Increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity in rheumatoid arthritis.
Increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity in rheumatoid arthritis.
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DOI：
10.1113/jp272944
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发表时间：
2017-02-01
期刊：
影响因子：
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通讯作者：
Fisher JP
中科院分区：
文献类型：
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作者：
Adlan AM;Paton JF;Lip GY;Kitas GD;Fisher JP
风湿性关节炎（RA）是一种慢性炎症性疾病，与心血管死亡风险增加有关。交感神经活动增加和心脏压力反射敏感性降低增加心血管风险，尽管这种自主神经功能障碍是否存在于RA中尚不清楚。在本研究中，我们观察到增加交感神经活动和降低心脏压力反射敏感性RA患者相比，匹配的对照。疼痛与交感神经活性呈正相关，与心脏压力反射敏感性呈负相关。我们描述的自主神经功能障碍的模式可能有助于解释RA心血管风险增加，并提出了优化疼痛管理可能解决RA自主神经功能障碍的可能性。风湿性关节炎（RA）是一种慢性炎症性疾病，与心血管发病率/死亡率增加和不完全理解的病理生理学相关。在动物研究中，中枢和血液传播的炎性细胞因子，可以在RA中升高，引起交感神经活动的致病性增加和压力反射敏感性（BRS）的降低。我们假设RA患者的肌肉交感神经活动（MSNA）增加，BRS减少。在年龄和性别匹配的RA-血压正常（n = 13）、RA-高血压患者（RA-HTN; n = 17）、血压正常（NC; n = 17）和高血压对照（HTN; n = 16）中记录MSNA、血压和心率（HR）。使用改良的Oxford技术测定BRS。分别使用血清高敏C反应蛋白（hs-CRP）和视觉模拟量表（VAS）确定炎症和疼痛。RA、RA‐HTN和HTN患者的MSNA升高相似（32 ± 9、35 ± 14、37 ± 8次爆发min-1），与NC（22 ± 9次爆发min-1; P = 0.004）相比。两组间交感神经BRS相似（P = 0.927），而RA、RA‐HTN和HTN患者的心脏BRS（cBRS）[5（3-8）、4（2-7）、6（4-9）ms mmHg-1]与NC [11（8-15）ms mmHg-1; P = 0.002]相比降低。HR与hs-CRP独立相关。MSNA升高和cBRS降低与hs-CRP相关，尽管在多变量分析中存在混淆。VAS与MSNA爆发频率、cBRS和HR独立相关。我们首次提供了RA交感神经流出增加和cBRS减少与高血压无关的证据。在RA患者中，报告的疼痛与MSNA呈正相关，与cBRS呈负相关。未来的研究应评估是否治疗，以减轻疼痛和炎症的RA恢复自主神经平衡，减少心血管事件。风湿性关节炎（RA）是一种慢性炎症性疾病，与心血管死亡风险增加有关。交感神经活动增加和心脏压力反射敏感性降低增加心血管风险，尽管这种自主神经功能障碍是否存在于RA中尚不清楚。在本研究中，我们观察到增加交感神经活动和降低心脏压力反射敏感性RA患者相比，匹配的对照。疼痛与交感神经活性呈正相关，与心脏压力反射敏感性呈负相关。我们描述的自主神经功能障碍的模式可能有助于解释RA心血管风险增加，并提出了优化疼痛管理可能解决RA自主神经功能障碍的可能性。
Rheumatoid arthritis (RA) is a chronic inflammatory condition associated with an increased risk of cardiovascular mortality. Increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity heighten cardiovascular risk, althogh whether such autonomic dysfunction is present in RA is not known. In the present study, we observed an increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity in patients with RA compared to matched controls. Pain was positively correlated with sympathetic nerve activity and negatively correlated with cardiac baroreflex sensitivity. The pattern of autonomic dysfunction that we describe may help to explain the increased cardiovascular risk in RA, and raises the possibility that optimizing pain management may resolve autonomic dysfunction in RA. Rheumatoid arthritis (RA) is a chronic inflammatory condition associated with increased cardiovascular morbidity/mortality and an incompletely understood pathophysiology. In animal studies, central and blood borne inflammatory cytokines that can be elevated in RA evoke pathogenic increases in sympathetic activity and reductions in baroreflex sensitivity (BRS). We hypothesized that muscle sympathetic nerve activity (MSNA) was increased and BRS decreased in RA. MSNA, blood pressure and heart rate (HR) were recorded in age‐ and sex‐matched RA‐normotensive (n = 13), RA‐hypertensive patients (RA‐HTN; n = 17), normotensive (NC; n = 17) and hypertensive controls (HTN; n = 16). BRS was determined using the modified Oxford technique. Inflammation and pain were determined using serum high sensitivity C‐reactive protein (hs‐CRP) and a visual analogue scale (VAS), respectively. MSNA was elevated similarly in RA, RA‐HTN and HTN patients (32 ± 9, 35 ± 14, 37 ± 8 bursts min–1) compared to NC (22 ± 9 bursts min–1; P = 0.004). Sympathetic BRS was similar between groups (P = 0.927), whereas cardiac BRS (cBRS) was reduced in RA, RA‐HTN and HTN patients [5(3–8), 4 (2–7), 6 (4–9) ms mmHg–1] compared to NC [11 (8–15) ms mmHg–1; P = 0.002]. HR was independently associated with hs‐CRP. Increased MSNA and reduced cBRS were associated with hs‐CRP although confounded in multivariable analysis. VAS was independently associated with MSNA burst frequency, cBRS and HR. We provide the first evidence for heightened sympathetic outflow and reduced cBRS in RA that can be independent of hypertension. In RA patients, reported pain was positively correlated with MSNA and negatively correlated with cBRS. Future studies should assess whether therapies to ameliorate pain and inflammation in RA restores autonomic balance and reduces cardiovascular events. Rheumatoid arthritis (RA) is a chronic inflammatory condition associated with an increased risk of cardiovascular mortality. Increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity heighten cardiovascular risk, althogh whether such autonomic dysfunction is present in RA is not known. In the present study, we observed an increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity in patients with RA compared to matched controls. Pain was positively correlated with sympathetic nerve activity and negatively correlated with cardiac baroreflex sensitivity. The pattern of autonomic dysfunction that we describe may help to explain the increased cardiovascular risk in RA, and raises the possibility that optimizing pain management may resolve autonomic dysfunction in RA.