RESUMEN

BACKGROUND: Cardiovascular (CV) disease is the leading cause of mortality in patients with end-stage kidney disease (ESKD). The aim of the present study was to determine whether Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) could be an independent predictor of CV events and all-cause mortality in black African haemodialysis patients. METHODS: We carried out a prospective cohort study of all consecutive hemodialysis (HD) patients between August 2016 and July 2020, admitted in six hemodialysis centers of Kinshasa, Democratic Republic of Congo. Independent determinants of plasma PCSK-9 measured by ELISA were sought using multiple linear regression analysis. Kaplan-Meier's method described the incidence of CV events while competitive and proportional risk models looked for independent risk factors for death at the .05 significance level. RESULTS: Out of 207 HD patients, 91 (43.9%) died; 116 (56.1%) have survived. PCSK9 level was significantly higher in deceased patients compared to survivors: 28.0 (24.0-31.0) ng/l vs 9.6 (8.6-11.6) ng/ml (p <  0.001). Patients with plasma PCSK9 levels in tertile 3 had a higher incidence of CV events and mortality compared to patients with plasma PCSK9 levels in tertile 2 or tertile 1 (p <  0.001). Tertile 3 negatively influence survival rates (26.6%) compared to tertile 2 (54.7%) and tertile 1 (85.3%). Patients in tertile 3 and tertile 2 had a 4-fold higher risk of death than patients in tertile 1. After adjustment for all parameters, competitive risk analysis showed that mortality was 2 times higher in patients with stroke. Similarly, serum albumin < 3.5 g/dL or PCSK9 in tertile 3 were respectively associated with 2 or 6 times higher rates of deaths. CONCLUSION: Elevated plasma PCSK9 level is an independent major predictor of incident CV events and all-cause mortality in black African HD patients.

Asunto(s)

RESUMEN

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.