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GDF-15 and TRAIL-R2 are powerful predictors of long-term mortality in patients with acute myocardial infarction
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Hosp Vastmanland, Dept Clin Physiol, SE-72189 Vasteras, Sweden.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Hosp Vastmanland, Dept Clin Physiol, SE-72189 Vasteras, Sweden.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås. Hosp Vastmanland, Dept Clin Physiol, SE-72189 Vasteras, Sweden.ORCID-id: 0000-0001-5731-966x
Vise andre og tillknytning
2017 (engelsk)Inngår i: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 24, nr 15, s. 1576-1583Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Background The Proximity Extension Assay proteomics chip provides a large-scale analysis of 92 biomarkers linked to cardiovascular disease or inflammation. We aimed to identify the biomarkers that best predicted long-term all-cause mortality in patients with acute myocardial infarction. Methods In this prospective cohort study, 92 biomarkers were analysed in 847 consecutive patients from the Vastmanland Myocardial Infarction Study with a median follow-up of 6.9 years. Results The mean ( standard deviation) age of the patients was 70 (11.8) years and 32.7% were female. Two hundred and seven patients had died after follow-up. The biomarkers most strongly linked to all-cause mortality were growth differentiation factor 15 (GDF-15) and tumour necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2). Cox regression analysis showed that GDF-15 (hazard ratio 1.25 per unit change, 95% confidence interval, 1.02-1.53, p=0.031) and TRAIL-R2 (hazard ratio 1.37 per unit change, 95% confidence interval 1.12-1.67, p=0.002) were independent predictors of long-term all-cause mortality after adjusting for age, gender, diabetes, previous myocardial infarction, stroke, heart failure, hypertension, smoking, hypercholesterolaemia, body mass index, ST-elevation myocardial infarction, left ventricular ejection fraction, troponin I, estimated glomerular filtration rate, N-terminal pro-brain natriuretic peptide and C-reactive protein. The combination of GDF-15 and TRAIL-R2 with established risk factors and biomarkers showed a discriminating accuracy of separating survivors from non-survivors with a cross-validated area under the receiving operating characteristics curve of 0.88 within five years. Conclusion GDF-15 and TRAIL-R2 were the most powerful Proximity Extension Assay chip biomarkers in predicting long-term all-cause mortality in patients with acute myocardial infarction.

sted, utgiver, år, opplag, sider
2017. Vol. 24, nr 15, s. 1576-1583
Emneord [en]
Myocardial infarction, biomarkers, mortality
HSV kategori
Identifikatorer
URN: urn:nbn:se:uu:diva-340093DOI: 10.1177/2047487317725017ISI: 000413162000002PubMedID: 28762762OAI: oai:DiVA.org:uu-340093DiVA, id: diva2:1179727
Tilgjengelig fra: 2018-02-02 Laget: 2018-02-02 Sist oppdatert: 2023-09-21
Inngår i avhandling
1. Targeted multiplex proteomics for risk stratification in patients with cardiovascular disease
Åpne denne publikasjonen i ny fane eller vindu >>Targeted multiplex proteomics for risk stratification in patients with cardiovascular disease
2023 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Risk stratification is valuable in patients with cardiovascular disease (CVD). Proteins involved in different pathophysiological processes in atherosclerosis have shown prognostic capacity. A new technology, Proximity Extension Assay (PEA), enables the simultaneous analysis of numerous plasma proteins from a minimal amount of plasma. 

In this thesis, the overall aim was to identify and study prognostic protein biomarkers that could become useful in risk stratification. We used PEA to identify the biomarkers with the best prediction of long-term mortality among patients with acute myocardial infarction (AMI) and peripheral arterial disease (PAD). 

The study populations included consecutive patients with AMI from the Västmanland Myocardial Infarction Study (VaMIS), outpatients with carotid or lower extremity PAD from the Peripheral Arterial Disease Study in Västmanland (PADVa), and a population-based control cohort. A set of 92 proteins was analysed with PEA and related to follow-up data in the populations. The biomarkers which were best at predicting all-cause mortality were identified using LASSO regression analyses. The added value of the identified biomarkers to clinical risk markers was evaluated by logistic or Cox regression models. 

The associations between the plasma concentrations of growth differentiation factor 15 (GDF-15) to clinical risk factors, indicators of atherosclerotic burden, and variables of cardiac geometry and function were analysed with linear regression models. 

Spearman’s rank correlation coefficients compared the plasma concentrations obtained from conventional immunoassays and PEA for GDF-15 and N-terminal pro-brain natriuretic peptide (NT-proBNP) in the PAD population and the population-based cohort without PAD. The association between the two assay data and outcome was evaluated separately with Cox regression.

GDF-15 and tumour necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2) had the best prognostic performance for all-cause mortality among individuals with AMI, and PAD, and improved the risk prediction beyond the established risk markers.

Circulating GDF-15 levels among individuals with PAD were independently associated with several of the clinical and biochemical risk variables, particularly diabetes and low low-density lipoprotein cholesterol.

We demonstrated an excellent correlation and a similar prognostic performance of plasma levels of NT-proBNP and GDF-15 obtained by conventional assays compared with PEA in both cohorts. Except for high levels of NT-proBNP, the PEA reliably reflects the serum levels obtained from the conventional assay.

Hopefully, our results can contribute to the finding of potential biomarkers useful in clinical practice in order to better identify subgroups among patients with CVD. In the long run, this might open up possibilities for individualised treatment and to more cost-effective follow-up routines, thus improving quality of life and longevity.

sted, utgiver, år, opplag, sider
Uppsala: Uppsala universitet, 2023. s. 83
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1975
Emneord
cardiovascular disease, proteomics, myocardial infarction, peripheral arterial disease, biomarker, GDF-15
HSV kategori
Forskningsprogram
Kardiologi
Identifikatorer
urn:nbn:se:uu:diva-511184 (URN)978-91-513-1899-8 (ISBN)
Disputas
2023-11-09, Aulan, ingång 21., Västmanlands sjukhus Västerås, Västerås, 09:00 (svensk)
Opponent
Veileder
Tilgjengelig fra: 2023-10-19 Laget: 2023-09-21 Sist oppdatert: 2023-10-19

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