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. 2022 May 5;11(9):2588.
doi: 10.3390/jcm11092588.

Relationships between Plasma Pyrophosphate, Vascular Calcification and Clinical Severity in Patients Affected by Pseudoxanthoma Elasticum

Georges Leftheriotis  1   2 , Nastassia Navasiolava  3 , Laetitia Clotaire  2 , Christophe Duranton  2 , Olivier Le Saux  4 , Saïd Bendahhou  2 , Audrey Laurain  2 , Isabelle Rubera  2 , Ludovic Martin  3
Affiliations

Relationships between Plasma Pyrophosphate, Vascular Calcification and Clinical Severity in Patients Affected by Pseudoxanthoma Elasticum

Georges Leftheriotis et al. J Clin Med. .

Abstract

Pseudoxanthoma elasticum (PXE; OMIM 264800) is an autosomal recessive metabolic disorder characterized by progressive calcification in the skin, the Bruch’s membrane, and the vasculature. Calcification in PXE results from a low level of circulating pyrophosphate (PPi) caused by ABCC6 deficiency. In this study, we used a cohort of 107 PXE patients to determine the pathophysiological relationship between plasma PPi, coronary calcification (CAC), lower limbs arterial calcification (LLAC), and disease severity. Overall, our data showed a deficit in plasma PPi in PXE patients compared to controls. Remarkably, affected females showed higher PPi levels than males, but a lower LLAC. There was a strong correlation between age and PPi in PXE patients (r = 0.423, p < 0.0001) but not in controls (r = 0.059, p = 0.828). A weak correlation was found between PPi and CAC (r = 0.266, p < 0.02); however, there was no statistically significant connection with LLAC (r = 0.068, p = 0.518) or a severity score (r = 0.077, p = 0.429). Surprisingly, we found no significant correlation between plasma alkaline phosphatase activity and PPi (r = 0.113, p = 0.252) or between a 10-year cardiovascular risk score and all other variables. Multivariate analysis confirmed that LLAC and CAC were strongly dependent on age, but not on PPi. Our data showed that arterial calcification is only weakly linked to circulating PPi levels and that time (i.e., age) appears to be the major determinant of disease severity and calcification in PXE. These data are important to better understand the natural history of this disease but also for the follow-up and management of patients, and the design of future clinical trials. Our results also show that PPi is not a good biomarker for the evaluation of disease severity and progression.

Keywords: PHENODEX score; PXE natural history; cardiovascular; disease severity; ectopic calcification; inorganic pyrophosphate; pseudoxanthoma elasticum.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Distribution of plasma pyrophosphate (PPi) measured in controls (n = 25, squares) and PXE patients (circles): women (open circles) and men (filled circles) as a function of age (year).
Figure 2
Figure 2
Coefficient plots from multivariable stepwise regression models with PPi (a), CAC (b) and LLAC (c) as dependent variables.
See this image and copyright information in PMC

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