title: Effects of combined antihypertensive therapy with losartan/hydrochlorothiazide on uric acid metabolism.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Kidney and Hypertension, Jikei University School of Medicine, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Hosoya
authors.forename: Satoru
authors.initials: S
authors.lastname: Kuriyama
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshizawa
authors.forename: Akimitsu
authors.initials: A
authors.lastname: Kobayashi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Otsuka
authors.forename: Iwao
authors.initials: I
authors.lastname: Ohno
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003404:Creatinine / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006852:Hydrochlorothiazide / Q000494:pharmacology / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016896:Treatment Outcome; D014527:Uric Acid / Q000378:metabolism*
chemical_list: D000959:Antihypertensive Agents; D006852:Hydrochlorothiazide; D014527:Uric Acid; D003404:Creatinine; D019808:Losartan