Gert-Jan Richter Ten Kate MS, MD, Presenter: Nothing to Disclose

Lisan Anna Neefjes MD, Abstract Co-Author: Nothing to Disclose

Admir Dedic MD, Abstract Co-Author: Nothing to Disclose

Koen Nieman MD, Abstract Co-Author: Nothing to Disclose

Gabriel P. Krestin MD, PhD, Abstract Co-Author: Consultant, General Electric Company Research Grant, General Electric Company Research Grant, Bayer AG Research Grant, Siemens AG

Eric Sijbrands, Abstract Co-Author: Nothing to Disclose

Pim J. De Feyter MD, PhD, Abstract Co-Author: Nothing to Disclose

It has been shown that LDLR-negative (LDLR-neg) genotype in heterozygous familial hypercholesterolemia (FH) is associated with relatively detrimental lipid profiles. However, the phenotypic consequences in terms of CT coronary atherosclerosis are unknown. In the present study we investigated CT coronary plaque burden in patients with a clinical diagnosis of FH.

In 144 patients with FH (92 men; mean age 52 ± 8) mutational screening of the LDLR and apolipoprotein B gene and CT coronary angiography (CTCA) were performed. The coronary plaque burden by CTCA was compared between two groups: 1) 54 patients (38%) heterozygous for LDLR-negative mutations (LDLR-neg) and 2) 90 patients (62%) with reduced or normal LDLR function (LDLR-positive); consisting of 32 LDLR-defective mutations (LDLR-def), 8 apolipoprotein B mutations (apoB) and 50 unidentified mutations. The plaque burden score was the primary endpoint defined as the integrated sum of stenosis severity and the number of coronary artery lesions: score=1 for 21-50% stenosis, score=2 for 51-70% stenosis and score=3 for >70% stenosis (median, IQR). The primary analysis was the comparison of plaque burden between LDLR-neg and LDLR-positive (LDLR-pos) mutational FH. In the LDLR-pos group a secondary analysis was performed between identified (LDLR-def/apoB) and unidentified mutational FH.  

The median plaque burden score in the LDLR-neg group was higher as compared to the LDLR-pos group (4 (0-5) and 2 (0-6); P=0.031). In the LDLR-pos group there was no difference in plaque burden score between LDLR-def/apoB and unidentified mutational FH. Wthin all groups, we found the complete spectrum ranging from normal to severely diseased coronary arteries.  

Statin treated patients with a clinical diagnosis  of FH, who are heterozygous for a known LDLR-neg mutation, have higher amounts of coronary plaque ranging from zero to extensive coronary artery disease.

Coronary plaque imaging may be a useful complement to the risk assessment in asymptomatic FH patients that has traditionally been based on lipid profiles, general risk-factors and mutational screening.

Ten Kate, G, Neefjes, L, Dedic, A, Nieman, K, Krestin, G, Sijbrands, E, De Feyter, P, The Effect of LDLR-negative Genotype on CT Coronary Atherosclerosis in Asymptomatic Statin Treated Patients with Heterozygous Familial Hypercholesterolemia.  Radiological Society of North America 2012 Scientific Assembly and Annual Meeting, November 25 - November 30, 2012 ,Chicago IL. http://archive.rsna.org/2012/12032520.html