Intracranial atherosclerosis in pseudoxanthoma elasticum: A case-control study. (June 2022)

• Record Type: Journal Article
• Authors: Lucci, Carlo; van den Beukel, Tim C.; Bartstra, Jonas W.; Zwanenburg, Jaco; van der Kolk, Anja; Takx, Richard; Hendrikse, Jeroen; Geerlings, Mirjam I.; Bos, Daniel; Spiering, Wilko; de Jong, Pim A.
• Is Part Of: Atherosclerosis. Volume 350(2022)
• Page Start: 19
• Page End: 24
• Publication Date: 2022-06
• Subjects: Intracranial atherosclerosis -- Vessel wall lesions -- Pseudoxanthoma elasticum -- Stroke -- MRI; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2022.04.014
• Languages: English
• ISSNs: 0021-9150

Abstract

Abstract: Background and aims: Pseudoxanthoma elasticum (PXE) is a genetic disorder characterized by systemic calcification of elastin fibers. Additionally, PXE is associated with an increased risk of stroke. It has been hypothesized that this may be caused by accelerated (intracranial) atherogenesis, as a consequence of specific genetic mutations underlying PXE. Hence, we compared the distribution and burden of intracranial atherosclerosis between PXE patients and healthy controls. Methods: Fifty PXE patients and 40 age-and-sex-matched healthy controls (without previous ischemic cerebrovascular disease) underwent 3T MRI to visualize atherosclerotic intracranial vessel wall lesions (VWLs). We compared the presence and burden of VWLs (total and for the anterior cerebral, middle cerebral, intracranial internal carotid, posterior cerebral, and basilar arteries separately) between PXE patients and healthy controls using logistic (presence versus absence) and negative binomial regression models (VWL count) adjusted for relevant confounders. All regressions included group (PXE patients vs. healthy controls) as independent variable. Results: We found that 34 (68.0%) PXE patients and 28 (70.0%) healthy controls had a VWL (odds ratio for presence 1.06 [95%CI 0.38–2.91]). In addition, the total burden of VWLs was similar between PXE patients (68 VWLs) and healthy controls (73 VWLs, incidence rate ratio for count 0.81 [95%CI 0.55–1.20]). Findings were similar when analyses were stratified for artery. Conclusions: The distribution and burden of intracranial atherosclerosis were similar between PXE patients and healthy controls. This implies PXE and its underlying mutations do not involve increased (intracranial) atherogenesis and that vascular calcification or other mechanisms explains the increased stroke risk in PXE. Graphical abstract: Image 1 Highlights: Pseudoxanthoma elasticum (PXE) is hypothesized to be involved in atherogenesis. PXE patients are at an increased risk for stroke. There is scientific debate on whether intracranial atherosclerosis plays a role. We found the distribution and burden of intracranial atherosclerosis were not increased in PXE patients compared to controls. Our findings imply PXE and its underlying mutations are not involved in atherogenesis.Other factors (calcification induced arterial stiffness or carotid hypoplasia) might explain the increased stroke risk in PXE. Other factors (calcification induced arterial stiffness or carotid hypoplasia) might explain the increased stroke risk in PXE.