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In the prospective, open-label, titrate-to-goal Blood Pressure Control in All Subgroups With Hypertension (BP-CRUSH) study, 999 patients with hypertension uncontrolled on monotherapy (mean age, 55.6 ± 11.4 years; baseline blood pressure [BP], 153.7 ± 9.2/91.9 ± 8.6 mm Hg) were switched to fixed-dose amlodipine/olmesartan medoxomil (AML/OM) 5/20 mg. Patients were uptitrated every 4 weeks to AML/OM 5/40 mg and 10/40 mg to achieve BP < 120/70 mm Hg. Patients were subsequently uptitrated every 4 weeks to AML/OM+hydrochlorothiazide (HCTZ) 10/40+12.5 mg and 10/40+25 mg to achieve BP <125/75 mm Hg. The primary end point, the cumulative percentage of patients achieving seated systolic BP < 140 mm Hg (< 130 mm Hg for patients with diabetes) by week 12, was 75.8%. The mean (± standard error) BP changes from baseline during the titration periods ranged from -14.2±0.4 mm Hg/-7.7 ± 0.3 mm Hg for AML/OM 5/20 mg to -25.1 ± 0.7 mm Hg/-13.7 ± 0.4 mm Hg for AML/OM+HCTZ 10/40+25 mg. By week 20, the cumulative BP threshold of <140/90 mm Hg was achieved by 90.3% of patients. An ambulatory BP monitoring substudy (n=243) showed that 24-hour efficacy was maintained. Treatment-emergent adverse events (TEAEs), mostly mild to moderate in severity, occurred in 529 patients (53.0%). Drug-related TEAEs occurred in 255 patients (25.5%). This well-tolerated, treat-to-goal algorithm enabled a large proportion of patients with uncontrolled hypertension on monotherapy to safely achieve BP control on single-pill AML/OM combination therapy or triple therapy with the addition of HCTZ. . [ABSTRACT FROM AUTHOR]

Since the first International Society on Hypertension in Blacks consensus statement on the "Management of High Blood Pressure in African American" in 2003, data from additional clinical trials have become available. We reviewed hypertension and cardiovascular disease prevention and treatment guidelines, pharmacological hypertension clinical end point trials, and blood pressure-lowering trials in blacks. Selected trials without significant black representation were considered. In this update, blacks with hypertension are divided into 2 risk strata, primary prevention, where elevated blood pressure without target organ damage, preclinical cardiovascular disease, or overt cardiovascular disease for whom blood pressure consistently <135/85 mm Hg is recommended, and secondary prevention, where elevated blood pressure with target organ damage, preclinical cardiovascular disease, and/or a history of cardiovascular disease, for whom blood pressure consistently <130/80 mm Hg is recommended. If blood pressure is ≤10 mm Hg above target levels, monotherapy with a diuretic or calcium channel blocker is preferred. When blood pressure is >15/10 mm Hg above target, 2-drug therapy is recommended, with either a calcium channel blocker plus a renin-angiotensin system blocker or, alternatively, in edematous and/or volume-overload states, with a thiazide diuretic plus a renin-angiotensin system blocker. Effective multidrug therapeutic combinations through 4 drugs are described. Comprehensive lifestyle modifications should be initiated in blacks when blood pressure is ≥115/75 mm Hg. The updated International Society on Hypertension in Blacks consensus statement on hypertension management in blacks lowers the minimum target blood pressure level for the lowest-risk blacks, emphasizes effective multidrug regimens, and de-emphasizes monotherapy. [ABSTRACT FROM AUTHOR]

Prehypertension, defined by Seventh Joint National Committee (JNC 7) as a blood pressure (BP) 120—139/80—89 mm Hg, was controversial. Approximately 31—37% of US adults are prehypertensive, and ∼12—14% have BP of 130—139/85—89 mm Hg or `Stage 2' prehypertension, is associated with ∼3-fold greater likelihood of developing hypertension and roughly twice the cardiovascular events than BP <120/80 mm Hg. Lifestyle change is the only intervention recommended for most prehypertensives. When fully implemented, lifestyle changes lower BP and prevent cardiovascular events, but evidence for community-wide effectiveness is limited. The Trial of Preventing Hypertension (TROPHY) documented that angiotensin receptor blockade safely lowers BP and prevents and/or delays hypertension in Stage 2 prehypertensives. Prehypertensives with diabetes or nephropathy are at high risk and should receive antihypertensive treatment according to JNC 7. Epidemiological data suggest that the number needed to treat to prevent a cardiovascular event in these at-risk Stage 2 prehypertensives is similar to Stage 1 hypertensives when both groups have one or more concomitant risk factors. Clinical trials are urgently needed to address this question. In the absence of clinical trials data, we believe it is prudent for the concerned clinician to consider initiating antihypertensive pharmacotherapy in selected Stage 2 prehypertensive patients at significant absolute risk for progression to hypertension and cardiovascular events. [ABSTRACT FROM PUBLISHER]

The Trial of Preventing Hypertension (TROPHY) demonstrated the feasibility of possibly reducing the incidence of hypertension with the angiotensin receptor blocker candesartan compared with placebo. The long-term benefits of pharmacologic therapy in high-normal blood pressure, or prehypertension are not known, and the long-term effect on health-related quality of life (HRQL) has not been determined. An analysis of covariance model was used to assess treatment differences from baseline in the HRQL scores using Short Form (SF)-36, and component measures at subsequent visits. Of the 809 randomized patients, 734 had both baseline and > or =1 HRQL follow-up assessment: 95% (379 of 397) of patients receiving candesartan and 91% (355 of 388) of patients receiving placebo. There were no statistically significant between-group differences in least-squares mean physical component survey and mental component survey scores or the individual scales at each scheduled visit relative to baseline values (P >.05). In TROPHY, patients with prehypertension had relatively high baseline HRQL, and HRQL was maintained with the angiotensin receptor blocker candesartan over both the 2-year treatment period and a total 4-year trial period. [ABSTRACT FROM AUTHOR]

Treating hypertension reduces the rates of myocardial infarction, stroke, and renal disease; however, clinical trial experience suggests that monotherapy is not likely to be successful for achieving goal blood pressure (BP) levels in many hypertensive patients. In multiple recent clinical trials including various subsets of hypertensive patients, the achievement of BP goal has typically required the combination of 2 or more medications, particularly in patients with BP levels >160/100 mm Hg. When initiating combination therapy for hypertension, careful consideration must be given to the choice of medication. Clinical trial evidence has shown the efficacy of various combinations of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, and diuretics in reducing BP and cardiovascular risk. Ongoing trials should provide additional guidance on the optimal choice of combination regimens in specific clinical settings. [ABSTRACT FROM AUTHOR]

Background: The Trial of Preventing Hypertension (TROPHY) Study is designed to establish whether treating high normal blood pressure with a low-dose angiotensin receptor blocker, candesartan cilexetil, for 2 years reduces the rate of progression to hypertension compared with placebo treatment over a 4-year observation period. We are presenting the baseline cardiovascular risk factor profile of the 809 subjects randomized in the TROPHY Study. The risk factors in this analysis were as follows: cholesterol ≥200 mg/dl; LDL-cholesterol ≥160 mg/dL; HDL-cholesterol ≤40 mg/dL (for men), ≤50 mg/dL (for women); triglycerides ≥150 mg/dL; body mass index ≥25 kg/m2 (overweight and obese), fasting insulin ≥20 mU/mL; heart rate ≥80 beats/min; hematocrit ≥43.5 % (men) and ≥41.2% (women). Methods: The TROPHY Study is a 4-year randomized, placebo-controlled, multicenter clinical trial of 809 subjects with high normal blood pressure (BP), which is currently in progress. Results: The participants of the TROPHY study (mean age 49 ± 8.1 years) with high normal BP (mean 134 ± 4/85 ± 4 mm Hg) had additional cardiovascular risk factors. Of the group, 96% had at least one, 81% had two or more, and 13% had five or more additional risk factors. Conclusions: Our data from individuals with high normal BP suggests clearly that the risk of cardiovascular disease begins to rise before the diagnosis of hypertension is evident. The overall risk in such subjects reflects both the rising BP and other concurring factors. It appears that truly low-risk hypertension only rarely exists. [Copyright &y& Elsevier]

We have seen relationships between whole blood viscosity (WBV) and components of the metabolic cardiovascular syndrome in borderline hypertensive young men and suggested that sympathetic nervous system (SNS) activity may be a mediator. In the present study we aimed to test this hypothesis in established hypertension and to investigate the relationship between WBV and cardiac dimensions. Unmedicated patients (n = 42) with stage II-III hypertension and electrocardiographic left ventricular hypertrophy (LVH) underwent hyperinsulinemic isoglycemic glucose clamp to assess glucose disposal rate (GDR) and echocardiographic studies. WBV, plasma catecholamines and insulin were measured in arterialized venous blood. WBV at high shear rate correlated with baseline plasma adrenaline (r = 0.33, p = 0.04) and fasting insulin (r = 0.34, p = 0.04) while there was a negative trend for GDR (r = -0.21, p = 0.2). WBV at low shear rate correlated with plasma adrenaline (r = 0.49, p = 0.002) and resting heart rate (r = 0.36, p = 0.02). WBV was higher in smokers than in non-smokers (p = 0.02) and in males than in females (p = 0.02). Fasting insulin independently explained 12% of the variation in WBV at high shear, while baseline adrenaline independently explained 17% of the variation in WBV at low shear. Systolic blood pressure explained 31% of the variation in LV mass index. Thus, we demonstrate positive relationships between blood viscosity versus plasma adrenaline and fasting insulin in hypertensive patients with LVH. We suggest that adrenergic activity may increase hematocrit and viscosity and hence reduce insulin sensitivity. [ABSTRACT FROM AUTHOR]

Prehypertension, defined by Seventh Joint National Committee (JNC 7) as a blood pressure (BP) 120-139/80-89 mm Hg, was controversial. Approximately 31-37% of US adults are prehypertensive, and approximately 12-14% have BP of 130-139/85-89 mm Hg or ;Stage 2' prehypertension, is associated with approximately 3-fold greater likelihood of developing hypertension and roughly twice the cardiovascular events than BP <120/80 mm Hg. Lifestyle change is the only intervention recommended for most prehypertensives. When fully implemented, lifestyle changes lower BP and prevent cardiovascular events, but evidence for community-wide effectiveness is limited. The Trial of Preventing Hypertension (TROPHY) documented that angiotensin receptor blockade safely lowers BP and prevents and/or delays hypertension in Stage 2 prehypertensives. Prehypertensives with diabetes or nephropathy are at high risk and should receive antihypertensive treatment according to JNC 7. Epidemiological data suggest that the number needed to treat to prevent a cardiovascular event in these at-risk Stage 2 prehypertensives is similar to Stage 1 hypertensives when both groups have one or more concomitant risk factors. Clinical trials are urgently needed to address this question. In the absence of clinical trials data, we believe it is prudent for the concerned clinician to consider initiating antihypertensive pharmacotherapy in selected Stage 2 prehypertensive patients at significant absolute risk for progression to hypertension and cardiovascular events.

Purpose of Review: Prehypertension is a recognized stage of blood pressure but treatment standards have not yet been established. This review will focus on the treatment considerations in prehypertension., Recent Findings: Previous approaches to prehypertensive blood pressure have focused on the role of nonpharmacologic modalities alone. The recently published Trial of Preventing Hypertension (TROPHY) is the first study of pharmacologic intervention in this category of blood pressure., Summary: TROPHY forged new territory in the area of pharmacologic treatment for prehypertension. The safety and tolerability of the angiotensin receptor blocker treatment in the trial offer a new option to clinicians attempting to avoid the ravages of hypertension in the patients they treat. Furthermore the stage is properly set for additional research in treatments for prehypertension.

The Trial of Preventing Hypertension (TROPHY) investigated pharmacologic intervention in patients with prehypertension. TROPHY confirmed that treatment with candesartan 16 mg can prevent or postpone the development of hypertension, demonstrating a 66.3% reduction in hypertension incidence relative to placebo (26.8% absolute reduction) at 2 years, and a 15.6% reduction in hypertension incidence relative to placebo (9.8% absolute reduction) at 4 years. Further analyses of TROPHY may help to delineate the mechanisms behind this result more specifically, including those relating to components of the metabolic syndrome and markers of inflammation and early vascular change. The rate of progression and the concurrence of risk factors make a strong case for the development of a directive for closer follow-up and treatment. The potential for success in reducing cardiovascular events is great, given the prevalence of prehypertension and the likelihood of progression.