oru.sePublikationer
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Unrecognized myocardial infarction and cardiac biochemical markers in patients with stable coronary artery disease
Örebro University, School of Medical Sciences.
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Aim: The overarching aim of the thesis was to explore the occurrence and clinical importance of two manifestations of myocardial injury; unrecognized myocardial injury (UMI) and altered levels of cardiac biochemical markers in patients with stable coronary artery disease (CAD).

Methods: A prospective multicenter cohort study investigated the prevalence, localization, size, and prognostic implication of UMI in 235 patients with stable CAD. Late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) imaging and coronary angiography were used. The relationship between UMI and severe CAD and cardiac biochemical markers was explored. In a substudy the short- and longterm individual variation in cardiac troponins I and T (cTnI, cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were investigated.

Results: The prevalence of UMI was 25%. Subjects with severe CAD were significantly more likely to exhibit UMI than subjects without CAD. There was a strong association between stenosis ≥70% and presence of UMI in the myocardial segments downstream. The presence of UMI was associated with a significant threefold risk of adverse events during follow up. After adjustments UMI was associated with a nonsignificant numerically doubled risk. The levels of cTnI, NT-proBNP, and Galacin-3 were associated with the presence of UMI in univariate analyses. The association between levels of cTnI and presence of UMI remained significant after adjustment. The individual variation in cTnI, cTnT, and NT-proBNP in subjects with stable CAD appeared similar to the biological variation in healthy individuals.

Conclusions: UMI is common and is associated with significant CAD, levels of biochemical markers, and an increased risk for adverse events. A change of >50% is required for a reliable short-term change in cardiac troponins, and a rise of >76% or a fall of >43% is required to detect a long-term reliable change in NT-proBNP.

Place, publisher, year, edition, pages
Örebro: Örebro university , 2016. , 125 p.
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 142
Keyword [en]
Unrecognized myocardial infarction, Coronary artery disease, Prevalence, Prognosis, Troponin, NT-proBNP, Galectin-3
National Category
Family Medicine
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-48240ISBN: 978-91-7529-125-3 (print)OAI: oai:DiVA.org:oru-48240DiVA: diva2:903209
Public defence
2016-05-13, Universitetssjukhuset, hörsal C3, Södra Grev Rosengatan, Örebro, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2016-02-15 Created: 2016-02-15 Last updated: 2016-04-21Bibliographically approved
List of papers
1. Unrecognized myocardial infarctions assessed by cardiovascular magnetic resonance are associated with the severity of the stenosis in the supplying coronary artery
Open this publication in new window or tab >>Unrecognized myocardial infarctions assessed by cardiovascular magnetic resonance are associated with the severity of the stenosis in the supplying coronary artery
Show others...
2015 (English)In: Journal of Cardiovascular Magnetic Resonance, ISSN 1097-6647, E-ISSN 1532-429X, Vol. 17, 98Article in journal (Refereed) Published
Abstract [en]

Background: A previous study has shown an increased prevalence of late gadolinium enhancement cardiovascular magnetic resonance (LGE CMR) detected unrecognized myocardial infarction (UMI) with increasing extent and severity of coronary artery disease. However, the coronary artery disease was evaluated on a patient level assuming normal coronary anatomy. Therefore, the aims of the present study were to investigate the prevalence of UMI identified by LGE CMR imaging in patients with stable angina pectoris and no known previous myocardial infarction; and to investigate whether presence of UMI is associated with stenotic lesions in the coronary artery supplying the segment of the myocardium in which the UMI is located, using coronary angiography to determine the individual coronary anatomy in each patient.

Methods: In this prospective multicenter study, we included patients with stable angina pectoris and without prior myocardial infarction, scheduled for coronary angiography. A LGE CMR examination was performed prior to the coronary angiography. The study cohort consisted of 235 patients (80 women, 155 men) with a mean age of 64.8 years.

Results: UMIs were found in 25 % of patients. There was a strong association between stenotic lesions (>= 70 % stenosis) in a coronary artery and the presence of an UMI in the myocardial segments supplied by the stenotic artery; it was significantly more likely to have an UMI downstream a stenosis >= 70 % as compared to <70 % (OR 5.1, CI 3.1-8.3, p < 0.0001). 56 % of the UMIs were located in the inferior and infero-lateral myocardial segments, despite predominance for stenotic lesions in the left anterior descending artery.

Conclusion: UMI is common in patients with stable angina and the results indicate that the majority of the UMIs are of ischemic origin due to severe coronary atherosclerosis. In contrast to what is seen in recognized myocardial infarctions, UMIs are predominately located in the inferior and infero-lateral myocardial segments.

Place, publisher, year, edition, pages
BioMed Central, 2015
Keyword
Angiography, Coronary disease, Imaging, Infarction, Cardiovascular magnetic resonance
National Category
Family Medicine Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:oru:diva-49862 (URN)10.1186/s12968-015-0202-5 (DOI)000365177100001 ()26585508 (PubMedID)2-s2.0-84947798080 (Scopus ID)
Available from: 2016-04-18 Created: 2016-04-18 Last updated: 2017-03-15Bibliographically approved
2. Unrecognized myocardial infarction assessed by cardiac magnetic resonance imaging: prognostic implications
Open this publication in new window or tab >>Unrecognized myocardial infarction assessed by cardiac magnetic resonance imaging: prognostic implications
Show others...
2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 2, e0148803Article in journal (Refereed) Published
Abstract [en]

Background: Clinically unrecognized myocardial infarctions (UMI) are not uncommon and may be associated with adverse outcome. The aims of this study were to determine the prognostic implication of UMI in patients with stable suspected coronary artery disease (CAD) and to investigate the associations of UMI with the presence of CAD.

Methods and Findings: In total 235 patients late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) imaging and coronary angiography were performed. For each patient with UMI, the stenosis grade of the coronary branch supplying the infarcted area was determined. UMIs were present in 25% of the patients and 67% of the UMIs were located in an area supplied by a coronary artery with a stenosis grade >= 70%. In an age-and gender-adjusted model, UMI independently predicted the primary endpoint (composite of death, myocardial infarction, resuscitated cardiac arrest, hospitalization for unstable angina pectoris or heart failure within 2 years of follow-up) with an odds ratio of 2.9; 95% confidence interval 1.1-7.9. However, this association was abrogated after adjustment for age and presence of significant coronary disease. There was no difference in the primary endpoint rates between UMI patients with or without a significant stenosis in the corresponding coronary artery.

Conclusions: The presence of UMI was associated with a threefold increased risk of adverse events during follow up. However, the difference was no longer statistically significant after adjustments for age and severity of CAD. Thus, the results do not support that patients with suspicion of CAD should be routinely investigated by LGE-CMR for UMI. However, coronary angiography should be considered in patients with UMI detected by LGE-CMR.

Place, publisher, year, edition, pages
Public Library Science, 2016
National Category
Family Medicine
Research subject
Family Medicine
Identifiers
urn:nbn:se:oru:diva-49552 (URN)10.1371/journal.pone.0148803 (DOI)000371218400049 ()26885831 (PubMedID)2-s2.0-84960516971 (Scopus ID)
Funder
Swedish Research CouncilSwedish Heart Lung Foundation, 20140486
Note

Funding Agencies:

Regional Research Council, Uppsala-Örebro region RFR-84261

Center for Clinical Research in Vastmanland from Bayer Pharmaceuticals Sweden

Available from: 2016-03-29 Created: 2016-03-29 Last updated: 2016-04-18Bibliographically approved
3. Unrecognized myocardial infarctions detected by cardiac magnetic resonance imaging are associated with cardiac troponin I levels
Open this publication in new window or tab >>Unrecognized myocardial infarctions detected by cardiac magnetic resonance imaging are associated with cardiac troponin I levels
Show others...
2016 (English)In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 455, 189-194 p.Article in journal (Refereed) Published
Abstract [en]

Background: Both unrecognized myocardial infarction (UMI) and elevated levels of biomarkers are common in patients with stable coronary artery disease (CAD). The objective of this study was to determine the association between levels of cardiac biomarkers, UMI and extent of CAD in patients with stable CAD.

Methods: A total of 235 patients (median age: 65years; 34% women) with stable CAD without previously known myocardial infarction were examined with late gadolinium enhancement cardiovascular magnetic resonance imaging and coronary angiography. Blood samples were drawn at enrolment and high sensitivity cardiac troponin I (cTnI), NT-proBNP and Galectin-3 were analyzed.

Results: UMI was detected in 58 patients (25%). The median levels of cTnI, NT-proBNP and Galectin-3 were significantly higher in patients with UMI compared to those without, (p<0.001, p=0.006 and p=0.033, respectively). After adjustment for cardiovascular risk factors, left ventricular ejection fraction and renal function, cTnI remained independently associated with the presence of UMI (p=0.031) and the extent of CAD (p=0.047). Neither NT-proBNP, nor Galectin-3, was independently associated with UMI or extent of CAD.

Conclusions: The independent association between levels of cTnI and UMI indicates a common pathophysiological pathway for the cTnI elevation and development of UMI.

Clinical trial registration: ClinicalTrials.gov (NCT01257282).

Place, publisher, year, edition, pages
Amsterdam, Netherlands: Elsevier, 2016
Keyword
Cardiac troponin, NT-proBNP, unrecognized myocardial infarction, coronary artery disease, cardiac magnetic resonance imaging
National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
urn:nbn:se:oru:diva-49645 (URN)10.1016/j.cca.2016.01.029 (DOI)000373655100030 ()26828531 (PubMedID)2-s2.0-84961878512 (Scopus ID)
Available from: 2016-04-13 Created: 2016-04-05 Last updated: 2016-05-02Bibliographically approved
4. Short- and long-term individual variation in cardiac troponin in patients with stable coronary artery disease
Open this publication in new window or tab >>Short- and long-term individual variation in cardiac troponin in patients with stable coronary artery disease
Show others...
2013 (English)In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 59, no 2, 401-409 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: A rise or fall of cardiac troponin is a prerequisite for the diagnosis of acute myocardial infarction. Defining significant changes requires knowledge of both biological and analytical variation. The short-term biological variation of cardiac troponin in healthy individuals is 3%-48%. However, healthy individuals may not be representative for patients in whom cardiac troponin measurement is often of clinical importance. Therefore, we studied the individual variation of cardiac troponin in patients with symptoms of stable coronary artery disease.

METHODS: Twenty-four patients scheduled for elective coronary angiography were included. Blood samples were drawn once at enrollment and serially at six 4-h intervals on the day before coronary angiography. Cardiac troponin was measured with hs-cTn assays from Abbott Laboratories (premarket cTnI assay) and Roche Diagnostics (Elecsys® cTnT assay with two different lots).

RESULTS: The short-term individual variation in cardiac troponin I (cTnI) was 14%, the reference change value (RCV) 49%, and RCV-log-normal (rise/fall) 54%/-35%. The corresponding values for cTnT were 7%, 23%, and 26%/-21%. The long-term variation for cTnI was 24%, RCV 69%, and RCV-log-normal (rise/fall) 97%/-49%. The corresponding values for cTnT were 11%, 32%, and 37%/-27%.

CONCLUSIONS: The short-term individual variation of cardiac troponin in patients with symptoms of stable coronary artery disease is similar to the biological variation previously demonstrated in healthy individuals. Our results suggest that a change in cardiac troponin concentrations of >50% can be used in attempting to diagnose acute myocardial injury. To detect significant long-term changes in cardiac troponin concentrations, larger changes will be required.

Place, publisher, year, edition, pages
American Association for Clinical Chemistry, 2013
National Category
Cardiac and Cardiovascular Systems
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-27602 (URN)10.1373/clinchem.2012.191700 (DOI)000317337000013 ()23143329 (PubMedID)2-s2.0-84873183598 (Scopus ID)
Available from: 2013-02-16 Created: 2013-02-16 Last updated: 2017-03-21Bibliographically approved
5. Short-and long-term individual variation in NT-proBNP levels in patients with stable coronary artery disease
Open this publication in new window or tab >>Short-and long-term individual variation in NT-proBNP levels in patients with stable coronary artery disease
Show others...
2013 (English)In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 422, no 25, 15-20 p.Article in journal (Refereed) Published
Abstract [en]

Background: In addition to diagnosis of heart failure (HF) natriuretic peptides (BNP and NT-proBNP) may be used for risk prediction in stable and acute coronary artery disease. The aim of the study was to evaluate the short- and long-term individual variation of NT-proBNP in patients with stable coronary artery disease.

Methods: Twenty-four patients with suspected stable coronary artery disease and scheduled for elective coronary angiography were included. Blood samples were drawn at enrolment and, on average 3 weeks later, serially the day prior to coronary angiography. NT-proBNP was determined using Elecsys proBNP sandwich immunoassay (Roche Diagnostics).

Results: The individual variation in NT-proBNP over 4 h was 11.8%, over 20 h 12.4% and over 3 weeks 20.4%. The corresponding positive and negative lognormal reference change values (RCV) were +41/-29%, +42/-30% and + 76/-43%, respectively. No significant circadian variation was found.

Conclusions: Our results suggest that an increase in NT-proBNP levels of >42% or a decrease of >30% is needed to indicate a reliable short-term change; and for a long-term change an increase of >76% or a decrease of >43% is required. This should be considered when interpreting changes in NT-proBNP levels.

Place, publisher, year, edition, pages
Elsevier, 2013
Keyword
NT-proBNP, Cardiovascular diseases/diagnosis, Individual variation, Reference change values, Immunoassay
National Category
Family Medicine Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:oru:diva-49860 (URN)10.1016/j.cca.2013.03.025 (DOI)000320894400004 ()23566928 (PubMedID)2-s2.0-84876716804 (Scopus ID)
Available from: 2016-04-18 Created: 2016-04-18 Last updated: 2017-03-21Bibliographically approved

Open Access in DiVA

Spikblad(136 kB)19 downloads
File information
File name SPIKBLAD01.pdfFile size 136 kBChecksum SHA-512
6a8a0d0a7d3badc6e9be800c4da04f3dfc451b2dd5c883b6a07810b001e0de607c717a5b356598a6f16eaedc03f7e8c38379e922851f1a5be518b4d1671ed50c
Type spikbladMimetype application/pdf
Cover(1411 kB)18 downloads
File information
File name COVER01.pdfFile size 1411 kBChecksum SHA-512
fb5224f3d7cd146be9476644af3a9cfd7e358ba661851e25634dc55af4e09a899659c2ea5927764c0c1e9afe84f422292be3f2577019294643bd1a2327d476be
Type coverMimetype application/pdf
Introductory chapter(1921 kB)104 downloads
File information
File name FULLTEXT01.pdfFile size 1921 kBChecksum SHA-512
3a8be47f7a75ef43fcec3f26d81c9d4cd02c98e82cf0831b5cf84eac6753f402c409e6642bb24382e35d7b21da4c7467afb92557bf520e4c3d863b7f3c3bda35
Type fulltextMimetype application/pdf

Search in DiVA

By author/editor
Nordenskjöld, Anna
By organisation
School of Medical Sciences
Family Medicine

Search outside of DiVA

GoogleGoogle Scholar
Total: 104 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Total: 726 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf