Supplementation with Octacosanol Affects the Level of PCSK9 and Restore Its Physiologic Relation with LDL-C in Patients on Chronic Statin Therapy

Abstract

Dietary supplementation with sugar cane derivates may modulate low-density lipoprotein cholesterol (LDL-C) and proprotein convertase subtilisin/kexin type 9 (PCSK9) levels. The purpose of this study was to determine if dietary supplement (DS), containing Octacosanol (20 mg) and vitamin K2 (45 µg), could restore the disrupted physiologic relation between LDL-C and serum PCSK9. Double-blind, randomized, placebo-controlled, single-center study including 87 patients on chronic atorvastatin therapy was conducted. Eighty-seven patients were randomized to receive DS (n = 42) or placebo (n = 45), and followed for 13 weeks. Serum PCSK9 levels, lipid parameters and their relationship were the main efficacy endpoints. The absolute levels of PCSK9 and LDL-C were not significantly different from baseline to 13 weeks. However, physiologic correlation between % change of PCSK9 and % change of LDL-C levels was normalized only in the group of patients treated with DS (r = 0.409, p = 0.012). This study shows that DS can restore statin disrupted physiologic positive correlation between PCSK9 and LDL-C. Elevated PCSK9 level is an independent risk factor so controlling its rise by statins may be important in prevention of cardiovascular events.

Association of octacosanol supplementation with redox status in patients on chronic statin therapy

“…TG, triglycerides; ApoA1: Apolipoprotein A1; ApoB100: Apolipoprotein B100; PCSK9: Proprotein convertase subtilisin/kexin type 9; CRP: C-reactive protein; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CK, creatine phosphokinase; AOPP, advanced oxidation protein products; PAB, prooxidant antioxidant balance; SHG, sulphydryl groups; SOD, superoxide dismutase; TAS, total antioxidant status; TOS, total oxidant status; PON1, paraoxonase1. a Only variables with factor loadings | ≥ 0.5| are displayed and listed in order for simplicity and easy of interpretation b Non-responders' factors; Dyslipidemia-redox balance factor: TOS, TAS, PON1, PAB and PCSK9; Lipid risk-inflammation protein related factor: TG, CRP, SHG and ApoB100; Metabolic-related lipid protective factor: ALT, AST and ApoA1; Intervention-related metabolic antioxidant factor: SOD, glucose and octacosanol supplement c Responders' factors; Dyslipidemia-redox balance inflammation related factor: TOS, TAS, PAB, PCSK9 and CRP; Coronary risk intervention-related factor: Total CK activity, ALT, AST and octacosanol supplement; Lipid risk-protein related redox factor: AOPP, SHG and ApoB100; Metabolic-related antioxidant factor: ApoA1, Glucose and PON1 mentation on PCSK9 levels in patients on chronic statin therapy have been published in our previous report (32) and may be referred to for more detailed information not related to this article.…”

“…In our previously published study (32), we used the strategy of sub-dividing the participants into groups according to changes in lipid parameters that have already made the distinction of the participants into responders and non-responders. Thus, in this randomized double-blind, placebo-controlled study, we aimed to investigate the potential of standard biochemical analysis and parameters of redox status and antioxidant defense to predict the responsiveness to supplement usage of octacosanol in patients on chronic statin therapy.…”

“…All patients had a diagnosis of hypercholesterolemia or mixed dyslipidaemia with a minimum four-month using atorvastatin (20 mg/day) prior to study. The power calculation has been done before the study and was described in detail in our previous report (32). Patients with acute coronary syndrome (within the previous month), serious heart failure, renal dysfunction, liver disorders, cerebral vascular disease or mental illness were excluded from the study.…”

Effect of statins combined with PCSK9 inhibitors on the prognosis of patients with acute coronary syndromes after interventional therapy

“…As an effective treatment for patients with acute ACS, the use of PCI therapy can increase the rate of open blocked blood vessels, and improve myocardial reperfusion, but the operation is easy to cause platelet activation, and ischemia-reperfusion injury can induce platelet activation, and compound body/local inflammatory response (24). Once a sustained severe inflammatory reaction occurs, it will promote the necrosis of cardiomyocytes and cardiac remodeling, and then cause a series of adverse cardiovascular events, delay the prognosis of patients, increase the cost of treatment, and increase the psychological and economic burden of patients.…”