Proprotein convertase subtilisin/kexin type 9 (PCSK9) and clinical outcomes in dialysis patients

Claudia Torino; Federico Carbone; Patrizia Pizzini; Sabrina Mezzatesta; Graziella D'Arrigo; Mercedes Gori; Luca Liberale; Margherita Moriero; Cristina Michelauz; Federica Frè; Simone Isoppo; Aurora Gavoci; Federica La Rosa; Alessandro Scuricini; Amedeo Tirandi; Davide Ramoni; Francesca Mallamaci; Giovanni Tripepi; Fabrizio Montecucco; Carmine Zoccali

doi:10.1111/eci.14235

Proprotein convertase subtilisin/kexin type 9 (PCSK9) and clinical outcomes in dialysis patients

Eur J Clin Invest. 2024 May 11:e14235. doi: 10.1111/eci.14235. Online ahead of print.

Authors

Claudia Torino¹, Federico Carbone^{2

3}, Patrizia Pizzini¹, Sabrina Mezzatesta¹, Graziella D'Arrigo¹, Mercedes Gori⁴, Luca Liberale^{2

3}, Margherita Moriero², Cristina Michelauz², Federica Frè², Simone Isoppo², Aurora Gavoci², Federica La Rosa², Alessandro Scuricini², Amedeo Tirandi², Davide Ramoni², Francesca Mallamaci^{1

5}, Giovanni Tripepi¹, Fabrizio Montecucco^{2

3}, Carmine Zoccali^{6

7}

Affiliations

¹ Clinical Epidemiology of Renal Disease and Hypertension Unit, Reggio Cal CNR Unit of the Pisa CNR Institute of Clinical Physiology, Pisa, Italy.
² First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.
³ IRCCS Ospedale Policlinico San Martino, Genoa-Italian Cardiovascular Network, Genoa, Italy.
⁴ CNR-IFC, Rome, Italy.
⁵ Nephrology, Hypertension and Renal Transplantation Unit, Grande Ospedale Metropolitano, Reggio Calabria, Italy.
⁶ Renal Research Institute, New York, USA.
⁷ IPNET, c/o Nefrologia delGrande Ospedale Metropolitano, Reggio Calabria, Italy.

PMID: 38733147
DOI: 10.1111/eci.14235

Abstract

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9), a factor accelerating the degradation of LDL receptors, was associated with a gender-dependent risk for cardiovascular (CV) events in the general population and with all-cause and CV mortality in two relatively small studies in black Africans and South Korean haemodialysis patients. The effect modification by gender was untested in these studies.

Methods: The study enrolled 1188 dialysis patients from the Prospective Registry of The Working Group of Epidemiology of Dialysis Region Calabria (PROGREDIRE) cohort. PCSK9 was measured by colorimetric enzyme-linked immunosorbent assay. The primary outcomes were all-cause and CV mortality. Statistical analysis included Cox regression analysis and effect modification analysis.

Results: During a median 2.9-year follow-up, out of 494 deaths, 278 were CV-related. In unadjusted analyses, PCSK9 levels correlated with increased all-cause (HR_{for1ln unit increase}: 1.23, 95% CI 1.06-1.43, p =.008) and CV mortality (HR_{for1ln unit increase}: 1.26, 95% CI 1.03-1.54, p =.03). After multivariate adjustment, these associations were no longer significant (all-cause mortality, HR_{for 1 ln unit increase}: 1.16, 95% CI .99-1.36, p =.07; CV mortality, HR_{for1ln unit increase}: 1.18, 95% CI .95-1.46, p =.14). However, in fully adjusted interaction analyses, a doubling in the risk of this outcome in women was registered (Women, HR_{for1ln unit increase}: 1.88, 95% CI 1.27-2.78, p =.002; Men, HR_{for1ln unit increase}: 1.07, 95% CI .83-1.38, p =.61; p for effect modification: .02).

Conclusions: PCSK9 levels are unrelated to all-cause mortality in haemodialysis patients but, like in studies of the general population, independently of other risk factors, entail a doubling in the risk of CV events in women in this population.

Keywords: ESKD; PCSK9; cardiovascular; clinical outcomes; dialysis.