Nicoll R, Henein M
Department of Public Health and Clinical Medicine, Umeå University, Heart Centre, Umea, Sweden.
Department of Public Health and Clinical Medicine, Umeå University, Heart Centre, Umea, Sweden.
Int J Cardiol. 2017 Feb 1;228:11-22. doi: 10.1016/j.ijcard.2016.11.099. Epub 2016 Nov 9.
Arterial calcification is commonly seen in atherosclerosis, chronic kidney disease (CKD) and diabetes and has long been considered a natural progression of atherosclerosis. Yet it is a systemic condition, occurring in a wide and diverse range of disease states and no medical treatment for cardiovascular disease has yet found a way to regress it; on the contrary, lipid-lowering therapy may worsen its progression. Although numerous studies have found associations between calcification and biomarkers, none has yet found a unifying mechanism that explains the calcification found in atherosclerosis, CKD or diabetes and many of the biomarkers are equally associated with atheroma development and cardiovascular events. Furthermore, both presence and absence of coronary artery calcification appear predictive of plaque rupture and cardiovascular events, indicating that the association is not causal. This suggests that we are no further forward in understanding the true nature of arterial calcification or its pathogenesis, other than noting that it is 'multifactorial'. This is because most researchers view arterial calcification as a progressive pathological condition which must be treated. Instead, we hypothesise that calcification develops as an immune response to endothelial injury, such as shear stress or oxidative stress in diabetics, and is consequently part of the body's natural defences. This would explain why it has been found to be protective of plaque rupture and why it is unresponsive to lipid-lowering agents. We propose that instead of attempting to treat arterial calcification, we should instead be attempting to prevent or treat all causes of endothelial injury.
动脉钙化在动脉粥样硬化、慢性肾脏病（CKD）和糖尿病中很常见，长期以来一直被认为是动脉粥样硬化的自然进展。然而，它是一种全身性疾病，发生在广泛多样的疾病状态中，目前尚无针对心血管疾病的医学治疗方法能够使其消退；相反，降脂治疗可能会使其进展恶化。尽管众多研究已发现钙化与生物标志物之间存在关联，但尚未找到一种统一的机制来解释在动脉粥样硬化、CKD或糖尿病中发现的钙化现象，而且许多生物标志物与动脉粥样硬化发展和心血管事件同样相关。此外，冠状动脉钙化的存在与否似乎都能预测斑块破裂和心血管事件，这表明这种关联并非因果关系。这表明，除了注意到它是“多因素的”之外，我们在理解动脉钙化的真正本质或其发病机制方面并没有取得进一步进展。这是因为大多数研究人员将动脉钙化视为一种必须治疗的进行性病理状况。相反，我们假设钙化是作为对内皮损伤的免疫反应而发展的，比如糖尿病患者中的剪切应力或氧化应激，因此它是身体自然防御的一部分。这就解释了为什么它被发现对斑块破裂有保护作用，以及为什么它对降脂药物无反应。我们建议，与其试图治疗动脉钙化，不如尝试预防或治疗所有导致内皮损伤的原因。
