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

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          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 significant relationship between changes in UACR and changes in e′ velocity ( r = −0.144; P = 0.0257) and between changes in estimated glomerular filtration rate and changes in the E/e′ ratio ( r = −0.130; P = 0.0436). Among patients without DM, there was a significant 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 A 1c 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.

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          Author and article information

          Drug Des Devel Ther
          Drug Des Devel Ther
          Drug Design, Development and Therapy
          Dove Medical Press
          12 September 2012
          : 6
          : 225-233
          [1 ]Department of Internal Medicine, Clinic Jingumae, Kashihara, Japan
          [2 ]Department of Cardiovascular Medicine, Okayama University, Graduate School of Medicine, Okayama, Japan
          [3 ]Department of Cardiology, Kansai Electric Power Hospital, Osaka, Japan
          [4 ]Department of Internal Medicine and Cardiology, Osaka City University of Medicine, Osaka, Japan
          [5 ]Cardiovascular Center, Sakurabashi Watanabe Hospital, Osaka, Japan
          [6 ]Department of Cardiology, Sakakibara Heart Institute, Tokyo, Japan
          [7 ]Department of Medicine, Osaka Ekisaikai Hospital, Osaka, Japan
          [8 ]Nishinomiya Watanabe Cardiovascular Center, Nishinomiya, Japan
          Author notes
          Correspondence: Takeshi Takami, Department of Internal Medicine, Clinic Jingumae, Confort Yagi 5-4-41 Naizencho, Kashihara, Nara 634-0804, Japan, Tel +81 744 238 568, Fax +81 744 236 818, Email takami66@ 123456m5.kcn.ne.jp
          © 2012 Takami et al, publisher and licensee Dove Medical Press Ltd.

          This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

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