Department of Cardiovascular Science, Sheffield University, Medical School, Beech Hill Road, Sheffield S10 2RX, United Kingdom.
Atherosclerosis. 2012 Feb;220(2):310-8. doi: 10.1016/j.atherosclerosis.2011.09.002. Epub 2011 Sep 9.
Higher serum phosphate levels within the normal range are associated with substantially increased risk of cardiovascular disease events. Whether this reflects a causative relationship is unknown. Phosphate-responsive hormones (fibroblast growth factor-23, parathyroid hormone and calcitriol) are also predictors of cardiovascular mortality in populations without kidney disease or recognised disturbances of bone mineral metabolism. The high bioavailable phosphate content of Western diets may contribute to this apparent discrepancy between 'normal' and optimal phosphate axis parameters. Although uremic hyperphosphatemia is recognised to cause vascular medial calcification, this does not readily explain the association of higher-normal phosphate with common athero-occlusive phenomena. The phosphate axis may in fact play a role in atherogenesis; observational data link higher levels of phosphate and fibroblast growth factor-23 with coronary atheroma burden, whilst dietary phosphate supplementation accelerates atherosclerosis in a mouse model. In vitro studies show adverse effects of phosphate increases on both vascular smooth muscle cells and endothelium, though these observations have not yet been extended to phosphate increments within the normal range. Receptors for phosphate-responsive hormones are present throughout the cardiovascular system and may mediate atherogenic effects. Since interventions are already available to manipulate the phosphate axis, this is an important issue. If an atherogenic role for phosphate exposure is demonstrated then phosphate binders could become the new statins.
血清磷酸盐水平在正常范围内升高与心血管疾病事件的风险显著增加有关。目前尚不清楚这是否反映了因果关系。在没有肾脏疾病或已知骨矿物质代谢紊乱的人群中，磷酸盐反应激素（成纤维细胞生长因子 23、甲状旁腺激素和 1,25-二羟维生素 D3）也是心血管死亡率的预测因子。西方饮食中高生物可利用的磷酸盐含量可能导致“正常”和最佳磷酸盐轴参数之间出现这种明显差异。尽管尿毒症高磷血症可导致血管中层钙化，但这并不能很好地解释较高正常磷酸盐与常见动脉粥样硬化闭塞现象的关联。磷酸盐轴实际上可能在动脉粥样硬化形成中起作用；观察性数据表明，较高的磷酸盐和成纤维细胞生长因子 23 水平与冠状动脉粥样斑块负担有关，而饮食磷酸盐补充加速了小鼠模型中的动脉粥样硬化。体外研究表明，磷酸盐增加对血管平滑肌细胞和内皮均有不良影响，但这些观察结果尚未扩展到正常范围内的磷酸盐增加。磷酸盐反应激素的受体存在于整个心血管系统中，可能介导动脉粥样硬化形成的作用。由于已经有干预措施来操纵磷酸盐轴，因此这是一个重要问题。如果磷酸盐暴露具有动脉粥样硬化作用，那么磷酸盐结合剂可能成为新的他汀类药物。
