SUPPLEMENTAL MATERIAL

High-Sensitivity Troponins and Outcomes After Myocardial Infarction

Maria Odqvist, MDa,b; Per-Ola Andersson, MD, PhDa,b; Hans Tygesen, MD, PhDa,b; Kai M

Eggers, MD, PhDc; Martin J Holzmann, MD, PhDd,e

aDepartment of Medicine, South Älvsborg Hospital, 501 82 Borås, Sweden

bDepartment of Medicine, Sahlgrenska Academy, Gothenburg University, 405 30

Gothenburg, Sweden

cDepartment of Medical Sciences, Uppsala University, 751 85, Uppsala, Sweden

dFunctional Area of Emergency Medicine, Karolinska University Hospital, Huddinge, 141

86, Stockholm, Sweden

eDepartment of Internal Medicine, Solna, Karolinska Institutet, 171 76, Stockholm, Sweden

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Table of contents

Swedish national registers 3

Personal identity number 3

National Patient Register 3

Prescribed Drug Register 4

SWEDEHEART 5

Construction of the database 5

Online Table 1 5

Online Table 2 6

Online Table 3 6

Online Table 4 7

Online Table 5 7

Online Figure 1 8

Online Figure 2 9

Online Figure 3 10

References 11

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Swedish National Registers

Personal Identity Number

Since 1947 a ten-digit personal Identity Number (PIN) has been given to all individuals that

resided in Sweden. The PIN is maintained by the National Tax Board. All national registries

use the Swedish PIN as a unique identifier, and it is used as a tool for linkages between

medical registers, and other data sources and allows for nearly 100% coverage of the Swedish

health care system1. The construction of the current dataset was made possible by the PIN

which was available in all registers used in the present study.

National Patient Register

The Swedish National Patient Register (NPR), is maintained by the Swedish National Board

of Health and Welfare. NPR holds information on all hospital stays at public hospitals,

including all emergency hospitals in Sweden since 1957. The NPR has complete nationwide

coverage since 1987, including all discharge diagnoses and surgical procedures which are

coded according to the International Classification of Disease (ICD). In addition, there is

information on length of stay, in which hospital and department the patient stayed, and when

the hospital stay occurred. For the purposes of this study no information from the outpatient

part of NPR was used. Primary health care is not covered in the NPR. The discharge

diagnoses that the patients received in the register is decided by a consultant physician who is

in charge of the patient at the time of discharge. Thereafter, all information is electronically

forwarded to the National Board of Health and Welfare by a standardized procedure, and the

underreporting for inpatient data has been estimated to < 1 %. Validations of hospital

discharge diagnoses by the National Board of Health and Welfare have found that 85-95% of

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all diagnoses are valid. For the diagnosis of myocardial infarction, the positive predictive

value has been found to be 98-100%2.

Prescribed Drug Register

The Swedish Prescribed Drug Register contains information about all prescribed and

dispensed medications at pharmacies in Sweden since July 1, 2005, and is maintained by the

Swedish National Board of Health and Welfare. The register includes information about

prescribed and the dispensed medications including date, type of medicine, package size, and

dosage instructions and amount3.

The SWEDEHEART register

SWEDEHEART which is a nationwide register enrolling consecutive patients admitted to

Swedish coronary care units or other specialized facilities because of suspected acute

coronary syndrome.4 SWEDEHEART prospectively collects information on >100 variables

including biomarkers of myocardial damage. SWEDEHEART is regularly merged with the

Swedish population register which includes information about the vital status of all Swedish

residents. To ensure the correctness and quality of data in the SWEDEHEART register,

hospitals are monitored on a regular basis. The agreement of the data entered in the register

with the medical records is around 96%.4 Patients included in the register are informed about

their participation which they have the right to decline.

Construction of the database

The Swedish National Board of Health and Welfare, responsible for all the abovementioned

registers except for the SWEDEHEART register, constructed a database that consisted of all

(n=567,211) patients who at any time during 1995 to 2013 had been hospitalized for MI, or

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had undergone percutaneous coronary intervention (PCI), or coronary artery bypass grafting

(CABG) in Sweden. They linked information about comorbidities, and outcomes from the

Patient Register, about all-cause mortality, and causes of death from the Cause-of-Death

Register, and medication from the Prescribed Drug Register to all individuals, and

anonymized data before it was returned to the research group.

Tables and figures

Online Table 1. Dates and hospitals in Sweden where the high-sensitivity cardiac troponin T assay was

used concurrently with a higher decision level for myocardial infarction than the 99th percentile value

for a limited period of time

Hospital Period Decision limit

Sollefteå 08/10/2009-01/31/2011 >40 ng/l

Jönköping 08/01/2009-09/01/2010 >30 ng/l

Värnamo 01/14/2010-09/01/2010 >30 ng/l

Kungälv 02/15/2010-02/20/2012 >40 ng/l

Mölndal (Göteborg) 12/01/2009-01/30/2012 >40 ng/l

Sahlgrenska (Göteborg) 12/01/2009-01/30/2012 >40 ng/l

Östra (Göteborg) 02/15/2010-01/30/2012 >40 ng/l

Varberg 04/26/2010-04/22/2013 >30 ng/l

Halmstad 04/26/2010-04/22/2013 >30 ng/l

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Online Table 2. ICD codes used for comorbidities and outcomes.Myocardial infarctionICD-9ICD-10

410I21, I22.1, I22.8

Unstable anginaICD-10 I20

StrokeICD-9ICD-10

430 to 438I60 to I64

Chronic obstructive pulmonary diseaseICD-9ICD-10

490 to 496J44

Heart failureICD-9ICD-10

428I50

Chronic kidney diseaseICD-9ICD-10

585, 586N18

Coronary angiographyICD-9 and ICD-10 AF037

RevascularizationICD-9 and ICD-10 FNG05, FNG02, FNA00, FNA10, FNC10,

FNC20, FNC30, FNC40 or FNG00.

Online Table 3. ATC codes used for medication at baseline and discharge.StatinsC10AA

AspirinB01AC06

P2Y12 inhibitorsB01AC04 (clopidogrel), B01AC24 (ticagrelor), B01AC22 (prasugrel)

BetablockersC07

ACE/ARBC09

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Online Table 4. Troponin assay used to diagnose reinfarctions in relation to troponin assay used to diagnose the

first myocardial infarction

First MI diagnosed with cTn First MI diagnosed with hs-cTnT

Year Total

number of

reinfarctions

Same hospital

for reinfarction

hospitalization

as first MI, n (%)

Reinfarction

diagnosed with

cTn, n (%)

Reinfarction

diagnosed with

hs-cTnT, n (%)

Reinfarction

diagnosed with

cTn, n (%)

Reinfarction

diagnosed with

hs-cTnT, n (%)

2009-2013 15,766 10,291 (65%) 7816 (83%) 1649 (17%) 1179 (19%) 5122 (81%)

2009 4247 2756 (65%) 3419 (81%) 779 (19%) 11 (23%) 38 (77%)

2010 3474 2258 (65%) 2037 (79%) 551 (21%) 175 (20%) 711 (80%)

2011 2965 1905 (64%) 1012 (84%) 194 (16%) 334 (19%) 1425 (81%)

2012 2821 1857 (66%) 764 (90%) 84 (10%) 392 (20%) 1581 (80%)

2013 2259 1515 (67%) 584 (93%) 41 (7%) 267 (16%) 1367 (84%)

Table 5, supplemental material. Medication at Discharge in Relation to Troponin Method Used to Diagnose Myocardial Infarction

cTn hs-cTnT2009

Aspirin, n (%) 14,988 (90) 257 (90)P2Y12 inhibitors, n (%) 11,602 (69) 196 (69)Beta-blockers, n (%) 14,565 (87) 250 (88)ACE/ARB, n (%) 12,197 (73) 203 (71)Statins, n (%) 13,000 (78) 231 (81)

2010Aspirin, n (%) 9965 (90) 3723 (90)P2Y12 inhibitors, n (%) 8002 (72) 2939 (71)Beta-blockers, n (%) 9780 (89) 3535 (85)ACE/ARB, n (%) 8272 (75) 3130 (75)Statins, n (%) 8691 (79) 3344 (81)

2011Aspirin, n (%) 5212 (89) 8375 (91)P2Y12 inhibitors, n (%) 4306 (74) 6945 (75)Beta-blockers, n (%) 5089 (87) 8098 (88)ACE/ARB, n (%) 4410 (76) 7101 (77)Statins, n (%) 4475 (77) 7621 (83)

2012Aspirin, n (%) 4068 (90) 10,355 (90)P2Y12 inhibitors, n (%) 3460 (76) 8762 (76)Beta-blockers, n (%) 3946 (87) 10077 (87)ACE/ARB, n (%) 3478 (77) 8925 (77)Statins, n (%) 3544 (78) 9533 (83)

2013Aspirin, n (%) 3382 (89) 10,089 (88)P2Y12 inhibitors, n (%) 3000 (79) 8897 (78)Beta-blockers, n (%) 3353 (88) 10083 (88)ACE/ARB, n (%) 2976 (78) 8907 (78)Statins, n (%) 3102 (81) 9580 (84)

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Figure 1

Figure 1, supplemental material shows the first 3 months compared with the 3 preceding months before the hs-cTnT assay was introduced in hospitals where a higher decision limit for myocardial infarction than the 99th percentile value was used initially.

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Figure 2

Figure 2, supplemental material shows the change in the number of coronary angiographies the first 3 months following, compared with the 3 months preceding the introduction of the hs-cTnT assay.

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Figure 3

Figure 3, supplemental material shows the change in the number of revascularizations the first 3 months following, compared with the 3 months preceding the introduction of the hs-cTnT assay.

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REFERENCES

1. Ludvigsson JF, Otterblad-Olausson P, Pettersson BU, Ekbom A. The swedish personal

identity number: Possibilities and pitfalls in healthcare and medical research.

European journal of epidemiology. 2009;24:659-67.

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. The Swedish National Board of Health, website:

http://www.socialstyrelsen.se/register/halsodataregister/lakemedelsregistret, accessed

May 31, 2017

4. 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;96:1617–21.

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