Patients with pseudoxanthoma elasticum (PXE) do not have dyslipidemia

Abstract

Abstract Background Pseudoxanthoma elasticum (PXE) is a rare genetic disease caused by low inorganic pyrophosphate and is characterized by medial arterial calcification, leading to peripheral arterial disease and ischemic cerebral disease. Animal studies and small human studies have reported an association between PXE and dyslipidemia and therefore suggest that atherosclerosis is a second pathway contributing to cardiovascular disease in PXE patients. The association between PXE and dyslipidemia was however not consistent across these studies and there are several biological hypotheses proposed where the affected gene in PXE (ABCC6) could affect the cholesterol pathway: ABCC might influence HMA-CoA reductase – and increase total cholesterol and LDL-c – on one hand, but there is also evidence that points toward influence of ABCC6 on the reversed cholesterol pathway, influencing HDL-c. This study is important to analyze if PXE subjects, from the larges PXE cohort in the world, indeed do have a different a different lipid profile compared to well matched controls. Purpose To evaluate whether PXE patients have a different lipid profile compared to non-PXE patients. Methods A cross-sectional patient-control study was done at the Dutch Expertise Center for PXE in the University Medical Center Utrecht. Patients were all diagnosed conform the Plomp cirteria. The control population consisted of acquaintances of PXE patients, excluding first and second-degree relatives. Total cholesterol, LDL-c, HDL-c and triglycerides were assessed in both patients and controls and if lipid-lowering treatment (LLT) was used pre-treatment levels were calculated using known effects of LLT on lipids. To eliminate the imbalances between patients and controls, we used Coursened Exact Matching (CEM), to investigate the effect of PXE on lipids. Results The study population included 323 PXE patients and 57 controls. Their characteristics are displayed in Figure 1. After CEM 186 patients (weighted means: age 57.8±9.9 years, 58% females, BMI 25.5±2.9 kg/m2) and 52 controls (age 57.3±43.1 years, 58% females, BMI 25.5±17 kg/m2) were left for analyses. The univariate, weighted regression analysis of the effect of having PXE on lipid profile shows that the differences in lipids between patients and controls were 0.22 mmol/L for total cholesterol (p=0.299), 0.15 mmol/L for LDL-c (p=0.524), 0.07 mmol/L for HDL-c (p=0.314) and 0.10 mmol/L for triglycerides (p=0.433). A sensitivity analysis where only the crude values of untreated subjects were included in the analysis showed that LDL-c was sginficantly lower in PXE-patients. Probably due to the fact that only the very healthy PXE patients were included. Conclusion There are no differences in levels of total cholesterol, LDL-c, HDL-c, and triglycerides between PXE patients and matched controls. Funding Acknowledgement Type of funding sources: None.