Aortic Calcification Progression in Heterozygote Familial Hypercholesterolemia

Background: Patients with homozygous and heterozygous familial hypercholesterolemia (HeFH) develop severe aortic calcifications in an age- and gene dosage-dependent manner. The purpose of this study was to determine the rate of progression of aortic calcification in patients with HeFH. Methods: We performed thoracoabdominal computed tomography scans and quantified aortic calcium (AoCa) score in 16 HeFH patients, all with the null low-density lipoprotein (LDL) receptor DEL15Kb mutation. Patients (12 men, 4 women) were rescanned an average of 8.2 +/- 0.8 years after the first scan. Results: Mean LDL cholesterol (LDL-C) during treatment was 2.53 mmol/L; all patients were receiving high-dose statin/ezetimibe; 5 of 16 were receiving evolocumab. Baseline LDL-C was 7.6 +/- 1.3 mmol/L. Aortic calcifications increased in all patients in an exponential fashion with respect to age. Age was the strongest correlate of AoCa score. Cholesterol, LDL-C, or age x cholesterol did not correlate with AoCa score or its progression. Control patients (n = 31; 8 male, 23 female; mean age 61 +/- 11 years) who underwent virtual colonoscopy were rescanned over the same period and showed an abdominal AoCa score of 1472 +/- 2489 compared with 7916 +/- 7060 Agatston U (P < 0.001) in patients with HeFH during treatment (mean age, 60 +/- 14 years). The rate of progression was 159 vs 312 Agatston U/y in control participants vs those with HeFH. Conclusions: HeFH patients exhibit accelerated aortic calcification that increases exponentially with age. LDL-C at baseline or during treatment seems to have little effect on the rate of progression of AoCa score. Strategies to prevent aortic calcifications with statins have not met with clinical success and novel approaches are required; statins might also contribute to the process of arterial calcification.