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STATIN TREATMENT AND PREVALENT CVD INFLUENCE THE ASSOCIATION BETWEEN PCSK9 AND INCIDENT CVD IN PATIENTS WITH MODERATELY DECREASED KIDNEY FUNCTION: RESULTS FROM THE GCKD STUDY
Abstract
Background and Aims
Dyslipidemia contributes to the pronounced interconnection between chronic kidney disease (CKD) and cardiovascular disease (CVD). Discovery of the role of proprotein convertase subtilisin/kexin type 9 (PCSK9) led to the development of PCSK9 inhibitors that effectively lower LDL-cholesterol concentrations. Few studies with contradicting results have investigated the association between PCSK9 serum concentrations and cardiovascular outcomes in CKD patients.
Methods
The German Chronic Kidney Disease (GCKD) study is an ongoing study with a median follow-up of 6.5 years that includes 5,217 Caucasian patients with eGFR of 30-60 mL/min/1.73 m2 or an eGFR>60 mL/min/1.73m² in presence of overt proteinuria. PCSK9 serum concentrations were determined in 5,138 participants and the association of PCSK9 with prevalent and incident CVD were assessed using logistic and Cox regression analyses.
Results
At baseline, 1,289 patients had already experienced a CVD event. Increasing quartiles of PCSK9 were significantly associated with increasing CVD risk in a model adjusted for major confounders (quartiles 3 and 4 with 36% and 51% higher odds). This association was consistent in non-statin users but not in statin users. During follow-up, 473 patients experienced 3-point-MACE. Patients in PCSK9 quartiles 2-4 had a 32%-47% higher risk compared to quartile 1 (p<0.05). Only in patients with baseline CVD, higher PCSK9 levels were significantly associated with 76%-79% increased risk in the upper three quartiles.
Conclusions
Higher baseline PCSK9 concentrations in patients with moderate CKD are associated with prevalent and incident CVD. This observation would argue for a pronounced lipid-lowering therapy especially in patients with prevalent CVD.