Navaneethan Sankar D, Beddhu Srinivasan
Department of Nephrology and Hypertension, Cleveland Clinic, Cleveland, OH, USA.
Nephrol Dial Transplant. 2009 Apr;24(4):1260-6. doi: 10.1093/ndt/gfn621. Epub 2008 Nov 25.
It is unclear whether the presence of kidney disease modifies the associations of uric acid with cardiovascular events and death.
In the limited access, public use Atherosclerosis Risk In Communities (ARIC) database, associations of serum uric acid levels with cardiovascular events and death were analysed using a parametric proportional hazards model and the modification of these associations by the presence of CKD was assessed using a likelihood ratio test.
Of the 15 366 ARIC participants included in this analysis, 461 had CKD (eGFR <60 ml/min/1.73 m(2)). In both non-CKD and CKD sub-groups, participants with hyperuricaemia (> or = 7 mg/dl in men and > or = 6 mg/dl in women) compared to those with normal serum uric acid levels had higher waist circumference and fasting serum insulin levels. In the entire cohort, in a multivariate parametric proportional hazards model, each mg/dl increase in serum uric acid was associated with an increased hazard of cardiovascular events (HR 1.09, 95% CI 1.05-1.12) and death. A multiplicative interaction term of serum uric acid and CKD when added to the above models was significant (P < 0.001). The likelihood ratio test of the models with and without the interaction term was also significant (P < 0.001). In the non-CKD population, a multivariate analysis after adjusting for comorbidities and metabolic syndrome showed a significant association between hyperuricaemia and mortality (HR 1.18, 95% CI 1.04-1.33) but not for cardiovascular events (HR 1.07, 95% CI 0.96-1.19). In the CKD population, the association was not significant for both mortality and cardiovascular events.
We conclude that hyperuricaemia is associated with insulin resistance and mortality in the non-CKD population. The presence of CKD attenuates the associations of uric acid with mortality. Interventional studies are warranted to establish the biological role of hyperuricaemia in mortality in non-CKD and CKD populations.
尚不清楚肾脏疾病的存在是否会改变尿酸与心血管事件及死亡之间的关联。
在有限访问的公开可用社区动脉粥样硬化风险（ARIC）数据库中，使用参数化比例风险模型分析血清尿酸水平与心血管事件及死亡之间的关联，并使用似然比检验评估慢性肾脏病（CKD）的存在对这些关联的影响。
本分析纳入的15366名ARIC参与者中，461人患有CKD（估算肾小球滤过率<60 ml/min/1.73 m²）。在非CKD和CKD亚组中，与血清尿酸水平正常者相比，高尿酸血症患者（男性≥7 mg/dl，女性≥6 mg/dl）的腰围和空腹血清胰岛素水平更高。在整个队列中，在多变量参数化比例风险模型中，血清尿酸每增加1 mg/dl与心血管事件（风险比1.09，95%置信区间1.05 - 1.12）及死亡风险增加相关。当将血清尿酸与CKD的相乘交互项添加到上述模型中时具有显著性（P < 0.001）。有交互项和无交互项模型的似然比检验也具有显著性（P < 0.001）。在非CKD人群中，在调整合并症和代谢综合征后的多变量分析显示，高尿酸血症与死亡率之间存在显著关联（风险比1.18，95%置信区间1.04 - 1.33），但与心血管事件无关（风险比1.07，95%置信区间0.96 - 1.19）。在CKD人群中，高尿酸血症与死亡率和心血管事件的关联均不显著。
我们得出结论，在非CKD人群中，高尿酸血症与胰岛素抵抗及死亡率相关。CKD的存在减弱了尿酸与死亡率之间的关联。有必要进行干预性研究以确定高尿酸血症在非CKD和CKD人群死亡率中的生物学作用。
