Abstract 18200: Sortilin Levels Correlated With Renal Function and Reduced by Strong Statins With Increased PCSK9 in Primary Dyslipidemia
Sortilin is encoded by the well-known cardiovascular risk gene SORT1, however Sortilin seems to modulate cardiovascular disease not only with lipids, and its function has not been well elucidated. Recent basic reports showed new aspects of Sortilin that it can bind to PCSK9, and also can enhance vascular calcification with non-lipid tissue nonspecific alkaline phosphatase. We investigated the clinical roles of Sortilin in statin-treated primary dyslipidemia.
Methods: A total of 62 patients (Male 33, Age 65±11 yrs) with primary dyslipidemia including 18 genetically confirmed heterozygous familial hypercholesterolemia were included. Non-FH group was treated with 10mg Atorvastatin, and FH group was treated with 20mg Rosuvastatin for 8 weeks. ELISA determined plasma levels of Sortilin and PCSK9 (free-fragment and hetero-dimer).
Results: Strong statins lowered LDL-C (-44% in non-FH, -54% in FH), and increased hetero-dimer PCSK9 (+21% in non-FH, +102% in FH) but not in free-fragment PCSK9. Statins decreased Sortilin in non-FH (-19%, p<0.0001), but no significance in FH (-5%, ns). Change rates of Sortilin showed positive correlation with that of hetero-dimer PCSK9 in non-FH (R2 9%, p<0.01) not that with LDL-C in non-FH. These date suggested interaction of PCSK9 and Sortilin. Intriguingly, Sortilin levels are positively correlated with Cr (p<0.05) and negatively with eGFR (p<0.05), but negatively with age (p<0.05), suggesting independent effect of renal function from age. Also Sortilin showed positive correlation with apo-CIII (p<0.001), RLP-C (p<0.01), and HOMA-R (p<0.01), implying association with atherogenic metabolic profiles.
Conclusion: Statin treatment decreased Sortilin with correlation with hetero-dimer PCSK9 in non-FH. Sortilin showed association with reduced renal function, and may associate with vascular calcification mechanism among chronic kidney disease.
Author Disclosures: A. Nohara: Other Research Support; Modest; Shionogi, Aegerion, Kowa, Synageva. Other Research Support; Significant; Keitai-Kai Medical Crop.. Consultant/Advisory Board; Modest; Sanofi, Amgen. M. Kawashiri: None. H. Tada: None. H. Hattori: None. T. Iwasaki: None. M. Yoshida: None. M. Mori: None. C. Nakanishi: None. K. Yagi: None. A. Inazu: None. M. Yamagishi: None. H. Mabuchi: None.
- © 2016 by American Heart Association, Inc.