In patients with primary hypercholesterolemia, short-term treatment with simvastatin improved the lipid profile and also exerted a beneficial effect on a wide range of proatherogenic and prothrombotic parameters, according to study results published in BioMed Research International.

Statin drugs have been shown to confer a platelet antiaggregating effect, but it remains unclear whether it is mediated by statin effects on low-density lipoprotein (LDL) cholesterol, inflammation, or both, or statins act directly on platelets. In this study, researchers examined the correlation between platelet inhibition with simvastatin and simvastatin’s effects on lipid levels, inflammation, oxidative stress, and endothelial and platelet activation.

The cohort included 45 patients with newly diagnosed primary hypercholesterolemia who were randomly assigned to treatment with diet plus simvastatin 40 mg for 2 months (n = 25) or diet alone (n = 20). Platelet aggregating responses to adenosine diphosphate, collagen, and arachidonic acid were evaluated, as well as the effect of aspirin on arachidonic acid-induced aggregation. Proinflammatory and proatherogenic mediators (interleukin [IL]-1β, IL-5, IL-6, IL-7, IL-8, IL-9, IL-12, IL-13, interferon-inducible protein, interferon-𝛾, eotaxin, and monocyte chemoattractant protein-1), anti-inflammatory and antiatherogenic markers (IL-10 and soluble receptor of advanced glycation end products), markers of endothelial activation (soluble E-selectin and vascular endothelial growth factor), platelet activation markers (soluble P-selectin, sCD-40L, RANTES, and platelet derived growth factor-BB), and oxidative stress markers (8-hydroxy-2′-deoxyguanosine) were measured.

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LDL cholesterol appeared to be the strongest predictor for most parameters of platelet reactivity. After 2 months of treatment with simvastatin, there was a reduction in platelet aggregation to adenosine diphosphate (22%, P <.0001), collagen (21%, P <.0001), and arachidonic acid (19%, P <.0001), as well a higher antiaggregating effect of aspirin in the presence of arachidonic acid (65%, P =.0001). In addition, circulating levels of IL-6 (P =.0034), IL-13 (P <.0001), interferon-𝛾 (P <.0001), vascular endothelial growth factor (P <.0001), soluble E-selectin (P <.0001), sCD-40L (P <.0001), soluble P-selectin (P =.003), and 8-hydroxy-2′-deoxyguanosine (P <.0001) were reduced. Significant increases in IL-10 (P <.0001) and soluble receptor of advanced glycation end products (P <.0001) were also observed.

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“Simvastatin therapy, beside its hypocholesterolemic effect, (i) decreases oxidative stress, proatherogenic, and proinflammatory markers, (ii) increases antiatherogenic and anti-inflammatory markers, (iii) reduces platelet aggregation to physiological agonists, and (iv) increases platelet sensitivity to the antiaggregating effects of aspirin.”

These results suggest a “primary role for LDL cholesterol in determining the cascade of inflammatory events responsible also for the impaired platelet function,” concluded the researchers.

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Barale C, Frascaroli C, Senkeev R, Cavalot F, Russo I. Simvastatin effects on inflammation and platelet activation markers in hypercholesterolemia. Biomed Res Int. 2018;2018:6508709.