PCSK9 Plasma Concentrations Are Independent of GFR and Do Not Predict Cardiovascular Events in Patients with Decreased GFR

Abstract

BackgroundImpaired renal function causes dyslipidemia that contributes to elevated cardiovascular risk in patients with chronic kidney disease (CKD). The proprotein convertase subtilisin/kexin type 9 (PCSK9) is a regulator of the LDL receptor and plasma cholesterol concentrations. Its relationship to kidney function and cardiovascular events in patients with reduced glomerular filtration rate (GFR) has not been explored.MethodsLipid parameters including PCSK9 were measured in two independent cohorts. CARE FOR HOMe (Cardiovascular and Renal Outcome in CKD 2–4 Patients—The Forth Homburg evaluation) enrolled 443 patients with reduced GFR (between 90 and 15 ml/min/1.73 m2) referred for nephrological care that were prospectively followed for the occurrence of a composite cardiovascular endpoint. As a replication cohort, PCSK9 was quantitated in 1450 patients with GFR between 90 and 15 ml/min/1.73 m2 enrolled in the Ludwigshafen Risk and Cardiovascular Health Study (LURIC) that were prospectively followed for cardiovascular deaths.ResultsPCSK9 concentrations did not correlate with baseline GFR (CARE FOR HOMe: r = -0.034; p = 0.479; LURIC: r = -0.017; p = 0.512). 91 patients in CARE FOR HOMe and 335 patients in LURIC reached an endpoint during a median follow-up of 3.0 [1.8–4.1] years and 10.0 [7.3–10.6] years, respectively. Kaplan-Meier analyses showed that PCSK9 concentrations did not predict cardiovascular events in either cohort [CARE FOR HOMe (p = 0.622); LURIC (p = 0.729)]. Sensitivity analyses according to statin intake yielded similar results.ConclusionIn two well characterized independent cohort studies, PCSK9 plasma levels did not correlate with kidney function. Furthermore, PCSK9 plasma concentrations were not associated with cardiovascular events in patients with reduced renal function.

Disorders of Lipid Metabolism in Chronic Kidney Disease

“…In contrast, Rogacev et al [47] found no correlation between eGFR and PCSK9 levels in CKD patients. Furthermore, PCSK9 concentrations did not predict new CVD events in this study [47]. Lastly, PCSK9 levels are positively correlated with proteinuria in patients with nephrotic syndrome [48].…”

“…PCSK9 levels were found to be almost 2 times higher in CKD patients compared with subjects with normal kidney function [46]. In contrast, Rogacev et al [47] found no correlation between eGFR and PCSK9 levels in CKD patients. Furthermore, PCSK9 concentrations did not predict new CVD events in this study [47].…”

Circulating Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Concentration and Risk of Cardiovascular Events ― Systematic Review and Meta-Analysis of Prospective Studies ―

“…Study sample size ranged from 443 to 4,232 (total, 10,068). Of the 6 cohort studies, 1 study was conducted in patients with chronic kidney disease, 25 1 among community-based adults, 24 3 in CAD patients, and 1 in male fire- Age, smoking, and HRT.…”

Relationship between Plasma Proprotein Convertase Subtilisin/Kexin Type 9 and Estimated Glomerular Filtration Rate in the General Chinese Population

“…Unfortunately, they found that plasma PCSK9 levels did not vary significantly between different CKD stages and that PCSK9 levels were not associated with eGFR. Another study conducted by Rogacev et al [15] in 729 patients who received statins showed that no correlation between eGFR and PCSK9 levels existed. Based on the disparity of studies, it is necessary to further examine the relationship between PCSK9 and kidney function at different stages in different populations.…”

“…However, the results remained inconsistent. Several studies revealed that plasma PCSK9 levels are influenced by kidney function in severe kidney disease [10][11][12][13], whereas other research found that plasma PCSK9 levels are not associated with kidney function [14,15]. Indeed, this disparity regarding the relationship of PCSK9 with kidney dysfunction in different studies might be due to confounders, including the different state of kidney injury.…”