Abstract 20674: Genetic CETP Deficiency Associated With Higher eGFR and Lower Coronary Stenosis Index in Dyslipdemic Patients in Japan

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Background: It is still controversial whether lower CETP is anti-atherogenic or not. Genetic deficiency should have greater impact on clinical course because its lifetime long effect. We evaluated impact of CETP deficiency on coronary atherosclerosis among dyslipidemic patients with non-familial hypercholesterolemia (non-FH) and with FH in Japanese population that include approximately 10% of heterozygous CETP deficiency. Methods: 374 non-FH dyslipidemic patients (170 males, mean age of 58 ± 14) including 201 subjects coronary angiography (CAG) assessed, and 235 genetically confirmed FH heterozygotes (121 males, mean age of 47 ± 17) including 61 CAG assessed were enrolled. Two common CETP variant, intron 14 G(+1)-to-A transition and D442G missense mutation in exon 15, were genotyped. Fasting lipid profiles without lipid drugs were analysed. Subgroup with LDL-C ≥140mg/dL (52% of non-FH) was defined as “hyper-LDL” in this study. Estimated Glomerular Filtration Rate (eGFR) and other conventional coronary risk factors were also analyzed. Results: Heterozygotes of CETP mutations were identified in 12% in non-FH group, and 8% in FH group. There were no differences in age or sex. In non-FH group, CETP mutations showed higher HDL-C (56 ± 22 vs. 50 ± 15 mg/dL, p <0.05), lower non-HDL-C (172 ± 39 vs. 188 ± 48 mg/dL, p <0.05), lower plasma CETP (2.1 ± 0.8 vs. 2.5 ± 0.7 μg/mL, p <0.05), higher eGFR (83.6 ± 18 vs. 78.1 ± 21 ml/min/1.73m 2 , p <0.05), and lower coronary stenosis index (CSI) (7.0 ± 7 vs. 11.1 ± 11, p <0.05) in CAG. Plasma CETP showed strong positive correlation with LDL-C ( p <0.0001, R 2 13%). In non-FH subgroup, CETP mutation showed lower CSI in hyper-LDL group (5.7 ± 8 vs. 12.6 ± 11, p <0.05), but no difference in normal-LDL group (8.0 ± 7 vs. 10.2 ± 11, ns ). In FH group, CETP mutations showed higher HDL-C (58 ± 19 vs. 48 ± 14 mg/dL, p <0.005), tendency of lower LDL-C (258 ± 51 vs. 275 ± 102 mg/dL, ns ) and higher eGFR (92.4 ± 27 vs. 83.1 ± 21 ml/min/1.73m 2 , ns ), but no difference in CSI (16.2 ± 15 vs. 19.2 ± 11, ns ). High HDL may have favorable effect also on kidney function, but further study will be required for the mechanism. Conclusion: CETP deficiency carriers showed favourable lipid profiles, eGFR, and CSI in non-FH dyslipidemic group especially with high LDL-C.