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      Azelnidipine plus olmesartan versus amlodipine plus olmesartan on arterial stiffness and cardiac function in hypertensive patients: a randomized trial

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          Abstract

          Purpose

          To compare the long-term effects of olmesartan combined with either azelnidipine or amlodipine on central blood pressure (CBP), left ventricular (LV) mass index (LVMI), LV diastolic function (e′ velocity, E/e′ ratio, E/A ratio) and arterial stiffness (brachial-ankle pulse wave velocity [baPWV] and augmentation index normalized for a heart rate of 75 bpm [AIx]).

          Patients and methods

          Patients with systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg received olmesartan monotherapy (20 mg/day) for 12 weeks. They were then randomly assigned to fixed-dose add-on therapy with azelnidipine (16 mg/day; n = 26) or amlodipine (5 mg/day; n = 26) for a further 2 years. CBP, LVMI, e′ velocity, E/e′ ratio, E/A ratio, baPWV, and AIx were measured at baseline, 6 months, and 2 years.

          Results

          Baseline characteristics of both groups were similar. The decrease in brachial BP over 2 years was similar in both groups. CBP, LVMI, E/e′ ratio, baPWV, and AIx decreased significantly, and the E/A ratio and e′ velocity increased significantly in both groups. The decreases in CBP ( P < 0.001), AIx ( P < 0.001), baPWV ( P < 0.001), LVMI ( P < 0.001), and E/e′ ( P = 0.002) as well as the increase in E/A ratio ( P = 0.03) over 2 years were significantly greater in the olmesartan/azelnidipine group than in the olmesartan/amlodipine group. Multivariate linear regression analyses showed that the changes in baPWV (β = 0.41, P < 0.001) and CBP (β = 0.47, P = 0.01) were independently associated with the change in LVMI, the change in baPWV (β = 0.25, P < 0.001) was independently associated with the change in E/e′ ratio, and the changes in baPWV (β = 0.21, P = 0.001) and AIx (β = 0.25, P = 0.03) were independently associated with the change in E/A ratio.

          Conclusion

          Treatment with olmesartan/azelnidipine for 2 years resulted in greater improvements in CBP, LVMI, and LV diastolic function, and arterial stiffness compared with olmesartan/amlodipine. Improvements in LV diastolic function were associated with improvements in arterial stiffness.

          Most cited references28

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          The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2009).

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            Noninvasive estimation of left ventricular filling pressure by E/e' is a powerful predictor of survival after acute myocardial infarction.

            The aim of this study was to assess the prognostic value of a noninvasive measure of left ventricular diastolic pressure (LVDP) early after acute myocardial infarction (MI). The early diastolic velocity of the mitral valve annulus (e') reflects the rate of myocardial relaxation. When combined with measurement of the early transmitral flow velocity (E), the resultant ratio (E/e') correlates well with mean LVDP. In particular, an E/e' ratio >15 is an excellent predictor of an elevated mean LVDP. We hypothesized that an E/e' ratio >15 would predict poorer survival after acute MI. Echocardiograms were obtained in 250 unselected patients 1.6 days after admission for MI. Patients were followed for a median of 13 months. The end point was all-cause mortality. Seventy-three patients (29%) had an E/e' >15. This was associated with excess mortality (log-rank statistic 21.3, p 15 improved the prognostic utility of a model containing clinical variables and conventional echocardiographic indexes of left ventricular systolic and diastolic function (p = 0.001). E/e' is a powerful predictor of survival after acute MI. An E/e' ratio >15 is superior, in this respect, to other clinical or echocardiographic features. Furthermore, it provides prognostic information incremental to these parameters.
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              Relation of arterial stiffness to diastolic dysfunction in hypertensive heart disease.

              To examine the relation of arterial compliance to diastolic dysfunction in hypertensive patients with suspected diastolic heart failure (HF). 70 medically treated hypertensive patients with exertional dyspnoea (40 women, mean (SD) age 58 (8) years) and 15 normotensive controls. Mitral annular early diastolic velocity with tissue Doppler imaging and flow propagation velocity were used as linear measures of diastolic function. Arterial compliance was determined by the pulse pressure method. According to conventional Doppler echocardiography of transmitral and pulmonary venous flow, diastolic function was classified as normal in 33 patients and abnormal in 37 patients. Of those with diastolic dysfunction, 28 had mild (impaired relaxation) and nine had advanced (pseudonormal filling) dysfunction. Arterial compliance was highest in controls (mean (SD) 1.32 (0.58) ml/mm Hg) and became progressively lower in patients with hypertension and normal function (1.04 (0.37) ml/mm Hg), impaired relaxation (0.89 (0.42) ml/mm Hg), and pseudonormal filling (0.80 (0.45) ml/mm Hg, p = 0.011). In patients with diastolic dysfunction, arterial compliance was inversely related to age (p = 0.02), blood pressure (p < 0.001), and estimated filling pressures (p < 0.01) and directly related to diastolic function (p < 0.01). After adjustment for age, sex, body size, blood pressure, and ventricular hypertrophy, arterial compliance was independently predictive of diastolic dysfunction. In hypertensive patients with exertional dyspnoea, progressively abnormal diastolic function is associated with reduced arterial compliance. Arterial compliance is an independent predictor of diastolic dysfunction in patients with hypertensive heart disease and should be considered a potential target for intervention in diastolic HF.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2013
                22 March 2013
                : 7
                : 175-183
                Affiliations
                [1 ]Department of Internal Medicine, Clinic Jingumae, Kashihara, Japan
                [2 ]First Department of Internal Medicine, Nara Medical University, Kashihara, Japan
                Author notes
                Correspondence: Takeshi Takami, Department of Internal Medicine, Clinic Jingumae, 5-4-41 Naizencho, Kashihara, Nara 634-0804, Japan, Tel +81 744 23 8568, Fax +81 744 23 6818, Email takami66@ 123456m5.kcn.ne.jp
                Article
                dddt-7-175
                10.2147/DDDT.S42338
                3610435
                23662047
                c5217453-2fc3-4000-a5d6-13b65298e6c7
                © 2013 Takami and Saito, 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.

                History
                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine
                central blood pressure,arterial stiffness,left ventricular mass index,left ventricular diastolic function,olmesartan/azelnidipine

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