Analysis of decreases in systemic arterial pressure and heart rate in response to the hydrogen sulfide donor sodium sulfide.

The actions of hydrogen sulfide (H2S) on the heart and vasculature have been extensively reported. However, the mechanisms underlying the effects of H2S are unclear in the anesthetized rat. The objective of the present study was to investigate the effect of H2S on the electrocardiogram and examine the relationship between H2S-induced changes in heart rate (HR), mean arterial pressure (MAP), and respiratory function. Intravenous administration of the H2S donor Na2S in the anesthetized Sprague-Dawley rat decreased MAP and HR and produced changes in respiratory function. The administration of Na2S significantly increased the RR interval at some doses but had no effect on PR or corrected QT(n)-B intervals. In experiments where respiration was maintained with a mechanical ventilator, we observed that Na2S-induced decreases in MAP and HR were independent of respiration. In experiments where respiration was maintained by mechanical ventilation and HR was maintained by cardiac pacing, Na2S-induced changes in MAP were not significantly altered, whereas changes in HR were abolished. Coadministration of glybenclamide significantly increased MAP and HR responses at some doses, but methylene blue, diltiazem, and ivabradine had no significant effect compared with control. The decreases in MAP and HR in response to Na2S could be dissociated and were independent of changes in respiratory function, ATP-sensitive K+ channels, methylene blue-sensitive mechanism involving L-type voltage-sensitive Ca2+ channels, or hyperpolarization-activated cyclic nucleotide-gated channels. Cardiovascular responses observed in spontaneously hypertensive rats were more robust than those in Sprague-Dawley rats.NEW & NOTEWORTHY H2S is a gasotransmitter capable of producing a decrease in mean arterial pressure and heart rate. The hypotensive and bradycardic effects of H2S can be dissociated, as shown with cardiac pacing experiments. Responses were not blocked by diltiazem, ivabradine, methylene blue, or glybenclamide.

Prehypertension: Defining the Transitional Phenotype.

More than a simple "transitional stage" defined by covenanted cut points of systolic pressure from 120 to 139 mm of mercury (mm Hg) or a diastolic pressure from 80 to 89 mm Hg, prehypertension should be referred to as a categorical term that defines a specific phenotype in the progression from the "absence of disease" to clinically overt disease. While the currently utilized definition of prehypertension stresses the use of blood pressure cut points to establish the diagnosis, it is of relevance to direct our attention to the structural and functional hemodynamic alterations that occur in response to the two cardinal abnormalities in the development of prehypertension and hypertension: autonomic dysfunction and arterial remodeling. Our current review addresses these aspects of the pathophysiology or prehypertension on its progression to hypertension and suggests a new approach to its classification.

Nebivolol has a beneficial effect in monocrotaline-induced pulmonary hypertension.

Pulmonary hypertension is a rare disorder that, without treatment, is progressive and fatal within 3-4 years. Current treatment involves a diverse group of drugs that target the pulmonary vascular bed. In addition, strategies that increase nitric oxide (NO) formation have a beneficial effect in rodents and patients. Nebivolol, a selective ß1 adrenergic receptor-blocking agent reported to increase NO production and stimulate ß3 receptors, has vasodilator properties suggesting that it may be beneficial in the treatment of pulmonary hypertension. The present study was undertaken to determine whether nebivolol has a beneficial effect in monocrotaline-induced (60 mg/kg) pulmonary hypertension in the rat. These results show that nebivolol treatment (10 mg/kg, once or twice daily) attenuates pulmonary hypertension, reduces right ventricular hypertrophy, and improves pulmonary artery remodeling in monocrotaline-induced pulmonary hypertension. This study demonstrates the presence of ß3 adrenergic receptor immunoreactivity in pulmonary arteries and airways and that nebivolol has pulmonary vasodilator activity. Studies with ß3 receptor agonists (mirabegron, BRL 37344) and antagonists suggest that ß3 receptor-mediated decreases in systemic arterial pressure occur independent of NO release. Our results suggest that nebivolol, a selective vasodilating ß1 receptor antagonist that stimulates ß3 adrenergic receptors and induces vasodilation by increasing NO production, may be beneficial in treating pulmonary hypertensive disorders.

Efficacy and safety of nebivolol and valsartan as fixed-dose combination in hypertension: a randomised, multicentre study.

BACKGROUND: The fixed-dose combination of any two antihypertensive drugs from different drug classes is typically more effective in reducing blood pressure than a dose increase of component monotherapy. We assessed the efficacy and safety of a fixed-dose combination of a vasodilating ß blocker (nebivolol) and an angiotensin II receptor blocker (valsartan) in adults with hypertension. METHODS: We did an 8-week, phase 3, multicentre, randomised, double-blind, placebo-controlled, parallel-group trial at 401 US sites. Participants (age ≥18 years) with hypertension but with blood pressure less than 180/110 mm Hg were randomly assigned (2:2:2:2:2:2:2:1) by a 24-h interactive web response system in blocks of 15 to 4 weeks of double-blind treatment with nebivolol and valsartan fixed-dose combination (5 and 80 mg/day, 5 and 160 mg/day, or 10 and 160 mg/day), nebivolol (5 mg/day or 20 mg/day), valsartan (80 mg/day or 160 mg/day), or placebo. Doses were doubled in weeks 5-8; results are reported according to the final dose. Participants and research staff were masked to treatment allocation. The primary and key secondary endpoints were changes from baseline to week 8 in diastolic and systolic blood pressure, respectively. The primary statistical comparison was between the highest fixed-dose combination dose and the highest monotherapy doses; lower doses were then compared if this comparison was positive (Hochberg method for multiple testing). Efficacy analyses were by intention to treat. Safety assessments included monitoring of adverse events. Continuous efficacy parameters were analysed using an ANCOVA model; binary outcomes were analysed using a logistic regression model. This study is registered with ClinicalTrials.gov, NCT01508026. FINDINGS: Between Jan 6, 2012, and March 15, 2013, 4161 patients were randomly assigned (277 to placebo and 554-555 to each active comparator group), 4118 of whom were included in the primary analysis. At week 8, the fixed-dose combination 20 and 320 mg/day group had significantly greater reductions in diastolic blood pressure from baseline than both nebivolol 40 mg/day (least-squares mean difference -1·2 mm Hg, 95% CI -2·3 to -0·1; p=0·030) and valsartan 320 mg/day (-4·4 mm Hg, -5·4 to -3·3; p<0·0001); all other comparisons were also significant, favouring the fixed-dose combinations (all p<0·0001). All systolic blood pressure comparisons were also significant (all p<0·01). At least one treatment-emergent adverse event was experienced by 30-36% of participants in each group. INTERPRETATION: Nebivolol and valsartan fixed-dose combination is an effective and well-tolerated treatment option for patients with hypertension. FUNDING: Forest Research Institute.

Predictors of stroke in patients with impaired glucose tolerance: results from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research trial.

BACKGROUND AND PURPOSE: Risk factors for stroke are well-established in general populations but sparsely studied in individuals with impaired glucose tolerance. METHODS: We identified predictors of stroke among participants with impaired glucose tolerance in the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial. Cox proportional-hazard regression models were constructed using baseline variables, including the 2 medications studied, valsartan and nateglinide. RESULTS: Among 9306 participants, 237 experienced a stroke over 6.4 years. Predictors of stroke included classical risk factors such as existing cerebrovascular and coronary heart disease, higher pulse pressure, higher low-density lipoprotein cholesterol, older age, and atrial fibrillation. Other factors, including previous venous thromboembolism, higher waist circumference, lower estimated glomerular filtration rate, lower heart rate, and lower body mass index, provided additional important predictive information, yielding a C-index of 0.72. Glycemic measures were not predictive of stroke. Variables associated with stroke were similar in participants with no prior history of cerebrovascular disease at baseline. CONCLUSIONS: The most powerful predictors of stroke in patients with impaired glucose tolerance included a combination of established risk factors and novel variables, such as previous venous thromboembolism and elevated waist circumference, allowing moderately effective identification of high-risk individuals.

Incidence of atrial fibrillation in a population with impaired glucose tolerance: the contribution of glucose metabolism and other risk factors. A post hoc analysis of the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research trial.

BACKGROUND: The role of dysglycemia as an additional risk factor for atrial fibrillation (AF) is controversial. Therefore, it was of interest to assess risk factors for incident AF in a large, representative population of patients with cardiovascular risk factors and impaired glucose tolerance but not overt diabetes in NAVIGATOR. METHODS: Predictors of incident AF were analyzed in 8,943 patients without AF at baseline by Cox proportional hazards regression. Study treatments (valsartan vs no valsartan and nateglinide vs no nateglinide) and the time-dependent covariate for progression to type 2 diabetes mellitus were added separately to the model. RESULTS: The median age of the 8,943 patients included in the present analysis of the NAVIGATOR trial was 63 years. Half of those patients were men, 6,922 (77.4%) had a history of hypertension, and 255 (2.9%) had heart failure. The median glycated hemoglobin was 6%. During the study, 613 of the 8,943 patients without AF at baseline presented with at least 1 episode of AF (6.9% 5-year incidence). Besides established predictors of incident AF, a 1 mmol/L increment of baseline fasting glucose, but not progression to diabetes, was found to be associated with a 33% increased risk of incident AF. Neither valsartan nor nateglinide affected AF incidence. CONCLUSIONS: In a trial population with impaired glucose tolerance, fasting plasma glucose and well-known risk factors (age, hypertension, and elevated body weight), but not progression to diabetes, predict risk of AF.

Resistant hypertension: concepts and approach to management.

Resistant hypertension (RH), defined simply, is blood pressure (BP) requiring the use of four or more antihypertensive agents, whether controlled or uncontrolled. RH is an increasingly common problem in elderly patients and may affect as many as 20% of the hypertensive population. Unfortunately, at least 30% of patients evaluated for RH are actually adequately controlled when more carefully assessed by home BP monitoring or ambulatory BP monitoring, thus representing a white coat effect. It is also essential to exclude pseudoresistance resulting from improper BP recording techniques or failure of the patient to adhere to the prescribed treatment regimen. Concurrent use of drugs that may interfere with prescribed antihypertensive agents, including many over the counter herbal preparations, must also be excluded. The underlying mechanisms principally driving true RH include pathophysiologic abnormalities of aldosterone signaling, sodium and water retention, excessive sympathetic nervous system activity, and obstructive sleep apnea. Appropriate treatment regimens will usually include an inhibitor of the renin-angiotensin-aldosterone system, a calcium channel blocker, and a diuretic. An aldosterone receptor blocker can be instituted at any step, and is very effective as a fourth drug. Beta-blockers can also be integrated into these treatment plans and may be especially helpful when excessive sympathetic nervous system activity is suspected. Novel device therapies that interrupt sympathetic nerve stimulation at the carotid sinus and kidney are under investigation, and may add entirely new directions in the management of RH. What is most important is that treatment regimens should be targeted to specific patient profiles.

What is the blood pressure goal for the elder patient 75 years of age or older?

High blood pressure (BP), once believed to represent a normal and progressive component of the aging process, is now recognized as a manifestation of structural and physiologic abnormalities of arterial function. Two phenotypes exist in the older patient: elevated systolic blood pressure (SBP) and diastolic blood pressure (DBP) with a normal pulse pressure (PP), and elevated SBP with an increased PP. Elevated SBP and increased PP unquestionably increase the risk of both fatal and nonfatal cardiovascular events, including stroke, myocardial infarction, and heart failure. Isolated systolic hypertension, defined as an SBP ≥140 mm Hg with a DBP less than 90 mm Hg, affects the majority of individuals ages 60 years and older. A number of clinical trials have clearly demonstrated that treatment of hypertension significantly reduces the cardiovascular event rate in older patients. However, controversy continues as to the choice of antihypertensive agents and combinations of agents. It is both appropriate and necessary to treat elderly hypertensive patients aggressively to the same target BPs identified for younger patients. It is also appropriate to initiate treatment with lower doses of antihypertensive agents and to bring the pressure down more slowly, monitoring for orthostatic hypotension, impaired cognition, and electrolyte abnormalities.

The evolving definition of systemic arterial hypertension.

Systemic hypertension is an important risk factor for premature cardiovascular disease. Hypertension also contributes to excessive morbidity and mortality. Whereas excellent therapeutic options are available to treat hypertension, there is an unsettled issue about the very definition of hypertension. At what level of blood pressure should we treat hypertension? Does the definition of hypertension change in the presence of co-morbid conditions? This article covers in detail the evolving concepts in the diagnosis and management of hypertension.

Resistant hypertension: diagnosis, evaluation, and treatment: a scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research.

Resistant hypertension is a common clinical problem faced by both primary care clinicians and specialists. While the exact prevalence of resistant hypertension is unknown, clinical trials suggest that it is not rare, involving perhaps 20% to 30% of study participants. As older age and obesity are 2 of the strongest risk factors for uncontrolled hypertension, the incidence of resistant hypertension will likely increase as the population becomes more elderly and heavier. The prognosis of resistant hypertension is unknown, but cardiovascular risk is undoubtedly increased as patients often have a history of long-standing, severe hypertension complicated by multiple other cardiovascular risk factors such as obesity, sleep apnea, diabetes, and chronic kidney disease. The diagnosis of resistant hypertension requires use of good blood pressure technique to confirm persistently elevated blood pressure levels. Pseudoresistance, including lack of blood pressure control secondary to poor medication adherence or white coat hypertension, must be excluded. Resistant hypertension is almost always multifactorial in etiology. Successful treatment requires identification and reversal of lifestyle factors contributing to treatment resistance; diagnosis and appropriate treatment of secondary causes of hypertension; and use of effective multidrug regimens. As a subgroup, patients with resistant hypertension have not been widely studied. Observational assessments have allowed for identification of demographic and lifestyle characteristics associated with resistant hypertension, and the role of secondary causes of hypertension in promoting treatment resistance is well documented; however, identification of broader mechanisms of treatment resistance is lacking. In particular, attempts to elucidate potential genetic causes of resistant hypertension have been limited. Recommendations for the pharmacological treatment of resistant hypertension remain largely empiric due to the lack of systematic assessments of 3 or 4 drug combinations. Studies of resistant hypertension are limited by the high cardiovascular risk of patients within this subgroup, which generally precludes safe withdrawal of medications; the presence of multiple disease processes (eg, sleep apnea, diabetes, chronic kidney disease, atherosclerotic disease) and their associated medical therapies, which confound interpretation of study results; and the difficulty in enrolling large numbers of study participants. Expanding our understanding of the causes of resistant hypertension and thereby potentially allowing for more effective prevention and/or treatment will be essential to improve the long-term clinical management of this disorder.

Evolving mechanisms of action of beta blockers: focus on nebivolol.

Beta (beta) blockers are widely used for treatment of cardiovascular and noncardiovascular diseases. Nevertheless, their mechanism of action is not fully understood and differs significantly among agents in this class. Chronic increases in adrenergic activity in heart failure result in desensitization of cardiac beta-adrenergic receptor signal transduction and adverse effects on myocytes. By reducing heart rate and decreasing myocardial workload, the pathologic remodeling of the heart may be reversed with beta-blocking agents. Among beta-blockers, there are clear differences in pharmacodynamic and pharmacokinetic properties. Newer beta-blockers differ from older agents with respect to beta-adrenoceptor affinity and selectivity and partial agonist activity, which may affect their mechanism of action and be important in clinical use.The first beta-antagonist compounds were nonselective; the next generation of beta-blockers was selective for beta1-receptors. The most recent beta-blockers may be nonselective or selective, and they have the additional ancillary property of vasodilation. Nebivolol is among the newer third-generation beta-blockers. It is unique in the class, since apart from its cardioselectivity, it also produces nitric oxide-mediated vasodilation. As a result, its hemodynamic profile is clearly different from those of traditional beta-blockers. This review will evaluate this class of agents and the basis for their differences in clinical use.

Pioglitazone and heart failure: results from a controlled study in patients with type 2 diabetes mellitus and systolic dysfunction.

BACKGROUND: Thiazolidinediones are associated with fluid retention, often interpreted as worsening cardiac function, limiting their use in patients with heart failure (HF). We compared the effects of pioglitazone and glyburide on cardiac function in patients with type 2 diabetes, systolic dysfunction, and New York Heart Association (NYHA) functional Class II/III HF. METHODS AND RESULTS: Participants received pioglitazone or glyburide (+/-insulin) for 6 months in this double-blind, randomized, multicenter study. The primary end point was time to HF, a composite of cardiovascular mortality and hospitalization or emergency room (ER) visit for HF. Secondary endpoints included echocardiographic and functional classification assessments. An earlier time to onset and higher incidence of the primary endpoint was noted with pioglitazone (13%) versus glyburide (8%) (P = .024). Hospitalization or ER visit occurred in 30 pioglitazone and 15 glyburide participants, 19 and 12 of whom, respectively, continued treatment. Cardiac mortality (5 versus 6 participants, respectively) and cardiac function, as measured by change in ventricular mass index (P = .959), ejection fraction (P = .413), or fractional shortening (P = .280), were similar between treatments. CONCLUSIONS: Pioglitazone was associated with a higher incidence of hospitalization for HF without an increase in cardiovascular mortality or worsening cardiac function (by echocardiography).

Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism.

Obesity is becoming a global epidemic in both children and adults. It is associated with numerous comorbidities such as cardiovascular diseases (CVD), type 2 diabetes, hypertension, certain cancers, and sleep apnea/sleep-disordered breathing. In fact, obesity is an independent risk factor for CVD, and CVD risks have also been documented in obese children. Obesity is associated with an increased risk of morbidity and mortality as well as reduced life expectancy. Health service use and medical costs associated with obesity and related diseases have risen dramatically and are expected to continue to rise. Besides an altered metabolic profile, a variety of adaptations/alterations in cardiac structure and function occur in the individual as adipose tissue accumulates in excess amounts, even in the absence of comorbidities. Hence, obesity may affect the heart through its influence on known risk factors such as dyslipidemia, hypertension, glucose intolerance, inflammatory markers, obstructive sleep apnea/hypoventilation, and the prothrombotic state, in addition to as-yet-unrecognized mechanisms. On the whole, overweight and obesity predispose to or are associated with numerous cardiac complications such as coronary heart disease, heart failure, and sudden death because of their impact on the cardiovascular system. The pathophysiology of these entities that are linked to obesity will be discussed. However, the cardiovascular clinical evaluation of obese patients may be limited because of the morphology of the individual. In this statement, we review the available evidence of the impact of obesity on CVD with emphasis on the evaluation of cardiac structure and function in obese patients and the effect of weight loss on the cardiovascular system.

Renin-angiotensin system modulation for treatment and prevention of cardiovascular diseases: toward an optimal therapeutic strategy.

The unraveling of the role of the renin-angiotensin system (RAS) in health and disease is an example of how basic and applied scientists can decipher a complex biological system to better understand the pathophysiology of disease. Moreover, clinicians have been provided with drugs to modulate the RAS, including the angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). ACE inhibitors and ARBs have revolutionized the way in which many diseases are treated, including hypertension, heart failure, diabetes mellitus, and kidney disease. Yet, despite the undoubted successes of these drugs, cardiovascular morbidity and mortality remain high. Clearly, lower blood pressure goals may be required. Because ACE inhibitors and ARBs target specific areas of the RAS, more impressive results might be obtained with a more global reduction in RAS activity. This article examines the results of clinical trials of ACE inhibitors and ARBs and assesses the potential for improving outcomes through a more global inhibition of the RAS with renin inhibitors.

A perspective on telmisartan and cardiovascular risk.

The angiotensin receptor blockers (ARBs) are well established as safe and effective in the treatment of arterial hypertension. Telmisartan is an ARB with potent blood-pressure lowering effects. It has a long terminal half-life of about 24 hours (the longest of any of the ARBs), which enables it to sustain blood pressure reductions in the early morning hours, after the previous morning dosing. Unlike the angiotensin-converting enzyme (ACE) inhibitors, the ARBs have not been shown to reduce mortality and morbidity in high-risk patients with coronary disease, peripheral vascular disease, cerebrovascular disease, or diabetes with cardiovascular risk factors without evidence of heart failure or low ejection fraction. Two studies, the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) and the Telmisartan Randomized AssessmeNt Study in ACE-I INtolerant Subjects with Cardiovascular Disease (TRANSCEND) trial, are examining the benefits of ARBs alone and in combination with ACE inhibitors in high-risk patients.

Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss.

Obesity is becoming a global epidemic in both children and adults, and it is associated with numerous co-morbidities such as cardiovascular diseases (CVD), type 2 diabetes, hypertension, certain cancers, and sleep apnea/sleep-disordered breathing. In fact, is an independent risk factor for CVD and CVD risks have been also documented in obese children, and is associated with reduced life expectancy. A variety of adaptations/alterations in cardiac structure and function occur in the individual as adipose tissue accumulates in excess amount. As a whole, overweight/obesity predispose or is associated with numerous cardiac complications such as coronary heart disease, heart failure, and sudden death through its impact on the cardiovascular system.

Where are we going? Beyond JNC 7.

On August 15, 2007, a panel discussion was held to discuss hypertension. The panel was moderated by Thomas D. Giles, MD, Tulane University School of Medicine, New Orleans, LA. Discussants included Suzanne Oparil, MD, University of Alabama at Birmingham, Birmingham, AL, and Thomas G. Pickering, MD, DPhil, Columbia Presbyterian Medical Center, New York, NY.

Comparison of increasing doses of olmesartan medoxomil, losartan potassium, and valsartan in patients with essential hypertension.

This 12-week, randomized, double-blind, forced-titration study compared the efficacy of 3 angiotensin receptor blockers. Patients received olmesartan medoxomil 20 mg, losartan potassium 50 mg, valsartan 80 mg, or placebo once daily. At week 4, doses were titrated to 40, 100, and 160 mg once daily for olmesartan, losartan, and valsartan, respectively. At week 8, losartan was increased to 50 mg twice daily and valsartan increased to 320 mg once daily (olmesartan remained at 40 mg once daily). The primary end point was mean change from baseline in seated diastolic blood pressure (SeDBP) at week 8. All 3 medications significantly reduced mean SeDBP from baseline compared with placebo at weeks 4, 8, and 12 (P<.001). At week 8, olmesartan reduced mean SeDBP more than losartan (P<.001); more patients in the olmesartan medoxomil group achieved a blood pressure goal of <140/90 mm Hg (P<.001). Olmesartan did not reduce mean SeDBP significantly compared with valsartan, although more patients attained blood pressure goal with olmesartan (P=.031). At week 12, all agents lowered blood pressure equivalently.

Rationale for nebivolol/valsartan combination for hypertension: review of preclinical and clinical data.

: To treat hypertension, combining two or more antihypertensive drugs from different classes is often necessary. ß-Blockers and renin-angiotensin-aldosterone system inhibitors, when combined, have been deemed 'less effective' based on partially overlapping mechanisms of action and limited evidence. Recently, the single-pill combination (SPC) of nebivolol (Neb) 5 mg - a vasodilatory ß1-selective antagonist/ß3 agonist - and valsartan 80 mg, an angiotensin II receptor blocker, was US Food and Drug Administration-approved for hypertension. Pharmacological profiles of Neb and valsartan, alone and combined, are well characterized. In addition, a large 8-week randomized trial in stages I-II hypertensive patients (N = 4161) demonstrated greater blood pressure-reducing efficacy for Neb/valsartan SPCs than component monotherapies with comparable tolerability. In a biomarkers substudy (N = 805), Neb/valsartan SPCs prevented valsartan-induced increases in plasma renin, and a greater reduction in plasma aldosterone was observed with the highest SPC dose vs. valsartan 320 mg/day. This review summarizes preclinical and clinical evidence supporting Neb/valsartan as an efficacious and well tolerated combination treatment for hypertension.

Efficacy of nebivolol-valsartan single-pill combination in obese and nonobese patients with hypertension.

Antihypertensive efficacy of single-pill combinations (SPCs) consisting of a ß1 -selective adrenergic blocker with vasodilatory properties via ß3 -agonism (nebivolol) and an angiotensin II receptor blocker (valsartan) was demonstrated in an 8-week phase 3 trial (NCT01508026). In this post hoc analysis, seated blood pressure, heart rate, 24-hour ambulatory blood pressure monitoring, plasma aldosterone, estimated glomerular filtration rate, and safety measures were assessed in obese (body mass index >32 kg/m2 ; n=1823) and nonobese (body mass index <27 kg/m2 ; n=847) adults with hypertension (stage I or II) treated with nebivolol-valsartan SPCs, nebivolol or valsartan monotherapy, or placebo. At week 8, reductions from baseline in blood pressure and ambulatory blood pressure monitoring were greater with SPCs and most nebivolol and valsartan monotherapy doses vs placebo regardless of obesity status. Aldosterone declined with all active treatments and estimated glomerular filtration rate remained steady. The nebivolol-valsartan 5/80 mg/d SPC was efficacious regardless of degree of obesity.