IL-6 as a Mediator of the Association Between Traditional Risk Factors and Future Myocardial Infarction: A Nested Case-Control Study

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Fältnamn	Indikatorer	Metadata
000		05010naa a2200469 4500
001		oai:DiVA.org:oru-90144
003		SwePub
008		210305s2021 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
009		oai:DiVA.org:umu-182362
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-901442 URI
024	7	a https://doi.org/10.1161/ATVBAHA.120.3157932 DOI
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1823622 URI
040		a (SwePub)orud (SwePub)umu
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Zegeye, Mulugeta M,d 1986-u Örebro universitet,Institutionen för medicinska vetenskaper,Cardiovascular Research Centre, School of Medical Sciences, D.R., Örebro University, A.S4 aut0 (Swepub:oru)zma
245	1 0	a IL-6 as a Mediator of the Association Between Traditional Risk Factors and Future Myocardial Infarction :b A Nested Case-Control Study
264	1	b Lippincott Williams & Wilkins,c 2021
338		a print2 rdacarrier
500		a Funding Agency:Foundation for Old Servants 2019-00851 2018-00654 2017-00579
520		a OBJECTIVE: Studies elucidating the importance of IL (interleukin)-6 trans-signaling associated with risk of future myocardial infarction (MI) are scarce. Additionally, whether elevation in IL-6 explains part of the association between traditional risk factors and future MI has not been explored.Approach and Results: We conducted a nested case-control study including a total of 584 participants (292 cases and 292 controls) from Västerbotten Intervention Programme and MONICA (Multinational Monitoring of Trends and Determinants in Cardiovascular Disease) cohorts. At baseline, plasma cholesterol levels were measured, and clinical characteristics of participants were collected. In this study, we measured the plasma concentration of IL-6, sIL-6R (soluble IL-6 receptor), and sgp130 (soluble-gp130). To estimate extent of IL-6 trans-signaling, we estimated plasma concentration of a novel biomarker, the IL-6 binary complex. IL-6 binary complex concentration was significantly elevated in participants who experienced MI compared with those who did not. Univariate analyses showed that a 2-fold increase in IL-6 binary complex was associated with 2.45× higher risk of future MI (95% CI relative risk, 1.65-3.66, P<0.001). Receiver operating characteristics analyses revealed that the predictive performance of IL-6 binary complex (area under the curve, 0.614) was equivalent to that of IL-6 (area under the curve, 0.603). Furthermore, using Process mediation analyses tool, we found statistically significant indirect effect of smoking and hypertension on future MI that is mediated through increased IL-6 binary complex or plasma IL-6.CONCLUSIONS: IL-6 and IL-6 binary complex concentration in plasma were significantly associated with future MI. Our data additionally imply that both the elevated plasma IL-6, and the IL-6 binary complex concentration could partly explain, and, thus, might hypothetically be functionally associated with the increased risk of MI in smokers and hypertensive participants.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Kardiologi0 (SwePub)302062 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cardiac and Cardiovascular Systems0 (SwePub)302062 hsv//eng
653		a Acute coronary syndrome
653		a atherosclerosis
653		a biomarker
653		a hypertension
653		a smoking
700	1	a Andersson, Jonas S. O.,d 1977-u Umeå universitet,Avdelningen för medicin4 aut0 (Swepub:umu)jasaon96
700	1	a Wennberg, Patrik,d 1972-u Umeå universitet,Allmänmedicin4 aut0 (Swepub:umu)pawe0002
700	1	a Repsilber, Dirk,d 1971-u Örebro universitet,Institutionen för medicinska vetenskaper,Cardiovascular Research Centre, School of Medical Sciences, D.R., Örebro University, A.S4 aut0 (Swepub:oru)drr
700	1	a Sirsjö, Allan,d 1959-u Örebro universitet,Institutionen för medicinska vetenskaper,Cardiovascular Research Centre, School of Medical Sciences, D.R., Örebro University, A.S4 aut0 (Swepub:oru)aso
700	1	a Ljungberg, Liza,d 1980-u Örebro universitet,Institutionen för medicinska vetenskaper,Cardiovascular Research Centre, School of Medical Sciences, D.R., Örebro University, A.S4 aut0 (Swepub:oru)lzlg
710	2	a Örebro universitetb Institutionen för medicinska vetenskaper4 org
773	0	t Arteriosclerosis, Thrombosis and Vascular Biologyd : Lippincott Williams & Wilkinsg 41:4, s. 1570-1579q 41:4<1570-1579x 1079-5642x 1524-4636
856	4	u https://doi.org/10.1161/ATVBAHA.120.315793y Fulltext
856	4	u https://umu.diva-portal.org/smash/get/diva2:1547421/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-90144
856	4 8	u https://doi.org/10.1161/ATVBAHA.120.315793
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-182362

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Av författaren/redakt...: Zegeye, Mulugeta ...; Andersson, Jonas ...; Wennberg, Patrik ...; Repsilber, Dirk, ...; Sirsjö, Allan, 1 ...; Ljungberg, Liza, ...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Kardiologi

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Av lärosätet: Örebro universitet; Umeå universitet

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