TY - JOUR
T1 - Lipoprotein(a) levels and atherosclerotic plaque characteristics in the carotid artery
T2 - The Plaque at RISK (PARISK) study
AU - Van Dam-Nolen, Dianne H. K.
AU - van Dijk, Anouk C.
AU - Crombag, Genevieve A. J. C.
AU - Lucci, Carlo
AU - Kooi, M. Eline
AU - Hendrikse, Jeroen
AU - Nederkoorn, Paul J.
AU - Daemen, Mat J. A. P.
AU - van der Steen, Antonius F. W.
AU - Koudstaal, Peter J.
AU - Kronenberg, Florian
AU - van Lennep, Jeanine E. Roeters
AU - Mulder, Monique T.
AU - van der Lugt, Aad
N1 - Funding Information:
This research was supported by the Dutch Heart Foundation and performed within the framework of the Center for Translational Molecular Medicine ( www.ctmm.nl ), project PARISK (Plaque At RISK; grant number 01C-202).
Publisher Copyright:
© 2021 The Author(s)
PY - 2021/7
Y1 - 2021/7
N2 - 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 (beta = 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 (beta = 0.58, 95% CI: 0.04; 1.12). Rs10455872 was significantly associated with increased calcification volume (beta = 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 (beta = -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.
AB - 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 (beta = 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 (beta = 0.58, 95% CI: 0.04; 1.12). Rs10455872 was significantly associated with increased calcification volume (beta = 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 (beta = -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.
KW - SURFACE-MORPHOLOGY
KW - ASSOCIATION
KW - STENOSIS
KW - DISEASE
KW - APOLIPOPROTEIN
KW - THICKNESS
KW - GENETICS
KW - STROKE
KW - LP(A)
U2 - 10.1016/j.atherosclerosis.2021.06.004
DO - 10.1016/j.atherosclerosis.2021.06.004
M3 - Article
C2 - 34216874
SN - 0021-9150
VL - 329
SP - 22
EP - 29
JO - Atherosclerosis
JF - Atherosclerosis
ER -