High levels of LDL-C combined with low levels of HDL-C further increase platelet activation in hypercholesterolemic patients

Abstract

High levels of low-density lipoprotein cholesterol (LDL-C) enhance platelet activation, whereas high levels of high-density lipoprotein cholesterol (HDL-C) exert a cardioprotective effect. However, the effects on platelet activation of high levels of LDL-C combined with low levels of HDL-C (HLC) have not yet been reported. We aimed to evaluate the platelet activation marker of HLC patients and investigate the antiplatelet effect of atorvastatin on this population. Forty-eight patients with high levels of LDL-C were enrolled. Among these, 23 had HLC and the other 25 had high levels of LDL-C combined with normal levels of HDL-C (HNC). A total of 35 normocholesterolemic (NOMC) volunteers were included as controls. Whole blood flow cytometry and platelet aggregation measurements were performed on all participants to detect the following platelet activation markers: CD62p (P-selectin), PAC-1 (GPIIb/IIIa), and maximal platelet aggregation (MPAG). A daily dose of 20 mg atorvastatin was administered to patients with high levels of LDL-C, and the above assessments were obtained at baseline and after 1 and 2 months of treatment. The expression of platelets CD62p and PAC-1 was increased in HNC patients compared to NOMC volunteers (P<0.01 and P<0.05). Furthermore, the surface expression of platelets CD62p and PAC-1 was greater among HLC patients than among HNC patients (P<0.01 and P<0.05). Although the expression of CD62p and PAC-1 decreased significantly after atorvastatin treatment, it remained higher in the HLC group than in the HNC group (P<0.05 and P=0.116). The reduction of HDL-C further increased platelet activation in patients with high levels of LDL-C. Platelet activation remained higher among HLC patients regardless of atorvastatin treatment.

Bilateral upper extremity severe ecchymosis in a patient on alirocumab, rivaroxaban, and clopidogrel therapy

“…[14,21] When LDLC is lowered in patients with normal high den-sity lipoprotein cholesterol (HDLC), there is a significant decrease in platelet activation. [22] Previous studies with atorvastatin 20 mg/day therapy revealed that it normalized platelet hyperfunction and significantly reduced GPIIb/IIIa response to ADP. [23] When atorvastatin 20 mg/day was given to patients with high LDLC and low HDLC vs. high LDLC and normal HDLC, platelet activation was not significantly decreased in the high LDLC and low HDLC versus high LDLC and normal HDLC group.…”

“…[23] When atorvastatin 20 mg/day was given to patients with high LDLC and low HDLC vs. high LDLC and normal HDLC, platelet activation was not significantly decreased in the high LDLC and low HDLC versus high LDLC and normal HDLC group. [22] Increased LDL cholesterol is associated with increased platelet aggregation. [22][23][24][25] Hypercholesterolemic patients have been shown to have high percentage of GPIIb/IIIaphosphatidylserine, and CD62p positive platelets, increased plasma viscosity, and high erythrocyte aggregation index compared to controls.…”

“…[22] Increased LDL cholesterol is associated with increased platelet aggregation. [22][23][24][25] Hypercholesterolemic patients have been shown to have high percentage of GPIIb/IIIaphosphatidylserine, and CD62p positive platelets, increased plasma viscosity, and high erythrocyte aggregation index compared to controls. [22][23][24] Furthermore, in hypercholesterolemic individuals, platelets generate oxidized-LDL which leads to more platelet aggregation.…”

“…[22][23][24][25] Hypercholesterolemic patients have been shown to have high percentage of GPIIb/IIIaphosphatidylserine, and CD62p positive platelets, increased plasma viscosity, and high erythrocyte aggregation index compared to controls. [22][23][24] Furthermore, in hypercholesterolemic individuals, platelets generate oxidized-LDL which leads to more platelet aggregation. [25] We cannot completely rule out the unlikely possibility of drug induced transient acquired hemophilia leading to the ecchymosis and bruising in the skin.…”

Pharmacological Effects of Atorvastatin in Platelet Function and Plaque Rupture

“…After atorvastatin treatment, the expression of CD62p and PAC-1 decreased significantly. The reduction of high-density lipoprotein (HDL) cholesterol and increased platelet activation is seen in patients with high levels of LDL cholesterol (Chan et al, 2015). High platelet reactivity during co-administration of clopidogrel and a CYP3A4-metabolized statin (i.e.…”