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Showing papers by "Joseph L. Izzo published in 2013"


Journal ArticleDOI
TL;DR: Attenuated responses in women and among obese subjects suggest that structure-function changes may be less reversible in these groups, possibly explaining their greater susceptibility to ultimately develop heart failure.
Abstract: Aims To investigate the effect of antihypertensive therapy on ventricular–arterial mechanics, coupling, and efficiency in early-stage hypertension. Methods and results We studied 527 participants from two clinical trials assessing the effect of blood pressure lowering on diastolic function. Participants were aged ≥45 years with early-stage hypertension, no heart failure, ejection fraction (EF) ≥50%, and diastolic dysfunction using Doppler echocardiography. Effective arterial afterload and its components were assessed along with measures of left ventricular (LV) structure and function prior to and after 24–38 weeks of antihypertensive therapy. Systolic blood pressure decreased from 154 ± 18 to 137 ± 15 mmHg at follow-up. Blood pressure reduction was associated with decreases in ventricular and arterial stiffness, improvements in systemic arterial compliance and resistance, enhanced LV ejection, and reduction in cardiac work (all P < 0.001). Changes in Ea/Ees ratio were inversely correlated with those in EF ( r = −0.25; P < 0.001), stroke work index ( r = −0.13; P = 0.007), and LV efficiency ( r = −0.98; P < 0.001); and directly related to changes in mitral E / e ′ ( r = 0.12; P = 0.01). Adjusting for age and blood pressure change, women and obese individuals had less enhancement in ventricular–arterial coupling and efficiency compared with men and non-obese individuals ( P = 0.04 and 0.007, respectively). Conclusion Antihypertensive therapy reduces arterial and ventricular stiffness, enhances ventricular–arterial coupling, reduces cardiac work, and improves LV efficiency, systolic, and diastolic function. Attenuated responses in women and among obese subjects suggest that structure–function changes may be less reversible in these groups, possibly explaining their greater susceptibility to ultimately develop heart failure.

52 citations


Journal ArticleDOI
TL;DR: Triple-combination treatment was more effective than dual- Combination treatments in enabling participants to reach SeBP goal and well tolerated and more effective in lowering BP than the component dual-combinations in elderly and non-lderly subgroups.
Abstract: Hypertension is often inadequately controlled in older people. This prespecified subgroup analysis assessed the efficacy and safety of an olmesartan medoxomil (OM) 40 mg/amlodipine besylate (AML) 10 mg/hydrochlorothiazide (HCTZ) 25 mg triple-combination treatment compared with the 3 components as dual-combination treatments in participants with hypertension who were 9 %). Participants were randomized, stratified by age, diabetes status, and race to one of four treatment assignments: OM 40/AML 10/HCTZ 25 mg, OM 40/AML 10 mg, OM 40/HCTZ 25 mg, or AML 10/HCTZ 25 mg. Least squares (LS) mean change from baseline in seated diastolic blood pressure (SeDBP) at week 12 (last observation carried forward) in each age subgroup (prespecified analysis). Of the 2492 randomized participants in the study (total cohort), 2021 (81.1 %) were <65 and 471 (18.9 %) were ≥65 years of age, including 79 (3.2 %) who were ≥75 years of age. OM 40/AML 10/HCTZ 25 mg triple-combination treatment resulted in a significantly greater reduction in LS mean SeDBP at week 12 than dual-combination component treatments in participants in both cohorts: <65 years (21.0 vs. 14.2–17.2 mmHg; p < 0.0001) and ≥65 years (23.7 vs. 17.3–20.0 mmHg; p ≤ 0.002). Similarly, triple-combination treatment resulted in a greater reduction in LS mean seated systolic blood pressure (SeSBP) at week 12 than dual-combination component treatments: <65 years (38.2 vs. 28.3–31.4 mmHg; p < 0.0001) and ≥65 years (39.2 vs. 29.3–31.1 mmHg; p < 0.0001). Triple-combination treatment was more effective than dual-combination treatments in enabling participants to reach SeBP goal (<140/90 mmHg [<130/80 mmHg in participants with diabetes, chronic kidney disease, or chronic cardiovascular disease]) in both age subgroups (<65 years: 65 vs. 34–50 %, respectively, p < 0.0001 and ≥65 years: 63 vs. 32–39 %; p ≤ 0.0004). All 4 treatments were safe and well tolerated with low discontinuation rates in both age subgroups. There were no clinically relevant differences in the incidence of treatment-emergent adverse events between participants <65 and ≥65 years of age receiving triple-combination treatment. Triple-combination treatment with OM 40/AML 10/HCTZ 25 mg was well tolerated and more effective in lowering BP than the component dual-combination treatments in elderly and non-elderly subgroups.

9 citations