Adding thiazide to a rennin-angiotensin blocker regimen to improve left ventricular relaxation in diabetes and nondiabetes patients with hypertension

Takeshi Takami, Hiroshi Itoh, Katsuhisa Ishii, Kenei Shimada, Katsuomi Iwakura, Hiroyuki Watanabe, Shota Fukuda, Junichi Yoshikawa

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3 Citations (Scopus)


The urinary albumin to creatinine ratio (UACR) is an independent predictor of outcomes in patients with diastolic dysfunction. Thus, we investigated the relationship between diastolic dysfunction, UACR, and diabetes mellitus (DM) in the EDEN study. We investigated the effect of switching from an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) to a combination of losartan and hydrochlorothiazide on left ventricular (LV) relaxation in patients with hypertension and diastolic dysfunction. We enrolled 106 patients with and 265 patients without DM. All patients had diastolic dysfunction and had not achieved their treatment goals with an ACEi or ARB. The measurements of e′ velocity and E/e′ ratio was performed with echocardiography as markers of LV diastolic function. We switched the ACEi or ARB to losartan/hydrochlorothiazide and followed these patients for 24 weeks. UACR was decreased in patients with DM (123.4 ± 288.4 to 66.5 ± 169.2 mg/g creatinine; P = 0.0024), but not in patients without DM (51.2 ± 181.8 to 39.2 ± 247.9 mg/g creatinine; P = 0.1051). Among DM patients, there was a signifcant relationship between changes in UACR and changes in e′ velocity (r = -0.144; P = 0.0257) and between changes in estimated glomerular fltration rate and changes in the E/e′ ratio (r = -0.130; P = 0.0436). Among patients without DM, there was a signifcant relationship between changes in high-sensitivity C-reactive protein (hs-CRP) and changes in E/e′ (r = 0.205; P = 0.0010). Multivariate analysis demonstrated changes in hemoglobin A1c levels as one of the determinants of change of e′ and E/e′ in patients with DM, whereas hs-CRP was the determinant of change of e′ among patients without DM. These data suggest that improvement in LV diastolic function is associated with an improvement of DM and a concomitant reduction in UACR among DM patients, and with a reduction of hs-CRP in patients without DM when thiazide is added to a renin-angiotensin blocker treatment regimen.

Original languageEnglish
Pages (from-to)225-233
Number of pages9
JournalDrug Design, Development and Therapy
Publication statusPublished - Sep 11 2012



  • Diabetes
  • Diastolic dysfunction
  • HCTZ
  • Losartan
  • Urinary albumin to creatinine ratio

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Pharmacology
  • Drug Discovery

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