TY - JOUR
T1 - Aortic calcifications in familial hypercholesterolemia
T2 - Potential role of the low-density lipoprotein receptor gene
AU - Alrasadi, Khalid
AU - Alwaili, Khalid
AU - Awan, Zuhier
AU - Valenti, David
AU - Couture, Patrick
AU - Genest, Jacques
PY - 2009/1
Y1 - 2009/1
N2 - Background: We have previously reported premature, extensive aortic calcifications in patients with homozygous familial hypercholesterolemia (hmzFH) due to mutations in the low-density lipoprotein receptor gene (LDL-R). The objective of this study was to measure the degree of aortic calcification in heterozygous FH (htzFH) compared to both hmzFH and controls. We hypothesized that the LDL-R gene may contribute to aortic calcifications in a gene-dosage effect. Method: Patients with htzFH due to the French Canadian mutation (Δ15 kb del. null allele) were selected. All patients underwent computed tomographic scan to measure vascular calcification. We used 22 hmzFH patients from our previous study and patients undergoing computed tomographic virtual colonoscopy as controls. Results: Mean age for htzFH was 50 ± 15 years; initial cholesterol level before treatment was 10.45 ± 1.73 mmol/L. Major cardiovascular events occurred in 9 of 17 patients. A strong correlation between age and calcium score was found (r = 0.72, P = .0016). There was a strong correlation between the cholesterol-year score (an index of lifelong cholesterol burden) and the aortic calcium score (r = 0.62, P = .0105). Aortic calcifications in htzFH subjects occurred later than in hmzFH patients, but much earlier than in controls, suggesting a gene-dosage effect of LDL-R mutations and aortic calcium deposition. Conclusion: Aortic calcification was observed in patients with htzFH but presented at a later time and were less extensive than in hmzFH (34 vs 14 years, respectively). Because aortic calcifications may be partly independent of serum cholesterol levels in patients with familial hypercholesterolemia, implications for screening and the timing of treatment initiation may need reassessment.
AB - Background: We have previously reported premature, extensive aortic calcifications in patients with homozygous familial hypercholesterolemia (hmzFH) due to mutations in the low-density lipoprotein receptor gene (LDL-R). The objective of this study was to measure the degree of aortic calcification in heterozygous FH (htzFH) compared to both hmzFH and controls. We hypothesized that the LDL-R gene may contribute to aortic calcifications in a gene-dosage effect. Method: Patients with htzFH due to the French Canadian mutation (Δ15 kb del. null allele) were selected. All patients underwent computed tomographic scan to measure vascular calcification. We used 22 hmzFH patients from our previous study and patients undergoing computed tomographic virtual colonoscopy as controls. Results: Mean age for htzFH was 50 ± 15 years; initial cholesterol level before treatment was 10.45 ± 1.73 mmol/L. Major cardiovascular events occurred in 9 of 17 patients. A strong correlation between age and calcium score was found (r = 0.72, P = .0016). There was a strong correlation between the cholesterol-year score (an index of lifelong cholesterol burden) and the aortic calcium score (r = 0.62, P = .0105). Aortic calcifications in htzFH subjects occurred later than in hmzFH patients, but much earlier than in controls, suggesting a gene-dosage effect of LDL-R mutations and aortic calcium deposition. Conclusion: Aortic calcification was observed in patients with htzFH but presented at a later time and were less extensive than in hmzFH (34 vs 14 years, respectively). Because aortic calcifications may be partly independent of serum cholesterol levels in patients with familial hypercholesterolemia, implications for screening and the timing of treatment initiation may need reassessment.
UR - http://www.scopus.com/inward/record.url?scp=57149095250&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=57149095250&partnerID=8YFLogxK
U2 - 10.1016/j.ahj.2008.08.021
DO - 10.1016/j.ahj.2008.08.021
M3 - Article
C2 - 19081415
AN - SCOPUS:57149095250
SN - 0002-8703
VL - 157
SP - 170
EP - 176
JO - American Heart Journal
JF - American Heart Journal
IS - 1
ER -