Clinical & Experimental Endocrinology, Department Chronic Diseases, Metabolism and Ageing, KU Leuven, Herestraat 49 ON1 box 902, 3000, Leuven, Belgium.
Osteoporos Int. 2019 Nov;30(11):2167-2181. doi: 10.1007/s00198-019-05098-0. Epub 2019 Aug 11.
Vitamin D is necessary for bone health but may also have many extra-skeletal effects. The vitamin D endocrine system has major effects on gene and protein expression in many cells and tissues related to the cardiovascular system. In addition, many preclinical studies in animals with vitamin D deficiency or genetically silenced expression of the vitamin D receptor or vitamin D metabolizing enzymes suggest that the absence of vitamin D action may result in cardiovascular events. This includes dysfunctions of endothelial cells, thereby accelerating the process of atherosclerosis, hypertension or abnormal coagulation, ultimately resulting in higher risks for all major cardiovascular or cerebrovascular events. A wealth of observational studies in different parts of the world have fairly consistently found a strong association between a poor vitamin D status and surrogate markers or hard cardiovascular events. A few Mendelian randomization studies did, however, not find a link between genetically lower serum 25OHD concentrations and cardiovascular events. Finally, many RCTs could not demonstrate a consistent effect on surrogate markers, and a limited number of RCTs did so far not find whatever effect on hard cardiovascular endpoints such as myocardial ischemia or infarction, stroke, or cardiovascular death. In conclusion, preclinical data generated a plausible hypothesis of a link between vitamin D status and extra-skeletal events, including cardiovascular endpoints. Whether the vitamin D endocrine system is redundant for the human vascular system or whether the RCTs have not been optimally designed to answer the research question is thus not yet settled.
维生素 D 对骨骼健康是必需的，但它也可能对许多骨骼外的器官有影响。维生素 D 内分泌系统对与心血管系统相关的许多细胞和组织中的基因和蛋白质表达有重要影响。此外，许多维生素 D 缺乏或维生素 D 受体或维生素 D 代谢酶基因沉默的动物的临床前研究表明，缺乏维生素 D 作用可能导致心血管事件。这包括内皮细胞功能障碍，从而加速动脉粥样硬化、高血压或异常凝血的进程，最终导致所有主要心血管或脑血管事件的风险更高。世界各地大量的观察性研究相当一致地发现，维生素 D 状态不良与替代标志物或严重心血管事件之间存在很强的关联。然而，少数孟德尔随机研究并未发现血清 25（OH）D 浓度与心血管事件之间存在遗传相关性。最后，许多 RCT 未能证明对替代标志物有一致的影响，而且到目前为止，有限数量的 RCT 也没有发现对心肌缺血或梗死、中风或心血管死亡等严重心血管终点有任何影响。总之，临床前数据产生了一个合理的假设，即维生素 D 状态与骨骼外事件（包括心血管终点）之间存在关联。维生素 D 内分泌系统对人类血管系统是否是多余的，或者 RCT 是否没有被优化设计来回答研究问题，目前尚未确定。
