Free Fatty Acids Link Residual Lipid and Thrombotic Risk via Impairment of Aspirin Antiplatelet Effects

Abstract

Background

Insufficient lipid-lowering therapy is associated with residual cardiovascular risk. Low-density lipoprotein (LDL) is well known to promote atherosclerosis and cardiovascular disease (CVD) and during lipoprotein metabolism, free fatty acids (FFA) are generated. Besides this, residual thrombotic risk occurs in patients with impaired pharmacodynamic response to aspirin—so-called high on-treatment platelet reactivity (HTPR). Until now, it is not known if there is a mutual link.

Methods

For in vitro analyses, blood from healthy donors was used and incubated with different concentrations of LDL, FFA, and acetylsalicylic acid. Arachidonic acid (AA)-induced light transmittance aggregometry (LTA), thromboxane (TX) formation, and cyclooxygenase (COX)-1 activity were measured. In a cross-sectional analysis, aspirin antiplatelet effects, and LDL and FFA concentrations were measured in 612 aspirin-treated CVD patients.

Results

In vitro administration of LDL and FFA impaired aspirin antiplatelet effects. In patients, FFA levels were associated with HTPR to aspirin. FFA levels and plasma LDL correlated with AA-induced platelet aggregation. Statin medication improved aspirin antiplatelet effects. AA-induced platelet aggregation was decreased in patients with statin medication.

Conclusion

In this study, we were able to demonstrate a link between residual lipid and thrombotic risk in patients with cardiovascular disease. We could show that LDL and FFA impair pharmacodynamic response to aspirin at the level of COX. Statin therapy improved aspirin antiplatelet effects.

Keywords

aggregation - aspirin - platelet activation - platelet inhibition - statins

• References

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