Department of Cardiology, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
Clinical Chemistry, Ospedale "Maggiore della Carità", Eastern Piedmont University, Novara, Italy.
Thromb Res. 2017 Feb;150:90-95. doi: 10.1016/j.thromres.2016.12.019. Epub 2016 Dec 28.
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.
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).
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).
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.
他汀类药物是治疗冠状动脉疾病的主要方法，除了降低血脂外，它还具有降低心血管风险的作用。然而，他汀类药物的这些“多效性”益处的机制还不太清楚。维生素 D 被认为是他汀类药物抗炎、抗血栓和血管保护作用的潜在介质。本研究旨在评估高强度他汀类药物治疗对冠状动脉疾病患者维生素 D 水平和血小板功能的影响。
ACS 或择期 PCI 后接受双联抗血小板治疗和高强度他汀类药物治疗的患者，在出院后 30-90 天进行主要化学和维生素 D 水平评估。通过化学发光法通过 LIAISON®维生素 D 测定法（Diasorin Inc）进行维生素 D（25-OHD）剂量测定。通过 Multiplate®（多血小板功能分析仪；罗氏诊断公司）评估血小板功能。
在 246 名纳入的患者中，142 名患者接受了新的他汀类药物治疗或增加了先前的剂量（Inc-S），而 104 名患者在入院时已经接受了高剂量他汀类药物治疗且剂量不变（Eq-S）。中位随访时间为 75.5 天。Inc-S 组患者更年轻（p=0.01），吸烟者（p<0.001），更少有高胆固醇血症（p=0.05）、糖尿病（p=0.03）、高血压（p=0.02）或既往心血管事件史（p<0.001）。他们更常因急性冠状动脉综合征入院（p<0.001），且使用的抗高血压药物或硝酸盐较少。Inc-S 组患者的总循环钙水平较高（p=0.004），而两组的基线维生素 D 水平相似（p=0.30）。Inc-S 组患者的循环低密度脂蛋白（LDL）胆固醇显著降低。Inc-S 组患者的维生素 D 水平升高，但 Eq-S 组患者的维生素 D 水平没有升高（25-OHD 差值：23.2±20.5% vs 3.1±4.7%，p=0.003），维生素 D 升高幅度与 LDL 胆固醇降低幅度呈线性关系（r=-0.17，p=0.01）。Inc-S 患者的血小板反应性明显降低，当评估不同血小板激活刺激物（花生四烯酸、胶原、凝血酶激活肽、ADP）的聚集时（p=0.02、p=0.004、p=0.07、p=0.002）。
在冠状动脉疾病患者中，除了降脂作用外，添加高强度他汀类药物治疗还与维生素 D 水平的显著升高和血小板反应性降低相关，这可能解释了他汀类药物治疗在心血管疾病中的“多效性”益处。
