Relation of High Lipoprotein (a) Concentrations to Platelet Reactivity in Individuals with and Without Coronary Artery Disease

Abstract

Introduction Lipoprotein ( a ) [Lp( a )] is a risk factor for coronary artery disease (CAD). To the best of our knowledge, this is the first study addressing the relationship between Lp( a ) and platelet reactivity in primary and secondary prevention. Methods Lp( a ) was evaluated in 396 individuals with (82.3%) and without (17.7%) obstructive CAD. The population was divided into two groups according to Lp( a ) concentrations with a cutoff value of 50 mg/dL. The primary objective was to evaluate the association between Lp( a ) and adenosine diphosphate (ADP)-induced platelet reactivity using the VerifyNow™ P2Y 12 assay. Platelet reactivity was also induced by arachidonic acid and collagen–epinephrine (C-EPI) and assessed by Multiplate™, platelet function analyzer™ 100 (PFA-100), and light transmission aggregometry (LTA) assays. Secondary objectives included the assessment of the primary endpoint in individuals with or without CAD. Results Overall, 294 (74.2%) individuals had Lp( a ) < 50 mg/dL [median (IQR) 13.2 (5.8–27.9) mg/dL] and 102 (25.8%) had Lp( a ) ≥ 50 mg/dL [82.5 (67.6–114.5) mg/dL], P < 0.001. Univariate analysis in the entire population revealed no differences in ADP-induced platelet reactivity between individuals with Lp( a ) ≥ 50 mg/dL (249.4 ± 43.8 PRU) versus Lp( a ) < 50 mg/dL (243.1 ± 52.2 PRU), P = 0.277. Similar findings were present in individuals with ( P = 0.228) and without ( P = 0.669) CAD, and regardless of the agonist used or method of analysis (all P > 0.05). Finally, multivariable analysis did not show a significant association between ADP-induced platelet reactivity and Lp( a ) ≥ 50 mg/dL [adjusted OR = 1.00 [(95% CI 0.99–1.01), P = 0.590]. Conclusion In individuals with or without CAD, Lp( a ) ≥ 50 mg/dL was not associated with higher platelet reactivity. Electronic supplementary material The online version of this article (10.1007/s12325-020-01483-y) contains supplementary material, which is available to authorized users.

Independent association of Lp(a) with platelet reactivity in subjects without statins or antiplatelet agents

“…This result is supported by findings that elevated Lp(a) concentrations did not lead to altered ADP-induced platelet aggregation in vitro studies 27 , 37 . Similar to our findings, Salsoso et al found that in patients with and without aspirin and statin therapy, serum Lp(a) levels was not associated with ADP-induced platelet aggregation 38 . But the opposite results showed that higher serum Lp(a) levels had higher ADP-induced platelet aggregation in patients with dual antiplatelet therapy 11 .…”

Association of lipoprotein(a) with intrinsic and on-clopidogrel platelet reactivity

“…Similar results were seen in a recently published small in-vivo study that did not find any difference between intrinsic platelet reactivity in patients with levels of Lp(a) < 50 mg/dl versus ≥ 50 mg/dl [ 28 ]. These findings are in contrast to the results of in-vitro studies showing multiple different pathways of interaction between Lp(a) and platelets (Fig.…”

“…These findings may have implications in the mechanism of any potential benefit in an ongoing trial testing the "Lp(a) hypothesis" with Lp(a) lowering by an antisense oligonucleotide (ClinicalTrials.gov Identifier: NCT04023552). Similar results were seen in a recently published small invivo study that did not find any difference between intrinsic platelet reactivity in patients with levels of Lp(a) < 50 mg/ dl versus ≥ 50 mg/dl [28]. These findings are in contrast to the results of in-vitro studies showing multiple different Fig.…”