Objective: To evaluate the influence of LDL receptor (LDLR) -negative mutational status on CT coronary atherosclerosis in asymptomatic statin treated patients with heterozygous familial hypercholesterolemia (FH). Methods: Coronary CT angiography (CCTA) was performed in 145 FH patients (93 men; mean age 52 ± 8) screened for LDLR and apolipoprotein B (APOB) mutations. The extent of coronary plaque was compared between two groups: 1) 59 patients (41%) heterozygous for LDLR-negative mutations (LDLR-negative) and 2) 86 patients (59%) with reduced or normal LDLR function (LDLR-positive) consisting of 32 LDLR-defective mutations, 8 APOB mutations and 46 patients in whom no mutation could be identified.The diseased segments score (DSS) was the primary study endpoint defined as the number of coronary artery segments (0-17) with >20% luminal diameter narrowing. We compared the DSS between LDLR-negative and LDLR-positive patients. Within the LDLR-positive group a secondary analysis was performed between identified (LDLR-defective, APOB) and unidentified mutational status. Results: The median DSS was higher in LDLR-negative than in LDLR-positive patients (4 (1-7) and 2 (0-5); P = 0.017). After adjustment for risk factors, LDLR-negative mutational status remained an independent predictor of the DSS (B = 1.09; P = 0.047). The DSS in the LDLR-positive group was similar for patients with identified and patients with unidentified mutational status. Conclusion: In asymptomatic statin treated patients with a clinical diagnosis of FH, LDLR-negative mutational status is associated with a higher extent of subclinical CT coronary atherosclerosis.

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doi.org/10.1016/j.atherosclerosis.2012.12.016, hdl.handle.net/1765/39359
Erasmus MC: University Medical Center Rotterdam

ten Kate, G-J.R, Neefjes, L.A.E, Dedic, A, Nieman, K, Langendonk, J.G, Galema-Boers, J.M.H, … de Feyter, P.J. (2013). The effect of LDLR-negative genotype on CT coronary atherosclerosis in asymptomatic statin treated patients with heterozygous familial hypercholesterolemia. Atherosclerosis, 227(2), 334–341. doi:10.1016/j.atherosclerosis.2012.12.016