Plasma lipids in Pseudoxanthoma Elasticum (PXE) patients: A comparative study with population-based reference values and Non-PXE controls.

Background and aims: - Pseudoxanthoma elasticum (PXE) is a rare genetic disease caused by pathogenic mutations in the ABCC6 gene, resulting in low values of inorganic pyrophosphate (PPi). While low PPi is thought to contribute to arterial calcification, it remains unclear whether this fully explains premature calcification in PXE. It has been hypothesized that the ABCC6 gene could be related to dyslipidemia, which could contribute to vascular calcification seen in PXE. The aim of this study is to evaluate the relation between PXE and plasma lipid concentrations in a large cohort of PXE patients compared with reference values for the general population and compared with non-PXE controls. Methods: - The plasma concentrations of total cholesterol, HDL-cholesterol, tiglycerides, and LDL-cholesterol of 312 PXE patients were compared to age- and sex-matched modeled data of the general Dutch population. Differences in median lipid levels were compared with Mann-Whitney-U test. Secondly, plasma lipid concentrations of 44 PXE patients were compared to 44 not-genetically related relatives (spouses or friends), with linear models adjusted for age, sex and BMI. Results: - Total cholesterol in PXE patients was 5.6 [IQR 4.6-6.4] mmol/L versus 5.3 [IQR 4.7-6.0] mmol/L (p < 0.01) in the general population; triglycerides were 1.1 [IQR 0.9-1.7] mmol/L versus 1.0 [0.7-1.4] mmol/L (p < 0.01); HDL-c was 1.4 [IQR 1.2-1.7] mmol/L versus 1.5 [IQR 1.2-1.8] mmol/L (p = 0.03) and LDL-c was 3.3 [IQR 2.7-4.1] mmol/L versus 3.2 [IQR 2.7-3.8] mmol/L (p = 0.01). In the patient control analysis with 44 pairs and age, sex and BMI adjusted, comparison with the non-PXE controls only triglycerides were significantly different (mean difference: 0.38 (0.13-0.63)). Conclusion: -The lipid profiles of PXE patients are marginally different from the general population or compared to a matched control group, but the differences are unlikely to be clinically relevant. It is therefore unlikely that plasma lipids contribute to the premature vascular calcifications in PXE patients.

Do pseudoxanthoma elasticum patients have higher prevalence of kidney stones on computed tomography compared to hospital controls?

BACKGROUND: Pseudoxanthoma elasticum (PXE) is an autosomal recessive disease characterized by diminished inorganic plasma pyrophosphate (PPi), a strong calcification inhibitor. In addition to more typical calcification of skin, retina and arterial wall a diminished plasma PPi could lead to other ectopic calcification, such as formation of kidney stones. OBJECTIVE: To compare the prevalence of kidney stones between PXE patients and hospital controls on computed tomography (CT). METHOD: Low-dose CT images of PXE patients and controls were assessed by one radiologist, who was blinded for the diagnosis PXE. The number of kidney stones, and the size of the largest stone was recorded. Odds ratios (ORs) for having kidney stone were calculated using multivariable adjusted logistic regression. RESULTS: Our study comprised 273 PXE patients and 125 controls. The mean age of PXE patients was 51.5 ± 15.9 years compared to 54.9 ± 14.2 in the control group (p = 0.04) and PXE patients more often were women (63 vs. 50%, p = 0.013). The prevalence of kidney stones on CT was similar: 6.9% in PXE patients, compared to 5.6% in controls (p = 0.6). In the multivariate analysis adjusting for age and sex, there was no significantly higher odds for PXE patients on having stones, compared to controls: OR 1.48 (95% CI 0.62-3.96). CONCLUSION: There is no significant difference in the prevalence of incidental kidney stones on CT in PXE patients versus controls.

The Association Between the Kyphosis Angle and Physical Performance in Community-Dwelling Older Adults.

BACKGROUND: We investigated prospectively among community-dwelling older adults aged 65 years and older whether a larger kyphosis angle is associated with poorer physical performance (balance, muscle strength, or both), and whether this association is unidirectional. METHODS: Male and female participants performed a multicomponent physical performance test with subscores for gait, muscle strength, and balance at baseline and after 2 years. Hand grip strength was also measured at baseline and at follow-up. The Cobb angle was measured on DXA-based Vertebral Fracture Assessments, made at the baseline and follow-up visit. Through linear and logistic regression analysis, we investigated the association between the kyphosis angle and physical performance and vice versa. We stratified for sex, and tested for effect modification by age and study center. RESULTS: The mean kyphosis angle was 37° and 15% of the participants (n = 1 220, mean age 72.9 ± 5.7 years) had hyperkyphosis (Cobb angle ≥50°). A larger kyphosis angle at baseline was independently associated with a poorer total physical performance score in women of the oldest quartile (≥77 years) in both the cross-sectional and longitudinal analyses (baseline B -0.32, 95% confidence interval [CI] -0.56-0.08; follow-up B 0.32, 95% CI -0.55-0.10). There was no association between physical performance at baseline and kyphosis progression. CONCLUSION: A larger kyphosis angle is independently associated with a poorer physical performance at baseline and over time, and the direction of this association is unidirectional. These results emphasize the importance of early detection and treatment of hyperkyphosis to prevent further worsening of the kyphosis angle, thereby potentially preserving physical performance.