痛风患者有动脉功能障碍和全身炎症,即使在关键事件中,这可能是未来不良心血管结局的标志。我们进行了一项前瞻性观察性研究,以评估秋水仙碱和降尿酸黄嘌呤氧化酶抑制剂(XOI)的指南一致痛风治疗是否可以改善动脉功能并减轻炎症。
38名未经治疗的痛风患者符合美国风湿病学会(ACR)/欧洲抗风湿病联盟对痛风的分类标准和ACR指南开始降尿酸治疗(ULT),接受秋水仙碱(0.6mg,每日两次,或每天一次耐受)和XOI(别嘌呤醇或非布索坦)滴定至ACR指南定义的血清尿酸(sU)目标。在临界期开始治疗。秋水仙碱和XOI的起始是交错的,以允许评估秋水仙碱的潜在独立作用。肱动脉血流介导的扩张(FMD)和硝酸盐介导的扩张(NMD)评估了内皮依赖性和非内皮依赖性(平滑肌)动脉反应性,分别。高敏C反应蛋白(hsCRP),IL-1β,IL-6,髓过氧化物酶(MPO)浓度,和红细胞沉降率(ESR)评估全身炎症。
在秋水仙碱加XOI上达到目标sU浓度四周后,口蹄疫明显改善(增加58%,p=0.03)。hsCRP,ESR,IL-1β,和IL-6也都显著改善(30%,27%,19.5%,分别下降18.8%;所有p≤0.03)。在添加XOI之前,单独用秋水仙碱治疗导致口蹄疫的数值改善较小,hsCRP,和ESR(20.7%,8.9%,减少13%,分别;所有非显著),但不是IL-1β或IL-6。MPO和NMD没有随着治疗而改变。我们观察到hsCRP浓度与FMD反应性之间存在中度负相关(R=-0.41,p=0.01)。亚组分析表明,在没有心血管危险因素和合并症但没有确定的患者中,在达到目标sU浓度后,FMD有所改善。特别是高血压和高脂血症。
开始指南一致的痛风治疗可减少关键的全身性炎症并改善内皮依赖性动脉功能,特别是在没有心血管合并症的患者中。
Patients with gout have arterial dysfunction and systemic inflammation, even during intercritical episodes, which may be markers of future adverse cardiovascular outcomes. We conducted a prospective observational study to assess whether initiating
guideline-concordant gout therapy with colchicine and a urate-lowering xanthine oxidase inhibitor (XOI) improves arterial function and reduces inflammation.
Thirty-eight untreated gout patients meeting American College of Rheumatology (ACR)/European League Against Rheumatism classification criteria for gout and ACR
guidelines for initiating urate-lowering therapy (ULT) received colchicine (0.6 mg twice daily, or once daily for tolerance) and an XOI (
allopurinol or febuxostat) titrated to ACR
guideline-defined serum urate (sU) target. Treatment was begun during intercritical periods. The initiation of colchicine and XOI was staggered to permit assessment of a potential independent effect of colchicine. Brachial artery flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) assessed endothelium-dependent and endothelium-independent (smooth muscle) arterial responsiveness, respectively. High-sensitivity C-reactive protein (hsCRP), IL-1β, IL-6, myeloperoxidase (MPO) concentrations, and erythrocyte sedimentation rate (ESR) assessed systemic inflammation.
Four weeks after achieving target sU concentration on colchicine plus an XOI, FMD was significantly improved (58% increase, p = 0.03). hsCRP, ESR, IL-1β, and IL-6 also all significantly improved (30%, 27%, 19.5%, and 18.8% decrease respectively; all p ≤ 0.03). Prior to addition of XOI, treatment with colchicine alone resulted in smaller numerical improvements in FMD, hsCRP, and ESR (20.7%, 8.9%, 13% reductions, respectively; all non-significant), but not IL-1β or IL-6. MPO and NMD did not change with therapy. We observed a moderate inverse correlation between hsCRP concentration and FMD responsiveness (R = - 0.41, p = 0.01). Subgroup analyses demonstrated improvement in FMD after achieving target sU concentration in patients without but not with established cardiovascular risk factors and comorbidities, particularly hypertension and hyperlipidemia.
Initiating
guideline-concordant gout treatment reduces intercritical systemic inflammation and improves endothelial-dependent arterial function, particularly in patients without established cardiovascular comorbidities.