title: Impact of high-dose statins on vitamin D levels and platelet function in patients with coronary artery disease.
abstract: BACKGROUND
  Statins represent a pivotal treatment in coronary artery disease, offering a reduction in cardiovascular risk even beyond their lipid-lowering action. However, the mechanism of these "pleiotropic" benefits of statins is poorly understood. Vitamin D has been suggested as a potential mediator of the anti-inflammatory, anti-thrombotic and vascular protecting effects of statins. Aim of present study was to assess the impact of a high-intensity statin therapy on vitamin D levels and platelet function in patients with coronary artery disease.
  
  
  METHODS
  Patients discharged on dual antiplatelet therapy and high-intensity statins after an ACS or elective PCI were scheduled for main chemistry and vitamin D levels assessment at 30-90days post-discharge. Vitamin D (25-OHD) dosing was performed by chemiluminescence method through the LIAISON® Vitamin D assay (Diasorin Inc). Platelet function was assessed by Multiplate® (multiple platelet function analyser; Roche Diagnostics AG).
  
  
  RESULTS
  Among 246 patients included, 142 were discharged on a new statin therapy or with an increase in previous dose (Inc-S), while 104 were already receiving a high-dose statin at admission, that remained unchanged (Eq-S). Median follow-up was 75.5days. Patients in the Inc-S group were younger (p=0.01), smokers (p<0.001), with a less frequent history of hypercholesterolemia (p=0.05), diabetes (p=0.03), hypertension (p=0.02), or previous cardiovascular events (p<0.001). They were more often admitted for an acute coronary syndrome (p<0.001) and used less anti-hypertensive drugs or nitrates. Higher total circulating calcium was observed in the Inc-S group (p=0.004), while baseline vitamin D levels were similar in the 2 groups (p=0.30). A significant reduction in the circulating low-density lipoprotein (LDL) cholesterol was observed in the Inc-S group. Vitamin D levels increased in the Inc-S patients but not in the Eq-S group (delta-25OHD: 23.2±20.5% vs 3.1±4.7%, p=0.003), with a linear relationship between the magnitude of vitamin D elevation and the reduction of LDL cholesterol (r=-0.17, p=0.01). Platelet reactivity was significantly lower in the Inc-S patients, when evaluating aggregation with different platelet activating stimuli (arachidonic acid, p=0.02, collagen, p=0.004, thrombin-activating peptide, p=0.07, ADP, p=0.002).
  
  
  CONCLUSIONS
  In patients with coronary artery disease, the addition of a high-intensity statin treatment, besides the lipid-lowering effects, is associated to a significant increase in vitamin D levels and lower platelet reactivity, potentially providing explanation of the "pleiotropic" benefits of statins therapy in cardiovascular disease.
authors.affiliation: Department of Cardiology, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy. Electronic address: ve.monica@libero.it.
authors.forename: Monica
authors.initials: M
authors.lastname: Verdoia
authors.affiliation: Clinical Chemistry, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pergolini
authors.affiliation: Clinical Chemistry, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Rolla
authors.affiliation: Department of Cardiology, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy; Department of Internal Medicine, Spedali Civili Hospital, Brescia, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Nardin
authors.affiliation: Department of Cardiology, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: Alon
authors.initials: A
authors.lastname: Schaffer
authors.affiliation: Department of Cardiology, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy; Cardiologia, Ospedale S. Andrea, Vercelli, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Barbieri
authors.affiliation: Department of Cardiology, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Daffara
authors.affiliation: Department of Cardiology, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Marino
authors.affiliation: Clinical Chemistry, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bellomo
authors.affiliation: Department of Cardiology, UMC St Radboud, Nijmegen, The Netherlands.
authors.forename: Harry
authors.initials: H
authors.lastname: Suryapranata
authors.affiliation: Department of Cardiology, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy. Electronic address: giuseppe.deluca@maggioreosp.novara.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Luca
mesh_terms: D000368:Aged; D000069059:Atorvastatin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects* / Q000473:pathology; D003324:Coronary Artery Disease / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000068718:Rosuvastatin Calcium / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D014807:Vitamin D / Q000097:blood*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors; D014807:Vitamin D; D000068718:Rosuvastatin Calcium; D000069059:Atorvastatin; D019821:Simvastatin
keywords: Coronary artery disease; Platelet aggregation; Statins; Vitamin D