Vitamin D levels and platelet reactivity in diabetic patients receiving dual antiplatelet therapy.


Journal

Vascular pharmacology
ISSN: 1879-3649
Titre abrégé: Vascul Pharmacol
Pays: United States
ID NLM: 101130615

Informations de publication

Date de publication:
09 2019
Historique:
received: 20 01 2019
revised: 08 04 2019
accepted: 27 05 2019
pubmed: 10 6 2019
medline: 27 5 2020
entrez: 10 6 2019
Statut: ppublish

Résumé

Hypovitaminosis D represents an emerging cardiovascular risk factor, and especially among higher-risk subsets of patients, such as in those with diabetes mellitus. The anti-inflammatory and anti-thrombotic properties of vitamin D, in fact, could be even more beneficial among diabetics, where platelet hyperreactivity and suboptimal response to antiplatelet drugs has been associated with poorer outcomes. However, no study has so far evaluated the impact of vitamin D levels on platelet reactivity and high-on treatment platelet reactivity (HRPR) among diabetic patients receiving dial antiplatelet therapy (DAPT). Our population is represented by a consecutive cohort ofdiabetic patients treated with DAPT (ASA + clopidogrel or ticagrelor or dose-adjusted prasugrel) for an acute coronary syndrome or elective PCI, undergoing platelet reactivity assessment at 30-90 days post-discharge. Aggregation was assessed by multiple-electrode aggregometry. HRPR was defined for values above the lower limit of normality (in non-treated patients). We included 440 patients, that were divided according to quartiles values of vitamin D (< 9.4; 9.4-15.59; 15.6-21.64; ≥ 21.65 ng/ml). Among them, 31 were excluded as chronically treated with vitamin D supplementation. Lower vitamin D quartiles were associated with more advanced age (p = 0.01), female gender (p = 0.04), renal failure (p = 0.005), history of previous MI (p = 0.01), CABG and use of diuretics (p = 0.003), severe coronary disease (p = 0.002), but lower ejection fraction (p = 0.001), treatment with statins (p = 0.04) and new ADP-antagonists (p = 0.002). Vitamin D levels related with higher HbA1c (p = 0.001), cholesterol (p = 0.02) and creatinine (p = 0.004) and lower hemoglobin (p = 0.004). The prevalence of HRPR with ASA was low and not related to vitamin D quartiles (3.4% vs 2.7% vs 1.8% vs 2.1%, p = 0.44; adjusted OR[95%CI] = 1.16[0.60-2.26], p = 0.67). The prevalence of HRPR for ADP antagonists was associated to hypovitaminosis D (40.2% vs 29.1% vs 29.4% vs 25.5%, p = 0.03; (adjusted OR[95%CI] = 1.76[1.04-2.98], p = 0.036for I vs II-IV quartile). The impact of vitamin D quartiles, was significant only in patients on new ADP antagonists (n = 225, of whom 81 on prasugrel 5 mg; p = 0.03; adjusted OR[95%CI] = 3.12[1.34-7.49], p = 0.009) but not with clopidogrel (p = 0.85, adjusted OR[95%CI] = 1.05[0.49-2.24], p = 0.89). Among diabetic patients receiving dual antiplatelet therapy for an acute coronary syndrome or elective percutaneous coronary intervention, severe vitamin D deficiency is associated with a higher ADP-mediated platelet reactivity and rate of HRPR, and especially for new ADP-antagonists over clopidogrel.

Sections du résumé

BACKGROUND
Hypovitaminosis D represents an emerging cardiovascular risk factor, and especially among higher-risk subsets of patients, such as in those with diabetes mellitus. The anti-inflammatory and anti-thrombotic properties of vitamin D, in fact, could be even more beneficial among diabetics, where platelet hyperreactivity and suboptimal response to antiplatelet drugs has been associated with poorer outcomes. However, no study has so far evaluated the impact of vitamin D levels on platelet reactivity and high-on treatment platelet reactivity (HRPR) among diabetic patients receiving dial antiplatelet therapy (DAPT).
METHODS
Our population is represented by a consecutive cohort ofdiabetic patients treated with DAPT (ASA + clopidogrel or ticagrelor or dose-adjusted prasugrel) for an acute coronary syndrome or elective PCI, undergoing platelet reactivity assessment at 30-90 days post-discharge. Aggregation was assessed by multiple-electrode aggregometry. HRPR was defined for values above the lower limit of normality (in non-treated patients).
RESULTS
We included 440 patients, that were divided according to quartiles values of vitamin D (< 9.4; 9.4-15.59; 15.6-21.64; ≥ 21.65 ng/ml). Among them, 31 were excluded as chronically treated with vitamin D supplementation. Lower vitamin D quartiles were associated with more advanced age (p = 0.01), female gender (p = 0.04), renal failure (p = 0.005), history of previous MI (p = 0.01), CABG and use of diuretics (p = 0.003), severe coronary disease (p = 0.002), but lower ejection fraction (p = 0.001), treatment with statins (p = 0.04) and new ADP-antagonists (p = 0.002). Vitamin D levels related with higher HbA1c (p = 0.001), cholesterol (p = 0.02) and creatinine (p = 0.004) and lower hemoglobin (p = 0.004). The prevalence of HRPR with ASA was low and not related to vitamin D quartiles (3.4% vs 2.7% vs 1.8% vs 2.1%, p = 0.44; adjusted OR[95%CI] = 1.16[0.60-2.26], p = 0.67). The prevalence of HRPR for ADP antagonists was associated to hypovitaminosis D (40.2% vs 29.1% vs 29.4% vs 25.5%, p = 0.03; (adjusted OR[95%CI] = 1.76[1.04-2.98], p = 0.036for I vs II-IV quartile). The impact of vitamin D quartiles, was significant only in patients on new ADP antagonists (n = 225, of whom 81 on prasugrel 5 mg; p = 0.03; adjusted OR[95%CI] = 3.12[1.34-7.49], p = 0.009) but not with clopidogrel (p = 0.85, adjusted OR[95%CI] = 1.05[0.49-2.24], p = 0.89).
CONCLUSIONS
Among diabetic patients receiving dual antiplatelet therapy for an acute coronary syndrome or elective percutaneous coronary intervention, severe vitamin D deficiency is associated with a higher ADP-mediated platelet reactivity and rate of HRPR, and especially for new ADP-antagonists over clopidogrel.

Identifiants

pubmed: 31176855
pii: S1537-1891(19)30009-6
doi: 10.1016/j.vph.2019.106564
pii:
doi:

Substances chimiques

Biomarkers 0
Platelet Aggregation Inhibitors 0
Vitamin D 1406-16-2
Clopidogrel A74586SNO7
Prasugrel Hydrochloride G89JQ59I13
Ticagrelor GLH0314RVC
Aspirin R16CO5Y76E

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

106564

Informations de copyright

Copyright © 2019. Published by Elsevier Inc.

Auteurs

Monica Verdoia (M)

Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", EasternPiedmontUniversity, Novara, Italy; Cardiology, Ospedale degli Infermi, ASL Biella, Italy.

Patrizia Pergolini (P)

ClinicalChemistry, Azienda Ospedaliera-Universitaria "Maggiore della Carità", EasternPiedmontUniversity, Novara, Italy.

Matteo Nardin (M)

Internal Medicine, ASST Spedali Civili, University of Brescia, Brescia, Italy.

Roberta Rolla (R)

ClinicalChemistry, Azienda Ospedaliera-Universitaria "Maggiore della Carità", EasternPiedmontUniversity, Novara, Italy.

Federica Negro (F)

Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", EasternPiedmontUniversity, Novara, Italy.

Elvin Kedhi (E)

Department of Cardiology, ISALA Hospital, Zwolle, the Netherlands.

Harry Suryapranata (H)

Department of Cardiology, UMC St Radboud, Nijmegen, the Netherlands.

Marco Marcolongo (M)

Cardiology, Ospedale degli Infermi, ASL Biella, Italy; Internal Medicine, ASST Spedali Civili, University of Brescia, Brescia, Italy.

Alessandro Carriero (A)

Radiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", EasternPiedmontUniversity, Novara, Italy.

Giuseppe De Luca (G)

Division of Cardiology, Azienda Ospedaliera-Universitaria "Maggiore della Carità", EasternPiedmontUniversity, Novara, Italy. Electronic address: giuseppe.deluca@maggioreosp.novara.it.

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Classifications MeSH