ELEVATED PCSK9 LEVELS MAY CONTRIBUTE TO DYSLIPIDEMIA EARLY AFTER CARDIAC TRANSPLANTATION

Background: Dyslipidemia after heart transplantation (HTx) contributes to early intimal thickening and development of coronary allograft vasculopathy (CAV) which is the main reason for late graft loss. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme that regulates stability of LDL-C receptor and is novel drug target. The goal was to analyze the dynamics and the determinants of PCSK9 levels prior and during the first year after HTx.

Methods: We investigated 25 patients with advanced HF (16 males, age 53±13 years) who underwent heart transplantation in 2015-2016. Blood samples were obtained immediately prior HTx, 1, 6 and 12 months after HTx. After HTx, all received induction with thymoglobulin, followed by immunosuppression with tacrolimus (TAC), mycophenolate and prednisone. PCSK9 was measured by ELISA (CircuLex, MBL, Japan). Blood lipids and TAC through levels were measured by conventional assays.

Results: 1. month after Tx, PCSK9 increased from pretransplant level by 54.5%. At 6 and 12 months, PCSK9 dropped, but levels were still 39% and 21% above the pretransplant level. Similar dynamics at pretransplant, 1 6 and 12 month sample was also observed in total cholesterol (Ch), LDL-Ch and HDL-Ch. In pooled data, PCSK9 correlated (p<0.01) with total-Ch (r=0.33), LDL-Ch (r=0.21) and HDL-Ch (r=0.31), but not with triglycerides. The increase in PCSK9 after Tx was unrelated to change in body weight, but was likely related to immunosupressives. In the pooled data, PCSK9 correlated with TAC levels (r=0. 32, p=0.001) and even stronger with prednisone daily dose (r=0.42, p˂0.0001).

Conclusion: Increased PCSK9 after HTx contributes to dyslipidemia after HTx. The strongest determinant of PCSK9 level was the daily steroid dose. Potential benefits of PCKSK9 inhibitors on dyslipidemia and CAV should be examined in patients after HTx.