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The obesity pandemic, with its associated comorbidities of hypertension and diabetes, constitutes a global public health issue. Importantly, there is an increasing prevalence of aldosterone excess related to obesity and resultant poor health outcomes. Nevertheless, the association between aldosterone and obesity still needs to be clarified. In this review, the authors discuss the role of white adipose tissue in linking obesity, aldosterone excess, and hypertension. The consequences of aldosterone excess in obesity are presented as genomic, non-genomic, and non-epithelial effects. Moreover, the authors emphasize the value of interference with aldosterone pathophysiology (as with mineralocorticoid antagonists) in obesity, thus reducing the adverse clinical impact of aldosterone in myocardial infarction, heart failure, kidney dysfunction, and associated mortality., (© 2024 The Author(s). The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

The clinical implications of hypertension in addition to a high prevalence of both uncontrolled blood pressure and medication nonadherence promote interest in developing device-based approaches to hypertension treatment. The expansion of device-based therapies and ongoing clinical trials underscores the need for consistency in trial design, conduct, and definitions of clinical study elements to permit trial comparability and data poolability. Standardizing methods of blood pressure assessment, effectiveness measures beyond blood pressure alone, and safety outcomes are paramount. The Hypertension Academic Research Consortium (HARC) document represents an integration of evolving evidence and consensus opinion among leading experts in cardiovascular medicine and hypertension research with regulatory perspectives on clinical trial design and methodology. The HARC document integrates the collective information among device-based therapies for hypertension to better address existing challenges and identify unmet needs for technologies proposed to treat the world's leading cause of death and disability. Consistent with the Academic Research Consortium charter, this document proposes pragmatic consensus clinical design principles and outcomes definitions for studies aimed at evaluating device-based hypertension therapies.

Severe hypertension (HTN) that develops during hospitalization is more common than admission for HTN; however, it is poorly studied, and treatment guidelines are lacking. Our goal is to characterize hospitalized patients who develop severe HTN and assess blood pressure (BP) response to treatment. This is a multi-hospital retrospective cohort study of adults admitted for reasons other than HTN who developed severe HTN. The authors defined severe inpatient HTN as the first documented BP elevation (systolic BP > 180 or diastolic BP > 110) at least 1 hour after admission. Treatment was defined as receiving antihypertensives (intravenous [IV] or oral) within 6h of BP elevation. As a measure of possible overtreatment, the authors studied the association between treatment and time to mean arterial pressure (MAP) drop ≥ 30% using the Cox proportional hazards model. Among 224 265 hospitalized adults, 10% developed severe HTN of which 40% were treated. Compared to patients who did not develop severe HTN, those who did were older, more commonly women and black, and had more comorbidities. Incident MAP drop ≥ 30% among treated and untreated patients with severe HTN was 2.2 versus 5.7/1000 person-hours. After adjustment, treated versus. untreated patients had lower rates of MAP drop ≥ 30% (hazard rate [HR]: 0.9 [0.8, 0.99]). However, those receiving only IV treatment versus untreated had greater rates of MAP drop ≥ 30% (1.4 [1.2, 1.7]). Overall, the authors found that clinically significant MAP drop is observed among inpatients with severe HTN irrespective of treatment, with greater rates observed among patients treated only with IV antihypertensives. Further research is needed to phenotype inpatients with severe HTN., (© 2022 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

High blood pressure (BP) is the leading cause of worldwide cardiovascular disease morbidity and mortality. Patients and clinicians dealing with hypertension have benefited from the evidence of event-based randomized controlled clinical trials. One result from those trials has been the development of evidence-based guidelines. The commitment to using evidence from these event-based randomized trials has been a cornerstone in the development of guideline treatment recommendations. However, in some situations, evidence from event-based trials is not available to guideline writers or clinicians for assistance in treatment decision making. Such is the case for the management of many patients with stage 1 hypertension. The purpose of this scientific statement is to provide information complementary to the 2017 Hypertension Clinical Practice Guidelines for the patient with untreated stage 1 hypertension (systolic BP/diastolic BP, 130-139/80-89 mm Hg) with a 10-year risk for atherosclerotic cardiovascular disease <10% who fails to meet the systolic BP/diastolic goal (<130/80 mm Hg) after 6 months of guideline-recommended lifestyle therapy. This statement provides evidence from sources other than event-based randomized controlled clinical trials and offers therapy options for consideration by clinicians.

The effect of clinic-based intensive hypertension treatment on ambulatory blood pressure (BP) is unknown. The goal of the SPRINT (Systolic Blood Pressure Intervention Trial) ambulatory BP ancillary study was to evaluate the effect of intensive versus standard clinic-based BP targets on ambulatory BP. Ambulatory BP was obtained within 3 weeks of the 27-month study visit in 897 SPRINT participants. Intensive treatment resulted in lower clinic systolic BP (mean difference between groups=16.0 mm Hg; 95% confidence interval, 14.1-17.8 mm Hg), nighttime systolic BP (mean difference=9.6 mm Hg; 95% confidence interval, 7.7-11.5 mm Hg), daytime systolic BP (mean difference=12.3 mm Hg; 95% confidence interval, 10.6-13.9 mm Hg), and 24-hour systolic BP (mean difference=11.2 mm Hg; 95% confidence interval, 9.7-12.8 mm Hg). The night/day systolic BP ratio was similar between the intensive (0.92±0.09) and standard-treatment groups (0.91±0.09). There was considerable lack of agreement within participants between clinic systolic BP and daytime ambulatory systolic BP with wide limits of agreement on Bland-Altman plots. In conclusion, targeting a systolic BP of <120 mm Hg, when compared with <140 mm Hg, resulted in lower nighttime, daytime, and 24-hour systolic BP, but did not change the night/day systolic BP ratio. Ambulatory BP monitoring may be required to assess the effect of targeted hypertension therapy on out of office BP. Further studies are needed to assess whether targeting hypertension therapy based on ambulatory BP improves clinical outcomes., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01835249., Competing Interests: The remaining authors report no conflicts of interest., (© 2016 American Heart Association, Inc.)

Renal sympathetic activation plays a key role in the pathogenesis of hypertension, as demonstrated by high renal norepinephrine spillover into plasma of patients with essential hypertension. Renal denervation has demonstrated a significant reduction in blood pressure in unblinded studies of hypertensive patients. The SYMPLICITY HTN-3 trial, the first prospective, masked, randomized study of renal denervation versus sham control, failed its primary efficacy end point and raised important questions around potentially confounding factors, such as drug changes and adherence, study population, and procedural methods. The SPYRAL HTN Global Clinical Trial Program is designed to address limitations associated with predicate studies and provide insight into the impact of pharmacotherapy on renal denervation efficacy. The 2 initial trials of the program focus on the effect of renal denervation using the Symplicity Spyral multielectrode renal denervation catheter in hypertensive patients in the absence (SPYRAL HTN OFF-MED) and presence (SPYRAL HTN ON-MED) of antihypertensive medications. The SPYRAL HTN ON-MED study requires patients to be treated with a consistent triple therapy antihypertensive regimen, whereas the SPYRAL HTN OFF-MED study includes a 3- to 4-week drug washout period followed by a 3-month efficacy and safety end point in the absence of antihypertensive medications. The studies will randomize patients with combined systolic-diastolic hypertension to renal denervation or sham procedure. Both studies allow renal denervation treatments in renal artery branches and accessories. These studies will inform the design of the second pivotal phase of the program, which will more definitively analyze the antihypertensive effect of renal denervation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Accurate blood pressure measurement is critical to properly identify and treat individuals with hypertension. In 2005, the Canadian Hypertension Education Program produced a revised algorithm to be used for the diagnosis of hypertension. Subsequent annual reviews of the literature have identified 2 major deficiencies in the current diagnostic process. First, auscultatory measurements performed in routine clinical settings have serious accuracy limitations that have not been overcome despite great efforts to educate health care professionals over several years. Thus, alternatives to auscultatory measurements should be used. Second, recent data indicate that patients with white coat hypertension must be identified earlier in the process and in a systematic manner rather than on an ad hoc or voluntary basis so they are not unnecessarily treated with antihypertensive medications. The economic and health consequences of white coat hypertension are reviewed. In this article evidence for a revised algorithm to diagnose hypertension is presented. Protocols for home blood pressure measurement and ambulatory blood pressure monitoring are reviewed. The role of automated office blood pressure measurement is updated. The revised algorithm strongly encourages the use of validated electronic digital oscillometric devices and recommends that out-of-office blood pressure measurements, ambulatory blood pressure monitoring (preferred), or home blood pressure measurement, should be performed to confirm the diagnosis of hypertension., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Hypertension is a leading cause of cardiovascular morbidity and mortality, and uncontrolled hypertension remains common despite the availability of several classes of effective antihypertensive medications. Combination therapy with antihypertensive agents of complementary actions has been advocated in the management of hypertension to maximize efficacy and minimize side effects., Areas Covered: This review summarizes the current data on the triple combination therapy of aliskiren with amlodipine and hydrochlorothiazide, and discusses the clinical use of single pill triple combination of aliskiren, amlodipine and hydrochlorothiazide in the treatment of hypertension and associated cardiovascular conditions., Expert Opinion: Combination therapy with antihypertensive agents of complementary actions is more effective than monotherapy in the management of hypertension. Combining an agent in renin-angiotensin blockade with a dihydropyridine calcium channel blocker (CCB) and a thiazide diuretic has plausibility in maximizing blood pressure reduction and minimizing side effects. The combination of aliskiren with amlodipine and hydrochlorothiazide has shown effective blood pressure lowering and noteworthy tolerability. The single pill triple combination of aliskiren, amlodipine, and hydrochlorothiazide offers five different formulations of escalating dosages of the three agents, allowing dosing flexibility. The decreased pill burden and simplified treatment options with the single pill triple combination provide an opportunity to improve blood pressure control through improved adherence and reduced treatment inertia.

Important questions concerning the comparative effectiveness of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) remain unanswered, including whether they are equally effective in reducing clinical end points and in which populations. An incident cohort of adult patients 18 years and older prescribed an ACE inhibitor or ARB between 2001 and 2008 was identified from Geisinger Clinic, a large community-based set of medical practices that uses a common electronic health record. Propensity score matching was used to balance the groups on baseline factors. The authors examined differences in mortality and new-onset coronary disease, chronic kidney disease, stroke, and diabetes for different patient subgroups based on sex and age. A total of 25,035 hypertensive patients newly prescribed an ACE inhibitor or ARB were identified. No differences were found in risk of death, coronary disease, chronic kidney disease, or stroke between those prescribed ACE inhibitors and those prescribed ARBs. Patients prescribed ARBs had a greater rate of new-onset diabetes (hazard ratio [HR], 1.28; confidence interval [CI], 1.08-1.52), and this was especially true for women (HR, 1.93; CI, 1.22-3.07). Within a large medical-practice based population, there was no evidence of differential effectiveness between ACE inhibitors and ARBs for most outcomes, with diabetes being the notable exception., (© 2012 Wiley Periodicals, Inc.)

Peripheral brachial blood pressure measurements by sphygmomanometry remains the standard for measuring and managing blood pressure. Elevated brachial blood pressure is a major risk for cardiovascular disease, and reduction of bracial blood pressure decreases target organ damage and cardiovascular events. However, many patients still succumb to heart disease, stroke, kidney failure, and death even when the brachial blood pressures appear adequately controlled. Central aortic pressure may be more relevant to the pathogenesis of cardiovascular disease, which is not always accurately represented by brachial blood pressure. Noninvasive applanation tonometry can now assess central aortic pressure easily and reliably. Emerging data suggest that central arotic pressure and related parameters are often better and more robust predictors of cardiovascular outcome than peripheral brachial blood pressures.

The blood pressure (BP) effects of naproxcinod and naproxen were assessed in an 8-week, double-blind, crossover study in 131 hypertensive patients aged 50 to 74 years. Patients received naproxcinod 750 mg twice daily or naproxen 500 mg twice daily, then the alternate treatment, each for 14 days, with placebo run-in/washout before each active treatment period and 24-hour ambulatory BP monitoring conducted before and after each active treatment period. Mean change from baseline in average 24-hour systolic BP (SBP) after 2 weeks of treatment numerically favored naproxcinod 750 mg twice daily (least-squares [LS] mean for naproxcinod minus naproxen: -1.6 mm Hg; P=.12). Post hoc analyses showed statistically significant SBP differences favoring naproxcinod for the 8 elapsed hours (LS mean: -4.4 mm Hg; P<.0001) and the 24 hours following morning dosing (LS mean: -2.4 mm Hg; P=.006). Naproxcinod may be a beneficial alternative for patients with osteoarthritis requiring nonsteroidal anti-inflammatory drugs., (© 2011 Wiley Periodicals, Inc.)

Efficacy of antihypertensive agents on central blood pressure (BP) in African Americans is not well studied. The authors report on an 8-week double-blind, randomized study of African American patients with stage 2 hypertension that compared brachial and central BP responses (substudy of 53 patients) to combination aliskiren/hydrochlorthiazide (HCTZ) and amlodipine monotherapy. Following a 1- to 4-week washout, initial therapy was aliskiren/HCTZ 150/12.5 mg (n=166) or amlodipine 5 mg (n=166) for 1 week, forced-titrated to aliskiren/HCTZ 300/25 mg or amlodipine 10 mg for 7 weeks. Mean seated systolic BP reductions from baseline was similar with both treatments (-28.6 mm Hg with aliskiren/HCTZ vs -28.2 mm Hg with amlodipine). In the substudy, significantly greater reductions in central systolic BP was observed with aliskiren/HCTZ vs amlodipine (-30.1 mm Hg vs -21.2; P=.031), although 24-hour mean ambulatory BP reductions between the two groups were similar. Central pressure is considered an important risk factor in African Americans, and these findings may suggest a new treatment option for these patients., (© 2011 Wiley Periodicals, Inc.)

Background: A low rate of blood pressure control has been reported in patients with chronic kidney disease (CKD). These data were derived from population-based samples with a low rate of CKD awareness., Study Design: Cross-sectional., Setting & Participants: Data from the baseline visit of the Chronic Renal Insufficiency Cohort (CRIC) Study (n = 3,612) were analyzed. Participants with an estimated glomerular filtration rate of 20-70 mL/min/1.73 m(2) were identified from physician offices and review of laboratory databases., Outcomes: Prevalence and awareness of hypertension, treatment patterns, control rates, and factors associated with hypertension control., Measurements: Following a standardized protocol, blood pressure was measured 3 times by trained staff, and hypertension was defined as systolic blood pressure > or =140 mm Hg and/or diastolic blood pressure > or =90 mm Hg and/or self-reported antihypertensive medication use. Patients' awareness and treatment of hypertension were defined using self-report, and 2 levels of hypertension control were evaluated: systolic/diastolic blood pressure <140/90 and <130/80 mm Hg., Results: The prevalence of hypertension was 85.7%, and 98.9% of CRIC participants were aware of this diagnosis and 98.3% were treated with medications, whereas 67.1% and 46.1% had hypertension controlled to <140/90 and <130/80 mm Hg, respectively. Of CRIC participants with hypertension, 15%, 25%, 26%, and 32% were using 1, 2, 3, and > or =4 antihypertensive medications, respectively. After multivariable adjustment, older patients, blacks, and those with higher urinary albumin excretion were less likely, whereas participants using angiotensin-converting enzyme inhibitors and angiotensin receptor blockers were more likely to have controlled their hypertension to <140/90 and <130/80 mm Hg., Limitations: Data were derived from a single study visit., Conclusions: Despite almost universal hypertension awareness and treatment in this cohort of patients with CKD, rates of hypertension control were suboptimal., (Copyright 2010 National Kidney Foundation, Inc. All rights reserved.)

Although resting hemodynamic load has been extensively investigated as a determinant of left ventricular (LV) hypertrophy, little is known about the relationship between provoked hemodynamic load and the risk of LV hypertrophy. We studied central pressure-flow relations among 40 hypertensive and 19 normotensive adults using carotid applanation tonometry and Doppler echocardiography at rest and during a 40% maximal voluntary forearm contraction (handgrip) maneuver. Carotid-femoral pulse wave velocity (CF-PWV) was measured at rest. Hypertensive subjects demonstrated various abnormalities in resting and induced pulsatile load. Isometric exercise significantly increased systemic vascular resistance, aortic characteristic impedance (Zc), induced earlier wave reflections, increased augmentation index, and decreased total arterial compliance (TAC; all P < or = 0.01). In hypertensive subjects, CF-PWV was the strongest resting predictor of LV mass index (LVMI) and remained an independent predictor after adjustment for age, gender, systemic vascular resistance, reflection magnitude, aortic Zc, and TAC (beta = 2.52 m/s; P < 0.0001). Age, sex, CF-PWV, and resting hemodynamic indexes explained 48% of the interindividual variability in LVMI. In stepwise regression, TAC (beta = -17.85; P < 0.0001) during handgrip, Zc during handgrip (beta = -150; P < 0.0001), and the change in the timing of wave reflections during handgrip (beta = -0.63; P = 0.03) were independent predictors of LVMI. A model that included indexes of provoked hemodynamic load explained 68% of the interindividual variability in LVMI. Hemodynamic load provoked by isometric exercise strongly predicts LVMI in hypertension. The magnitude of this association is far greater than for resting hemodynamic load, suggesting that provoked testing captures important arterial properties that are not apparent at rest and is advantageous to assess dynamic arterial load in hypertension.

Background: Myocardial afterload depends on left ventricular (LV) cavity size, pressure, and wall thickness, all of which change markedly throughout ejection. We assessed the relationship between instantaneous ejection-phase pressure and myocardial stress and the effect of arterial wave reflections on myocardial stress in hypertensive and normotensive adults., Methods and Results: We studied 42 untreated hypertensive, 42 treated hypertensive, and 42 normotensive adults with normal LV ejection fraction. Time-resolved central pressure, flow, and LV geometry were measured with carotid tonometry, Doppler, and speckle-tracking echocardiography for computation of arterial load and time-varying circumferential and longitudinal myocardial stress. In all 3 groups, peak myocardial stress typically occurred in early systole (within the first 100 milliseconds of ejection), followed by a marked midsystolic shift in the pressure-stress relationship, which favored lower late systolic stress values (P<0.001) relative to pressure. The mean magnitude of this midsystolic shift was quantitatively important in all 3 groups (circumferential stress, 144 to 148 kdynes/cm(2)) and was independently predicted by a higher LV ejection fraction and ratio of LV end-diastolic cavity to wall volume. Time of peak myocardial stress independently correlated with time of the first systolic but not with time of the second systolic central pressure peak., Conclusions: Peak myocardial stress occurs in early systole, before important contributions of reflected waves to central pressure. In the presence of normal LV ejection fraction, a midsystolic shift in the pressure-stress relationship protects cardiomyocytes against excessive late systolic stress (despite pressure augmentation associated with wave reflections), a coupling mechanism that may be altered in various disease states.

Following a hypertension symposium in Philadelphia in September 2005, a roundtable was convened to discuss the significance of out-of-office blood pressure. Dr. Marvin Moser of the Yale School of Medicine, New Haven, CT, moderated the panel discussion. Participants included Dr. Raymond Townsend of the University of Pennsylvania School of Medicine, Philadelphia, PA, and Dr. Norman Kaplan of the University of Texas Health Science Center in Dallas, Dallas, TX.

The ability of angiotensin converting enzyme (ACE) inhibitors to lower blood pressure may in part be due to the formation of vasodilatory prostaglandins. Inhibition of prostaglandin synthesis with aspirin may therefore theoretically attenuate the antihypertensive effect of ACE inhibitors. This trial studied the interaction between aspirin (ASA) and enalapril, an ACE inhibitor, and ASA and losartan, an angiotensin subtype 1 receptor antagonist. Seventeen essential hypertensive patients were studied, maintained on a stable dose of either enalapril (n = 7) or losartan (n = 10) monotherapy for > or =12 weeks before and throughout the study. Each patient received a 2-week course of placebo, 81 mg/day ASA, and 325 mg/day ASA, each treatment separated by a 2-week washout period. Blood pressure (BP) and serum thromboxane B2 (TXB2) samples were obtained at the end of each treatment period. Placebo was compared with each dose of ASA for each group. In both the enalapril and losartan groups, mean, systolic, and diastolic BP were unchanged with the addition of ASA. Concentrations of TXB2 were suppressed to <10% in both groups with ASA. This study demonstrates that 81 to 325 mg/day ASA exerts no significant effect on BP in essential hypertensives taking enalapril or losartan.

Health and disease management, a clinical improvement process that integrates best practice principles in a comprehensive manner throughout the entire continuum of care, is likely to be the dominant style of health care delivery in the future. The goal of these programs is to eliminate or reduce unacceptable variations in cost and quality between various providers by developing guidelines that will achieve measurable outcomes for specific diseases. These protocols also emphasize wellness and disease prevention, coordinate resources across the entire continuum of care, and define interventions for the entire duration of the disease. Conditions most suited to this management strategy include diseases that are of high volume and cost, complex to manage, and present chronically over a long period of the patient's life. Such programs are developed by a multidisciplinary team that is also charged with obtaining buy-in and championing the program to their peers. Among the many components of a comprehensive health and disease management program, intensive education for patients and families and altering physician behavior to obtain compliance are key areas on which to focus. Hypertension is an ideal condition to manage in this way. It is frequently the most common reason for patients to be seen by a primary care provider, is an expensive disease to treat, and is an important cause of major organ damage from inadequate treatment. Successfully adopting a disease management model for hypertension treatment that will integrate all health care providers and offer intensive education of patients and providers to encourage adherence to the highly effective therapies currently available should afford a major opportunity for a dramatic reduction in complications and costs, with enhanced clinical outcomes and quality of life for these patients.

Hypertension is a common component of the morbidity associated with renal failure. The mechanisms that contribute to high blood pressure are reviewed in this section. Also covered are therapies to reduce hypertension, the treatment goals of those therapies, and the outcomes of antihypertensive therapy on kidney function in patients with renal failure. Various antihypertensive agents are specifically addressed, and a treatment paradigm is presented for combination antihypertensive drug therapy, which is usually necessary in the antihypertensive therapy of patients with renal failure.

Obese persons with hypertension are at greater risk for diabetes and hyperlipidemia than normotensive obese persons. It has been postulated that increased lipolytic rates contribute to these metabolic diseases. Therefore, we evaluated the glycerol rate of appearance (Ra) in plasma, an index of whole-body lipolytic activity, during basal conditions and during 60 minutes of epinephrine infusion after 12 and 84 hours of fasting in six normotensive (body mass index [BMI], 39.9 +/- 1.8 kg/m2) and six hypertensive (BMI, 38.7 +/- 1.6 kg/m2) obese persons. Basal glycerol Ra was lower in hypertensive than in normotensive subjects at both 12 hours (1.58 +/- 0.21 v 2.27 +/- 0.28 mumol/kg/min, respectively; P < .01) and 84 hours (2.04 +/- 0.06 v 2.50 +/- 0.13 mumol/kg/min, respectively; P < .01) of fasting. Peak glycerol Ra during epinephrine infusion after 84 hours of fasting (5.69 +/- 0.72 and 11.40 +/- 0.78 mumol/kg/min for hypertensive and normotensive subjects, respectively) was significantly greater than at 12 hours (3.09 +/- 0.29 and 5.06 +/- 0.69 mumol/kg/min) in both hypertensive and normotensive subjects. However, peak glycerol Ra was lower in hypertensive than in normotensive subjects after 12 and 84 hours of fasting (P < .01 for 84 hours). We conclude that hypertension in obese persons is associated with a decrease in both basal lipolytic rates and lipolytic sensitivity to epinephrine infusion.

Despite tremendous advances in detection and treatment, including both non-pharmacologic and pharmacologic methods, hypertension continues to be a major health concern. In addition to efforts at reducing mortality, recent clinical and research attention has been focused on reducing morbidity from hypertension. Therefore, such efforts are focused on the effect of an elevated blood pressure on individual target organs and in particular on the heart, brain, and kidney. Although the role of blood pressure reduction alone in preserving target organ damage from hypertension is intensely debated, there is little debate that reducing blood pressure is important. The primary manner in which the blood pressure level is determined in the clinical setting continues to be the casual office measurement of blood pressure. However, the clinical use of ambulatory blood pressure determinations, including 24-hour automated blood pressure monitoring, is increasing. Recent data suggest that the determination of ambulatory blood pressures may be a better predictor not only of mortality but also of target organ damage from hypertension. This article will review recent key clinical studies addressing the role of ambulatory blood pressure on certain cardiac, cerebral, and renal manifestations of hypertension.

The long-term benefits and risks of using calcium channel blockers to treat hypertension have been called into question by reports of increased incidence of myocardial infarction and death among patients taking these drugs. There is now a worldwide effort, involving more than 30 countries and 100,000 patients, to provide a comprehensive data-base for making informed decisions.

Purpose: This trial was designed to evaluate the efficacy and safety of three different classes of antihypertensive agents in elderly women., Patients and Methods: The trial had three phases: 4 to 8 weeks of placebo, 6 weeks of titration, and 16 weeks of maintenance. White women between 60 and 80 years old with sitting diastolic blood pressures (DBPs) from 95 through 114 mm Hg treated with placebo were evaluated by history, physical examination, laboratory studies, and quality-of-life interview. After double-blind randomization with low-dose atenolol, enalapril, or isradipine, the dose was increased stepwise and hydrochlorothiazide added as needed to achieve goal DBP (less than 90 mm Hg and greater than 10 mm Hg below baseline). During maintenance, patients not at goal were "stepped up," and patients with uncontrolled DBP at maximum dosage were removed from the study. The pretreatment (baseline) blood pressure of the 315 randomized participants averaged 161/100 mm Hg; 92% had been treated previously for hypertension, 15% had diabetes mellitus, 11% smoked, and 38% consumed alcohol., Results: For 245 patients completing the trial, the average decrease in blood pressure during treatment was 18.2/15.6 mm Hg. Antihypertensive efficacy was similar for the monotherapy drug regimens, with 84%, 71%, and 80% of patients receiving atenolol, enalapril, and isradipine, respectively, achieving DBP goal. Of the 70 patients who did not complete the trial, 42 left because of symptoms and 19 because of uncontrolled DBP. No important, unexpected drug-induced changes in symptoms or blood chemistries were noted. Symptom frequency differed little among the three dosage levels, becoming maximal by the second visit at the same dosage level., Conclusion: All three drugs lowered DBP comparably, and none produced alarming effects. Thirteen percent of patients left the study because of symptoms.

The clinical laboratory is essential to the successful and complete evaluation of the patient with hypertension. A reasonably thorough knowledge of the important physiologic components of blood pressure regulation, in conjunction with a good history and physical examination and a simple panel of screening tests serve to detect or rule out the presence of secondary forms of hypertension in the majority of patients.

Severe hypertension frequently requires hospitalization. Although hospital admission is undesirable for most patients, others are motivated to achieve hospitalization status for secondary gain. The authors present a case of a prison inmate who simulated severe hypertension with a combination of Valsalva's maneuver and arm flexion, on the background of preexisting essential hypertension and mitral valve prolapse. His secondary intent--to avoid his prison duties--classifies him as a malingerer. The differences between this malingering and the psychiatric diagnosis of Munchausen syndrome are discussed. The contributions of essential hypertension and mitral valve prolapse to the self-induced blood pressure elevations also are considered.

In this randomised double-blind parallel study, we compared the efficacy of labetalol and atenolol in a group of black (n = 33) and white (n = 34) hypertensives with uncomplicated essential hypertension after obtaining pretreatment renin profiles. After single-blind placebo (14-21 days), patients with standing diastolic BP between 105-119 mmHg were randomised to receive either labetalol (100-800 mg twice daily) or atenolol (50-100 mg once daily) to achieve a DBP less than 90 mmHg. Dosage titration occurred at weekly intervals for labetalol and biweekly for atenolol. The supine BP decrease with atenolol was -18/-14 vs. -6/-6 mmHg in whites vs. blacks respectively. With labetalol, it was -13/-12 in whites and -2/-7 mmHg in blacks. Standing BPs were: -19/-14 vs. -4/-5, whites vs. blacks with atenolol and -17/-17 vs. -19/-9 mmHg with labetalol. Neither labetalol nor atenolol was as effective in black compared with white hypertensives. The atenolol but not labetalol BP response was positively correlated with pretreatment renin values.

The purpose of this multicenter investigation was to determine the efficacy and safety of the alpha/beta-blocker labetalol versus the beta 1-selective beta-blocker atenolol in white and black patients with essential hypertension. Equal numbers of black and white patients were enlisted to form four treatment groups (white patients taking either labetalol or atenolol and black patients taking either labetalol or atenolol). Two hundred ninety-two patients (152 white and 140 black patients) with essential hypertension characterized by a standing diastolic blood pressure of 105 to 119 mm Hg (inclusive) were recruited for this trial. Patients were randomized to either labetalol (dosage titrated from 200 to 1600 mg/day) or atenolol (dosage titrated from 50 to 100 mg/day). The therapeutic goal was achievement of a standing diastolic blood pressure of 90 mm Hg or less or a fall of 15 mm Hg in diastolic pressure from baseline value at the end of the placebo run in period. At the end of the study there were no significant differences in blood pressure or heart rate changes in the supine position between the labetalol and atenolol groups. In contrast, labetalol produced greater reduction in both the standing systolic and diastolic blood pressure (-12/-13 mm Hg, respectively) compared with atenolol (-7/-9 mm Hg; p less than 0.05; p less than 0.005, respectively). The greatest decrease in blood pressure was observed in white patients receiving labetalol. In black patients the decrease in blood pressure was greater in those treated with labetalol compared with atenolol, particularly with respect to the systolic blood pressure. We conclude that the alpha 1-blocking property of labetalol provides an additional lowering of the blood pressure over that seen with beta 1-blockade alone, especially in the standing position, and this enhanced efficacy is not confined to one radical group.

Calcium channel blockers may alter parathyroid hormone secretion in vitro, which would alter calcium homeostasis. To determine the chronic effect of calcium channel blockade in vivo, we conducted a randomized, double blind, 16 week study comparing the effects of two pharmacologic antihypertensive agents, the calcium channel blocker diltiazem and the angiotensin-converting enzyme inhibitor captopril on parameters of calcium homeostasis. Both diltiazem and captopril lowered blood pressure to a similar degree. Neither drug produced any significant change in blood levels of total and ionized calcium, magnesium, or phosphorus, which affect the regulation of parathyroid hormone and vitamin D. In addition, at eight or 16 weeks following initiation, neither drug altered the serum levels of parathyroid hormone (PTH) or 1,25-(OH)2-vitamin D3 (1,25-D). Chronic calcium channel blockade with diltiazem does not alter serum parameters of calcium homeostasis and, thus, should not affect bone mineralization.

In recent years there has been increased discussion about goals of antihypertensive therapy other than blood pressure reduction. The development of angiotensin-converting enzyme inhibitors has provided a class of drugs with a very low side-effect profile. However, single-drug therapy is effective in only about half of hypertensive patients. In the past, diuretics have traditionally been used as the initial or second antihypertensive. Increasingly, diuretic therapy is being avoided, and other antihypertensive combinations are being used. In controlled trials, combination converting enzyme inhibitor-diuretic therapy is effective in about 85% of patients. This synergistic combination allows the diuretic dose to be reduced so that the adverse effects and metabolic complications are minimized. At this time, the combination of converting enzyme inhibitor and diuretic provides an ideal choice in terms of efficacy, compliance, side effects, and cost.

Left ventricular diastolic filling was investigated in 12 black and 15 white subjects before and after double-blinded randomized treatment of mild to moderate hypertension with combined alpha- and beta-adrenergic receptor blockade (labetalol) and beta-blockade alone (atenolol). At baseline (off medication), both groups were similar for age (46 +/- 8 years v 48 +/- 12 years), mean blood pressure (121 +/- 8 mm Hg v 115 +/- 8 mm Hg), left ventricular dimensions, left ventricular mass index (118 +/- 24 g/m2 v 113 +/- 13 g/m2), and left ventricular filling as reflected by transmitral flow velocity ratio A/E (0.97 +/- 0.33 v 0.92 +/- 0.19, normal age-matched control A/E ratio is 0.64 +/- 14). There were 6 blacks and 6 whites in the labetalol group; 6 blacks and 9 whites in the atenolol group. At six weeks of treatment, whites in the labetalol group showed a significantly greater drop in mean blood pressure (114 +/- 7/102 +/- 11, P less than .007 v 123 +/- 9/114 +/- 11, P = NS) and correspondingly greater improvement in A/E ratio (1.04 +/- 0.14/0.74 +/- 0.23, P less than .024 v 1.02 +/- 0.23/0.89 +/- 0.16, P = NS). However, this difference was no longer significant when controlling for age and blood pressure level. In the atenolol group, whites showed a significant increase in the rapid filling phase velocity E, while late filling phase velocity A significantly dropped only in blacks, without significant improvement in A/E ratio in either subgroup. In conclusion, greater improvement in left ventricular filling is seen with combined alpha-beta-blockade than beta-blockade alone.(ABSTRACT TRUNCATED AT 250 WORDS)

A placebo-controlled, double-blind multicenter trial was conducted in 123 patients with severe hypertension to examine the efficacy and safety of intravenously administered nicardipine hydrochloride in controlling blood pressure. Seventy-three patients were initially randomized to receive nicardipine treatment. This group had an initial blood pressure of 213 +/- 3/126 +/- 2 mm Hg. Sixty-seven patients achieved the therapeutic goal (diastolic blood pressure less than or equal to 95 mm Hg; systolic blood pressure less than or equal to 160 mm Hg). Fifty patients were randomized to receive placebo solution. Blood pressure in these patients was 216 +/- 3/125 +/- 2 mm Hg. No patient in this group achieved the therapeutic goal during the "blinded" portion of the study. Forty-four of 49 patients who did not respond to placebo administration responded to subsequent treatment with nicardipine. Patients with end-organ damage were included in the study. These included patients with left ventricular hypertrophy, retinopathy, and renal insufficiency. Patients with and without end-organ damage responded equally well to nicardipine treatment. Serious adverse experiences were infrequent, the most common adverse reaction being headache in 24% of the patients studied.

We previously used the Doppler transmitral flow velocity ratio A/E (A = late ventricular filling peak velocity; E = early ventricular filling peak velocity) and the age-adjusted ratio A/E/Age to detect left ventricular filling abnormalities in untreated mild hypertension. This study is a double-blind assessment of the effect of combined alpha- and beta-blockade (labetalol) and beta-blockade alone (atenolol) on left ventricular filling in mild hypertension. Twenty-seven patients blindly randomized to labetalol (12 patients) and atenolol (15 patients) treatment completed the echocardiographic and Doppler studies. Clinical and echo-Doppler data obtained at baseline and 6 weeks after initiation of therapy showed no difference between the two groups for age (49 +/- 10 vs 46 +/- 10 years), mean blood pressure (before therapy, 118 +/- 9 vs 117 +/- 8 mm Hg; after therapy, 108 +/- 12 mm Hg), left ventricular dimensions, wall thickness, systolic function, and mean late filling velocity A. There was no significant change in left ventricular mass and mass index with labetalol (left ventricular mass, 211 +/- 36 vs 216 +/- 38; mass index, 110 +/- 17 vs 112 +/- 16) or atenolol (245 +/- 41 vs 271 +/- 65; 120 +/- 18 vs 130 +/- 35). The mean velocity E, A/E, and A/E/Age ratios significantly improved with labetalol (p less than 0.05) but did not change significantly with atenolol. The improvement in A/E and A/E/Age ratios was primarily due to an increase in early filling velocity E.(ABSTRACT TRUNCATED AT 250 WORDS)

The observations that atherosclerosis often occurs in non-smokers without elevated levels of low-density lipoprotein cholesterol, and that most atherosclerosis loci so far identified in mice do not affect systemic risk factors associated with atherosclerosis, suggest that as-yet-unidentified mechanisms must contribute to vascular disease. Arterial walls undergo regional disturbances of metabolism that include the uncoupling of respiration and oxidative phosphorylation, a process that occurs to some extent in all cells and may be characteristic of blood vessels being predisposed to the development of atherosclerosis. To test the hypothesis that inefficient metabolism in blood vessels promotes vascular disease, we generated mice with doxycycline-inducible expression of uncoupling protein-1 (UCP1) in the artery wall. Here we show that UCP1 expression in aortic smooth muscle cells causes hypertension and increases dietary atherosclerosis without affecting cholesterol levels. UCP1 expression also increases superoxide production and decreases the availability of nitric oxide, evidence of oxidative stress. These results provide proof of principle that inefficient metabolism in blood vessels can cause vascular disease. [ABSTRACT FROM AUTHOR]

Hypertension, an insidious condition affecting approximately 50 million US adults, remains a central factor contributing to cardiac and other target organ disease. Despite increased detection and numerous therapeutic advances, three out of four people with hypertension in the US have uncontrolled or poorly controlled blood pressure. While hypertension is a leading reason for primary care office visits and antihypertensive medications are widely prescribed, most individuals are not achieving goal systolic/diastolic blood pressure of 140/90mm Hg or less. While the definition of adequate blood pressure control varies in different countries, the problem of inadequate control is universal. Numerous barriers contributing to the suboptimal health outcomes have been recognized, including issues related to healthcare providers as well as patient compliance with medication and lifestyle changes. Recently, healthcare provider systems and health plans have turned to disease management strategies to better address quality and outcomes issues in hypertension management. Disease management, a systematic clinical improvement process, encompasses provider and patient education employing national or locally developed best practice guidelines and behavioral interventions coupled with close monitoring of clinical processes and outcomes of care. Disease management programs seek to define a comprehensive and coordinated approach to care across multiple providers and patient subgroups. Through risk assessment and stratification, patients at higher risk of complications can be identified, and customized intensive care support can be offered. Other types of intervention for lower risk individuals include brief visits with a cardiovascular educator or care manager, group classes, or self-instructional programs. Several successful programs initiated by healthcare systems and health plans are described. Adequate blood pressure control is essential to reduce cardiac, renal, and stroke disease later in life. However, large numbers of individuals must be effectively managed for years or decades to achieve reductions in complications and cost savings. Unlike more acute conditions that frequently result in hospitalization and loss of function, the immediate cost offsets of hypertension disease management efforts are less defined, although the eventual savings to society could be vast. Less costly methods to promote healthy outcomes across large, relatively stable populations are needed. Automated systems employing clinical decision support at the point of care and internet-based patient support strategies offer the hope that comprehensive, individualized disease management for hypertension can be affordable as well as effective. In the meantime, the fact that the National Committee on Quality Assurance has included blood pressure control as a future measure of health plan performance will almost certainly lead to the expanded development of hypertension disease management initiatives. [ABSTRACT FROM AUTHOR]