title: Comparative effectiveness of a fixed-dose combination of losartan + HCTZ versus bisoprolol + HCTZ in patients with moderate-to-severe hypertension: results of the 6-month ELIZA trial Comparison of the Effects of Antihypertensive Agents on Central Blood Pressure and Arterial Stiffness in Isolated Systolic Hypertension A Randomized Controlled Study on the Effects of Bisoprolol and Atenolol on Sympathetic Nervous Activity and Central Aortic Pressure in Patients with Essential Hypertension Arterial dilation and reduced wave reflection. Benefit of dilevalol in hypertension. Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study. Effects of renin-angiotensin-aldosterone system inhibitors and beta-blockers on markers of arterial stiffness. Hemodynamic effects of amlodipine, bisoprolol, and lisinopril in hypertensive patients after liver transplantation1 Different Aortic Reflection Wave Responses Following Long‐Term Angiotensin‐Converting Enzyme Inhibition And Beta‐Blocker In Essential Hypertension A comparison of atenolol and nebivolol in isolated systolic hypertension Efficacy of losartan and carvedilol on central hemodynamics in hypertensives: a prospective, randomized, open, blinded end point, multicenter study Effect of angiotensin receptor blockade on central haemodynamics in essential hypertension: results of a randomised trial Amlodipine-Valsartan Combination Decreases Central Systolic Blood Pressure More Effectively Than the Amlodipine-Atenolol Combination: The EXPLOR Study Improvement in Blood Pressure, Arterial Stiffness and Wave Reflections With a Very-Low-Dose Perindopril/Indapamide Combination in Hypertensive Patient: A Comparison With Atenolol Selective reduction of cardiac mass and central blood pressure on low-dose combination perindopril/indapamide in hypertensive subjects Differential Effects of Nebivolol and Metoprolol on Central Aortic Pressure and Left Ventricular Wall Thickness Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol Acute &bgr;-Adrenergic Blockade Increases Aortic Wave Reflection in Young Men and Women: Differing Mechanisms Between Sexes Hemodynamic and central blood pressure differences between carvedilol and valsartan added to lisinopril at rest and during exercise stress. Lack of difference between nebivolol/hydrochlorothiazide and metoprolol/hydrochlorothiazide on aortic wave augmentation and central blood pressure Effects of nebivolol on aortic compliance in patients with diabetes and maximal renin angiotensin system blockade: the EFFORT study. Atenolol and eprosartan: differential effects on central blood pressure and aortic pulse wave velocity. Carvedilol reduces aortic wave reflection and improves left ventricular/vascular coupling: a comparison with atenolol (CENTRAL Study). Different effects of fosinopril and atenolol on wave reflections in hypertensive patients. Aortic Pressure Augmentation Predicts Adverse Cardiovascular Events in Patients With Established Coronary Artery Disease Central versus peripheral blood pressure in malignant hypertension; effects of antihypertensive treatment. Central hemodynamics in prehypertension: effect of the β-adrenergic antagonist nebivolol. Effects of Celiprolol and Bisoprolol on Blood Pressure, Vascular Stiffness, and Baroreflex Sensitivity. Local pulse pressure and regression of arterial wall hypertrophy during long-term antihypertensive treatment. Mechanism(s) of selective systolic blood pressure reduction after a low-dose combination of perindopril/indapamide in hypertensive subjects: comparison with atenolol. The effect of low-dose carvedilol, nebivolol, and metoprolol on central arterial pressure and its determinants: a randomized clinical trial. Effects of nebivolol and atenolol on central aortic pressure in hypertensive patients: A multicenter, randomized, double-blind study Benefits from angiotensin-converting enzyme inhibitor ‘beyond blood pressure lowering’: beyond blood pressure or beyond the brachial artery? Effects of atenolol, perindopril and verapamil on haemodynamic and vascular function in Marfan syndrome - a randomised, double-blind, crossover trial. Beta-blockers reduce aortic stiffness in hypertension but nebivolol, not atenolol, reduces wave reflection. A prospective, randomized, open-label, active-controlled, clinical trial to assess central haemodynamic effects of bisoprolol and atenolol in hypertensive patients 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). Differential effects of beta-adrenoreceptor antagonists on central and peripheral blood pressure at rest and during exercise.
abstract: Background The aim of this study was to compare the antihypertensive efficacy of losartan 100 mg + hydrochlorothiazide ( HCTZ ) 25 mg versus bisoprolol 10 mg + HCTZ 25 mg and their influence on arterial stiffness and central blood pressure ( BP ) . Methods Of 60 patients with a mean BP of 173.3 ± 1.7/98.4 ± 1.2 mmHg , 59 were r and om-ized to losartan + HCTZ ( n = 32 ) or bisoprolol + HCTZ ( n = 27 ) .  Amlodipine was added if target BP was not achieved at 1 month , and doxazosin was added if target BP was not achieved after 3 months . Body mass index , office and 24-hour ambulatory BP , pulse wave velocity ( carotid-femoral [ PWVE ] and radial [ PWVM ] ) , noninvasive central systolic BP , augmentation index ( AIx ) , laboratory investigations , and electrocardiography were done at baseline and after 6 months of treatment . Results Losartan + HCTZ was as effective as bisoprolol + HCTZ , with target office BP achieved in 96.9 % and 92.6 % of patients and target 24-hour BP in 75 % and 66.7 % of patients , respectively , after 6 months . Effective treatment of BP led to significant lowering of central systolic BP , but this was decreased to a significantly ( P < 0.05 ) greater extent by losartan + HCTZ ( −23.0 ± 2.3 mmHg ) than by bisoprolol + HCTZ ( −15.4 ± 2.9 mmHg ) despite equal lowering of brachial BP . Factors correlated with central systolic BP and its lowering differed between the treatment groups . Losartan + HCTZ did not alter arterial stiffness patterns significantly , but bisoprolol + HCTZ significantly increased AIx . We noted differences in ΔPWVE , ΔPWVM , and ΔAIx between the groups in favor of losartan + HCTZ . Decreased heart rate was associated with higher central systolic BP and AIx in the bisoprolol + HCTZ group , but was not associated with increased AIx in the losartan + HCTZ group . Conclusion Although both treatments decreased both office and 24-hour BP  , losartan + HCTZ  significantly decreased central systolic BP and had a more positive influence on pulse wave velocity , with a less negative effect of decreased heart rate on AIx and central systolic BP Isolated systolic hypertension is an important risk factor for cardiovascular disease and results primarily from elastic artery stiffening . Although various drug therapies are used to lower peripheral blood pressure ( BP ) in patients with isolated systolic hypertension , the effects of the 4 major classes of antihypertensive agents on central BP , pulse pressure ( PP ) amplification , and arterial stiffness in this condition are not clear . Fifty-nine patients over the age of 60 years with untreated isolated systolic hypertension ( systolic BP ≥140 mm Hg and diastolic BP ≤90 mm Hg ) were r and omly assigned to receive 1 of the following 4 antihypertensive agents : perindopril , atenolol , lercanidipine , or bendrofluazide  . BP was measured using a mercury sphygmomanometer , and augmentation index and carotid-femoral ( aortic ) pulse wave velocity were measured at baseline , after 2 weeks of placebo therapy , and at the end of 10 weeks of active therapy . Peripheral systolic BP and peripheral PP were reduced similarly after treatment with all 4 classes of drug . However , central PP was only reduced significantly by perindopril , lercanidipine , and bendrofluazide , whereas atenolol had no effect . Lercanidipine reduced the augmentation index , whereas atenolol increased it . Aortic pulse wave velocity was not changed by any of the drugs . In summary , despite similar reductions in peripheral systolic and PPs with the 4 classes of drug , changes in central pressure and augmentation index varied . Because central PP and increased wave reflections are considered important risk factors in patients with isolated systolic hypertension , the choice of therapy may be influenced by these findings in the future Objective β-blockers ( BBs ) with different pharmacological properties may have heterogeneous effects on sympathetic nervous activity ( SNA ) and central aortic pressure ( CAP ) , which are independent cardiovascular factors for hypertension . Hence , we analyzed the effects of bisoprolol and atenolol on SNA and CAP in hypertensive patients . Methods This was a prospect i ve , r and omized , controlled study in 109 never-treated hypertensive subjects r and omized to bisoprolol ( 5 mg ) or atenolol ( 50 mg ) for 4–8 weeks .  SNA , baroreflex sensitivity ( BRS ) and heart rate ( HR ) variability ( HRV ) were measured using power spectral analysis using a Finometer . CAP and related parameters were determined using the SphygmoCor device ( pulse wave analysis ) . Results Both drugs were similarly effective in reducing brachial BP . However , central systolic BP ( −14±10 mm Hg vs −6±9 mm Hg ; P<0.001 ) and aortic pulse pressure ( −3±10 mm Hg vs + 3±8 mm Hg ; P<0.001 ) decreased more significantly with bisoprolol than with atenolol .  The augmentation index at a HR of 75 bpm ( AIxatHR75 ) was significantly decreased ( 29%±11 % to 25%±12 % ; P = 0.026 ) in the bisoprolol group only . Furthermore , the change in BRS in the bisoprolol group ( 3.99±4.19 ms/mmHg ) was higher than in the atenolol group ( 2.66±3.78 ms/mmHg ) , although not statistically significant ( P>0.05 ) . BRS was stable when RHR was controlled ( RHR≤65 bpm ) , and the two treatments had similar effects on the low frequency/high frequency ( HF ) ratio and on HF . Conclusion BBs seem to have different effects on arterial distensibility and compliance in hypertensive subjects . Compared with atenolol , bisoprolol may have a better effect on CAP . Trial Registration Clinical Trials.gov We compared dilevalol ( an isomer of labetalol ) , 200 - 400 mg daily , against atenolol , 50 - 100 mg daily , in a double-blind , crossover , placebo-controlled trial with respect to effects on arterial distensibility ( measured as pulse wave velocity [ PWV ] ) and wave reflection ( assessed from carotid pressure wave contour ) . Twelve patients of mean age 58 years ( range 44 - 73 years ) with essential hypertension ( supine diastolic blood pressure 95 - 114 mm Hg ) took active therapy for 12 weeks , separated by a 2 - 4 week placebo period .  Carotid pressure waveforms were recorded noninvasively by applanation tonometry with a Millar micromanometer-tipped probe .  PWV was measured between carotid and femoral arteries ( aortic PWV ) , carotid and radial arteries ( arm PWV ) , and femoral and pedal arteries ( leg PWV ) . Early wave reflection was calculated from the ratio of the height of the peak of the carotid wave above its shoulder to the pulse pressure and was expressed as an augmentation index . Both drugs were equally effective in reducing brachial sphygmomanometric pressure and PWV in all three regions ( active vs. placebo , p less than 0.001 ) , but there was no significant difference between the two active therapies . However , the augmentation index ( averaged during the treatment period ) was significantly lower with dilevalol ( 19 % ) than with atenolol ( 28 % , p less than 0.01 ) , corresponding to a greater decrease of 5 - 8 mm Hg in carotid systolic pressure compared with the brachial artery . Although both drugs were equally effective in reducing arterial distensibility , the vasodilating action of dilevalol gave added benefit in reducing wave reflection , presumably through its vasodilatory effect on peripheral conduit arteries BACKGROUND Different blood pressure (BP)-lowering drugs could have different effects on central aortic pressures and thus cardiovascular outcome despite similar effects on brachial BP . The Conduit Artery Function Evaluation ( CAFE ) study , a sub study of the Anglo-Sc and inavian Cardiac Outcomes Trial ( ASCOT ) , examined the impact of 2 different BP lowering-regimens ( atenolol+/-thiazide-based versus amlodipine+/-perindopril-based therapy ) on derived central aortic pressures and hemodynamics . METHODS AND RESULTS The CAFE study recruited 2199 patients in 5 ASCOT centers . Radial artery applanation tonometry and pulse wave analysis were used to derive central aortic pressures and hemodynamic indexes on repeated visits for up to 4 years . Most patients received combination therapy throughout the study . Despite similar brachial systolic BPs between treatment groups ( Delta0.7 mm Hg ; 95 % CI , -0.4 to 1.7 ; P=0.2 ) , there were substantial reductions in central aortic pressures with the amlodipine regimen ( central aortic systolic BP , Delta4.3 mm Hg ; 95 % CI , 3.3 to 5.4 ; P<0.0001 ; central aortic pulse pressure , Delta3.0 mm Hg ; 95 % CI , 2.1 to 3.9 ; P<0.0001 ) . Cox proportional-hazards modeling showed that central pulse pressure was significantly associated with a post hoc-defined composite outcome of total cardiovascular events/ procedures and development of renal impairment in the CAFE cohort ( unadjusted , P<0.0001 ; adjusted for baseline variables , P<0.05 ) . CONCLUSIONS BP-lowering drugs can have substantially different effects on central aortic pressures and hemodynamics despite a similar impact on brachial BP . Moreover , central aortic pulse pressure may be a determinant of clinical outcomes , and differences in central aortic pressures may be a potential mechanism to explain the different clinical outcomes between the 2 BP treatment arms in ASCOT Antihypertensive agents may , even within the same class , exert variable effects on arterial stiffness variables .  Nebivolol could have a better impact than atenolol on arterial stiffness , by increasing the bioavailability of endothelium-derived nitric oxide . Angiotensin-converting enzyme inhibitors ( ACEIs ) and angiotensin receptor blockers ( ARBs ) increase plasma renin activity ( enhancing the production of angiotensin II via non-ACE-related pathways ) whereas aliskiren does not , potentially affecting central hemodynamics differently . We compared the effects of two renin-angiotensin-aldosterone system ( RAAS ) inhibitors ( quinapril and aliskiren ) and 2 beta-blockers ( atenolol and nebivolol ) on arterial stiffness variables . Treatment-naïve patients ( n = 72 ; 68.1 % males ; age , 47.6 ± 10.6 years ) with uncomplicated stage I-II essential hypertension were r and omly assigned to quinapril , aliskiren , atenolol , or nebivolol for 10 weeks . Central systolic and diastolic blood pressure ( BP ) , central pulse pressure ( PP ) , augmentation index ( AIx ) , and pulse wave velocity ( PWV ) were measured at baseline , 2 , and 10 weeks . The same measurements were performed in 20 normotensive subjects ( 65.0 % males ; age , 40.0 ± 8.9 years ) . Peripheral and central systolic and diastolic BP , peripheral PP , and PWV were significantly and similarly reduced by all agents . However , PWV continued to decline between the second and last visit in patients on quinapril and aliskiren but did not change in those on nebivolol or atenolol  . Central PP and AIx decreased in patients on quinapril , aliskiren , and nebivolol but did not change in those taking atenolol . The decrease in central PP and AIx did not differ between patients on quinapril , aliskiren , and nebivolol . Despite similar reductions in peripheral BP , atenolol is less effective than nebivolol and RAAS inhibitors in improving central pulsatile hemodynamics . Aliskiren exerts similar effects on markers of arterial stiffness  as quinapril . The clinical relevance of these differences remains to be established Background . Hypertension is common after liver transplantation . There are few published data on optimum treatment . Augmentation index ( AIx ) is a measure of arterial wave reflection determined by pulse wave analysis . Methods . Amlodipine was administered to 24 hypertensive liver transplant recipients . Thirteen patients intolerant of or unresponsive to amlodipine  were r and omized to a crossover study comparing bisoprolol with lisinopril . Results . With amlodipine  , systolic blood pressure ( SBP ) fell from 154±2 mm Hg to 130±2 mm Hg , and AIx also fell . With bisoprolol  , SBP fell from 154±2 mm Hg to 142±4 mm Hg , but AIx increased . With lisinopril  , SBP fell from 154±2 mm Hg to 130±5 mm Hg , and AIx also fell ( P < 0.001 throughout ) . Conclusions . Amlodipine is an effective treatment for hypertension . The increased AIx with bisoprolol indicates increased wave reflection such that central aortic pressure is reduced less than peripheral SBP  . Lisinopril reduces AIx and reduces SBP more than bisoprolol and is the preferred drug 1 . In arterial hypertension , aortic wave reflections contribute to determining central systolic and pulse pressures . The present study assessed the central pressure alterations at the level of the common carotid artery following 1 month treatment with perindopril or atenolol and investigated during the 8 h following drug intake Objectives Some β-blockers are less effective in reducing central blood pressure than other antihypertensive drugs , which may explain the higher rate of events in subjects r and omized to atenolol in recent trials . We hypothesized that nebivolol , a mixed β-blocker/nitro-vasodilator , would be more effective than atenolol in reducing central blood pressure and augmentation index ( AIx ) . The aim of the present study was to test this in a double-blind , r and omized , cross-over study , in a cohort of subjects with isolated systolic hypertension . Methods Following a 2-week placebo run-in , 16 never-treated hypertensive subjects received atenolol ( 50 mg ) , nebivolol ( 5 mg ) and placebo , each for 5 weeks , in a r and om order . Seated brachial blood pressure and heart rate were measured . Aortic blood pressure , AIx and pulse wave velocity ( PWV ) were assessed non-invasively . Results The placebo-corrected fall in brachial pressure was similar between nebivolol and atenolol , as was the reduction in PWV ( mean change ± SEM : −1.0 ± 0.3 and −1.2 ± 0.2 m/s ; P = 0.2 ) . However , there was less reduction in heart rate ( −19 ± 2 versus −23 ± 2 beats/min ; P < 0.01 ) and increase in AIx ( + 6 ± 1 versus + 10 ± 1 % ; P = 0.04 ) , following nebivolol . Aortic pulse pressure was significantly lower ( 50 ± 2 versus 54 ± 2 mmHg ; P = 0.02 ) after nebivolol . N-terminal pro-B-type natriuretic peptide ( proBNP ) rose on both drugs ( 100 ± 33 versus 75 ± 80 pg/ml ; P < 0.01 for both , NS for comparison ) . Conclusions Nebivolol and atenolol have similar effects on brachial blood pressure and aortic stiffness . However , nebivolol reduces aortic pulse pressure more than atenolol , which may be related to a less pronounced rise in AIx and bradycardia . Whether this will translate into differences in clinical outcome requires further investigation Renin – angiotensin system ( RAS ) blockers have shown clinical outcomes superior to those of the beta (β)-blocker atenolol , despite similar reductions in the peripheral blood pressure ( BP ) , perhaps because of different impacts on central hemodynamics . However , few comparative studies of RAS blockers and newer vasodilating β-blockers have been performed . We compared the central hemodynamic effects of losartan and carvedilol in a prospect i ve , r and omized , open , blinded end point study . Of the 201 hypertensive patients enrolled , 182 ( 49.6±9.9 years , losartan group=88 and carvedilol group=94 ) were analyzed . Carotid-femoral pulse wave velocity ( cfPWV ) , aortic augmentation index ( AIx ) , AIx corrected for a heart rate ( HR ) of 75 beats per minute ( AIx@HR75 ) and central BP were measured noninvasively at baseline and after a 24-week treatment regimen with losartan or carvedilol . After 24 weeks , there were no between-group differences in the brachial BP , cfPWV , AIx@HR75 or central BP changes , except for a more favorable AIx effect with losartan . The changes in all measured metabolic and inflammatory parameters were also not significantly different between the two groups , except for uric acid . Losartan and carvedilol showed generally comparable effects on central hemodynamic indices , metabolic profile , inflammatory parameters and peripheral arterial pressure with a 24-week treatment Objective . Angiotensin-converting enzyme ( ACE ) inhibitors have been shown to lower central augmentation index ( cAI ) , an index of arterial wave reflection , more than β-blockers . We tested whether this is also true for long-term treatment with an angiotensin receptor blocker ( ARB ) . Methods . One-hundred and fifty-six subjects with essential hypertension were r and omised to treatment with either irbesartan or atenolol .  cAI and central blood pressure ( BP ) were determined by pulse wave analysis from the radial and the carotid artery after six and after 18 months treatment . Results . Peripheral and central systolic and diastolic BP were reduced to a similar extent A in the two groups . cAI was reduced with irbesartan , but increased with atenolol ( derived from the carotid artery : -6±10 vs. -4±12 % after six months , p<0.001 ; —4±12 vs. + 1±11 % after 18 months ; p=0.011 ) . Furthermore , central to peripheral pulse pressure ( PP ) amplification was unaffected by treatment with irbesartan , but decreased with atenolol . Conclusions . Although treatment with irbesartan and atenolol  similarly decreased peripheral and central BP , only treatment with irbesartan had beneficial effects on arterial wave reflection and preserved PP amplification . These haemodynamic effects may at least partly explain the reported differential effects of ARB versus β-blocker treatment on cardiovascular mortality in patients with essential hypertension The & bgr;-blocker atenolol is less effective than angiotensin-receptor blockers and calcium-channel blockers for reducing central blood pressure ( BP ) . The trial was design ed to determine whether the advantages of angiotensin-receptor blockers over atenolol remained significant when both were combined with the calcium-channel blocker amlodipine . A prospect i ve , r and omized , blinded endpoint ( PROBE design ) parallel group , multicenter trial including 393 patients with essential hypertension resistant to 4 weeks of 5 mg of amlodipine  was set out . Central systolic BP , augmentation index ( AIx ; either rough or adjusted on heart rate ) , and carotid-to-femoral pulse wave velocity were measured with applanation tonometry ( SphygmoCor ) at inclusion and after 8 and 24 weeks of active treatment with an amlodipine-valsartan combination ( 5/80 mg and then 10/160 mg ) or an amlodipine-atenolol combination ( 5/50 mg and then 10/100 mg ) . From baseline to week 24 , central systolic BP decreased significantly more in the amlodipine-valsartan group ( −13.70±1.15 mm Hg ; P<0.0001 ) than in the amlodipine-atenolol group ( −9.70±1.10 mm Hg ; P<0.0001 ; difference : −4.00 mm Hg [ 95 % CI : −7.10 to −0.90 ] ; P=0.013 ) , despite similar changes in brachial systolic BP . The difference in rough AIx reduction was −6.5 % ( 95 % CI : −8.3 to −4.7 ; P<0.0001 ) in favor of amlodipine-valsartan  . AIx adjusted on heart rate was significantly reduced in favor of amlodipine-valsartan ( −2.8 % [ 95 % CI : −4.92 to −0.68 ] ; P<0.01 ) . Heart rate decreased significantly more with amlodipine-atenolol ( difference : −11 bpm [ 95 % CI : −14 to −8 bpm ] ; P<0.001 ) . Pulse wave velocity decreased by 0.95 m/s in both groups with no significant difference . Differences in central systolic BP and rough AIx remained significant after adjustment to the changes in heart rate . The amlodipine-valsartan  combination decreased central ( systolic and pulse ) pressure and AIx more than the amlodipine-atenolol combination International guidelines recommend that antihypertensive drug therapy should normalize not only diastolic ( DBP ) but also systolic blood pressure ( SBP ) . Therapeutic trials based on cardiovascular mortality have recently shown that SBP reduction requires normalization of both large artery stiffness and wave reflections . The aim of the present study was to compare the antihypertensive effects of the very-low-dose combination indapamide ( 0.625 mg ) and perindopril ( 2 mg ) ( Per/Ind ) with the & bgr;-blocking agent atenolol ( 50 mg ) to determine whether Per/Ind decreases SBP and pulse pressure ( PP ) more than does atenolol and , if so , whether this decrease is predominantly due to reduction of aortic pulse wave velocity ( PWV ) ( automatic measurements ) and reduction of wave reflections ( pulse wave analysis , applanation tonometry ) . In a double-blind r and omized study , 471 patients with essential hypertension were followed for 12 months . For the same DBP reduction , Per/Ind decreased brachial SBP ( −6.02 mm Hg ; 95 % confidence interval , −8.90 to −3.14 ) and PP ( −5.57 ; 95 % confidence interval , −7.70 to −3.44 ) significantly more than did atenolol . This difference was significantly more pronounced for the carotid artery than for the brachial artery . Whereas the 2 antihypertensive agents decreased PWV to a similar degree , only Per/Ind significantly attenuated carotid wave reflections , result ing in a selective decrease in SBP and PP . The very-low-dose combination Per/Ind normalizes SBP , PP , and arterial function to a significantly larger extent than does atenolol , a hemodynamic profile that is known to improve survival in hypertensive population s with high cardiovascular risk Objective In hypertension , blockade of the renin – angiotensin system reduces left ventricular mass ( LVM ) independently of brachial systolic ( S ) , diastolic ( D ) , and mean ( M ) blood pressure ( BP ) . From central to peripheral arteries , MBP and DBP are practically unchanged , whereas SBP and pulse pressure ( PP ) increase significantly . The objective was to determine whether changes in LVM under drug treatment was preferentially associated with changes in central or brachial SBP and PP . Design A sub study of 146 subjects was selected from 469 hypertensive patients su bmi tted to a double-blind r and omized trial comparing the combination of perindopril ( 2 mg ; Per ) and indapamide ( 0.625 mg ; Ind ) with atenolol ( 50 mg , one tablet per day ) . Main outcome measures Before and after 1 year of treatment : LVM ( echocardiography ) in 146 subjects and , in 52 of them , central ( carotid ) BP and timing of wave reflections ( tonometry ) . Results LVM changes were significantly associated with antihypertensive treatment , with lower LVM with Per/Ind than with atenolol .  Changes in SBP and PP , but not in MBP and DBP , were more significantly associated with Per/Ind than with atenolol , with more pronounced effects using central than brachial measurements , and a longer delay in central return of wave reflections under Per/Ind . In the sampling of 52 patients with tonometry , the change in LVM between the two drug regimens was significantly linked to central , but not brachial , PP change . Conclusions This observational study shows a lower LVM under Per/Ind than under atenolol . The greater change in LVM on Per/Ind was linked to central and not brachial blood pressure The aim of this study was to investigate the effects of the vasodilating & bgr;-blocker nebivolol and the cardioselective & bgr;-blocker metoprolol succinate on aortic blood pressure and left ventricular wall thickness . We conducted a r and omized , double-blind study on 80 hypertensive patients . The patients received either 5 mg of nebivolol or 50 to 100 mg of metoprolol succinate daily for 1 year . Their heart rate , central and brachial blood pressures , mean arterial pressure , augmentation index , carotid-femoral pulse wave velocity , and left ventricular wall thickness were measured at baseline and at the end of the study . Nebivolol and metoprolol significantly reduced heart rate , brachial blood pressure , and mean arterial pressure to the same degree . However , reductions in central systolic and diastolic blood pressures , central pulse pressure , and left ventricular wall thickness were significant only in the nebivolol group . The change in left ventricular septal wall thickness was significantly correlated with central systolic blood pressure change ( r=0.41 ; P=0.001 ) and with central pulse pressure change ( r=0.32 ; P=0.01 ) . No significant changes in augmentation index or carotid-femoral pulse wave velocity were detected in either treatment group . This proof-of-principle study provides evidence to suggest that & bgr;-blockers with vasodilating properties may offer advantages over conventional & bgr;-blockers in antihypertensive therapy ; however , this remains to be tested in a larger trial BACKGROUND Blood pressure reduction achieved with beta-blockers and diuretics is the best recorded intervention to date for prevention of cardiovascular morbidity and death in patients with hypertension . Left ventricular hypertrophy ( LVH ) is a strong independent indicator of risk of cardiovascular morbidity and death . We aim ed to establish whether selective blocking of angiotensin II improves LVH beyond reducing blood pressure and , consequently , reduces cardiovascular morbidity and death . METHODS We did a double-masked , r and omised , parallel-group trial in 9193 participants aged 55 - 80 years with essential hypertension ( sitting blood pressure 160 - 200/95 - 115 mm Hg ) and LVH ascertained by electrocardiography ( ECG ) . We assigned participants once daily losartan-based or atenolol-based antihypertensive treatment for at least 4 years and until 1040 patients had a primary cardiovascular event ( death , myocardial infa rct ion , or stroke ) . We used Cox regression analysis to compare regimens . FINDINGS Blood pressure fell by 30.2/16.6 ( SD 18.5/10.1 ) and 29.1/16.8 mm Hg ( 19.2/10.1 ) in the losartan and atenolol groups , respectively . The primary composite endpoint occurred in 508 losartan ( 23.8 per 1000 patient-years ) and 588 atenolol patients ( 27.9 per 1000 patient-years ; relative risk 0.87 , 95 % CI 0.77 - 0.98 , p=0.021 ) . 204 losartan and 234 atenolol patients died from cardiovascular disease ( 0.89 , 0.73 - 1.07 , p=0.206 ) ; 232 and 309 , respectively , had fatal or non-fatal stroke ( 0.75 , 0.63 - 0.89 , p=0.001 ) ; and myocardial infa rct ion ( non-fatal and fatal ) occurred in 198 and 188 , respectively ( 1.07 , 0.88 - 1.31 , p=0.491 ) . New-onset diabetes was less frequent with losartan . Interpretation Losartan prevents more cardiovascular morbidity and death than atenolol for a similar reduction in blood pressure and is better tolerated . Losartan seems to confer benefits beyond reduction in blood pressure Acute & bgr;-adrenergic blockade increases aortic wave reflection ; however , the mechanisms remain unclear . Evidence suggests that & bgr;-adrenergic receptor sensitivity in the peripheral vasculature differs between sexes . Therefore , the goal of this study was to examine whether & bgr;-adrenergic blockade alters aortic wave reflection to a similar extent in young men and women . In 31 subjects ( 16 men and 15 women ; 26±1 years ) noninvasive aortic pressure waveforms were synthesized from high-fidelity radial pressure waveforms via applanation tonometry before and during systemic & bgr;-blockade ( 0.25 mg/kg bolus , followed by 0.004 mg/kg per minute of continuous infusion of propranolol ) . & bgr;-Blockade  increased aortic augmentation index and wave reflection amplitude ( aortic augmented pressure ) in both sexes ( P<0.01 ) . Although the increase in augmentation index was not significantly different between sexes ( 7.5±1.1 % versus 4.6±1.5 % ; P=0.07 ) , the increase in aortic augmented pressure was greater in women compared with men ( 2.8±0.5 versus 1.4±0.5 mm Hg ; P<0.05 ) . Aortic augmentation index adjusted for a heart rate of 75 bp increased in women ( 4.1±1.1 % ; P<0.05 ) after & bgr;-blockade , whereas it was unchanged in men ( 0.6±1.3 % ; P=0.33 ) . Moreover , the change in aortic augmentation index was inversely associated with the change in heart rate only in men ( r=−0.54 ; P<0.05 ) . Our data suggest that aortic wave reflection is increased to a greater extent in women after systemic & bgr;-blockade , and enhanced aortic wave reflection appears to be mediated by a reduced heart rate in men , whereas the mechanism is unclear in women There is little information about the hemodynamic and exercise-response implication s of renin-angiotensin system blocker combinations . After a 3-week lisinopril ( L ; 40 mg/day ) run-in , carvedilol ( C ; 20 then 40 mg/day ) or valsartan ( V ; 160 then 320 mg/day ) was added to L for 4 weeks each in a forced-titration , r and om order-entry crossover study in 30 subjects .  Arterial tonometry ( central pressures and time-tension index , TTI ) ; impedance cardiography ( steady-state hemodynamics ) , and ultrasound ( carotid flow )  were performed at rest and during supine bicycle exercise at 30 and 60 watts . At rest , both V and C lowered TTI similarly ( 7 % to 9 % , P = .05 compared with L , in part because they lowered blood pressure ( 3 to 7/3 to 4 mm Hg ) . V lowered central systolic pressure , augmentation pressure ( AP ) , and systemic vascular resistance ( SVR , all P < .02 ) ; C lowered heart rate but not central systolic pressure or SVR . During exercise , V persistently lowered central systolic pressure , AP , and SVR , whereas C did not . Neither drug affected exercise responses or carotid blood flow . Adding V or C to an angiotensin-converting enzyme inhibitor reduced cardiac workload by different mechanisms : vasodilation and reduced central blood pressure with V and lower heart rate with Background : The vasodilating beta-blocker nebivolol is thought to be superior in lowering wave reflection and central blood pressure ( BP ) compared to nonvasodilating beta-blockers . The results from studies comparing nebivolol with either metoprolol or atenolol , with or without hydrochlorothiazide ( HCTZ ) , are not unequivocal . Methods : We examined the effects of nebivolol 5 mg and metoprolol 100 mg with HCTZ 12.5 mg on aortic wave augmentation , central BP and hemodynamics using a r and omized , double-blind , crossover design . We included 22 patients ( 17 men , age 59.9 ± 6.4 years ) with office SBP of 155 ± 16 mmHg and DBP of 93 ± 10 mmHg .  Radial applanation tonometry and noninvasive , continuous finger arterial BP measurement was performed at baseline and after 4 weeks of treatment with either drug regimen , separated by a 4-week washout period . Results : Neither treatment affected aortic wave augmentation significantly . Augmentation index increased 1.0 ± 7.8 % ( P = 0.5 ) for nebivolol/HCTZ and 2.4 ± 6.6 % ( P = 0.07 ) for metoprolol/HCTZ . Nebivolol/HCTZ lowered central SBP by 15.8 ± 14.9 mmHg and DBP 10.5 ± 8.4 mmHg , and with metoprolol/HCTZ by 13.5 ± 12.3 mmHg for SBP and 9.5 ± 6.8 mmHg for DBP ( all P < 0.001 ) . Heart rate was lowered 8.1 ± 5.4 beats/min by nebivolol/HCTZ and 8.6 ± 4.9 beats/min by metoprolol/HCTZ . Peripheral BP was reduced to a similar extent as central BP . Peripheral BP decreased by 16.3 ± 14.9 mmHg systolic and 10.1 ± 8.2 mmHg diastolic with nebivolol/HCTZ , and by 15.2 ± 13.0 mmHg systolic and 9.1 ± 6.9 mmHg diastolic with metoprolol/HCTZ . Both treatment modalities had a similar effect on stroke volume , cardiac output , left-ventricular contractility and peripheral resistance . Conclusion : Nebivolol was not superior to metoprolol in reducing aortic wave augmentation or central BP when combined with HCTZ The beneficial effects of nebivolol on arterial stiffness and endothelial dysfunction are well documented in untreated hypertensive patients and differ from nonvasodilatory β-blockers . This study tests the hypothesis that the addition of nebivolol in predominantly African American patients with type 2 diabetes already receiving maximally tolerated doses of renin-angiotensin system ( RAS ) blockers will further improve large artery compliance . Patients with type 2 diabetes and hypertension on maximal RAS blockade ( n=70 ) were r and omized to nebivolol or metoprolol succinate daily . Doses were titrated until systolic blood pressure ( SBP ) was < 130 mm Hg . Radial artery applanation tonometry and pulse wave velocity ( PWV ) analysis were used to derive central aortic pressures and hemodynamic indices at repeated visits at intervals during a 6-month period . Both metoprolol succinate and nebivolol groups demonstrated reductions in brachial SBP ( -8.2±4.3 mm Hg [ P=.01 ] and -7.8±3.7 [ P=.002 ] , respectively ) and aortic DBP ( -2.4±1.8 [ P=.039 ] and -4.0±2.9 mm Hg [ P=.013 ] , respectively ) . Aortic SBP decreased in the nebivolol group only ( 125.3±8 to 121.6±8.2 , P=.025 ) . There were no between group differences in aortic SBP , DBP , augmentation index , or PWV reduction . A significant increase in hemoglobin A1c was observed only in the metoprolol group . In patients with well-controlled type 2 diabetes and hypertension treated with maximally tolerated RAS blockade , nebivolol does not offer significant reductions in aortic BP over metoprolol succinate but maintains a stable metabolic profile BACKGROUND Recent data suggest that atenolol may be inferior to other antihypertensive drugs in reducing cardiovascular risk in older individuals with hypertension , despite lowering peripheral blood pressure ( BP ) . We hypothesized that that atenolol fails to reduce central BP as much as other agents . The aim of the present study was to compare the hemodynamic effects of atenolol and eprosartan in a double-blind , r and omized , cross-over study . METHODS After a 2-week placebo run-in , 21 subjects with never-treated hypertension underwent 6 weeks of therapy with atenolol ( 50 mg ) and eprosartan ( 600 mg ) . Central BP and augmentation index were assessed using pulse wave analysis , and aortic pulse wave velocity was measured , at baseline and at the end of each treatment . RESULTS Both drugs reduced peripheral BP to the same degree . However , there was a significantly greater reduction in central systolic BP with eprosartan ( means + /- SEM : 16 + /- 3 v 11 + /- 2 mm Hg ; P = .03 ) . Despite identical reductions in mean pressure , atenolol reduced aortic pulse wave velocity more than eprosartan ( 0.8 + /- 0.1 v 0.5 + /- 0.1 m/sec ; P = .005 ) . Conversely , augmentation index and N-terminal pro-brain natiuretic peptide levels were reduced significantly after eprosartan ( 6 % + /- 2 % and 11 + /- 5 pg/mL , respectively ) but were increased after atenolol ( 7 % + /- 2 % and 67 + /- 24 pg/mL , respectively ) . CONCLUSIONS These data indicate that despite similar effects on peripheral BP and a greater effect on aortic stiffness , atenolol had less impact on central systolic BP than eprosartan because it failed to reduce wave reflection . This provides one potential explanation for the failure of atenolol to improve outcome in older patients with essential hypertension Blood pressure ( BP ) characteristics , such as central aortic pressure and arterial stiffness , independently predict cardiovascular events . The effects of pharmacologically dissimilar β-blockers on these properties have not been fully eluci date d. Patients with essential hypertension and without significant concomitant cardiovascular disease were r and omly assigned to controlled-release carvedilol , force-titrated to 80 mg ( n=22 ) , or atenolol , force-titrated to 100 mg ( n=19 ) ; each was given once daily for 4 weeks . Baseline characteristics were similar . At the end of week 4 , atenolol and carvedilol  reduced central and brachial systolic and diastolic BP to a similar extent . Central augmentation index was increased in atenolol-treated patients but not carvedilol-treated patients ( atenolol 4.47 % vs carvedilol -0.68 % ; P=.04 ) . Mean augmented central aortic pressure increased slightly during atenolol treatment ( + 1.1 mm Hg ) but decreased slightly during carvedilol treatment ( -1.1 mm Hg ) , although the difference in these changes was not statistically significant ( P=.23 ) . Pulse pressure amplification was reduced more with atenolol at week 4 ( atenolol -10.7 % vs carvedilol -1.8 % ; P=.02 ) . Therefore , we conclude that carvedilol results in more favorable pulse pressure amplification and augmentation index by increasing arterial compliance and reducing the magnitude of wave reflection , respectively , compared with atenolol We conducted this study to compare the effects of fosinopril versus atenolol on peripheral blood pressure , central arterial wave reflection , and left ventricular mass in a group of patients with essential hypertension . We conducted a double-blind , r and omized trial of fosinopril and atenolol in 79 hypertensive patients ( 52 men , 27 women ; mean age , 45.8 + /- 8.5 years ; range , 30 to 68 years ) .  Carotid pressure waveforms were recorded noninvasively by applanation tonometry with a Millar micromanometer-tipped probe . The extent of wave reflection was estimated by the augmentation index defined as the ratio of the amplitude of pressure wave above its systolic shoulder to the pulse pressure . The augmentation index , left ventricular mass index by two-dimensional echocardiography , and 24-hour ambulatory blood pressures were determined before and after 8 weeks of daily treatment with fosinopril ( 10 to 20 mg ) or atenolol ( 50 to 100 mg ) with or without diuretics and compared with those values in 79 normotensive control subjects . After 8 weeks of treatment , both drugs lowered 24-hour ambulatory peripheral systolic and diastolic pressures into the normal range to a similar extent ( fosinopril , -18/-13 mm Hg ; atenolol , -23/-17 mm Hg , both P = NS ) . On the other h and , whereas the elevated augmentation index in hypertensive patients compared with normotensive subjects ( 16 + /- 11 % versus 10 + /- 8 % ) was completely normalized by fosinopril ( -9.3 + /- 9.8 % , P < or = .002 ) , it was lowered by atenolol ( -4.8 + /- 8.9 % , P < .002 ) but to a significantly smaller extent ( fosinopril versus atenolol effect , P = .04 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Pulse pressure ( PP ) , a marker of arterial stiffness , predicts cardiovascular risk . We aim ed to determine whether augmentation pressure ( AP ) derived from the aortic pressure waveform predicts major adverse cardiovascular events ( MACE ) and death independently of PP in patients with established coronary artery disease ( CAD ) . We prospect ively followed-up 297 males undergoing coronary angiography for 1186±424 days .  Ascending aortic pressure tracings obtained during catheterization were used to calculate AP ( difference between the second and the first systolic peak ) .  Augmentation index  ( AIx ) was defined as AP as a percentage of PP . We evaluated whether AP and AIx can predict the risk of MACE ( unstable angina , acute myocardial infa rct ion , coronary revascularization , stroke , or death ) and death using Cox regression . All models evaluating AP included PP to assess whether AP adds to the information already provided by PP . Both AP and AIx significantly predicted MACE . The hazard ratio ( HR ) per 10 mm Hg increase in AP was 1.20 ( 95 % confidence interval [ CI ] , 1.08 to 1.34 ; P<0.001 ) ; the HR for each 10 % increase in AIx was 1.28 ( 95 % CI , 1.11 to 1.48 ; P=0.004 ) . After adjusting for other univariate predictors of MACE , age , and other potential confounders , AP remained a significant predictor of MACE ( HR per 10 mm Hg increase=1.19 ; 95 % CI , 1.06 to 1.34 ; P=0.002 ) , as did AIx ( adjusted HR , 1.28 ; 95 % CI , 1.09 to 1.50 ; P=0.003 ) . AP was a significant predictor of death ( HR per 10 mm Hg increase=1.18 ; 95 % CI , 1.02 to 1.39 ; P=0.03 ) . Higher AIx was associated with a trend toward increased mortality ( HR=1.22 ; 95 % CI , 0.98 to 1.52 ; P=0.056 ) . Aortic AP predicts adverse outcomes in patients with CAD independently of PP and other risk markers BACKGROUND Sodium nitroprusside ( SNP ) and labetalol are recommended for the immediate treatment of malignant hypertension . Both are intravenous agents but have different effects on systemic hemodynamics , and may have differential effects on pulse-wave reflection and pulse-pressure amplification , with consequences for peripheral versus central blood pressures ( BPs ) . METHODS We conducted a nonr and omized , open-label study of 8 patients treated with sodium nitroprusside ( mean age ( ±SD ) , 44±14 years ; 6 males ; diastolic/systolic BP , 225±22/135±8 mm Hg ) and 6 patients treated with intravenous labetalol ( mean age , 39±15 years ; 4 males ; systolic/diastolic BP , 232±22/138±17 mm Hg ) before and after treatment for malignant hypertension , aim ing at a 25 % reduction in mean arterial pressure . We measured peripheral pressures with an intra-arterial catheter in the radial artery and derived central pressures with a generalized transfer filter . RESULTS Mean arterial pressure was similarly reduced with sodium nitroprusside and labetalol ( by 27 % and 30 % , respectively ; P = 0.76 ) . There was a nonsignificantly greater reduction in peripheral systolic blood pressure ( SBP )  with labetalol than with sodium nitroprusside ( 29±11 % vs. 18±7 % , P = 0.08 ) . The decline in peripheral diastolic blood pressure ( DBP ) with the two agents was comparable , whereas the reduction in peripheral pulse pressure was 8±16 % with SNP and 33±17 % with labetalol ( P = 0.01 ) . The decline in reflection magnitude was greater with SNP than with labetalol . There were no significant differences in the reduction of central BP  with SNP and labetalol . The amplification of PP increased with SNP but did not change with labetalol . CONCLUSIONS We found no difference in central SBP or PP in subjects treated with SNP and labetalol , but labetalol produced a greater reduction in peripheral SBP and PP in the immediate treatment of malignant hypertension The aim of the current study was to characterize the effects of the novel β-adrenergic antagonist nebivolol on central aortic blood pressures , arterial properties , and nitroxidergic activity in individuals with prehypertension . Prehypertension is emerging as a major risk factor for several adverse cardiovascular consequences . Increased pulse wave velocity , aortic augmentation index , and aortic blood pressures have been linked with augmented risk of cardiovascular disease and mortality . While the effects of antihypertensive drugs on these parameters in hypertensive patients have been studied , there are limited data so far in prehypertension . Fifty individuals with prehypertension were r and omized to either nebivolol ( 5 mg per day ) or placebo in a double-blind clinical trial . Patients underwent measurement of pulse wave velocity as well as aortic blood pressure and aortic augmentation index via pulse wave analysis at baseline and 8 weeks . Patients also had blood and urine biochemistries done at each visit . Nebivolol achieved significant reductions in central aortic systolic ( P=.011 ) , diastolic ( P=.009 ) , and mean arterial blood pressure ( P=.002 ) . Pulse wave velocity trended toward improvement but did not achieve significance ( P=.088 ) . Nitric oxide production , measured as urinary nitrite/nitrite excretion , also rose substantially in the nebivolol group ( by approximately 60 % , P=.030 ) . Central blood pressures can be effectively lowered by β-blockade while patients are still in the prehypertension phase , and the effects may be coupled to improve nitric oxide release by the drug BACKGROUND We tested the hypothesis that celiprolol and bisoprolol have differential effects on blood pressure ( BP ) , flow-mediated dilation ( FMD ) , and vascular stiffness . METHODS We analyzed 102 hypertensives ( mean age : 59±14 years ) who were being treated other than beta-blockers . They were r and omized to receive add-on treatment with either celiprolol 100 - 200 mg ( C group ) or bisoprolol 2.5 - 5 mg ( B group ) , and followed up for 3 months . In addition to clinic , home , and ambulatory BP monitoring , the FMD , radial augmentation index ( AI ) , brachial-ankle pulse wave velocity ( baPWV ) , urine albumin-to-creatinine ratio , and baroreflex sensitivity ( BRS ) were measured at baseline and at the end of the study . RESULTS Compared to the baseline values , home and 24-hour BP were significantly lowered in the third month in both groups ( all Ps < 0.05 ) . Pulse rate ( PR ) and baPWV were reduced ( P < 0.001 ) , and BRS was increased significantly only in the B group ( P = 0.02 ) . Radial AI was unchanged in the C group but was significantly increased in the B group ( P < 0.001 ) . Central BP was significantly reduced in the C group ( P = 0.003 ) but was unchanged in the B group . FMD was significantly increased in both groups ( both P < 0.01 ) . CONCLUSION Bisoprolol achieved the greater reduction of PR and improved BRS and vascular stiffness , whereas , celiprolol reduced the central BP level . In treated hypertensive patients , add-on use of celiprolol may be favorable in uncomplicated stage of hypertension . On the other h and , bisoprolol may be useful in hypertensives with cardiac or vascular diseases who have advanced atherosclerotic changes and sympathetic nervous system activation BACKGROUND Local pulse pressure ( PP ) is an independent determinant of carotid artery wall thickness , stronger than mean blood pressure ( BP ) . The present study was design ed to assess whether a beta-adrenoceptor antagonist-based or an ACE inhibitor-based treatment was able to reduce carotid artery wall hypertrophy through a reduction in carotid PP rather than by lowering mean BP and whether the influence of local PP reduction could also be detected at the site of a muscular artery , the radial artery . METHODS AND RESULTS Ninety-eight essential hypertensive patients were r and omized to 9 months of double-blind treatment with either celiprolol or enalapril . Arterial parameters were determined with high-resolution echo-tracking systems . PP was measured locally with applanation tonometry and independently of mean BP . After 9 months of treatment , mean BP , carotid PP , and intimal-medial thickness ( IMT ) decreased significantly , with no difference between the 2 groups . The reduction in carotid PP but not in mean BP was a major independent determinant of the reduction in carotid IMT . Radial artery IMT and PP decreased significantly with both treatments . However , the reduction in radial artery IMT was not related to the changes in radial artery PP . CONCLUSIONS The regression of carotid artery wall hypertrophy during long-term antihypertensive treatment was dependent on the reduction in local PP rather than on the lowering of mean BP . The effect of PP lowering on IMT reduction was observed at the site of an elastic artery but not at the site of a muscular artery OBJECTIVES The goal of this study was to determine if a low-dose combination of the angiotensin-converting enzyme inhibitor perindopril ( Per ) and the diuretic indapamide ( Ind ) reduces central ( thoracic aorta , carotid artery ) as well as brachial systolic blood pressure ( SBP ) more than the beta-blocker atenolol and to determine the hemodynamic factors influencing independently brachial and central SBP : pulse wave velocity ( PWV ) and pattern of wave reflections . BACKGROUND In high cardiovascular risk population s , angiotensin blockade improves survival without affecting brachial SBP and diastolic blood pressure ( DBP ) . Whether central SBP , which is physiologically lower than brachial SBP , is significantly reduced has never been investigated . METHODS This study was a double-blind r and omized trial for one year in patients with essential hypertension . RESULTS For a similar DBP reduction , Per/Ind decreased SBP significantly more than atenolol , with a more pronounced reduction for central than for brachial SBP . After one year , the difference between brachial and central SBP was maintained by Per/Ind ( 8.28 + /- 1.53 mm Hg ) and significantly attenuated by atenolol ( 0.29 + /- 1.61 mm Hg ) . Under atenolol , the principal factor modulating SBP reduction was mean blood pressure . Under Per/Ind , this parameter played a minor role , and the central SBP reduction implied a major role for disturbed PWV and wave reflections . CONCLUSIONS Under Per/Ind , but not atenolol , normalization of brachial SBP is achieved with a significantly greater reduction of central SBP . This hemodynamic profile reflects changes of wave reflections issued from distal arterial and arteriolar territory , where Per/Ind , but not atenolol , is known to improve vessel wall structure In this prospect i ve , open-label , r and omized , controlled clinical trial the effects of low-dose carvedilol , nebivolol , and metoprolol on central arterial pressure and augmentation index ( AIx ) and its heart rate-corrected value ( AIx@75 ) were assessed . The authors r and omized 75 hypertensive patients ( 18 - 70 years ) to carvedilol 12.5/25 mg , metoprolol 50/100 mg , or nebivolol 2.5/5 mg daily and followed them up for 3 months .  Central arterial pressure and AIx were measured with applanation  tonometry  at baseline and at the end of follow-up . Analyses were restricted to 60 completers . Central systolic pressure decreased equally in all 3 treatment arms . AIx remained unchanged , while AIx@75 decreased significantly by 5.4%±2.5 % in the nebivolol group . According to general linear models , individual change in heart rate was a strong predictor of change in AIx in the carvedilol group ( r(2 ) = 0.23 , P=.03 ) although no similar association was found in the nebivolol group ( r(2 ) = 0.09 ) . The impact of β-blockers with vasodilator effects on pressure augmentation seems to be different with nebivolol having the largest potential of decreasing AIx@75 . While AIx changes associated with carvedilol treatment are strongly driven by heart rate changes , those associated with nebivolol treatment seem to be the result of other mechanisms Abstract Introduction . The main objective was to compare the mean change in augmentation index of hypertensive patients treated with nebivolol or atenolol . Methods . Multicenter , double-blind r and omized study conducted in six Spanish centers . We enrolled out patients between the ages of 40 and 65 years with mild or moderate essential hypertension ( systolic blood pressure , SBP ≥ 140 mmHg to ≤ 179 mmHg and diastolic blood pressure , DBP ≥ 90 mmHg to ≤ 109 mmHg after a 2-week run-in placebo period ) . Patients received nebivolol 5 mg or atenolol 50 mg once daily . At week 3 , atenolol could be titrated up to 100 mg qd for non-responders . Additionally , patients not achieving normal blood pressure after 6 weeks could be treated with 25 mg hydrochlorothiazide . Follow-up visits were at 3 , 6 and 10 weeks . Results . The final study population of 138 patients ( 58 % men ; median age 52.6 years , range 40–67 years ) was r and omized into two groups of 69 patients each . Baseline characteristics of the two groups were similar . At the screening visit , 69 % presented with mild hypertension . Nebivolol  modified the mean augmentation index to a lesser extent than atenolol after 10 weeks ( mean difference 3.1 % , 95 % CI 0.55–5.69 ; p = 0.027 ) . A higher proportion of patients in the atenolol group required a diuretic . Reductions in central aortic pressure and peripheral arterial pressure were similar for both treatment groups . Conclusions . The study confirms that nebivolol produces a less pronounced impact on augmentation index  than atenolol Objective The substantial benefits of ramipril over conventional therapy in high-risk patients are not always associated with clinical ly significant differences in brachial arterial pressure , and largely remain unexplained . We undertook this acute study to establish the magnitude of and reason for different acute effects of ramipril and atenolol on arterial pressure . Methods We enrolled 30 patients , who took 10 mg ramipril , 100 mg atenolol , and placebo at intervals of ≥ 7 days , in a r and omized , double-blind , placebo-controlled trial . After baseline , measurements were taken at 30–60 min intervals for 5 h , and comprised cuff brachial pressure , radial artery tonometry with generation of central aortic pressure , and pulse wave velocity for aorta , upper limb and lower limb arteries . Results Both ramipril and atenolol  reduced arterial pressure , and the diastolic pressure fall was similar in the aorta and brachial artery , but the systolic pressure fall for ramipril was greater than for atenolol ( by 5.2 mmHg , P < 0.0001 ) in the aorta compared with the brachial artery . The aortic systolic pressure difference with ramipril in comparison with atenolol was accompanied by an absolute difference of 10.7 % ( P < 0.0001 ) in the augmentation index , denoting a reduction in peripheral wave reflection by ramipril . The aortic pulse wave velocity fell to a similar degree with ramipril in comparison with atenolol , but fell to a greater degree ( 1.35 and 0.44 m/s , respectively , P < 0.0001 for both ) in muscular arteries of the lower and upper limbs . Conclusion A greater ( average , 5.2 mmHg ) decrease in aortic systolic pressure caused by ramipril may explain the greater benefit of ramipril over atenolol . The difference is attributable to decreased stiffness of peripheral arteries and a reduction in wave reflection BACKGROUND Aortic dilatation is the main therapeutic target in patients with Marfan syndrome . St and ard treatment with a β-blocker may not lower central pulse pressure - the major objective - because it does not do so in hypertension , unlike angiotensin-converting enzyme inhibitors and calcium-channel blockers . We therefore performed a prospect i ve , r and omised , double-blind , crossover trial to compare the effects of these three agents on large artery function and central aortic pressure in patients with Marfan syndrome . METHODS AND RESULTS Eighteen patients had applanation tonometry , pulse wave analysis and echocardiography , before and after atenolol 75 mg , perindopril 4 mg and verapamil 240 mg , each given for 4 weeks , in a r and om order , with 2 weeks between medications . Fourteen patients completed the study . Within-drug comparisons demonstrated that perindopril ( -10·3 mmHg , P = 0·002 ) , verapamil ( -9·2 mmHg , P = 0·003 ) and atenolol ( -7·1 mmHg , P = 0·01 ) all reduced central systolic pressure and brachial pressure ; central changes were least , and peripheral changes greatest with atenolol but between-drug comparisons ( analysis of covariance ) were not significant . There was a trend for augmentation to be reduced by perindopril ( -6·3 % , P = 0·05 ) , verapamil ( -5·5 % , P = 0·07 ) and atenolol ( -3·2 % , P = 0·09 ) . Only atenolol  reduced heart rate ( by 16 % ) and delayed expansion in the arch and abdominal aorta ( by 8 % and 11 % ) ( P < 0·001 , P < 0·01 and P < 0·05 , respectively , for between-drug comparisons ) . CONCLUSIONS Perindopril , verapamil and atenolol all reduced peripheral and central systolic pressure . As atenolol slowed heart rate and delayed aortic wave travel , β-blockade may have a continuing role in the treatment of patients with Marfan syndrome BACKGROUND There is conflicting information with regard to the effect of beta-blockers on arterial stiffness and wave reflection . We compared a vasodilating beta-blocker , nebivolol , with atenolol . METHODS We r and omized 40 subjects with untreated hypertension ( mean + /- s.e.m . systolic/diastolic blood pressure ( BP ) of 160 + /- 3/98 + /- 1 mm Hg , age 49 + /- 1 years ) 16 of whom were women , to atenolol 50 mg or nebivolol 5 mg daily for 4 weeks .  Arterial stiffness was assessed in terms of carotid-femoral pulse wave velocity ( PWV , Complior ) and arterial wave reflection ( augmentation index ( AIx ) by applanation tonometry , Sphygmocor ) . RESULTS Both beta-blockers produced an equal reduction in brachial BP but aortic pulse pressure ( PP ) was reduced to a greater extent by nebivolol ( P < 0.05 ) . PWV was decreased significantly by both therapies ( nebivolol : from 11.5 + /- 0.5 to 9.9 + /- 0.5 m/s ; atenolol : from 11.1 + /- 0.4 to 9.8 + /- 0.4 m/s ; P < 0.01 ) but only nebivolol significantly reduced AIx ( from 35 + /- 5 to 28 + /- 2 % , P < 0.05 ) . In addition , whereas PP amplification ( PP , mm Hg ) decreased with atenolol therapy ( from 10 + /- 1 to 7 + /- 1 , P < 0.01 ) , it increased with nebivolol therapy ( from 8 + /- 1 to 14 + /- 3 , P < 0.01 ) . Atenolol reduced heart rate to a greater extent than nebivolol did ( 14 + /- 3/min reduction by atenolol vs. 8 + /- 2/min reduction by nebivolol , P < 0.05 ) . There was no difference between the two treatments in respect of the effect on transit time . CONCLUSION The beta-blockers , atenolol and nebivolol , have a similar effect in reducing arterial stiffness in the large elastic aorta , largely secondary to BP reduction . Nebivolol , in contrast to atenolol , has an effect on small muscular arteries , increasing PP amplification and reducing wave reflection , possibly because of increased levels of nitric oxide ( NO ) . Such ancillary properties may impart important distinct hemodynamic effects , and therefore beta-blockers can not be regarded as a homogeneous group Objective : The results from the ASCOT CAFÉ study demonstrated the inferiority of beta blockers in reducing central aortic blood pressure . In this study , we wanted to demonstrate whether or not second-generation beta blockers with higher beta 1 selectivity , namely bisoprolol , may counterbalance the effect of bradycardia through reduced reflection wave magnitude result ing from the relative lack of increase in peripheral vascular resistance . Method : This was a prospect i ve , r and omized , open-label , active-controlled trial in 209 hypertensive patients to evaluate the effect of bisoprolol and atenolol on aortic pulse pressure . Patients received a once-daily 5 mg dose of bisoprolol ( n = 96 ) or 50 mg dose of atenolol ( n = 95 ) at baseline with titration up to bisprolol 10 mg and atenolol 100 mg allowed at the 4th week when the brachial blood pressure was above treatment goal ( average dose : bisoprolol : 5.4 mg , atenolol : 52.8 mg ) . Central blood pressure and augmentation index were measured at baseline and 12 weeks later , by pulse wave analysis with radial artery tonometry . The primary endpoint of the study was the difference in the central pulse pressure ( CPP ) at 12 weeks . Results : The results showed a significant reduction of CPP in both groups at week 12 of administration compared with the predose level ( P < 0.05 ) ; however , there was no significant difference in terms of CPP change  [ bisoprolol ( baseline CPP 47.49 ± 11.33 , follow-up 43.09 ± 11.67 ) vs. atenolol ( baseline CPP 45.93 ± 11.62 , follow-up 42.23 ± 9.92 ) , P = 0.594 ] . Conclusion : In this study , there was no significant difference between bisoprolol and atenolol in terms of reduction of aortic pulse pressure after 12 weeks of treatment Hypertension is the most common condition seen in primary care and leads to myocardial infa rct ion , stroke , renal failure , and death if not detected early and treated appropriately . Patients want to be assured that blood pressure ( BP ) treatment will reduce their disease burden , while clinicians want guidance on hypertension management using the best scientific evidence . This report takes a rigorous , evidence -based approach to recommend treatment thresholds , goals , and medications in the management of hypertension in adults . Evidence was drawn from r and omized controlled trials , which represent the gold st and ard for determining efficacy and effectiveness . Evidence quality and recommendations were grade d based on their effect on important outcomes . There is strong evidence to support treating hypertensive persons aged 60 years or older to a  BP goal  of less than 150/90 mm Hg and hypertensive persons 30 through 59 years of age to a diastolic goal of less than 90 mm Hg ; however , there is insufficient evidence in hypertensive persons younger than 60 years for a systolic goal , or in those younger than 30 years for a diastolic goal , so the panel recommends a BP of less than 140/90 mm Hg for those groups based on expert opinion . The same thresholds and goals are recommended for hypertensive adults with diabetes or nondiabetic chronic kidney disease ( CKD ) as for the general hypertensive population younger than 60 years . There is moderate evidence to support initiating drug treatment with an angiotensin-converting enzyme inhibitor , angiotensin receptor blocker , calcium channel blocker , or thiazide-type diuretic in the nonblack hypertensive population , including those with diabetes . In the black hypertensive population , including those with diabetes , a calcium channel blocker or thiazide-type diuretic is recommended as initial therapy . There is moderate evidence to support initial or add-on antihypertensive therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in persons with CKD to improve kidney outcomes . Although this guideline provides evidence -based recommendations for the management of high BP and should meet the clinical needs of most patients , these recommendations are not a substitute for clinical judgment , and decisions about care must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient BACKGROUND Differential effects of beta-adrenoreceptor antagonists ( beta-ARB ) on central and peripheral blood pressure may relate to change in heart rate and /or vasodilator tone and thus be exaggerated during exercise . AIMS To examine acute effects of selective and nonselective beta-ARB on central and peripheral blood pressure , cardiac output and peripheral vascular resistance during exercise . METHODS Healthy volunteers ( n= 20 , 18 men , 19 - 54 years ) received propranolol 80 mg , bisoprolol 20 mg , and placebo 1 h before bicycle ergometry ( 50 , 75 and 100 W each for 3 min ) in a r and omized , cross-over study . Cardiac output was determined by pulmonary uptake of soluble and inert gas tracers ( InnoCor , Innovision ) . Central systolic blood pressure ( SBP ) was determined from the late systolic shoulder of the digital artery pressure waveform ( Finometer , Finopres ) . RESULTS At rest , both beta-ARB reduced brachial but not central SBP ( compared with placebo ) . During exercise , beta-ARB reduced brachial SBP ( reductions of 19.9 + /- 4.3 mmHg and 23.2 + /- 2.7 mmHg for propranolol and bisoprolol , respectively , at 100 W , each P < 0.0001 ) but not central SBP . The difference between peripheral and central SBP was reduced , relative to that during placebo , by 21.5 mmHg ( 95 % confidence interval 8.8 , 34.1 ) and 26.4 mmHg ( 18.1 , 34.8 ) for propranolol and bisoprolol , respectively , at 100 W ( each P < 0.01 ) . There was no significant effect of beta-ARB on diastolic blood pressure or peripheral vascular resistance . CONCLUSIONS Despite reducing brachial blood pressure , acute beta-adrenoreceptor blockade in man at rest and during exercise does not reduce central blood pressure
target: In conclusion , NVBBs , but not VBBs , determine a lower reduction in cSBP than in pSBP .
  However , the difference in treatment-induced SBP amplification changes between NVBB and VBB is nearly abolished after accounting for differences in heart rate changes
background: β-Blockers are less effective than other antihypertensive drug classes in reducing central systolic blood pressure ( cSBP ) as compared with peripheral SBP ( pSBP ) .
  Whether this effect is less pronounced with vasodilating β-blockers ( VBB ) when compared with nonvasodilating β-blockers ( NVBB ) remains unsettled .