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Leukotriene A4 Hydrolase and Hepatocyte Growth Factor Are Risk Factors of Sudden Cardiac Death Due to First-Ever Myocardial Infarction
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.ORCID iD: 0000-0002-5695-2276
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.ORCID iD: 0000-0002-1617-6102
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.ORCID iD: 0000-0003-1962-5484
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2022 (English)In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, no 18, article id 10251Article in journal (Refereed) Published
Abstract [en]

Patients at a high risk for sudden cardiac death (SCD) without previous history of cardiovascular disease remain a challenge to identify. Atherosclerosis and prothrombotic states involve inflammation and non-cardiac tissue damage that may play active roles in SCD development. Therefore, we hypothesized that circulating proteins implicated in inflammation and tissue damage are linked to the future risk of SCD. We conducted a prospective nested case–control study of SCD cases with verified myocardial infarction (N = 224) and matched controls without myocardial infarction (N = 224), aged 60 ± 10 years time and median time to event was 8 years. Protein concentrations (N = 122) were measured using a proximity extension immunoassay. The analyses revealed 14 proteins significantly associated with an increased risk of SCD, from which two remained significant after adjusting for smoking status, systolic blood pressure, BMI, cholesterol, and glucose levels. We identified leukotriene A4 hydrolase (LTA4H, odds ratio 1.80, corrected confidence interval (CIcorr) 1.02–3.17) and hepatocyte growth factor (HGF; odds ratio 1.81, CIcorr 1.06–3.11) as independent risk markers of SCD. Elevated LTA4H may reflect increased systemic and pulmonary neutrophilic inflammatory processes that can contribute to atherosclerotic plaque instability. Increased HGF levels are linked to obesity-related metabolic disturbances that are more prevalent in SCD cases than the controls.

Place, publisher, year, edition, pages
MDPI, 2022. Vol. 23, no 18, article id 10251
Keywords [en]
circulating risk marker, myocardial infarction, plaque instability, plasma protein, sudden cardiac death
National Category
Cardiac and Cardiovascular Systems Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
URN: urn:nbn:se:umu:diva-200233DOI: 10.3390/ijms231810251ISI: 000857533300001PubMedID: 36142157Scopus ID: 2-s2.0-85138980596OAI: oai:DiVA.org:umu-200233DiVA, id: diva2:1703562
Funder
Region VästerbottenSwedish Heart Lung Foundation, 20180539Swedish Research Council, 2017-00650Available from: 2022-10-13 Created: 2022-10-13 Last updated: 2024-04-08Bibliographically approved

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Landfors, FredrikVikström, SimonWennberg, PatrikJansson, Jan-HåkanAndersson, JonasChorell, Elin

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