Abstract 1095: Vascular Calcifications in Homozygote Familial Hypercholesterolemia: the Canadian Experience
PURPOSE: Familial hypercholesterolemia is an autosomal co-dominant disease predominantly due to loss of function mutations of the LDL receptor gene. Patients with homozygous familial hypercholesterolemia (hmzFH) often did not reach the third decade of life but have shown a remarkable increase in survival over the last 25–30 years, due to extracorporeal LDL removal techniques and new medication. The known cardiovascular complications of hmzFH include very premature CAD and calcific aortic valve stenosis. In the present report, we describe severe, premature and extensive calcification of the entire aorta in hmzFH patients.
METHODS AND RESULTS: We examined all known cases of hmzFH in Canada (n=25) (14 males, 11 females); a molecular diagnosis is available in most patients (LDL-R mutations). Mean age is 35 years (range 4 –54 years); follow-up duration ranges from 4 to 35 years. The initial average cholesterol prior to treatment was 672±154 mg/dL (LDL-C 579±154 mg/dL); on-treatment cholesterol was 232±77 mg/dL (LDL-C 182±77 mg/dL). Computed tomography (CT) scanning of the aorta was performed in all but 3 subjects. A calcium score was calculated from the CT scans. In all adult subjects, extensive calcifications of the aorta were observed. The calcium score ranged from 27 (in a 14 years old boy) to >29,000 in a 49 years old woman); the mean calcium score was 8,832 and correlated with age (r=0.48, p=0.002) and cholesterol-age score (r=0.28, p=0.029) but not with initial or on-treatment cholesterol level (r=0.12, p=0.171). While LDL-C lowering decreases the progression of CAD, aortic valve stenosis and extensive calcification of the aorta do not appear to be modified by current therapies, so that many patients must undergo aortic valve surgery for severe aortic valve stenosis.
CONCLUSIONS: The presence of severe, extensive and premature calcification of the aorta (“porcelain aorta”) is a new clinical entity in hmzFH patients. These represent a considerable surgical challenge in a population of patients with increased survival but in whom repeated interventions (coronary by-pass and aortic valve surgery) are expected. Prospective studies to identify, measure and prevent such calcifications are needed.