Uncomplicated Essential Hypertension Research Articles

Clinical and Functional Correlates of Platelet Cyclic GMP in Essential Hypertensives

Platelets play a central role in atherothrombosis, which is responsible of major cardiovascular complications in human hypertension. Nitric oxide (NO) inhibits platelet aggregation via the second messenger cyclic guanosine monophosphate (cGMP). In essential hypertensives (EHs), we examined the relationship between platelet cGMP and clinical, hemodynamic, humoral variables as well as the responses to aggregating agents. In untreated EHs (male/female 106/43, age 44.4 +/- 1.1 years, smokers yes/no 38/111), blood pressure (BP), heart rate (HR), and stroke volume (SV) (impedance cardiography) were assessed after supine rest and venous blood was sampled for platelet cGMP (radioimmunoassay on acid extracts of washed platelets), plasma cGMP, atrial natriuretic peptide (ANP), renin activity, aldosterone and platelet aggregation to epinephrine (EPI, 5 micromol/l), and adenosine diphosphate (ADP) (4 micromol/l) (optical aggregometry on platelet-rich plasma (PRP)). Platelet cGMP (7.0 +/- 0.3 pmol/10(9) cells, mean +/- s.e.m.) was lower in males and smokers than in their counterparts (P < 0.01 for both). Among the variables tested, platelet cGMP was related to number of cigarettes (-0.21), high-density lipoprotein cholesterol (HDLc) (r = 0.32), aldosterone (r = -0.21), and hemoglobin (-0.16); in a multivariate analysis that also included sex, HDLc was the best predictor of platelet cGMP. The aggregating response to EPI (r = -0.28), but not to ADP (r = -0.07, ns), was inversely related to platelet cGMP levels. cGMP in resting platelets of EHs is positively predicted by HDLc and is inversely related to the aggregating response to EPI. It is suggested that a defect of the platelet NO/cGMP system could identify uncomplicated EHs at higher risk of thrombotic events during surges of sympathetic activity.

Aldosterone levels and stroke incidence in essential hypertensive patients

The aim of the present study was to assess the incidence of transient ischemic attack (TIA) and stroke in hypertensive patients according to their aldosterone levels.The study comprised 10,000 consecutive patients with uncomplicated essential hypertension who underwent full clinical and laboratory evaluation including 24 h urine collection.Patients with hALDO had significantly higher incidence of TIA (3.4% vs 1.9%) and stroke (3.5% vs 1.8%) compared to patients with lALDO levels, which remained significant after adjustment for age, gender, body mass index (BMI), diabetes mellitus, serum cholesterol and current smoking.Hypertensive patients with hALDO levels within the normal range present an increased incidence of stroke and TIA.

Left and right ventricular structural changes in obese hypertensives

Aim. Obesity is known to be independently related to left ventricular (LV) hypertrophy (LVH); however, in human hypertension the association of obesity with right ventricular hypertrophy (RVH) is still unsettled. We investigated the relationship of obesity with RVH and biventricular hypertrophy in essential hypertension. Methods. A cohort of untreated and treated uncomplicated essential hypertensives consecutively attending a hospital outpatient hypertension clinic, categorized in three groups according to body mass index (BMI) thresholds (<25, 25–29.9 and ≥30 kg/m2) was considered for the present analysis. RVH was defined by an anterior RV wall thickness equal or higher than 3.1/3.0 mm/m2 in men and women, respectively, and LVH by LV mass index (LVMI) equal or higher than 51 and 47 g/m2.7 in men and women, respectively. Results. A total of 124 patients (37.6%) had normal BMI, 151 patients (45.7%) were overweight and 55 (16.7%) obese. Prevalence rates of biventricular hypertrophy (i.e. LVMI>51 and 47 g/m2.7 and RVWT>3.1 and 3.0 mm) in the three groups were 7.3%, 21.2% and 32.7%, respectively. In a multivariate analysis, BMI (OR=3.58, 95% CI 1.82–7.03, p=0.0002), was the most important correlate of biventricular hypertrophy. Conclusions. Our findings extend previous data on the impact of obesity on cardiac structure by showing that this phenotype is strongly associated with biventricular hypertrophy.

Prolonged QT Interval and Reduced Heart Rate Variability in Patients with Uncomplicated Essential Hypertension

A prolonged QT interval is a risk factor for ischemic heart disease in hypertensive subjects. Heart rate variability (HRV) is both an index of autonomic function and an important prognostic factor in several diseases. The aim of the present study was to evaluate the relation between a prolonged QT interval and autonomic nervous system function in patients with untreated uncomplicated essential hypertension. Two hundred and fifteen untreated patients with essential hypertension underwent a Holter ECG equipped with software dedicated to HRV and QT analyses. Nine percent of the patients showed a corrected QT (QTc) >or=440 ms. The HRV indexes in the time domain (SDNN, SDNN index, RMSSD, and pNN50) were significantly reduced in the patients with a prolonged QTc compared to those with a normal QTc (SDNN 24 h: 126.4+/-29.9 vs. 143.9+/-35.4 ms, p=0.02; SDNN index [nighttime]: 85.9+/-32.4 vs. 115.5+/-36.7 ms, p=0.0006; RMSSD 24 h: 22.2+/-7.7 vs. 31.2+/-13.0 ms, p=0.0007; pNN50 24 h: 4.4+/-4.9 vs. 9.7+/-8.4%, p=0.0006). The linear correlation analysis between QTc length and HRV parameters showed a significant negative correlation with all the time-domain indexes. Such a correlation was maintained for RMSSD 24 h, pNN50 24 h and SDNN index (nighttime) after correction for gender and age. The present study shows that, even prior to the development of cardiac hypertensive disease, a prolongation of the QTc and a reduced HRV, both markers of cardiovascular risk, coexist in a proportion of patients with untreated essential hypertension. Further studies are warranted to evaluate whether the combination of such markers can identify hypertensive patients at risk for life-threatening arrhythmias and sudden death. (Hypertens Res 2008; 31: 2003-2010).

Effects of angiotensin converting enzyme gene polymorphism on endothelial function in patients with essential hypertension

Objective To investigate effects of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism on endothelial function in elderly patients with essential hypertension. Methods Seventy-three elderly patients with uncomplicated essential hypertension and 55 normal elderly people as control were recruited into the study. Their humeral arterial endothelial vasodilatation function was studied with high-resolution ultrasonography and ACE I/D genotypes were determined by polymerase chain reaction (PCR) technique. Results Endothelium-dependent vasodilatation function of the three-genotype subgroups of the elderly patients with essential hypertension was significantly lower than that in the controls with the same genotypes (5.5±1.9 vs 11.9±1.3 in Ⅱ genotypa, 4.7±2.0 vs 10.9±1.6 in ID genotype and 2.9±1.9 vs 9.4±2.6 in DD genotype, with all P<0.01 ). In both groups of hypertensives and normotensives, humeral arterial endothelium-dependent vasedilatation function was significantly lower in those with DD genotype than that in those with Ⅱ genotype (2.9±1.9 vs 5.5±1.9 in hypertensive group and 9.4±2.6 vs 11.9±1.3 in control group, both P<0.05 ). Multivariate linear regression analysis showed that endothelium-dependent vasodilatation function in hypertensive elderly people correlated in linearity with their ACE genotype (P<0.01 ). Conclusions ACE gene I/D polymorphism is associated with abnormal humeral arterial endothelium-dependent vasodilatation function of humeral artery in patients with essential hypertension. Key words: Hypertension; Peptidyl-dipeptidase A; Genotype; Endothelium , Vascular

Effects of hydrochlorothiazide and furosemide on creatinine clearance in some hypertensive Nigerians

Hydrochlorothiazide and furosemide have been reported to alter the glomerular filtration rate (GFR) and possibly the creatinine excretion by the kidneys. Also, therapy with these diuretics, especially in the elderly, can be complicated by volume depletion resulting in prerenal azotemia. Creatinine clearance (Clcr) is considered to be the most accurate test of renal function. Unfortunately, although these diuretics are widely used in the treatment of hypertension and heart failure in the young and elderly Nigerians, their effects on renal function have been poorly investigated. We, therefore, evaluated the effects of treatment with 21-day single daily oral doses of 25 mg hydrochlorothiazide or 40 mg furosemide on Clcr in this prospective randomized study of forty Nigerians with mild to moderate uncomplicated essential hypertension (20 males and 20 females) 32 to 80 years of age and 40 age and sex-matched healthy normotensive controls while on their usual diet. Blood and 24 h urine specimens were collected at baseline and on days 7, 14 and 21. Specimens were assayed for creatinine and the corresponding Clcr for each day was calculated. Analysis of variance did not show a statistically significant effect of the diuretic regimens on Clcr over the period. This study demonstrates that single daily doses of either of these diuretics do not have a significant effect on Clcr over a short-term monotherapy.

Kidney Function and Risk Factors for Left Ventricular Hypertrophy in Untreated Uncomplicated Essential Hypertension

Left ventricular (LV) hypertrophy and decreased kidney function are well-established cardiovascular risk factors in hypertensive patients. We investigated the relationship between creatinine level, creatinine clearance, and estimated glomerular filtration rate (eGFR) with LV mass (LVM) in a cross-sectional study. eGFR and serum creatinine level. LVM index (LVMI). 400 patients with untreated uncomplicated essential hypertension. LVMI, eGFR (Modification of Diet in Renal Disease Study equation), Framingham risk factors, and a series of specific risk factors, ie, endothelial function (acetylcholine [ACh]-stimulated forearm blood flow [FBF]), insulin sensitivity (Homeostatic Model Assessment for insulin resistance [HOMA-R] index), C-reactive protein (CRP), and uric acid. Both eGFR and creatinine level were significantly related to LVMI (r = -0.34 and r = 0.35; P < 0.001). In a multiple regression model adjusting for Framingham risk factors, eGFR was independently associated with LVMI. However, this association, although highly significant, lost substantial strength after adjustment for such specific risk factors as HOMA-R index, ACh-stimulated FBF, CRP level, and uric acid level. eGFR interacted with insulin resistance in explaining the variability in LVMI (P = 0.007). The cross-sectional nature of this study precludes cause-effect conclusions. Independently of other risk factors, decreased kidney function contributes to explain the variability in LVMI in patients with untreated uncomplicated essential hypertension. This association is attributable in part to the link between eGFR and such specific risk factors as HOMA-R index, ACh-stimulated FBF, CRP level, and uric acid level. Decreased kidney function and insulin resistance interact in explaining the variability in LVMI in these patients.

Microalbuminuria and global myocardial function in patients with essential hypertensive

Introduction The myocardial performance index, Tei index, is a relatively new echocardiography indice which is related to parameters which express both the systolic and diastolic myocardial function. The purpose of the present study was to investigate the possible correlation of Tei index to microalbuminuria, which is an indice of kidney target-organ damage in hypertensive patients. Materials and methods We evaluated 9680 consecutive patients (mean age 55.2 years, 5144 male and 4536 female) with chronic uncomplicated essential hypertension and the correlation between Tei index, defined as the sum of the isovolumetric relaxation and contraction time divided by the ejection time, and kidney target damage (microalbuminuria) was evaluated. Results In univariate analysis we noticed a positive correlation of Tei index with microalbuminuria ( r = 0.353 p < 0.001). Furthermore, a significant difference was found in each Tei quartile for microalbumin levels ( p < 0.001). In multivariate analysis with Tei index as a dependent variable (high versus low quartile) and independent variables gender, age, body mass index, plasma glucose, heart rate, blood pressure, kidney function indices and lipids, the independent prognostic correlation to microalbuminuria was noticed (ΟR: 1.002 p < 0.001). Conclusions In the present study we found that Tei index correlates with microalbuminuria in essential hypertensive patients. Thus we can assume that this index could be used not only for the evaluation of the global myocardial performance of hypertensive patients but also for the assessment of the cardiovascular risk in arterial hypertension since it correlates with kidney damage.

Association of augmentation index of radial pressure wave form with diurnal variation pattern of blood pressure in untreated patients with essential hypertension

The augmentation index of the radial pulse wave has been reported to be a sensitive aortic stiffness marker in relatively young but not in older individuals. We studied the relationship between augmentation index and the diurnal blood pressure profiles. Twenty-four-hour ambulatory blood pressure monitoring was performed in 90 untreated patients with uncomplicated essential hypertension. The patients were classified into four groups: dippers, extreme dippers, nondippers, and risers. Augmentation index was calculated as the percentage of the second systolic peak relative to the first systolic peak. No significant differences in the averaged whole 24-h systolic or diastolic blood pressure were observed in the whole set of patients or in subgroup patients with age 60 years or under. In the whole set of patients (58.7 +/- 12.9 years), there were significant differences in augmentation index between patients with abnormal (other than dippers) and normal diurnal blood pressure profiles (dippers). In subgroup patients with age 60 years or below (49.1 +/- 9.1 years, n = 48), the abnormal diurnal blood pressure profile group showed significantly higher augmentation index (89.6 +/- 10.3%) than dippers (80.5 +/- 11.8%). The area under the curve in the receiver operating characteristics curve for distinguishing between dippers than other dippers was 0.73 (P < 0.01). Multivariate analysis demonstrated that abnormal diurnal blood pressure profile was independently associated with increase in augmentation index. In contrast, these relationships were not significant in the over 60 years subgroup patients (69.8 +/- 5.6 years old, n = 42). The present study revealed that augmentation index was associated with dipping blood pressure patterns in untreated hypertensive patients aged 60 years or younger. Augmentation index determination would be useful for initial assessment in connection with possible abnormal diurnal blood pressure variability in patients with age 60 years or younger.

Beneficial Effect of Angiotensin II Type 1 Receptor Blocker Antihypertensive Treatment on Arterial Stiffness: The Role of Smoking

The purpose of the present study was to assess angiotensin receptor blocker (ARB) treatment on arterial stiffness in select hypertensive patients and define possible differences between smokers and nonsmokers. The authors evaluated 81 consecutive, nondiabetic patients (mean age, 52 years; 47 men) with uncomplicated essential hypertension with high plasma renin activity who were administered monotherapy with irbesartan, an ARB, at maximal dose. Patients were divided into smokers (n=24) and nonsmokers (n=57). Carotid-radial pulse wave velocity (PWVc-r), carotid-femoral pulse wave velocity (PWVc-f), and augmentation index (AIx) were measured before and 6 months after ARB antihypertensive treatment. All mean values of elastic effect indices were decreased after irbesartan monotherapy (AIx, from 26.3%to 21.2% [P<.01;] PWVc-f, from 7.7 m/s to 7.3 m/s [P<.05], and PWVc-r, from 8.9 m/s to 8.3 m/s [P<.001]). When comparing smokers vs nonsmokers, no difference was noted in AIx and PWVc-f change (P=not significant), while PWVc-r change was greater in smokers compared with nonsmokers (P<.05). Chronic ARB treatment may favorably affect arterial stiffness and wave reflections in hypertensive chronic smokers with elevated plasma renin levels.

Comparison of the Effects on Ambulatory Blood Pressure of Awakening versus Bedtime Administration of Torasemide in Essential Hypertension

Torasemide is a high‐ceiling loop diuretic frequently used in the treatment of congestive heart failure, renal failure, and hypertension. Low doses of torasemide (2.5 to 5 mg/day) do not elevate 24 h natriuresis, and they constitute effective monotherapy for mild‐to‐moderate uncomplicated essential hypertension according to results based on clinic blood pressure (BP). However, there has yet to be a proper evaluation of its 24 h efficacy or potential dependency of effects according to the circadian time of treatment. Accordingly, this trial investigated the administration time‐dependent efficacy of torasemide in uncomplicated essential hypertensive patients. We studied a total of 113 grade 1 and 2 hypertensive patients, 51.7±10.6 yrs of age, randomly assigned to receive torasemide (5 mg/day) as a monotherapy either upon awakening or at bedtime. BP was measured by ambulatory monitoring for 48 consecutive hours before and after six weeks of treatment. The efficacy of torasemide was significantly greater with bedtime dosing (i.e., 14.8 and 9.5 mmHg reduction in the 24 h mean systolic and diastolic BP, respectively) as compared with morning dosing upon awakening (i.e., 6.4 and 3.4 mmHg reduction in mean systolic and diastolic BP; p<0.001 between the two treatment‐time groups). The percentage of patients with controlled ambulatory BP after treatment was also higher after bedtime treatment (64 vs. 23%; p<0.001). Safety and tolerability were comparable between the two treatment‐time groups. A dose of 5 mg/day torasemide is more effective for BP reduction for uncomplicated essential hypertensive patients when ingested at bedtime than in the morning upon arising. The difference in antihypertensive efficacy as a function of the circadian dosing‐time of torasemide here documented should be taken into account when prescribing this loop diuretic to treat essential hypertensive patients.

Nebivolol Increases Atrial Natriuretic Peptide/Systolic Blood Pressure Ratio in Hypertensive Patients

The aim of this study is to evaluate the medium term treatment effects of the beta-blocker nebivolol on the endogenous anti-hypertensive and anti-inflammatory agent Atrial Natriuretic Peptide (ANP) plasma levels in patients with moderate uncomplicated essential hypertension. The drug was given orally for 30 days to 25 patients. The daily dose was 5 mg once every morning. Quantitative determination of ANP was made by Radioimmunoassay (RIA). At the end of this clinical trial, plasma ANP levels showed a statistically non significant tendency to increase by 10.99% while both systolic (SBP) and diastolic (DBP) blood pressure as well as the diameters of the left cardiac cavities showed a statistically significant decrease. What was interesting was the fact that there was a statistically significant increase of 44.7% in the ratio ANP/SBP following the reduction of arterial blood pressure. This increase was the most important and essential finding as it indicated a real increase of ANP plasma levels. This result was obtained even though pressure and afterload, the homologous mechanical stimulatory parameters for ANP secretion, of the left cavities were diminished. These findings provide strong indications which were supported by several previous trials, that the increase in plasma ANP following the administration of beta-adrenergic blockers to hypertensive patients was a primary effect of beta blockade and not a mechanical one secondary to a negative inotropic action on the left ventricle. This primary action contributed to the anti-hypertensive effect of nebivolol during this trial.

Evaluation of thiazide diuretic use as preferred therapy in uncomplicated essential hypertension patients.

Thiazide diuretics are effective antihypertensive medications shown to reduce the risk of cardiovascular events and stroke. Despite being the preferred choice for uncomplicated essential hypertension, thiazide diuretics continue to be underutilized. Uncomplicated essential hypertension patients taking a single antihypertensive medication were evaluated upon enrollment, diagnosis after enrollment or initiation of therapy in treatment naïve patients. Clinician prescribing habits were determined for both pre-existing and newly diagnosed hypertensive patients. For the cost savings analysis, hydrochlorothiazide (HCTZ) 25mg daily was selected as the preferred conversion medication. Four hundred seventy-eight patients were included. ACE inhibitors were the most prescribed at 35.4% (n=169), followed by dihydropyridine calcium channel blockers (DHP CCB) and thiazide diuretics, both at 20.3% (n=97). Only 12.9% (n=33) of patients with hypertension that were taking an antihypertensive medication upon enrollment were either continued or started on thiazide diuretic therapy. Newly diagnosed or treatment naïve patients were prescribed a thiazide diuretic 28.8% (n=64) of the time. DHP CCB accounted for 58.8% of the total medication cost per month with thiazide diuretics responsible for 0.8% of the cost. If all patients had been prescribed HCTZ 25mg daily, 95.8% of the total medication cost per month could have been saved. Thiazide diuretics were underutilized as preferred therapy in patients with pre-existing or newly diagnosed uncomplicated essential hypertension. While cost of therapy should not be the sole reason for medication selection, thiazide diuretics are an attractive option and should be considered as a preferred therapy in this patient population.

Benefits of First-Line Combination of Perindopril and Indapamide in Clinical Practice for Patients With Hypertension and Diabetes

Because of the importance of attaining rapid and tight blood-pressure (BP) control, those guidelines that base treatment recommendations on a risk-stratification approach include combination therapies as first-line pharmacologic treatment options. Monotherapies were shown to be ineffective in many patients, and delays in BP control significantly increase the risk of cardiac events, stroke, and death. In diabetic patients in whom BP control is particularly hard to achieve, the use of angiotensin-converting enzyme (ACE) inhibitors, which inhibit the renin-angiotensin system, has been recommended. Consistent with these guidelines, comparative clinical trials confirmed the value of the ACE inhibitor-and-diuretic combination treatment, perindopril/indapamide, in hypertensive diabetic patients and in patients with uncomplicated essential hypertension, multiple risk factors, and associated clinical conditions. Perindopril/indapamide was shown to have an early and sustained effect on systolic BP, and a specific and positive effect on hemodynamics. Treatment attenuates carotid-wave reflections and pulse-wave velocity, both of which are components of pulse pressure and are determinants of left-ventricular afterload, myocardial hypertrophy, and myocardial oxygen consumption. In diabetic patients with albuminuria, perindopril/indapamide treatment significantly reduces BP, the albumin excretion rate, and the urinary albumin:creatinine ratio. The nephroprotective effects of perindopril/indapamide remain significant after adjustment for changes in BP. Together, these data suggest that a combination of perindopril and indapamide, through its effect on BP-lowering and target-organ protection, is suited to the medical needs of a wide range of hypertensive patients, including those with diabetes.

Lack of Association Between Serum Uric Acid and Organ Damage in a Never-Treated Essential Hypertensive Population at Low Prevalence of Hyperuricemia

It is still undefined whether serum uric acid (SUA) is an independent risk factor for target organ damage (TOD) and cardiovascular events in human hypertension. We sought to investigate the association of SUA with subclinical cardiac, vascular, and renal alterations in never-treated uncomplicated essential hypertensives. A total of 580 subjects with recently diagnosed (<1 year) grade 1 and 2 hypertension, categorized by sex and tertiles of SUA levels, were considered for this analysis. All subjects underwent extensive clinical, laboratory, and ultrasonographic investigations searching for cardiac and extracardiac TOD. Hyperuricemia (SUA >7.0 mg/dL in men and >6 mg/dL in women) was present in 8.3% of the patients. The overall prevalence of left-ventricular hypertrophy (LVH), carotid alterations, and microalbuminuria was 28%, 27%, and 8%, respectively. No differences in the prevalence rates of these TOD markers were present across all SUA tertiles in the entire population, as well as in both sexes. The SUA levels were similar in patients with and without LVH, carotid alterations, or microalbuminuria. When patients were classified according to the number of organs involved, those with multiple TOD (2 or 3 organs) had significantly higher SUA levels (5.1 +/- 1.3 or 5.2 +/- 1.4 mg/dL), as compared with those with a single or no organ involvement (4.9 +/- 1.3 or 4.9 +/- 1.4 mg/dL, P < .05). The association, however, between SUA levels and multiple TOD was not confirmed in a logistic regression analysis. Our findings do not support the role of SUA as an independent risk factor for subclinical TOD in a selected population of recently diagnosed uncomplicated hypertensives at low prevalence of hyperuricemia.

Recent Advances in Arterial Stiffness and Wave Reflection in Human Hypertension

In recent years, great emphasis has been placed on the role of arterial stiffness and wave reflection in the development of cardiovascular (CV) diseases. Arterial stiffness and wave reflections, which are now well accepted as the most important determinants of increasing systolic and pulse pressures in aging societies, are increasingly used in the clinical assessment of patients with hypertension and various CV risk factors.1,2 This review addresses recent advances in our understanding of the role played by arterial stiffness and wave reflection in the pathophysiology and treatment of human hypertension. According to the editorial rules for “Hypertension Highlights”, and to better focus on recent research, apart from large clinical trials, only articles published during the last 2 years are quoted in this review. Research on the molecular determinants of arterial stiffness has focused for years on the structure and amount of the main load bearing proteins: elastin and collagens.3 Indeed, aging and blood pressure, the two major determinants of arterial stiffness, are associated with a number of molecular changes of the load-bearing media of elastic arteries: the orderly arrangement of elastic fibers and laminae is gradually lost over time, and thinning, splitting, fraying, and fragmentation are observed. The degeneration of elastic fibers is associated with an increase in collagenous material and in ground substance, often accompanied by calcium deposition in ground substance and in degenerate elastic fibers.4 However, quantitative changes in elastin and collagen may not explain, by themselves, paradoxical observations. For instance, the changes in arterial wall material which accompany arterial hypertrophy in animal models of essential hypertension (SHRs and SHR-SPs) and in middle-age hypertensive patients are not necessarily associated with an increased isobaric stiffness.5 We suggested5 that adaptive mechanisms may include a rearrangement of the arterial wall material through cell–matrix connections, with a …

A Modern Perspective on β‐Blocker Use in Hypertension: Clinical Trials and Their Influence on Clinical Practice

National guidelines recommend β‐blockers as second step agents after diuretic therapy in patients without compelling indications despite little clinical trial evidence of cardiovascular outcome benefits in uncomplicated essential hypertension. In high‐risk patients with hypertension, such as those with a previous myocardial infarction or diabetes, heart failure, or coronary artery disease, β‐blockers have been shown to reduce the risk of cardiovascular mortality and to reduce events beyond those ascribed to blood pressure (BP) lowering. The use of a β‐blocker‐based regimen in patients with diabetes has been shown to reduce cardiovascular mortality, progression of diabetic nephropathy, and stroke. Lowering BP in hypertensive patients is a primary goal, but it is also essential that goal BP be achieved with the fewest adverse consequences (ie, by choosing agents that do not worsen concomitant conditions or cause unacceptable side effects). Physicians must consider issues of possible worsening insulin resistance and dyslipidemia associated with some β‐blockers. These metabolic concerns, however, are not an issue for the combined β‐/αblocker carvedilol. This review highlights historical data and important clinical trials that underscore the importance of β‐blockade in specific patients and delineates situations where β‐blockers benefit patients with hypertension and/or cardiovascular disease.

The REDHY Study: Prevalence of Decreased Renal Function in Uncomplicated Essential Hypertension

The REDHY Study: Prevalence of Decreased Renal Function in Uncomplicated Essential Hypertension

Comparison of the Efficacy of Morning versus Evening Administration of Olmesartan in Uncomplicated Essential Hypertension

A total of 18 diurnally active subjects with uncomplicated, mild to moderate, essential hypertension were studied to compare the efficacy of the morning versus evening administration of an oral olmesartan medication. After a two‐week, wash‐out/placebo run‐in period, subjects with clinic diastolic blood pressure (DBP) ≥90 mm Hg and <110 mm Hg began 12 weeks of 20 mg olmesartan medoxomil tablet therapy at 08:00 h daily. Four of the 18 subjects required dose escalation to 40 mg at eight weeks because of clinic DBP≥90 mm Hg. After the 12‐week period of once‐a‐day 08:00 h treatment, subjects were immediately switched to an evening (20:00 h) drug‐ingestion schedule for another 12‐week period without change in dose. Subjects underwent 24 h ambulatory blood pressure monitoring (ABPM) before the initiation of morning treatment and at the end of both the 12‐week morning and evening treatment arms. Dosing time did not exert statistically significant differences on the efficacy of olmesartan: the reduction from baseline in the 24 h mean systolic (SBP) and DBP was, respectively, 18.8 and 14.6 mm Hg with morning dosing and 16.1 and 13.2 mm Hg with evening dosing (p>0.152 between groups). The amplitude of the BP 24 h pattern did not vary with dosing time, indicating full 24 h BP reduction no matter the clock hour of treatment. Although, the BP‐lowering effect was somewhat better with morning dosing, the results of this study suggest that the studied olmesartan medoxomil preparation efficiently reduces BP when ingested in the morning (08:00 h) or evening (20:00 h) in equivalent manner, based on statistical testing, throughout the 24 h.

Beneficial Effects of Angiotensin II Type 1 Receptor Blocker Antihypertensive Treatment on Inflammation Indices: The Effect of Smoking

The effect of long-term angiotensin II type 1 receptor blocker (ARB) therapy on inflammation indices has not been fully investigated in a hypertensive population. The authors evaluated 323 consecutive nondiabetic patients (mean age, 57 years; 176 men; 92 smokers) with high renin activity and uncomplicated essential hypertension whose blood pressure levels normalized (from 163.9/100.7 mm Hg to 131.6/82.8 mm Hg) after 4 weeks of ARB or ARB/diuretic treatment. All patients underwent full laboratory evaluation (routine examination of blood and urine, liver, kidney, thyroid function, and lipid and glucose profiles), including measurement of high-sensitivity C-reactive protein and serum amyloid A levels, at drug-free baseline, which was repeated after 6 months of ARB or ARB/diuretic treatment. A significant (P<.001) overall decrease was noted in both high-sensitivity C-reactive protein (-0.41+/-1.56 mg/dL) and serum amyloid A (-0.62+/-2.03 mg/dL), but a smaller decrease in high-sensitivity C-reactive protein and serum amyloid A change was seen in the smoker subgroup compared with nonsmokers (P<.05), indicating that the ARB or ARB/diuretic anti-inflammatory effect may be adversely affected by smoking status.