Low Levels of High-Density Lipoprotein Cholesterol Are Linked to Impaired Clopidogrel-Mediated Platelet Inhibition

Abstract

Low high-density lipoprotein cholesterol (HDL-C) levels are an independent predictor of ischemic events in patients with atherosclerotic cardiovascular disease. This may in part be due to decreased clopidogrel-mediated platelet inhibition in patients with low HDL-C. We investigated the association of HDL-C with on-treatment platelet reactivity to adenosine diphosphate (ADP) in 314 patients on dual antiplatelet therapy with clopidogrel and aspirin undergoing angioplasty and stenting. Platelet P-selectin expression was assessed by flow cytometry, and platelet aggregation was determined by the VerifyNow P2Y assay and the Impact-R. High-density lipoprotein cholesterol levels were inversely associated with P-selectin expression and the VerifyNow P2Y assay (both P ≤ .01). Moreover, we found a positive correlation of HDL-C with surface coverage by the Impact-R ( P = .003). Patients with low HDL-C (≤35 mg/dL) exhibited a significantly higher P-selectin expression in response to ADP and higher platelet aggregation by the VerifyNow P2Y assay and the Impact-R than patients with normal HDL-C (>35 mg/dL; all P < .05). High on-treatment residual platelet reactivity by the VerifyNow P2Y assay occurred significantly more frequently in patients with low HDL-C levels than in those with normal HDL-C (47.4% vs 30.1%, P = .01). In conclusion, low HDL-C is linked to impaired clopidogrel-mediated platelet inhibition after angioplasty and stenting.

CYP2C19 polymorphisms and lipoproteins associated with clopidogrel resistance in children with Kawasaki disease in China: A prospective study

“…In the present study it was found that HDL was a protective factor for the occurrence of CR in children with KD. Our finding was in line with a previous study of Wadowski et al suggesting that low HDL levels were linked to impaired clopidogrel-mediated platelet inhibition after angioplasty ( 35 ). Similarly, another study found that low HDL levels were associated with CR in CAD patients ( 36 ).…”

Low HDL Cholesterol Is Associated with Reduced Bleeding Risk in Patients Who Underwent PCI: Findings from the PRACTICE Study

“…29 Furthermore, a previous study also suggested that in patients with low HDL-C levels, patients' platelet reactivity was enhanced. 30 Interestingly, Wadowski et al 15 found a significant association of continuous HDL-C levels with residual ADP-inducible platelet activation and aggregation. After adjusting for confounders, low HDL-C remained independently linked to increased platelet aggregation.…”

“…Furthermore, a previous study also suggested that in patients with low HDL-C levels patients platelet reactivity was enhanced [32]. Interestingly, Wadowski et al [15] found a significant association of This article is protected by copyright. All rights reserved.…”

“…However, multivariate Cox regression analysis showed that the HDL-C level was not an independent risk factor for 2-year bleeding events. In addition, Wadow-ski et al 15 reported that low HDL-C is linked to impaired clopidogrel-mediated platelet inhibition after angioplasty and stenting. Although evidence linking cholesterol metabolism and platelet responsiveness and bleeding events was reported previously, the relationship between HDL-C and bleeding events remains unclear.…”

Predictors of Clopidogrel Hyper-Responsiveness in Neuro-Interventional Procedures

“…A few reports have observed an association between the LDL-C concentration and clopidogrel; all of these studies showed that the LDL-C concentration did not affect the pharmacological effect of clopidogrel. 6,33 Wadowski et al 33 showed that a low HDL concentration increased PRU values, indicating that it is a predictor of hypo-responsiveness to clopidogrel, whereas no relationship was detected between PRU values and LDL-C/TG concentrations. Several studies have shown that a higher LDL-C concentration elevates platelet activity 34 and causes aspirin resistance.…”