噻嗪类利尿剂、氯沙坦及其复方制剂对高血压患者的血清尿酸水平的影响

Serum uric acid prevalence and changes post various antihypertensive agents in patients with essential hypertension

目的观察原发性高血压病（EH）患者高尿酸血症的流行情况，以及噻嗪类利尿剂、血管紧张素受体拮抗剂氯沙坦和氯沙坦＋氢氯噻嗪6周降压治疗后EH患者血清尿酸（SUA）和电解质的变化。方法收集福州4家医院近3年连续的EH患者共1080例，其中男女之比662：418，平均年龄（60．9±12．3）岁，治疗前后血压记录完整者1000例，肾功能和电解质完整者600例。结果EH患者合并高尿酸血症的发生率为25．83％（279／1080），与EH组比较，EH合并高尿酸血症组患者体质指数、肌酐升高，内生肌酐清除率降低（P分别〈0．05和0．01）。降压治疗6周末69．40％（694／1000）患者收缩压〈140mmHg（1mmHg=0．133kPa），85．30％（853／1000）患者舒张压〈90mmHg。不同降压药物治疗后SUA和血钾的变化：低剂量利尿剂组SUA平均升高（43．81±71．79）μmol／L（P〈0．0001），氯沙坦组平均下降（44．96±90．63）μmol／L（P〈0．01，100mg组优于50mg组），氯沙坦＋氢氯噻嗪组平均下降（7．46±84．72）μmol／L，三组药物治疗后SUA之间的差异有统计学意义；低剂量利尿剂组血钾平均下降（0．30±0．44）mmol／L（P〈0．01），与氯沙坦组[（0．06±0．43）mmol／L]和氯沙坦＋氢氯噻嗪组[（-0．04±0．44）mmol／L]比较，差异也有统计学意义。结论EH患者25．83％合并高尿酸血症；高血压合并高尿酸血症者有体质指数增加和肾功能损害趋势；低剂量噻嗪类利尿剂会加重SUA增高和低血钾，氯沙坦可剂量依赖性的降低SUA，而氯沙坦＋氢氯噻嗪介于两者之间。

Objective To survey the prevalence of hyperuricacidemia and serum uric acid （SUA） changes and electrolyte changes after 6 weeks antihypertensive treatment with thiazide diuretics, losartan or losartan ± hydrochlorothiazide （Hyzaar） in patients with essential hypertension （EH）. Methods A total of 1080 consecutive EH patients [ 662 males, mean age （ 60. 9 ± 12. 3 ） years ] who seeked for medical consultation in study hospitals in Fuzhou city during October 2004 and October 2006 were included in this study. The blood pressure before and after antihypertensive treatments were obtained in 1000 patients, and the renal function and electrolyte before and after antihypertensive treatments were obtained in 600 patients. Patients with SBP 〉 140 and/or DBP 〉 90 mm Hg 2 weeks after initial antihypertensive agents were cotreated with felodipine, patients with SBP 〉 140 and/or DBP 〉 90 mm Hg 4 weeks after initial antihypertensive agents were cotreated with 13 and/or α blockers. Results The prevalence of hyperuricacidemia in EH patients was 25. 83% （279/1080）. Body mass index （BMI） and creatinine were significantly higher while creatinine clearance rate （Ccr） calculated by Cockcrofi-Gault equation was significantly lower in EH patients with hyperuricacidemia than EH patients without hyperuricacidemia （ all P 〈 0. 05 ）. Similar antihypertensive effects were observed in EH patients treated with thiazide diuretics （ n = 200）, losartan （ n = 324 ） or losartan ± hydrochlorothiazide （ Hyzaar, n =476） and SBP was lower than 140 mm Hg in 69.40% and DBP was less than 90 mmHg in 85. 30% EH patients 6 weeks after antihypertensive treatments. SUA was significantly increased （ 43, 81 μmol/L ± 71.79 μmol/L ） low dose diuretics group （ P 〈 0. 01 vs. pretreatment）, significantly reduced （44. 96 μmol/L ±90. 63 μmol/L） in losartan group （P 〈0. 0001 vs.pretreatment） and remained unchanged in Hyzaar group （7. 46 ± 84. 72 μmol/L, P 〉 0. 05 vs. pretreatment）. Serum potassium was significantly decreased （0. 30 ± 0. 44 mmol/L） in diuretic group （P 〈 0. 01 vs. pretreatment） and remained unchanged in losartan group （ ＋ 0. 06 ± 0.43 mmol/L） and Hyzaar group （ - 0. 04 ± 0. 44 mmol/L, all P 〉 0. 05 vs. pretreatment ） . Conclusion Hyperuricacidemia prevalence was 25. 83% and associated with higher BMI and abnormal renal function in examined EH patients. The low dose thiazide diuretics could further aggravate hyperuricacidemia and induce hypopotassemia while losartan could reduce hyperuricacidemia in EH patients.