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Showing papers by "Joseph L. Izzo published in 2010"


Journal ArticleDOI
TL;DR: The degree of improvement in annular relaxation velocity was associated with the extent of systolic blood pressure reduction, and patients with the lowest achieved systolics blood pressure had the highest final diastolic relaxation velocities.
Abstract: Diastolic dysfunction may precede development of heart failure in hypertensive patients. We randomized 228 patients with uncontrolled hypertension, preserved ejection fraction, and diastolic dysfunction to 2 targeted treatment strategies: intensive, with a systolic blood pressure target of P P P P P P =0.58). The degree of improvement in annular relaxation velocity was associated with the extent of systolic blood pressure reduction, and patients with the lowest achieved systolic blood pressure had the highest final diastolic relaxation velocities.

104 citations


Journal ArticleDOI
TL;DR: There are dramatic counterregulatory haemodynamic and hormonal adaptations to maintain a relatively constant BP in men and women with either normal BP or early hypertension.
Abstract: Seasonal variation in blood pressure (BP) has been described in some people, although the variation is small for both systolic and diastolic BPs. The aim of this study was to elucidate underlying haemodynamic and hormonal mechanisms that may occur to defend seasonal changes in BP. Participants were 27 men and 7 women with either normal BP or early hypertension. Measurements of haemodynamics (cardiac output by dual-gas rebreathing) and hormones (resting catecholamines, renin activity, and aldosterone by radioenzymatic assay or radioimmunoassay) were performed during the summer, fall, winter, and spring seasons. Student's paired t-test with Bonferroni modification and regression analyses were used to examine the data with a significance level of P<0.05. Systolic and diastolic BP remained relatively constant across seasons. Cardiac output and stroke volume significantly decreased 10 and 15%, respectively, from summer to winter, whereas heart rate and systemic vascular resistance significantly increased 5 and 11%, respectively. Plasma aldosterone (PA) significantly increased 59% from summer to winter, whereas plasma norepinephrine (PNE), plasma epinephrine, and plasma renin activity (PRA) increased 19, 2, and 17%, respectively (pNS for each). Across the four seasons, mean arterial pressure significantly correlated with PRA and PA, whereas systemic vascular resistance significantly correlated with PNE and PRA. There are dramatic counterregulatory haemodynamic and hormonal adaptations to maintain a relatively constant BP. Norepinephrine, PRA, and aldosterone have a function in mediating the changes in haemodynamics.

50 citations


Journal ArticleDOI
TL;DR: This poster presents a probabilistic procedure to assess the importance of baseline IgE levels in the decision-making process for ART and its applications in medicine and sport.
Abstract: Cardiovascular and chronic kidney disease are epidemic throughout industrialized societies. Diabetes leads to premature cardiovascular disease and is regarded by many as the most common etiological factor for chronic kidney disease. Because most studies of blood-pressure lowering agents in people with diabetes and hypertension have been conducted in individuals who already have some target organ damage, it is unclear whether earlier intervention could prevent or delay the onset of renal or systemic vascular disease. In early disease there is only a low possibility of observing cardiovascular or renal events; thus intervention trials in this population must rely on disease markers such as microalbuminuria. Accordingly, the authors review the evidence to support the use of microalbuminuria as a disease marker in diabetic patients based on its strong association with renal and cardiovascular events, and discuss recent trials that examine the impact of preventing or delaying the onset of microalbuminuria.

22 citations


Journal ArticleDOI
TL;DR: It is concluded that titration of amlodipine and benazepril in single-pill combinations is more effective than titrationOf amlODipine alone for rapid BP control in patients with severe hypertension.
Abstract: Comparative efficacy and safety of amlodipine/benazepril combination therapy and amlodipine monotherapy in severe hypertension

11 citations


Journal ArticleDOI
TL;DR: In subjects with type 2 diabetes and excellent blood pressure control early treatment with the ARB olmesartan showed a significant risk reduction regarding the ‘time to onset of microalbuminuria’.

7 citations


Journal ArticleDOI
TL;DR: Meta-analyses strongly suggest that the primary preventive benefit of antihypertensive therapy in uncomplicated individuals is the direct result of the lower blood pressure rather than the choice of agents.
Abstract: Meta-analyses strongly suggest that the primary preventive benefit of antihypertensive therapy in uncomplicated individuals is the direct result of the lower blood pressure (BP) rather than the choice of agents. In contrast, when comorbidities are present, therapeutic benefit is governed primarily by the appropriateness of the drug class for the comorbidity profile. As progressively lower BP levels are studied, conflicting results and uncertainties continue to emerge. Given the geometric nature of the BP-risk relationship, it is to be expected that benefits will be less dramatic at lower levels of BP. Conflicting results may emerge from intrinsic problems with clinical trials, including uncertainties related to confounded composite end points, interactions of comorbidities, selection bias from the heterogeneous population with hypertension, interindividual response differences, BP variation and measurement artifacts, multiple mechanisms of antihypertensive drugs, and other deficiencies in study design. The mandate for BP reduction remains strong in virtually all clinical situations. Because of clinical heterogeneity, however, no single drug class is preferred in all circumstances.

5 citations


Journal ArticleDOI
TL;DR: It was concluded that the combination A+AML resulted in greater reductions in BP, with similar tolerability compared to AML monotherapy in African Americans with stage 2 hypertension.
Abstract: Objective: African Americans have a high prevalence of hypertension and, like other patients with hypertension, are unlikely to achieve blood pressure (BP) goals with monotherapy. This 8-week, prospective, multicenter, randomized, double-blind study compared efficacy and safety of a combination of aliskiren (A) and amlodipine (AML) to AML in African American men and women with systolic (S) BP >=160-<200 mmHg. Design and Methods: After a 1–4 week washout period, patients received A+AML 150/5 mg or AML 5 mg for 1 week. Then patients were force-titrated to A+AML 300/10 mg or AML 10 mg for 7 weeks. Results: Baseline mean sitting SBP [msSBP ± standard deviation] was 167.4 ± 8.2 mmHg; mean age was 52.8 ± 10.0 years; and mean body mass index was 33.8 ± 7.9 kg/m2 at randomization. The primary efficacy variable, change in msSBP at week 8, was greater with A+AML than with AML (−34.1 ± 1.14 vs -28.9 ± 1.12; P < 0.001) in the overall study population. Similar findings in favor of A+AML were observed in both men and women. Overall, the BP control (<140/90 mmHg) rate at week 8 was 57.3% with A+AML and 48.0% with AML (P = 0.051). Both treatment groups had similar adverse event rates (overall, 35.0% with A+AML, 32.7% AML); most common events were peripheral edema (7.7% with A+AML and 9.0% AML), headache, fatigue, and nausea. Conclusion: We concluded that the combination A+AML resulted in greater reductions in BP, with similar tolerability compared to AML monotherapy in African Americans with stage 2 hypertension. Figure 1. No caption available.

4 citations


Journal ArticleDOI
TL;DR: Compared with AML alone, the combination of A+AML provided greater reductions in both clinic and ambulatory BP values in African Americans with stage 2 hypertension.
Abstract: Objective: Ambulatory blood pressure monitoring (ABPM) is a better predictor of cardiovascular outcomes than clinic blood pressure (BP). We previously showed in an 8-week, prospective, multicenter, randomized, double-blind study (N=443) that the combination of aliskiren (A), a direct renin inhibitor, and the calcium channel blocker, amlodipine (AML) (A+AML), provided greater clinic BP reductions than AML in African Americans with baseline mean sitting systolic BP (msSBP) >=160 mmHg and < 200 mmHg. Here we present results in a subset of subjects who underwent ABPM. Design and Methods: After a 1–4 week washout period, men and women received either A+AML 150/5 mg (n = 76) or AML 5 mg (n = 71) for 1 week, then were force-titrated to receive A+AML 300/10 mg or AML 10 mg for 7 weeks. Results: Baseline mean 24-hour ambulatory SBP (maSBP) was 152.8 mmHg in the A+AML group and 147.5 mmHg in the AML group. At week 8, clinic LSM msSBP reductions from baseline were significantly greater with A+AML (-32.5 mmHg) versus AML (-26.7 mmHg; least squares mean [LSM] difference P < 0.05). LSM reductions in maSBP were -19.0 mmHg for A+AML versus -15.2 mmHg for AML (p=ns). However, using repeated measure analysis of hourly aSBP and aDBP, LSM changes from baseline were significantly greater with A+AML than with AML (Table). In the overall study, adverse event rates were similar in both groups (35.0% in the A+AML group; 32.7% in the AML group); the most common events were peripheral edema, headache, fatigue, and nausea. Conclusion: Compared with AML alone, the combination of A+AML provided greater reductions in both clinic and ambulatory BP values in African Americans with stage 2 hypertension. Figure 1. No caption available.

3 citations



Journal ArticleDOI
TL;DR: It is concluded that the A+AML combination causes greater reductions in central blood pressures than AML monotherapy in African Americans with stage 2 hypertension.
Abstract: Objective: Elevated central systolic blood pressure (cSBP) is a validated risk factor for cardiovascular outcomes that may be more accurate than standard cuff blood pressure (BP) values due to inter-individual variations in pulse wave transmission and wave reflection. We report here the effects on central BP values obtained from pulse wave analysis (Sphygmocor, AtCor Medical, Sydney) comparing the combination of aliskiren and amlodipine (A+AML) with AML monotherapy in a subset (n=147) of a larger 8-week, prospective, multicenter, randomized, double-blind study (n=443) in African Americans with stage 2 hypertension. We have also reported that both office and 24-hour ambulatory BP values were lower with A+AML than AML. Design and Methods: Entry criteria included baseline mean sitting systolic BP (msSBP) >=160-<200 mmHg. Mean age of the randomized subjects was 53 ± 10 years. After a 1-4 week washout period, men and women were randomized to receive either A+AML 150/5 mg (n = 76) or AML 5 mg (n = 71) for 1 week; then the patients were force-titrated to receive A+AML 300/10 mg or AML 10 mg for 7 weeks. Results: The changes in central BP values from baseline to week 8 were significantly greater with A+AML than AML alone for cSBP (−29.8 vs −24.2; P < 0.05), central diastolic BP (-16.0 vs -9.9; P < 0.001), and central mean pressure (−21.9 vs −15.6; P < 0.001). There were no differences between treatment arms for the changes in central pulse pressure (PP), PP amplification ratio, or augmentation index. In the overall study, both treatments had similar tolerability. Conclusions: We conclude that the A+AML combination causes greater reductions in central blood pressures than AML monotherapy in African Americans with stage 2 hypertension. Figure 1. No caption available.

2 citations


Journal ArticleDOI
TL;DR: Combination therapy with A+AML is more effective than AML alone in obese or MetS African American individuals with stage 2 hypertension.
Abstract: Objective: Obesity and/or metabolic syndrome (MetS) is a frequent comorbidity with hypertension. Previously, an 8-week, prospective, multicenter, randomized, double-blind study of 443 African Americans with mean sitting systolic blood pressure (msSBP) from >=160- <200 mmHg found that combination of aliskiren (A) + amlodipine (AML) provided greater office BP reductions than AML alone. This analysis assesses the efficacy of combination therapy in obese subjects (n=221; body mass index [BMI] >=32.5 kg/m2 [the median BMI]) or in subjects with MetS (ATP III criteria; n=297). Design and Methods: After a 1–4 week washout period, subjects were randomized to receive either A+AML 150/5 mg or AML 5 mg for 1 week; then force-titrated to A+AML 300/10 mg or AML 10 mg for additional 7 weeks. Results: At Week 8, significantly greater reductions in both msSBP/mean sitting diastolic BP (msDBP) were observed with A+AML than AML (-34.1/-14.3 mmHg vs -28.9/-10.5 mmHg; P < 0.001). BP reductions and BP control were greater for A+AML vs AML in both obese and subjects with MetS (P < 0.001, Table). In the overall study, adverse event rates were similar for A+AML (35.0%) and AML (32.7%); most common were peripheral edema, headache, fatigue, and nausea. Conclusion: Combination therapy with A+AML is more effective than AML alone in obese or MetS African American individuals with stage 2 hypertension. Figure 1. No caption available.

Journal Article
TL;DR: In this paper, the authors investigated whether early treatment with an angiotensin receptor blocker (ARB) in diabetic subjects with normal albumin excretion delays the occurrence of microalbuminuria and concomitantly recorded cardiovascular and renal events.
Abstract: Background: Microalbuminuria is an early sign of diabetic nephropathy and increased cardiovascular risk. We investigated whether early treatment with an angiotensin receptor blocker (ARB) in diabetic subjects with normal albumin excretion delays the occurrence of microalbuminuria and concomitantly recorded cardiovascular and renal events. Methods: We studied 4,447 patients with type 2 diabetes and at least one additional cardiovascular risk factor in a randomized, double-blind, multicentre, controlled, and event-driven (onset of microalbuminuria) trial. They received either 40 mg olmesartan or placebo once daily for a median duration of 3.2 years. In both groups, additional antihypertensive drug treatment (except ACE inhibitors or ARBs) was used to reach the target blood pressure of <130/80 mmHg. Results: Baseline eGFR, blood pressure and cardiovascular disease (CVD) risk profiles were comparable in both groups. Nearly 80% of the subjects in the olmesartan group and 71% in the placebo group achieved target blood pressure at month 48. Kaplan-Meier analysis showed a cumulative incidence of microalbuminuria of 8.2% (n = 178) with olmesartan and 9.8% (n = 210) with placebo which represents a risk reduction of 23% (HR: 0.77; 95.1% CI: 0.63 to 0.94; p = 0.01) in favour of subjects receiving olmesartan. At study end eGFR was lower in the olmesartan-treated subjects (80.1 vs. 83.7 mL/min/1.73 m2, p < 0.001). In both groups 23 subjects had a doubling of the baseline serum creatinine. Overall cardiovascular morbidity and mortality rate was low and similar between groups with cardiovascular morbidity events in 81 (3.6%) and 91 (4.1%) patients, and total mortality in 26 (1.2%) and 15 (1.7%) on olmesartan and placebo, respectively (p > 0.1). Cardiovascular mortality however was higher (15 (0.7%) vs. 3 (0.1%); p = 0.01) in the olmesartan group, possibly due to hypotensive episodes in subjects with pre-existing CVD. Conclusions: In subjects with type 2 diabetes and excellent blood pressure control early treatment with the ARB olmesartan showed a significant risk reduction regarding the ‘time to onset of microalbuminuria’.

Journal ArticleDOI
TL;DR: 4 weeks of initial combination therapy resulted in a greater BP reduction from baseline vs monotherapy, demonstrating enhanced efficacy of V/HCTZ in elderly patients.
Abstract: Objective: Hypertension is very common and inadequately controlled among the elderly. Ambulatory blood pressure (ABP) measurement has a better predictive value than office blood pressure (BP) measurement. In a substudy of the VALVET trial, we examined the effect of combined valsartan/hydrochlorothiazide (V/HCTZ), or V or HCTZ alone on 24-h mean ABP in elderly subjects with systolic hypertension. Methods: Three hundred eighty-four subjects >=70 years old with mean sitting systolic BP >150 and =<200 mmHg were randomized to receive V/HCTZ 160/12.5 mg (n = 24), HCTZ 12.5 mg (n = 26), or V 160 mg (n = 31) for 4 weeks. At Week 4, subjects not achieving <140/90 mmHg received optional titration with V/HCTZ (160/12.5 mg in HCTZ and V groups; 320/12.5 mg in V/HCTZ group) up to a maximum dose of V/HCTZ 320/25 mg by Week 12. Results: Baseline ASBP/ADBP values ± SD were 141.1 ± 10.7/76.5 ± 9.3, 142.2 ± 9.3/78.7 ± 7.5, and 142.2 ± 10.6/78.3 ± 8.2 mmHg in the V/HCTZ, HCTZ, and V groups, respectively. At Week 4, reductions from baseline in 24-h mean ASBP and ADBP were greater in subjects initiating V/HCTZ than HCTZ or V alone (Table). At Week 16, differences were observed between V/HCTZ and HCTZ groups only. These results were largely consistent for nighttime vs daytime, and last-4-hours dosing analyses. Adverse events were similar across all groups; the most common being dizziness, fatigue, and headache. Conclusions: In conclusion, 4 weeks of initial combination therapy resulted in a greater BP reduction from baseline vs monotherapy, demonstrating enhanced efficacy of V/HCTZ in elderly patients. Figure 1. No caption available.

Journal ArticleDOI
TL;DR: Initiation of treatment with V/HCTZ lowered BP more effectively, controlled a higher proportion of individuals, reduced the time necessary to reach BP target, and was equally well tolerated compared with monotherapy with either component.
Abstract: Objective: Low rates of blood pressure (BP) control in the elderly are partly attributable to clinicians’ reluctance to initiate combination therapy. The 16-week Valsartan in the Very Elderly Trial (VALVET) investigated the efficacy and tolerability of initial single-pill combination therapy with valsartan (V) and hydrochlorothiazide (HCTZ) vs the individual components at similar doses. Methods: After a 3–14 day washout, subjects >=70 years of age (mean age: 77.5 years, sitting systolic BP [SBP]: 150–200 mmHg) were randomized to V/HCTZ 160/12.5 mg (n = 128), HCTZ 12.5 mg (n = 128), or V 160 mg (n = 128). Subjects not achieving BP goal <140/90 mmHg in any of the 3 groups could receive an optional titration up to a maximum dose of V/HCTZ 320/25 mg from Week 4 until Week 12: subjects in the V and HCTZ arms electively received V/HCTZ 160/12.5 mg at Week 4, 320/12.5 mg at Week 8, and the maximum dose 320/25 mg at Week 12. Results: Mean baseline clinic BP was 165/85 mmHg. At Week 2, there were greater SBP reductions from baseline in subjects assigned initially to the combination V/HCTZ (−18.6 mmHg) compared with those assigned to HCTZ (−13.0 mmHg, p < 0.005), or V (−10.8 mmHg, p < 0.001). Similar BP differences were maintained until the end of study, by which time 65% of subjects initiated on HCTZ and 78% initiated on V required combination therapy. Median time to BP control was lower with V/HCTZ (4 weeks) than with HCTZ (8 weeks, p < 0.05) or V (12 weeks, p < 0.0001). At Week 16, 52.0%, 49.5%, and 36.6% of subjects in the V/HCTZ, HCTZ, and V arms, respectively, achieved goal BP. Adverse events were similar across the 3 treatment groups; the most common events being dizziness, fatigue, and headache. Conclusion: Initiation of treatment with V/HCTZ lowered BP more effectively, controlled a higher proportion of individuals, reduced the time necessary to reach BP target, and was equally well tolerated compared with monotherapy with either component.

Journal ArticleDOI
TL;DR: HBPM measurements confirm that treatment initiated with V/HCTZ resulted in a greater BP reduction from baseline than treatment initiation with either monotherapy and HBPM provides a reliable indicator of BP control in elderly patients and may help guide drug dosing and titration.
Abstract: Objective: To evaluate whether home blood pressure monitoring (HBPM) may enhance assessment of blood pressure (BP) control. Methods: In the 16-week Valsartan in the Very Elderly Trial (VALVET) in individuals over age 70, male and female subjects with systolic BP 150–200 mmHg were randomly assigned to receive valsartan/hydrochlorothiazide (V/HCTZ) 160/12.5 mg (n = 128), HCTZ 12.5 mg (n = 128), or V 160 mg (n = 128) for 4 weeks. At Week 4, subjects not achieving BP goal (<140/90 mmHg) in all 3 groups received optional titration with V/HCTZ (160/12.5 mg in HCTZ and V groups and 320/12.5 mg in V/HCTZ group) up to maximum dose of 320/25 mg by Week 12. Subjects in each group were evaluated by HBPM using an automated device each week prior to taking daily study medication (n = 301). Results: At Week 4, differences between V/HCTZ and HCTZ or V were similar for both HBPM and clinic recordings, and results obtained by either technique correlated significantly (p < 0.0001; see table). Adverse events were similar between groups. Conclusion: In conclusion, (1) HBPM measurements confirm that treatment initiated with V/HCTZ resulted in a greater BP reduction from baseline than treatment initiated with either monotherapy and (2) HBPM provides a reliable indicator of BP control in elderly patients and may help guide drug dosing and titration. Figure 1. No caption available.