Dianne H K van Dam-Nolen1, Anouk C van Dijk2, Geneviève A J C Crombag3, Carlo Lucci4, M Eline Kooi3, Jeroen Hendrikse4, Paul J Nederkoorn5, Mat J A P Daemen6, Antonius F W van der Steen7, Peter J Koudstaal8, Florian Kronenberg9, Jeanine E Roeters van Lennep10, Monique T Mulder10, Aad van der Lugt2. 1. Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. Electronic address: h.nolen@erasmusmc.nl. 2. Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. 3. Department of Radiology and Nuclear Medicine, CARIM School for Cardiovascular Diseases, Maastricht University Medical Center, Maastricht, the Netherlands. 4. Department of Radiology, University Medical Center Utrecht, Utrecht, the Netherlands. 5. Department of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam Cardiovascular Science, Amsterdam the Netherlands. 6. Department of Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam the Netherlands. 7. Department of Biomedical Engineering, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. 8. Department of Neurology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands. 9. Division of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria. 10. Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Abstract
BACKGROUND AND AIMS: Lipoprotein(a) is an independent risk factor for cardiovascular disease and recurrent ischemic stroke. Lipoprotein(a) levels are known to be associated with carotid artery stenosis, but the relation of lipoprotein(a) levels to carotid atherosclerotic plaque composition and morphology is less known. We hypothesize that higher lipoprotein(a) levels and lipoprotein(a)-related SNPs are associated with a more vulnerable carotid plaque and that this effect is sex-specific. METHODS: In 182 patients of the Plaque At RISK study we determined lipoprotein(a) concentrations, apo(a) KIV-2 repeats and LPA SNPs. Imaging characteristics of carotid atherosclerosis were determined by MDCTA (n = 161) and/or MRI (n = 171). Regressions analyses were used to investigate sex-stratified associations between lipoprotein(a) levels, apo(a) KIV-2 repeats, and LPA SNPs and imaging characteristics. RESULTS: Lipoprotein(a) was associated with presence of lipid-rich necrotic core (LRNC) (aOR = 1.07, 95% CI: 1.00; 1.15), thin-or-ruptured fibrous cap (TRFC) (aOR = 1.07, 95% CI: 1.01; 1.14), and degree of stenosis (β = 0.44, 95% CI: 0.00; 0.88). In women, lipoprotein(a) was associated with presence of intraplaque hemorrhage (IPH) (aOR = 1.25, 95% CI: 1.06; 1.61). In men, lipoprotein(a) was associated with degree of stenosis (β = 0.58, 95% CI: 0.04; 1.12). Rs10455872 was significantly associated with increased calcification volume (β = 1.07, 95% CI: 0.25; 1.89) and absence of plaque ulceration (aOR = 0.25, 95% CI: 0.04; 0.93). T3888P was associated with absence of LRNC (aOR = 0.36, 95% CI: 0.16; 0.78) and smaller maximum vessel wall area (β = -10.24, 95%CI: -19.03; -1.44). CONCLUSIONS: In patients with symptomatic carotid artery stenosis, increased lipoprotein(a) levels were associated with degree of stenosis, and IPH, LRNC, and TRFC, known as vulnerable plaque characteristics, in the carotid artery. T3888P was associated with lower LRNC prevalence and smaller maximum vessel wall area. Further research in larger study populations is needed to confirm these results.
BACKGROUND AND AIMS: Lipoprotein(a) is an independent risk factor for cardiovascular disease and recurrent ischemic stroke. Lipoprotein(a) levels are known to be associated with carotid artery stenosis, but the relation of lipoprotein(a) levels to carotid atherosclerotic plaque composition and morphology is less known. We hypothesize that higher lipoprotein(a) levels and lipoprotein(a)-related SNPs are associated with a more vulnerable carotid plaque and that this effect is sex-specific. METHODS: In 182 patients of the Plaque At RISK study we determined lipoprotein(a) concentrations, apo(a) KIV-2 repeats and LPA SNPs. Imaging characteristics of carotid atherosclerosis were determined by MDCTA (n = 161) and/or MRI (n = 171). Regressions analyses were used to investigate sex-stratified associations between lipoprotein(a) levels, apo(a) KIV-2 repeats, and LPA SNPs and imaging characteristics. RESULTS:Lipoprotein(a) was associated with presence of lipid-rich necrotic core (LRNC) (aOR = 1.07, 95% CI: 1.00; 1.15), thin-or-ruptured fibrous cap (TRFC) (aOR = 1.07, 95% CI: 1.01; 1.14), and degree of stenosis (β = 0.44, 95% CI: 0.00; 0.88). In women, lipoprotein(a) was associated with presence of intraplaque hemorrhage (IPH) (aOR = 1.25, 95% CI: 1.06; 1.61). In men, lipoprotein(a) was associated with degree of stenosis (β = 0.58, 95% CI: 0.04; 1.12). Rs10455872 was significantly associated with increased calcification volume (β = 1.07, 95% CI: 0.25; 1.89) and absence of plaque ulceration (aOR = 0.25, 95% CI: 0.04; 0.93). T3888P was associated with absence of LRNC (aOR = 0.36, 95% CI: 0.16; 0.78) and smaller maximum vessel wall area (β = -10.24, 95%CI: -19.03; -1.44). CONCLUSIONS: In patients with symptomatic carotid artery stenosis, increased lipoprotein(a) levels were associated with degree of stenosis, and IPH, LRNC, and TRFC, known as vulnerable plaque characteristics, in the carotid artery. T3888P was associated with lower LRNC prevalence and smaller maximum vessel wall area. Further research in larger study populations is needed to confirm these results.
Authors: Martin Andreas Geiger; Ronald Luiz Gomes Flumignan; Marcone Lima Sobreira; Wagner Mauad Avelar; Carla Fingerhut; Sokrates Stein; Ana Terezinha Guillaumon Journal: Front Cardiovasc Med Date: 2022-05-16
Authors: Carlotta Onnis; Christian Cadeddu Dessalvi; Filippo Cademartiri; Giuseppe Muscogiuri; Simone Angius; Francesca Contini; Jasjit S Suri; Sandro Sironi; Rodrigo Salgado; Antonio Esposito; Luca Saba Journal: Front Cardiovasc Med Date: 2022-09-13