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

Abstract

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.

Keywords:

• diastolic dysfunction
• diabetes
• urinary albumin to creatinine ratio
• losartan
• HCTZ

Acknowledgments

This study was supported by the Osaka Prevention Institute for Cancer and the Cardiovascular Diseases Foundation. The authors also thank the EDEN trial investigators: Hajime Kihara, MD (Kihara Cardiovascular Clinic, Asahikawa, Japan); Noriaki Kasayuki, MD (Ishikiriseiki Hospital, Higashiosaka, Japan); Fumiaki Nakamura, MD (Ibaraki Iseikai Hospital, Ibaraki, Japan); Etsuko Fushimi, MD (Hiraga General Hospital, Yokote, Japan); Lim Young-Jae, MD (Kawachi General Hospital, Higashiosaka, Japan); Shin Takiuchi, MD (Higashi Takarazuka Satoh Hospital, Takarazuka, Japan); Junichi Nakagawa, MD (Sankeikai-Nakagawa Clinic, Amagasaki, Japan); Hen Yasuki, MD (Sakakibara Heart Institute Clinic, Fuchu, Japan); Kei Tawarahara, MD (Hamamatsu Red Cross Hospital, Hamamatsu, Japan); Akihiro Tani, MD (Kano General Hospital, Osaka, Japan); Hiroshi Matsuura MD (Matsuura Clinic of Medicine, Suita, Japan); Shigenori Sassa, MD (Sassa Medical Clinic, Osaka, Japan); Yasuji Doi, MD (Osaka Saiseikai Senri Hospital, Suita, Japan); Taro Minagawa, MD (Minagawa Clinic, Gifu, Japan); Yukio Abe, MD (Osaka City General Hospital, Osaka, Japan); Yoshio Kawase, MD (Izumi City General Hospital, Izumi, Japan); Toshihiko Nagano, MD (Iwasa Dai-ichi Hospital, Gifu, Japan); Naoki Gotoh, MD (Gotoh Clinic, Gifu, Japan); Kazunori Kasiwase, MD (Osaka Police Hospital, Osaka, Japan); Tsunemori Sakamoto, MD (Baba Memorial Hospital, Sakai, Japan); Keiji Ujino, MD (Tominaga Hospital, Osaka, Japan); Masahiro Yoshida, MD (Tsukushino Hospital, Fukui, Japan); Takahiko Kawarabayashi, MD (Higashisumiyoshi Morimoto Hospital, Osaka, Japan); and Yukinori Okazaki, MD (NTT West Osaka Hospital, Osaka, Japan).

Disclosure

The authors have no conflicts of interest to declare.