Hosoya Tatsuo, Kuriyama Satoru, Yoshizawa Takeo, Kobayashi Akimitsu, Otsuka Yasushi, Ohno Iwao
Division of Kidney and Hypertension, Jikei University School of Medicine, Japan.
Intern Med. 2012;51(18):2509-14. doi: 10.2169/internalmedicine.51.7584. Epub 2012 Sep 15.
The Jikei Optimal Antihypertensive Treatment (JOINT) study originally evaluated the effect of a fixed-dose formulation of losartan (LOS) (50 mg) plus 12.5 hydrochrolthiazide (HCTZ) for achieving better blood pressure (BP) control in patients with uncontrolled hypertension. This study is a sub-analysis of the JOINT study, focusing on the effect of LOS/HCTZ on the uric acid (UA) metabolism.
Among 228 participants in the JOINT study, a total of 164 patients whose blood and urinary UA specimens were available were included in the present analyses.
Six months after switching from the prior antihypertensive agent(s) to a single tablet formulation of LOS/HCTZ, the overall serum UA concentration (sUA) increased from 6.0 ± 1.6 mg/dL to 6.2 ± 1.6 mg/dL (p=0.029). The urinary UA/creatinine (Cr) ratio increased from 0.45 +/- 0.21 to 0.50 +/- 0.25 (p=0.014), and the fractional excretion of UA (FEUA) also increased, from 7.1 +/- 3.6 to 7.0 +/- 4.3, p=0.04). Multivariate regression analyses of the basal parameters showed the change in sUA (ΔUA) to correlate with the basal sUA (β=-0.483, p<0.001), estimated glomerular filtration rate (eGFR) (β=-0.202, p=0.007) and systolic BP (β=0.147, p=0.038). In addition, the ΔUA also correlated with the changes in the estimated glomerular filtration rate (ΔeGFR) (β=-0.332, p<0.001). When the patients were classified into two groups depending on their basal sUA, those with a basal sUA ≥ 7 mg/dL exhibited a decrease in their sUA, whereas the rest of those with a sUA <7 mg/dL experienced an increase. Furthermore, patients who had previously been treated with LOS alone had a greater increase in the sUA than those treated with an angiotensin II blocker (ARB) other than LOS alone.
Antihypertensive therapy with a single tablet formulation of LOS/HCTZ is considered to be a useful option for controlling both BP and sUA, especially in uncontrolled hypertensive patients with hyperuricemia.
日本庆应义塾大学最佳抗高血压治疗（JOINT）研究最初评估了氯沙坦（LOS）（50毫克）加12.5毫克氢氯噻嗪（HCTZ）的固定剂量配方对血压控制不佳的高血压患者实现更好血压（BP）控制的效果。本研究是JOINT研究的一项亚分析，重点关注LOS/HCTZ对尿酸（UA）代谢的影响。
在JOINT研究的228名参与者中，本分析纳入了总共164名有血液和尿液UA标本的患者。
从先前的抗高血压药物转换为LOS/HCTZ单片制剂6个月后，总体血清UA浓度（sUA）从6.0±1.6毫克/分升增加到6.2±1.6毫克/分升（p = 0.029）。尿UA/肌酐（Cr）比值从0.45 +/- 0.21增加到0.50 +/- 0.25（p = 0.014），UA的分数排泄（FEUA）也增加，从7.1 +/- 3.6增加到7.0 +/- 4.3，p = 0.04）。对基础参数的多变量回归分析显示，sUA的变化（ΔUA）与基础sUA（β=-0.483，p<0.001）、估计肾小球滤过率（eGFR）（β=-0.202，p = 0.007）和收缩压（β=0.147，p = 0.038）相关。此外，ΔUA还与估计肾小球滤过率的变化（ΔeGFR）相关（β=-0.332，p<0.001）。当根据患者的基础sUA将其分为两组时，基础sUA≥7毫克/分升的患者sUA下降，而其余sUA<7毫克/分升的患者sUA升高。此外，先前仅接受LOS治疗的患者的sUA升高幅度大于仅接受LOS以外的血管紧张素II受体阻滞剂（ARB）治疗者。
LOS/HCTZ单片制剂的抗高血压治疗被认为是控制血压和sUA的有用选择，特别是对于尿酸血症未控制的高血压患者。
