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

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.