Arterial calcification over time in pseudoxanthoma elasticum: a repeated measurements study

Abstract Background Pseudoxanthoma elasticum (PXE) is a rare genetic disorder, characterized by progressive systemic arterial calcification and an elevated cardiovascular disease risk. Although arterial calcification is an established risk factor of cardiovascular morbidity and mortality, insights into its artery-specific changes over time in PXE remain lacking. Objectives To assess artery-specific changes in arterial calcification over time in PXE and to investigate the associations of cardiovascular risk factors with these changes. Methods We prospectively included 311 PXE patients (mean age 53.1 years, 185 [59.5%] females). During a median follow-up of 3.7 (25th–75th percentiles 1.3–4.2) years patients underwent 472 full-body, non-contrast computed tomography (CT) scans (maximum of 6 CTs per patient) to quantify the volume (μL) of intracranial carotid artery calcification (ICAC), extracranial carotid artery calcification (ECAC), coronary artery calcification (CAC), aortic calcification (AoC), iliac artery calcification (IAC), and leg artery calcification (LAC) and total body calcification (sum of all arteries). We calculated absolute yearly change (follow-up volume × baseline volume / time difference) and relative yearly change (absolute change divided by baseline volume × 100%) in calcification. The correlations amongst arteries in absolute and relative calcification change were assessed using Spearman's correlation coefficients. Risk factors for change in arterial calcification were assessed using linear mixed models (including age as time variable and with all risk factors entered simultaneously into models). Results Calcification volume change ranged from 3% to 12% increase per year, with a total body calcification progression of 11% per year. The correlations amongst arteries in absolute and relative yearly progression of calcification were only weak to moderate (correlation coefficients ranged from 0.23 between CAC and ECAC to 0.38 between CAC and LAC). Hypertension was markedly associated with increased AoC (multiplicative change in calcification per 5 years of age 1.46 [95% CI 1.13–1.89]). Moreover, the strongest predictor of ICAC change was ever smoking (1.23 [95% CI 1.03–1.46]) and of ECAC change was hypercholesterolemia (1.21 [95% CI 1.02–1.43]). Conclusions Arterial calcification volume progressed with 11% per year in PXE, with considerable variation between and only moderate correlation amongst arteries. Moreover, we found several modifiable, artery-specific risk factors for the progression of calcification. Although both PXE and risk factor presence are considered systemic in nature, our findings highlight that considerable differences exist between arteries in susceptibility to calcification. As such, our results provide important insights into the mechanisms underlying arterial calcification in PXE, which might be used for more targeted treatment and prevention. Funding Acknowledgement Type of funding sources: None.