Abstract

Background and aimsLipoprotein(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. MethodsIn 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. ResultsLipoprotein(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). ConclusionsIn 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.

Highlights

  • Carotid artery atherosclerosis is one of the major causes of ischemic stroke

  • After adjustments for age, sex and additional cardiovascular risk factors, a 10 mg/dL increase of Lp(a) concentration was significantly associated with presence of lipid-rich necrotic core (LRNC) (odds ratio (OR) = 1.07 [95% confidence interval 1.00; 1.15]), thin-or-ruptured fibrous cap (TRFC) (OR = 1.07 [1.01; 1.14]) and degree of stenosis (β = 0.44 [0.00; 0.88]) in all patients

  • When we stratified the analyses for sex, we found that in women a 10 mg/dL increase of Lp(a) concentration was associated with presence of intraplaque hemorrhage (IPH) (OR = 1.25 [1.06; 1.61]) and in men with degree of stenosis (β = 0.58 [0.04; 1.12])

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Summary

Introduction

Carotid artery atherosclerosis is one of the major causes of ischemic stroke. Destabilization of an atherosclerotic plaque can cause plaque rupture, leading to thrombus formation and embolization of plaque material and thrombus into distally located intracranial arteries. Imaging techniques like multidetector-row computed tomographic angiography (MDCTA) and magnetic resonance imaging (MRI) can visualize and quantify atherosclerotic plaques. 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). 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). 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. Further research in larger study populations is needed to confirm these results

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