背景:骨关节炎(OA)是一种导致活动受限和疼痛的慢性退行性关节病,没有治愈性治疗。最近的体内研究表明,患者在OA进展过程中自主神经发生改变,然而,临床证据很少。因此,通过心率变异性(HRV)测量分析OA患者的自主神经张力。
方法:时域(SDRR,RMSSD,pRR50)和频域(LF,HF,确定LF/HF)HRV指数以量化交感神经和副交感神经活动。此外,感知压力,WOMAC疼痛以及血清儿茶酚胺,皮质醇和硫酸脱氢表雄酮(DHEA-S)进行分析。通过线性回归分析评估疾病分级(GoD)的影响,并与临床数据进行相关性分析。
结果:GoD显著影响OA患者的自主神经张力。所有时域参数反映早期OA患者的HRV略有下降,晚期OA患者的HRV明显降低。此外,频域分析显示所有OA患者的HF和LF功率降低,反映副交感神经和交感神经活动减少。然而,与晚期OA患者相比,早期OA患者的LF/HF比率显着升高,并暗示了明显的交感神经优势。此外,与健康对照相比,OA患者感觉到显著更高的慢性应激和WOMAC疼痛水平。血清皮质醇和皮质醇/DHEA-S比值随GoD显著升高,与WOMAC疼痛呈正相关。相比之下,血清儿茶酚胺仅随着GoD和疼痛水平而增加。
结论:这项前瞻性研究首次基于HRV分析,并通过血清应激激素测量进一步证实了早期和晚期膝关节OA患者自主神经功能障碍和间接交感神经优势。OA及其主要合并症中交感神经活动的增加和慢性低度炎症相互加强,因此可能会造成恶性循环。观察到的自主神经改变以及增加的压力和疼痛水平突出了HRV作为预后标志物的潜力。此外,自主活动的调节代表了一种有吸引力的未来治疗选择。
BACKGROUND: Osteoarthritis (OA) is a chronic degenerative joint disease causing limited mobility and pain, with no curative treatment available. Recent in vivo studies suggested autonomic alterations during OA progression in patients, yet clinical evidence is scarce. Therefore, autonomic tone was analyzed in OA patients via heart rate variability (HRV) measurements.
METHODS: Time-domain (SDRR, RMSSD, pRR50) and frequency-domain (LF, HF, LF/HF) HRV indices were determined to quantify sympathetic and parasympathetic activities. In addition, perceived stress, WOMAC pain as well as serum catecholamines, cortisol and dehydroepiandrosterone-sulphate (DHEA-S) were analyzed. The impact of the grade of disease (GoD) was evaluated by linear regression analysis and correlations with clinical data were performed.
RESULTS: GoD significantly impacted the autonomic tone in OA patients. All time-domain parameters reflected slightly decreased HRV in early OA patients and significantly reduced HRV in late OA patients. Moreover, frequency-domain analysis revealed decreased HF and LF power in all OA patients, reflecting diminished parasympathetic and sympathetic activities. However, LF/HF ratio was significantly higher in early OA patients compared to late OA patients and implied a clear sympathetic dominance. Furthermore, OA patients perceived significantly higher chronic stress and WOMAC pain levels compared to healthy controls. Serum cortisol and cortisol/DHEA-S ratio significantly increased with GoD and positively correlated with WOMAC pain. In contrast, serum catecholamines only trended to increase with GoD and pain level.
CONCLUSIONS: This prospective study provides compelling evidence of an autonomic dysfunction with indirect sympathetic dominance in early and late knee OA patients for the first time based on HRV analyses and further confirmed by serum stress hormone measurements. Increased sympathetic activity and chronic low-grade inflammation in OA as well as in its major comorbidities reinforce each other and might therefore create a vicious cycle. The observed autonomic alterations coupled with increased stress and pain levels highlight the potential of HRV as a prognostic marker. In addition, modulation of autonomic activity represents an attractive future therapeutic option.