15289-s-bos

4 65 | Rebuttal AoVC in FH Calcific aortic valve disease (CAVD) is the most common indication worldwide for valve intervention. For years, the mechanism for this calcification was thought to be due to a passive degenerative process. However, in the 21st century, the National Heart, Lung, and Blood Institute of the National Institutes of Health recognized that CAVD is an active biologic osteogenic process (1). Initiation of osteogenesis in the aortic valve depends on risk factors similar to those known to promote coronary artery disease, which cause myofibroblasts to differentiate via an osteogenic gene activation that results in valve calcification (1,2). In this issue of the  Journal , a study from the Netherlands by ten Kate et al. (3) tested the prevalence, extent, and risk modifiers of CAVD in patients with heterozygous familial hypercholesterolemia (he-FH). Clinically, the he-FH phenotype is encountered more often than the homozygous phenotype due to rapid progression of coronary artery disease in the homozygous patient population. The investigators therefore sought to determine the prevalence of CAVD in patients with he-FH by measuring the amount of calcification burden via computed tomography measurements of the coronary artery and aortic valve, low-density lipoprotein receptor (LDLR) function, and lipid levels and assessing their association with CAVD. LDL Receptor Density The investigators discovered that the prevalence of aortic valve calcification (AoVC) and the AoVC score (median [interquartile range]) were both higher in patients with he-FH than in control subjects: 41% versus 21%, respectively (p < 0.001) and 51 (9 to 117) versus 21 (3 to 49) (p = 0.007) (3). LDLR-negative mutational he-FH was the strongest predictor of the AoVC score (odds ratio: 4.81; 95% confidence interval: 2.22 to 10.40; p < 0.001). He-FH was associated with a high prevalence and a large extent of subclinical AoVC, especially in patients with LDLR-negative mutations, compared with the control subjects. Moreover, the AoVC scores increased faster with age in the LDLR-negative he- FH patients than in the LDLR-defective he-FH patients. Calcification Density The LDLR-negative mutation carrier status was a strong predictor of the extent of AoVC (3).The associationbetween coronary artery calcification andAoVCwas associated with a higher prevalence of AoVC, both in patients with he-FH and in control subjects. The authors hypothesized that the high level of coronary artery calcificationmay be due to confounding variables such as differences in statin therapy in the he-FH population