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The plasma protein profile and cardiovascular risk differ between intima-media thickness of the common carotid artery and the bulb: A meta-analysis and a longitudinal evaluation
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.ORCID iD: 0000-0003-2335-8542
Karolinska Inst, Dept Med, Bruna Gigante Unit Cardiovasc Med, Huddinge, Sweden.ORCID iD: 0000-0003-4508-7990
Lund Univ, Yan Borne Dept Clin Sci Malmo, Lund, Sweden.
Karolinska Inst, Dept Med, Bruna Gigante Unit Cardiovasc Med, Huddinge, Sweden.
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2020 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 295, p. 25-30Article in journal (Refereed) Published
Abstract [en]

Background and aims: Genetic loci associated with CHD show different relationships with intima-media thickness in the common carotid artery (IMT-CCA) and in the bulb (IMT-bulb). We evaluated if IMT-CCA and IMT-bulb differ also with respect to circulating protein profiles and risk of incident atherosclerotic disease.

Methods: In three Swedish cohorts (MDC, IMPROVE, PIVUS, total n > 7000), IMT-CCA and IMT-bulb were assessed by ultrasound at baseline, and 86 cardiovascular-related proteins were analyzed. In the PIVUS study only, IMT-CCA and IMT-bulb were investigated in relation to incident atherosclerotic disease over 10 years of follow-up.

Results: In a meta-analysis of the analysis performed separately in the cohorts, three proteins, matrix metalloproteinase-12 (MMP-12), hepatocyte growth factor (HGF) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), were associated with IMT-CCA when adjusted for traditional cardiovascular risk factors. Five proteins were associated with IMT-bulb (MMP-12, growth/differentiation factor 15 (GDF-15), osteoprotegerin, growth hormone and renin). Following adjustment for cardiovascular risk factors, IMT-bulb was significantly more closely related to incident stroke or myocardial infarction (total number of cases, 111) than IMT-CCA in the PIVUS study (HR 1.51 for 1 SD, 95%CI 1.21-1.87, p < 0.001 vs HR 1.17, 95%CI 0.93-1.47, p = 0.16). MMP-12 levels were related to this combined end-point (HR 1.30, 95%CI 1.08-1.56, p = 0.0061).

Conclusions: Elevated levels of MMP-12 were associated with both IMT-CCA and IMT-bulb, but other proteins were significantly related to IMT in only one of these locations. The finding that IMT-bulb was more closely related to incident atherosclerotic disease than IMT-CCA emphasizes a difference between these measurements of IMT.

Place, publisher, year, edition, pages
ELSEVIER IRELAND LTD , 2020. Vol. 295, p. 25-30
Keywords [en]
Atherosclerosis, Proteomics, Carotid artery, Meta-analysis, Ultrasound
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:uu:diva-407188DOI: 10.1016/j.atherosclerosis.2020.01.011ISI: 000512990500004PubMedID: 31981948OAI: oai:DiVA.org:uu-407188DiVA, id: diva2:1416063
Funder
Swedish Heart Lung FoundationSwedish Research CouncilStockholm County CouncilAvailable from: 2020-03-20 Created: 2020-03-20 Last updated: 2020-03-20Bibliographically approved

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Lind, LarsSundström, Johan

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