Effect of Urate-Lowering Therapy on All-Cause and Cardiovascular Mortality in Hyperuricemic Patients without Gout: A Case-Matched Cohort Study

ObjectivesAn increased risk of mortality in patients with hyperuricemia has been reported. We examined (1) the risk of all-cause and cardiovascular disease (CVD) mortality in untreated hyperuricemic patients who did not receive urate-lowering therapy (ULT), and (2) the impact of ULT on mortality risk in patients with hyperuricemia.MethodsIn this retrospective case-matched cohort study during a mean follow-up of 6.4 years, 40,118 Taiwanese individuals aged ≥17 years who had never used ULT and who had never had gout were examined. The mortality rate was compared between 3,088 hyperuricemic patients who did not receive ULT and reference subjects (no hyperuricemia, no gout, no ULT) matched for age and sex (1:3 hyperuricemic patients/reference subjects), and between 1,024 hyperuricemic patients who received ULT and 1,024 hyperuricemic patients who did not receive ULT (matched 1:1 based on their propensity score and the index date of ULT prescription). Cox proportional hazard modeling was used to estimate the respective risk of all-cause and CVD (ICD-9 code 390–459) mortality.ResultsAfter adjustment, hyperuricemic patients who did not receive ULT had increased risks of all-cause (hazard ratio, 1.24; 95% confidence interval, 0.97–1.59) and CVD (2.13; 1.34–3.39) mortality relative to the matched reference subjects. Hyperuricemic patients treated with ULT had a lower risk of all-cause death (0.60; 0.41–0.88) relative to hyperuricemic patients who did not receive ULT.ConclusionUnder-treatment of hyperuricemia has serious negative consequences. Hyperuricemic patients who received ULT had potentially better survival than patients who did not.

研究目的
已有文献报道高尿酸血症（hyperuricemia）患者的死亡风险升高。本研究旨在：(1) 评估未接受降尿酸治疗（urate-lowering therapy, ULT）的高尿酸血症患者的全因死亡及心血管疾病（cardiovascular disease, CVD）死亡风险；(2) 分析降尿酸治疗对高尿酸血症患者死亡风险的影响。

研究方法
本研究为回顾性病例匹配队列研究，平均随访时长为6.4年，共纳入40118名年龄≥17岁、既往未使用过降尿酸治疗且无痛风病史的中国台湾地区居民。研究以1:3的比例按年龄与性别进行匹配，比较3088名未接受降尿酸治疗的高尿酸血症患者与匹配对照人群（无高尿酸血症、无痛风病史、未使用降尿酸治疗）的死亡率；同时基于倾向得分（propensity score）与降尿酸治疗处方索引日期，以1:1匹配1024名接受降尿酸治疗的高尿酸血症患者与1024名未接受降尿酸治疗的高尿酸血症患者，比较两组死亡率。采用Cox比例风险模型（Cox proportional hazard model）估算全因死亡及心血管疾病死亡（国际疾病分类第9版（ICD-9）编码390–459）的相对风险。

研究结果
校正混杂因素后，与匹配对照人群相比，未接受降尿酸治疗的高尿酸血症患者全因死亡风险升高（风险比（hazard ratio, HR）=1.24，95%置信区间（95% confidence interval, 95%CI）：0.97–1.59），心血管疾病死亡风险亦显著升高（HR=2.13，95%CI：1.34–3.39）。与未接受降尿酸治疗的高尿酸血症患者相比，接受降尿酸治疗的高尿酸血症患者全因死亡风险更低（HR=0.60，95%CI：0.41–0.88）。

研究结论
高尿酸血症治疗不足会带来严重不良临床结局。接受降尿酸治疗的高尿酸血症患者的生存预后优于未接受治疗者。