Circulating Proprotein Convertase Subtilisin/Kexin Type 9 Levels Predict Future Cardiovascular Event Risks in Hemodialyzed Black African Patients

Abstract

Context and Objective: Cardiovascular diseases are the leading cause of mortality in patients. In this context, proprotein convertase subtilisin/kexin type 9 (PCSK9) appears to be the new biomarker identified as interfering in lipid homeostasis. This study aimed to investigate the association between PCSK9, dyslipidemia, and future risk of cardiovascular events in a population of black Africans. Methods: A cross-sectional study was conducted between August 2016 and July 2020 in six hemodialysis centers in the city of Kinshasa, Democratic Republic of the Congo. Serum PCSK9 was measured by ELISA; lipid levels of 251 chronic kidney disease grade 5 (CKD G5) hemodialysis patients and the Framingham predictive instrument were used for predicting cardiac events. Results: Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and triglycerides (TG) were significantly increased in the tertile with the highest PCSK9. By contrast, high-density lipoprotein cholesterol (HDL-c) was significantly decreased in the same tertile. A strong positive and significant correlation was found between PCSK9 and TC, TG, and LDL-c. Negative and significant correlation was observed between PCSK9 and HDL-c. The levels of PCSK9, smoking, overweight, and atherogenic dyslipidemia were associated with future risks for cardiovascular events in univariate analysis. After adjustment, all these variables persisted as independent determinants of future risk for cardiovascular events. The probability of having a cardiovascular event in this population was independently associated with PCSK9 levels. Compared to the patients in the lowest PCSK9 tertile, patients with PCSK9 levels in the middle (aOR 5.9, 95% CI 2.06–17.3, P<0.001) and highest tertiles (aOR 8.9, 95% CI 3.02–25.08, P<0.001) presented a greater risk of cardiac event. Conclusion: Increased PCSK9 serum levels are associated with higher levels of TC, LDL-c, and TG and lower levels of HDL-c in black African hemodialysis patients. Serum PCSK9 levels in these patients predict increased risk of cardiovascular events, independent of traditional potential confounders.

Correlations of PCSK9 and LDLR Gene Polymorphisms and Serum PCSK9 Levels With Atherosclerosis and Lipid Metabolism in Patients on Maintenance Hemodialysis

“…As reported, PCSK9 emerges as the new biomarker identified as interfering in lipid homeostasis. Raised serum PCSK9 levels have an association with higher TC and TG levels in Black African patients with HD 27 . Additionally, PCSK9 gene polymorphism functions in regulation of serum lipid levels, 28 and it is mainly associated with some serum lipid parameters in the Han population 29 .…”

“…Raised serum PCSK9 levels have an association with higher TC and TG levels in Black African patients with HD. 27 Additionally, PCSK9 gene polymorphism functions in regulation of serum lipid levels, 28 and it is mainly associated with some serum lipid parameters in the Han population. 29 It is also reported that PCSK9 E670G polymorphism is linked to CAD risk under different genetic models.…”

PCSK9 and Cardiovascular Disease in Individuals with Moderately Decreased Kidney Function

“…Studies investigating whether PCSK9 concentrations are influenced by kidney function have mostly been small and revealed divergent results (8) (an overview is in Supplemental Table 1). The same holds true for PCSK9 concentrations and cardiovascular disease outcomes in patients with CKD (9 –13) (Supplemental Table 2); most of the few studies conducted were either small and/or observed only a small number of cardiovascular disease events, which limits their conclusiveness.…”