Monica Verdoia1, Patrizia Pergolini2, Roberta Rolla2, Matteo Nardin3, Alon Schaffer4, Lucia Barbieri5, Veronica Daffara4, Paolo Marino4, Giorgio Bellomo2, Harry Suryapranata6, Giuseppe De Luca7. 1. Department of Cardiology, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy. Electronic address: ve.monica@libero.it. 2. Clinical Chemistry, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy. 3. Department of Cardiology, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy; Department of Internal Medicine, Spedali Civili Hospital, Brescia, Italy. 4. Department of Cardiology, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy. 5. Department of Cardiology, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy; Cardiologia, Ospedale S. Andrea, Vercelli, Italy. 6. Department of Cardiology, UMC St Radboud, Nijmegen, The Netherlands. 7. Department of Cardiology, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy. Electronic address: giuseppe.deluca@maggioreosp.novara.it.
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.
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: Hussein M Ismail; Abeer S Algrafi; Osama Amoudi; Sameh Ahmed; Sultan S Al-Thagfan; Hassan Shora; Mohammed Aljohani; Mohammed Almutairi; Fahad Alharbi; Abdullah Alhejaili; Majed Alamri; Abdullah Muhawish; Ayat Abdallah Journal: Vasc Health Risk Manag Date: 2021-08-10
Authors: Ewelina A Dziedzic; Jakub S Gąsior; Izabela Sowińska; Marek Dąbrowski; Piotr Jankowski Journal: J Clin Med Date: 2022-01-28 Impact factor: 4.241
Authors: Georg Gelbenegger; Marek Postula; Ladislav Pecen; Sigrun Halvorsen; Maciej Lesiak; Christian Schoergenhofer; Bernd Jilma; Christian Hengstenberg; Jolanta M Siller-Matula Journal: BMC Med Date: 2019-11-04 Impact factor: 8.775