Department of Regional Medicine, Tottori University Faculty of Medicine , Yonago , Japan .
Clin Exp Hypertens. 2014;36(4):251-7. doi: 10.3109/10641963.2013.810228. Epub 2013 Jul 18.
Long-term effects of a low-dose hydrochlorothiazide (HCTZ) with losartan (LOS) on uric acid (UA) metabolism as well as glucose metabolism have been studied in hypertensive patients in comparison with those of a low-dose HCTZ with telmisartan (TEL).
Fifty-nine hypertensive patients were allocated to a combination therapy with either losartan (50 mg/day)/HCTZ (12.5 mg/day) (LOS + HCTZ group: n = 37) or telmisartan (40 mg/day)/HCTZ (12.5 mg/day) (TEL + HCTZ group: n = 22), respectively. Before and 1 year after the treatment, blood pressure and biochemical parameters of blood and urine were evaluated.
Both systolic and diastolic blood pressures significantly decreased in two groups, without any statistical differences among them. LOS + HCTZ caused no changes in the serum UA level or the ratio of UA clearance to creatinine clearance (CUA/Ccr), whereas TEL + HCTZ significantly increased the serum UA level and reduced CUA/Ccr. LOS + HCTZ did not influence CUA/Ccr in patients with their serum UA below 5.4 mg/dl, while LOS + HCTZ significantly increased CUA/Ccr in patients with their serum UA above 5.5 mg/dl. TEL + HCTZ significantly reduced CUA/Ccr in patients with their serum UA below and above 5.4 mg/dl to increase serum UA level significantly. Neither combination therapies caused any changes in fasting plasma glucose, HbA1c and HOMA-R. In patients with their serum UA level above 5.4 mg/dl, TEL + HCTZ increased HOMA-R, whereas LOS + HCTZ did not.
LOS + HCTZ did not influence UA metabolism as well as glucose metabolism, likely because of inhibitory action of losartan on URAT1, although TEL + HCTZ were accompanied with impairment of the UA metabolism and glucose metabolism.
本研究旨在比较低剂量氢氯噻嗪(HCTZ)联合氯沙坦(LOS)与低剂量 HCTZ 联合替米沙坦(TEL)对高血压患者尿酸(UA)代谢和葡萄糖代谢的长期影响。
将 59 例高血压患者分别分配至 LOS+HCTZ(n=37)或 TEL+HCTZ(n=22)组。分别于治疗前和治疗 1 年后,评估患者的血压和血、尿生化参数。
两组患者的收缩压和舒张压均显著降低,两组间无统计学差异。LOS+HCTZ 治疗不影响血清 UA 水平或 UA 清除率与肌酐清除率的比值(CUA/Ccr),而 TEL+HCTZ 可显著升高血清 UA 水平并降低 CUA/Ccr。LOS+HCTZ 不影响血清 UA<5.4mg/dl 的患者的 CUA/Ccr,而在血清 UA>5.5mg/dl 的患者中,LOS+HCTZ 可显著升高 CUA/Ccr。TEL+HCTZ 可显著降低血清 UA<5.4mg/dl 和>5.4mg/dl 的患者的 CUA/Ccr,同时明显升高血清 UA 水平。两种联合治疗均不影响空腹血糖、HbA1c 和 HOMA-R。在血清 UA>5.4mg/dl 的患者中,TEL+HCTZ 可升高 HOMA-R,而 LOS+HCTZ 则无此作用。
LOS+HCTZ 不影响 UA 代谢和葡萄糖代谢,可能是由于氯沙坦对 URAT1 的抑制作用,但 TEL+HCTZ 可损害 UA 代谢和葡萄糖代谢。