Bellomo, G.

Carriero, A.

Daffara, V.

De Luca, G.

Marino, P.

Pergolini, P.

Rolla, R.

Verdoia, M.

English

Rolla R.

Verdoia M.

DaffaraV.

Pergolini P.

MarinoP.

Carriero A.

De Luca G.

Bellomo G.

Archivio Istituzionale della Ricerca- Università del Piemonte Orientale

Association between high-residual platelet reactivity in patients receiving dual antiplatelet therapy, Vitamin D plasma levels and Vitamin D Binding Protein rs7041 polymorphism.Roberta Rolla1, Monica Verdoia2, Veronica Daffara2, Patrizia Pergolini1, Paolo Marino2; Alessandro Carriero3, Giuseppe De Luca2 on behalf of the Novara Atherosclerosis Study Group (NAS), Giorgio Bellomo11Clinical Chemistry, “Maggiore della Carità” Hospital, Eastern Piedmont University, Novara, Italy; 2Department of Cardiology, “Maggiore della Carità” Hospital, Eastern Piedmont University, Novara, Italy, 3Department of Radiology, “Maggiore della Carità” Hospital, Eastern Piedmont University, Novara, Italy Background. Ex-vivo platelet function evaluation investigates (a) platelet disfunction and (b) the efficacy of antiplatelet therapy. Optimal antithrombotic therapy is crucial for the management of acute coronary syndromes (ACS). An association between high residual platelet reactivity (HRPR) on dual antiplatelet therapy (DAPT) and increased risk of recurrent ischemic events and stent thrombosis has been previously shown. Among clinical conditions enhancing platelet reactivity are vitamin D deficiency and rs7041 genetic polymorphism in the Vitamin D  Binding Protein (VDBP), that accounts for a significant variability in vitamin D levels. Aim of this study was to investigate the role of vitamin D plasma levels and of rs7041 polymorphism on platelet reactivity in patients on DAPT.Methods. We measured platelet function by Multiplate® (Roche Diagnostics AG), and VDBP genetic status by polymerase chain reaction and restriction fragment length polymorphism technique in 400 patients treated with DAPT (ASA and clopidogrel or ticagrelor) for an ACS at 30-90 days post-discharge. Fasting samples were obtained for main chemistry parameters and vitamin D levels. Results. 187 patients received clopidogrel and 213 ticagrelor. The genetic polymorphism rs7041 (T/G) was observed in 318 patients, (79.5%), in 38.7% of them in homozygosis.  Main clinical and chemistry features did not significantly differ according to genetic status, but for a higher rate of ACE-inhibitors and beta-blockers use among the carriers of the G allele (p=0.04 and p=0.01, respectively). VDBP genetic status did not affect the rate of HRPR with ADP-antagonists. However, the rate of HRPR with ADP-antagonists was influenced by severe hypovitaminosis D (< 10 ng/ml) only in patients carrying the G allele, especially in homozygosis (T/T: 25.9% vs 26.1%, p=0.99; G carriers: 22.1% vs 35.3%, p=0.02, p interaction=0.019; adjusted OR[95%CI]=1.93[1.11-3.34],p=0.02 for G carriers).Conclusion. Platelet reactivity and the rate of HRPR among patients receiving DAPT rs741 was no affected by polymorphism of Vitamin D Binding Protein. The carriage of the G allele could condition the impact of hypovitaminosis D on the response to antiplatelet agents, by increasing the occurrence of HRPR especially in homozygotes. 1

Association between high-residual platelet reactivity in patients receiving dual antiplatelet therapy, Vitamin D plasma levels and Vitamin D Binding Protein rs7041 polymorphism.

https://iris.uniupo.it/bitstream/11579/94100/1/Vitamin%20D%20Binding%20Protein%20rs7041%20polymorphism_1st%20Italian-UK%20Platelet%20Meeting%20_2017.doc

Association between high-residual platelet reactivity in patients receiving dual antiplatelet therapy, Vitamin D plasma levels and Vitamin D Binding Protein rs7041 polymorphism.

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Archivio Istituzionale della Ricerca- Università del Piemonte Orientale