Through the looking glass of rheumatoid arthritis to study inflammation and high-density lipoprotein.
Through the looking glass of rheumatoid arthritis to study inflammation and high-density lipoprotein.
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透过类风湿性关节炎的镜子来研究炎症和高密度脂蛋白。
DOI：
10.1136/heartjnl-2016-310764
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Liao,KatherineP
中科院分区：
文献类型：
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作者：
Liao,KatherineP
类风湿性关节炎（RA）中骨骼和软组织的破坏是由于不受控制的全身炎症而发生的。虽然肿胀和变形的关节很容易看到，但这种炎症过程对心血管系统的影响却不太明显。心血管疾病（CVD）是类风湿性关节炎患者死亡的主要原因。类风湿关节炎中心血管疾病的死亡率大约是具有相同年龄、性别和心血管危险因素的普通人群的1.5倍。1 .过多的心血管风险归因于炎症；然而，将炎症与心血管事件联系起来的途径和机制尚不清楚。脂质，特别是低密度脂蛋白胆固醇（LDL-C），被认为是普通人群动脉粥样硬化和心血管疾病的因果途径的一部分。然而，在RA中，LDL-C与CV风险之间的既定关系发生了改变。正如预期的那样，RA患者LDL-C水平升高与心血管风险增加有关；然而，低LDL-C也与心血管风险增加有关。2类风湿性关节炎患者炎症减轻，被认为对心血管风险有益，但同时LDL-C升高，3提示心血管风险增加的相反作用。对类风湿性关节炎治疗的随机对照试验中的脂质进行的事后研究表明，LDL-C的升高发生在不同类别的类风湿性关节炎治疗中。综上所述，这些数据表明，在普通人群中观察到的LDL-C、炎症和CV风险增加之间的关系在RA中变得不耦合。总胆固醇（TC）也有类似的解偶联现象。有趣的是，在检查高密度脂蛋白（HDL-C）水平和RA的心血管风险时，这种偏离既定关系的情况并不明显。最近的研究强调，即使在调整HDL- c水平后，HDL功能也是心血管事件的独立预测因子。以胆固醇外排能力衡量的HDL功能在一般人群中被认为是稳定的。虽然高HDL-C水平与降低心血管风险的预期关系在RA中得以保留，但RA受试者的胆固醇外排能力受损。此外，炎症的减少与胆固醇外排能力的显著改善有关，3表明HDL功能障碍可能解释了RA中心血管风险过高的一些原因。研究HDL的功能是O’neill等人6在本刊中提出的研究重点。用类风湿性关节炎作为模型来研究炎症和脂质之间的关系是理想的，有几个原因。首先，类风湿性关节炎患者的绝对炎症水平高于一般人群。在这项研究中，RA患者的中位c反应蛋白（CRP）为22.7 mg/L，而健康对照组为1.0 mg/L。其次，由于类风湿性关节炎患者的炎症水平较高，他们也会通过对治疗的反应或在类风湿性关节炎发作期间经历更大的炎症水平波动。图1显示了RA诊断第一年个体CRP水平的一个说明性例子。与在RA发作期间通常观察到的CRP≥10mg/L的变化相比，在对照患者中显示的1.0 mg/L的波动（其值范围从1.0 mg/L到2.0 mg/L）几乎不明显。较大程度的炎症和变化提供了检测关联的能力，否则在一般人群中可能无法观察到。然而，我们知道炎症，即使在3-10mg /L的范围内，对普通人群的心血管风险有显著影响。从不同的角度审视RA的典型病程，RA耀斑和随后的治疗可以…
Destruction of bone and soft tissue in rheumatoid arthritis (RA) occurs as a result of unchecked systemic inflammation. While swollen and deformed joints are easy to see, less obvious to the naked eye is the impact of this same inflammatory process on the cardiovascular (CV) system. Cardiovascular disease (CVD) is the leading cause of death in patients with RA. The mortality rate from CVD in RA is approximately 1.5 times that of individuals from the general population with the same age, sex and CV risk factors. 1 The excess CV risk has been attributed to inflammation; however, the pathways and mechanisms linking inflammation to CV events are less clear. Lipids, specifically low-density lipoprotein cholesterol (LDL-C), are considered part of the causal pathway for atherosclerosis and CVD in the general population. However, the established relationships between LDL-C and CV risk are altered in RA. As expected, elevated levels of LDL-C are associated with increased CV risk in RA; however, low LDL-C is also associated with increased CV risk. 2 Subjects with RA who experience a reduction in inflammation, considered beneficial for CV risk, have concomitant increases in LDL-C, 3 suggesting the opposite effect of increased CV risk. Post hoc studies of lipids from randomised controlled trials of RA therapies have shown that increases in LDL-C occur across different classes of RA therapies. 4 Together, these data demonstrate that the relationship between LDL-C, inflammation and increased CV risk, observed in the general population, becomes uncoupled in RA. A similar uncoupling was observed with total cholesterol (TC). Interestingly, the departure from established relationships was not as apparent when examining high-density lipoprotein (HDL-C) levels and CV risk in RA. Recent studies have highlighted that HDL function is an independent predictor of incident CV events, even after adjusting for HDL-C levels. 5 This HDL function, as measured by cholesterol efflux capacity, is considered to be stable in the general population. While the expected relationship of higher HDL-C levels and reduced CV risk is preserved in RA, cholesterol efflux capacity is impaired in RA subjects. Furthermore, a reduction in inflammation is associated with significant improvements in cholesterol efflux capacity, 3 suggesting that HDL dysfunction may explain some of the excess CV risk in RA. Studying HDL function is a focus of the study presented by O’Neill et al 6 in this journal.Using RA as a model to study the relationship between inflammation and lipids is ideal for several reasons. First, subjects with RA have higher absolute levels of inflammation than the general population. In this study, the median C-reactive protein (CRP) was 22.7 mg/L in RA compared with 1.0 mg/L in healthy controls. Second, since individuals with RA have higher levels of inflammation, they also experience larger swings in levels of inflammation through response to therapy or during RA flares. An illustrative example of CRP levels for an individual in the first year of RA diagnosis is shown in figure 1. A fluctuation of 1.0 mg/L, with values ranging from 1.0 mg to 2.0 mg/L, shown in the control patient is barely noticeable compared with changes in CRP of≥ 10mg/L typically observed during an RA flare. The larger magnitude of inflammation and magnitude of change provide the power to detect associations that may not otherwise be observed in the general population. However, we know that inflammation, even in the range of 3–10mg/L, has a significant impact on CV risk in the general population. Examining the typical course of RA through a different lens, RA flares and subsequent treatment can …