.002

Thrombolytic therapy 0.80 (0.69–0.92) 0.001 0.86 (0.74–0.99) 0.038

Statins at discharge 0.50 (0.46–0.55) <0.001 0.77 (0.69–0.85) <0.001

β-Blockers at discharge 0.71 (0.63–0.79) <0.001 0.90 (0.80–1.00) 0.056

ACE inhibitors at discharge 0.77 (0.70–0.84) <0.001 0.84 (0.77–0.93) <0.001

ASA at discharge 0.74 (0.67–0.82) <0.001 0.76 (0.67–0.86) <0.001

Warfarin at discharge 0.8 (0.73–0.98) 0.022 0.69 (0.58–0.82) <0.001

P2Y12 at discharge 0.60 (0.54–0.67) <0.001 0.88 (0.77–0.99) 0.038

Diuretics at discharge 1.78 (1.62–1.95) <0.001 1.18 (1.06–1.31) 0.003

Hazard ratios for age were calculated for an increase of 1 SD (SD, 12.1). ACE indicates angiotensin-converting enzyme; AMI, acute myocardial infarction; ASA, acetylsalicylic acid; CABG, coronary artery by-pass grafting; PCI, percutaneous coronary intervention.

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Anna Brammås, Stina Jakobsson, Anders Ulvenstam and Thomas Mooeand Trends Over Time in Sweden

Mortality After Ischemic Stroke in Patients With Acute Myocardial Infarction: Predictors

Print ISSN: 0039-2499. Online ISSN: 1524-4628 Copyright © 2013 American Heart Association, Inc. All rights reserved.

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ONLINE SUPPLEMENT

Mortality after ischemic stroke in patients with acute myocardial

infarction: Predictors and trends over time in Sweden

Anna Brammås1, Stina Jakobsson2, Anders Ulvenstam3, Thomas Mooe4

1Medical student, Department of Public Health and Clinical Medicine, Umeå University,

Sweden

2Medical student, Department of Public Health and Clinical Medicine, Umeå University,

Sweden

3MD, Department of Internal Medicine, Section of Cardiology, Östersund Hospital, Sweden

4MD, Ass Prof, Department of Public Health and Clinical Medicine, Umeå University and

Department of Internal Medicine, Section of Cardiology, Östersund Hospital, Sweden

Correspondence to:

Thomas Mooe; Östersunds sjukhus; Hus 10, Plan5; 83183 Östersund; Sweden

Phone: +46706400778, Fax: +4663153030, E-mail: thomas.mooe@medicin.umu.se

Supplemental methods- Explanation of used registers

The Swedish Web-system for Enhancement and Developmend of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART)

SWEDEHEART is a Swedish national registry of patients admitted to hospital for acute coronary syndrome (ACS) or undergoing coronary or valvular intervention. About 80 000 patients is registred each year, of which 20 000 with myocardial infarction (MI). The coverage is about 60% for all ACS cases and almost 100% for ACS cases admitted to a coronary care unit.1

At admission, information for 106 variables is collected such as risk factors, past medical history, medical treatment in hospital etc. Patients with MI and younger than 75 years is followed up after 6-10 weeks and after 12-14 months for collection of information for another 75 variables about for example smoking habits, blood pressure and lipid levels.

Every year SWEDEHEART is merged with the National Cause of Death register (including information about the vital status of all Swedes), with the National Patient Registry (including diagnoses at discharge for all hospital stays in Sweden), and with the National Registry of Drug prescriptions.

Register of Information and Knowledge About Swedish Heart Intensive Care Admissions (RIKS- HIA)

RIKS-HIA is a part of SWEDEHEART collecting information about acute cardiac care, and was started as a national quality register in 1995. RIKS-HIA was reviewed in 2007 with a 96.1% (92.6-97.4%) variable agreement when collected variables were compared to patient records.

National Patient Registry (NPR)

NPR includes different registers, of which we have used the Swedish National Inpatient Register (IPR). IPR was started in 1964 and has a complete national coverage since 1987. More than 99% of hospital discharges are registered. Diagnoses are coded according to the International Classification of Disease (ICD).2 IPR has a good coverage for diagnoses as Myocardial infarction (91.5%).3

1. Jernberg T, Attebring MF, Hambraeus K, Ivert T, James S, Jeppsson A et al. The swedish web-system for enhancement and development of evidence-based care in heart disease evaluated according to recommended therapies (swedeheart). Heart. 2010;96:1617-1621

2. Ludvigsson JF, Andersson E, Ekbom A, Feychting M, Kim JL, Reuterwall C et al. External review and validation of the swedish national inpatient register. BMC Public Health. 2011;11:450

3. Elo SL, Karlberg IH. Validity and utilization of epidemiological data: A study of ischaemic heart disease and coronary risk factors in a local population. Public Health. 2009;123:52-57

Supplemental tables

Table S I.  Characteristics of acute myocardial infarction (AMI) patients without ischemic

stroke within one year of AMI stratified by time period and survival.

1998-2000 2001-2002 2003-2004 2005-2006 2007-2008 No

stroke

n=

32757

No

stroke

and

death n=

9055

21.7%

No

stroke

n=

25028

No

stroke

and

death n=

6417

20.4%

No

stroke

n= 25565

No

stroke

and

death n=

5651

18.1%

No

stroke

n=

25519

No

stroke

and

death n=

4903

16.1%

No

stroke

n=

26795

No

stroke

and

death n=

4435

14.2%

Patient characteristics

Woman 34.0% 42.2% 35.4% 43.9% 35.2% 43.7% 34.9% 43.7% 34.9% 46.6%

Age

(mean)

68.7 78.2 69.2 79.1 69.2 79.5 69.4 80.0 69.1 80.2

BMI

(mean)

26.7

n=390

4

25.3

n=

571

26.7

n=463

9

24.9

n=686

26.7

n=105

87

25.5

n=151

2

26.7

n=152

72

24.9

n=2017

26.9

n=192

11

25.1

n=228

7

Co morbidity

Prior

stroke

8.2% 18.3% 8.6% 20.0% 8.4% 20.3% 8.4% 19.8% 8.0% 19.1%

Prior

ischemic

stroke

5.6%

13.0% 6.3% 16.0% 6.4% 16.6% 6.6% 16.1% 6.4% 16.2%

Prior AMI 17.4% 28.3% 15.0% 25.6% 12.7% 25.0% 11.2% 23.2% 9.9% 22.0%

Prior heart

failure

9.2% 27.4% 9.0% 27.9% 8.1% 26.8% 7.8% 26.4% 7.1% 26.8%

Prior

diabetes

mellitus

16.0% 23.7% 17.6% 24.3% 17.3% 25.3% 18.2% 26.6% 19.7% 27.4%

Prior renal

failure

1.1% 4.2% 1.4% 5.1% 1.4% 6.4% 1.6% 6.4% 1.9% 7.9%

Hypertensi

on

33.0% 35.1% 36.0% 38.4% 38.1% 40.9% 41.3% 42.9% 45.3% 50.5%

Atrial

fibrillation

13.2% 27.0% 13.1% 28.5% 12.5% 27.8% 12.5% 28.0% 11.8% 28.3%

Smoking 24.4% 14.3% 24.4% 15.3% 23.9% 14.2% 23.3% 12.9% 22.9% 13.0%

Clinical characteristics

Heartrate

(mean)

- - 78.2

n=215

8

90.5

n=500

78.7

n=108

59

89.4

n=225

9

79.7

n=228

33

89.8

n=4398

79.3

n=249

61

89.8

n=414

4

Systolic

blood

pressure

(mean)

141.5

n=146

2

131.4

n=349

144.4

n=281

2

130.0

n=610

146.9

n=106

20

131.3

n=225

9

147.8

n=226

58

132.7

n=4362

147.7

n=245

39

133.0

n=405

3

LDL

(mean)

3.5

n=

4003

3.2

n=384

3.4

n=130

65

3.1

n=171

7

3.2

n=158

50

2.9

n=186

5

3.1

n=167

04

2.7

n=1678

3.1

n=185

84

2.7

n=165

4

STEMI 42.0% 36.4% 37.4% 31.8% 35.7% 30.4% 34.8% 28.3% 31.4% 25.9%

Heart

failure

during

hospitaliza

tion

33.9% 66.0% 30.3% 63.9% 28.2% 63.6% 25.9% 63.0% 22.0% 58.6%

Treatment in hospital

Acute

CABG

0.2% 0.1% 0.3% 0.1% 0.2% 0.2% 0.3% 0.2% 0.2% 0.2%

Acute PCI 4.5% 1.9% 8.3% 2.6% 16.1% 5.2% 25.3% 10.9% 27.8% 12.9%

Thrombol

ysis

30.4% 21.9% 23.9% 17.6% 14.7% 12.5% 5.5% 6.1% 2.4% 2.4%

BMI=body mass index. LDL=low density lipoprotein. STEMI=ST-elevation myocardial

infarction. CABG=coronary artery by-pass grafting. PCI=percutaneous coronary intervention.

 

   

Table S II. Uni- and multivariate predictors of mortality for patients without ischemic stroke

within one year after acute myocardial infarction.

Variable Univariate hazard

ratio

P-value Multivariate

hazard ratio

P-value

Age 1.09 (1.09-1.09) 0.000 1.04 (1.04-1.05) 0.000

Sex (female) 1.34 (1.30-1.38) 0.000 0.84 (0.81-0.86) 0.000

BMI 0.91 (0.91-0.92 0.000 - 0.000

Prior heart failure 4.10 (3.97-4.23) 0.000 1.43 (1.38-1.49) 0.000

Prior hemorrhagic

stroke

1.98 (1.73-2.26) 0.000 1.21 (1.05-1.39) 0.011

Prior ischemic

stroke

2.52 (2.42-2.63) 0.000 1.32 (1.26-1.38) 0.000

Prior AMI 2.41 (2.33-2.49) 0.000 1.23 (1.18-1.27) 0.000

Prior diabetes 1.68 (1.63-1.74) 0.000 1.28 (1.24-1.33) 0.000

Prior renal failure 3.85 (3.63-4.09) 0.000 1.75 (1.64-1.86) 0.000

Prior peripheral

arterial disease

2.69 (2.57-2.82) 0.000 1.45 (1.38-1.52) 0.000

Hypertension 1.07 (1.06-1.09) 0.000 - 0.000

Atrial Fibrillation 2.50 (2.42-2.58) 0.000 1.17 (1.13-1.22) 0.000

Smoking 0.59 (0.56-0.62) 0.000 - 0.000

Heart failure

during

hospitalization

3.61 (3.50-3.73) 0.000 1.65 (1.59-1.71) 0.000

PCI 0.22 (0.21-0.23) 0.000 0.58 (0.55-0.61) 0.000

Thrombolytic

therapy

0.51 (0.49-0.54) 0.000 0.69 (0.65-0.73) 0.000

Statins at

discharge

0.27 (0.26-0.28) 0.000 0.64 (0.62-0.67) 0.000

Beta-blockers at

discharge

0.44 (0.42-0.45) 0.000 0.76 (0.73-0.78) 0.000

ACE-inhibitors at

discharge

0.86 (0.83-0.89) 0.000 0.85 (0.82-0.88) 0.000

BMI=body mass index. LDL=low density lipoprotein. CABG=coronary artery by-pass

grafting. PCI=percutaneous coronary intervention.

   

ASA at discharge 0.44 (0.43-0.46) 0.000 0.70 (0.67-0.73) 0.000

Warfarin at

discharge

1.38 (1.31-1.45) 0.000 0.72 (0.68-0.76) 0.000

P2Y12 at

discharge

0.34 (0.33-0.35) 0.000 0.79 (0.76-0.83) 0.000

Diuretics at

discharge

4.03 (3.90-4.17) 0.000 1.46 (1.40-1.51) 0.000

Supplemental figures

Figure SI

Figure S I.  Time trends for discharge medication use for acute myocardial infarction (AMI) patients without ischemic stroke that has survived (solid line) or died (broken line).

 

 

 

 

 

 

 

 

 

 

 

 

0  

10  

20  

30  

40  

50  

60  

70  

80  

90  

100  

1998-­‐2000   2001-­‐2002   2003-­‐2004   2005-­‐2006   2007-­‐2008  

Sta0ns  

ACE-­‐inhibitors  

Beta-­‐blockers  

ASA  

Warfarin  

P2Y12  

Diure0cs  

Figure SII

Figure SII. Cumulative survival for men (left) and women (right) with ischemic stroke within one year after myocardial infarction stratified by time period.