Lp(a) is linked to more vulnerable carotid plaque features, with sex-specific patterns, in the Dutch PARISK study of 182 patients (Atherosclerosis 2021)

Original title: Lipoprotein(a) levels and atherosclerotic plaque characteristics in the carotid artery: The Plaque at RISK (PARISK) study

Atherosclerosis · 11 June 2021 · 7

van Dam-Nolen DHK, van Dijk AC, Crombag GAJC, Lucci C, Kooi ME, Hendrikse J, Nederkoorn PJ, Daemen MJAP, van der Steen AFW, Koudstaal PJ, Kronenberg F, Roeters van Lennep JE et al.

In 182 patients with symptomatic carotid artery stenosis from the Plaque At RISK (PARISK) study in the Netherlands, higher Lp(a) was associated with lipid-rich necrotic core (adjusted OR 1.07, 95% CI 1.00-1.15), thin-or-ruptured fibrous cap (aOR 1.07, 95% CI 1.01-1.14), and greater degree of stenosis (beta 0.44, 95% CI 0.00-0.88) on carotid imaging. In women, Lp(a) was specifically associated with intraplaque haemorrhage (aOR 1.25, 95% CI 1.06-1.61), while in men it was associated with degree of stenosis (beta 0.58, 95% CI 0.04-1.12). The LPA variant rs10455872 was associated with increased calcification volume (beta 1.07, 95% CI 0.25-1.89) and absence of plaque ulceration, while T3888P was associated with absence of lipid-rich necrotic core and smaller maximum vessel wall area. The findings link elevated Lp(a) to multiple vulnerable carotid plaque characteristics, with distinct associations by sex, though the authors call for confirmation in larger populations.

Original 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.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.