Aortic valve calcium score in hypercholesterolemic patients with and without low-density lipoprotein receptor gene mutation.

Rafal Gałąska,Krzysztof Chlebus,Dorota Kulawiak-Gałąska,Magdalena Chmara,Marcin Gruchała,Andrzej Rynkiewicz,Michał Studniarek,Bartosz Wasąg,Marcin Fijałkowski,Ying-Mei Feng

doi:10.1371/journal.pone.0209229

Abstract

The aim of this study was a comparison of aortic valve calcium score (AVCS) between patients with hypercholesterolemia and genetic diagnosis of familial hypercholesterolemia with low-density lipoprotein receptor gene mutation (LDLR-M group), versus patients with hypercholesterolemia without LDLR gene mutation (LDLR-WT group). A total of 72 LDLR-M patients and 50 LDLR-WT patients were enrolled in the study and underwent CT as a part of an assessment of coronary calcium scoring. AVCS was determined and compared between the two patient groups. AVCS was significantly higher in the LDLR-M group in comparison to the LDLR-WT group (13.8 ± 37.9 vs. 0.94 ± 3.1, p = 0.03). The Yates' chi-squared test for independence revealed that LDLR mutation and AVCS were significantly dependable (Chi^2 = 6.106, p = 0.013). The LDLR mutation was a strong predictor of a high AVCS (OR 7.83, 95% CI 2.08–29.50, p = 0.002) on multivariate regression analysis. Among the traditional risk factors, age (odds ratio 1.12, 95% CI 1.05–1.18, p<0.001) and SBP (OR 1.04, 95% CI 1.00–1.07, p = 0.045) were also significant for high result of AVCS. An assessment of computed tomography calcium scores showed that LDLR-M patients have increased AVCS in comparison to those with LDLR-WT. In addition, LDLR mutation can be considered as an independent risk factor of having high AVSC even after adjustment for risk factors including cholesterol levels. This may result from the associated process connected with the regulatory role of LDLR in evolution of aortic valve calcifications.

Highlights

Familial hypercholesterolemia (FH) is an autosomal dominant disorder, characterized by high cholesterol levels, which can be caused by a mutation in the low-density lipoprotein receptor (LDLR) gene
For all FH patients having at least 3 points according to the Dutch Lipid Clinic Network, genomic DNA was isolated from their whole blood using standard methods and mutational analysis of LDLR and APOB was performed as previously described [7,8], We evaluated a total of 156 adult subjects with a DNA-based diagnosis of FH
aortic valve calcium score (AVCS) assessment was performed on a group of 50 randomly selected individuals who were diagnosed with severe hypercholesterolemia during the same period with nonconfirmed FH causing mutation (LDLR-WT group) and with an LDL-C level above 4,9 mmol/L (190 mg%)