Lars Lind1, Bruna Gigante2, Yan Borne3, Anders Mälarstig2, Johan Sundström4, Johan Ärnlöv5, Erik Ingelsson6, Damiano Baldassarre7, Elena Tremoli8, Fabrizio Veglia8, Anders Hamsten2, Marju Orho-Melander3, Jan Nilsson3, Olle Melander3, Gunnar Engström3. 1. Department of Medical Sciences, Uppsala University, Sweden. Electronic address: lars.lind@medsci.uu.se. 2. Bruna Gigante Unit of Cardiovascular Medicine, Dept of Medicine, Karolinska Institutet, Sweden. 3. Yan Borne Department of Clinical Sciences Malmö, Lund University, Sweden. 4. Department of Medical Sciences, Uppsala University, Uppsala, Sweden; The George Institute for Global Health, University of New South Wales, Sydney, Australia. 5. Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden; School of Health and Social Sciences, Dalarna University, Falun, Sweden. 6. Department of Medicine, Division of Cardiovascular Medicine, Stanford Cardiovascular Institute, Stanford Diabetes Research Center, Stanford University, Stanford, CA, 94305, USA. 7. Department of Medical Biotechnology and Translational Medicine, Università di Milano, Milan, Italy; Centro Cardiologico Monzino, IRCCS, Milan, Italy. Electronic address: damiano.baldassarre@cardiologicomonzino.it. 8. Centro Cardiologico Monzino, IRCCS, Milan, Italy.
Abstract
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.
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.
Authors: G V Papamichail; T E Markatseli; A N Georgiadis; V G Xydis; H Milionis; A A Drosos; P V Voulgari Journal: Heart Vessels Date: 2022-06-24 Impact factor: 1.814
Authors: Lars Lind; Bruna Gigante; Yan Borné; Tobias Feldreich; Jerzy Leppert; Pär Hedberg; Carl Johan Östgren; Fredrik H Nyström; Johan Sundström; Johan Ärnlöv; Damiano Baldassarre; Elena Tremoli; Fabrizio Veglia; Anders Hamsten; Christopher J O'Donnell; Nora Franceschini; Marju Orho-Melander; Jan Nilsson; Olle Melander; Gunnar Engström; Anders Mälarstig Journal: Arterioscler Thromb Vasc Biol Date: 2021-03-04 Impact factor: 8.311
Authors: Ankush D Jamthikar; Deep Gupta; Anudeep Puvvula; Amer M Johri; Narendra N Khanna; Luca Saba; Sophie Mavrogeni; John R Laird; Gyan Pareek; Martin Miner; Petros P Sfikakis; Athanasios Protogerou; George D Kitas; Raghu Kolluri; Aditya M Sharma; Vijay Viswanathan; Vijay S Rathore; Jasjit S Suri Journal: Rheumatol Int Date: 2020-08-28 Impact factor: 2.631