Blood pressure measurement modalities and indexed left ventricular mass in men with low-risk hypertension confirmed by ambulatory monitoring.

BACKGROUND: Blood pressure (BP) measurement modalities such as ambulatory monitoring (ABPM) and noninvasive central aortic systolic pressure (CASP), have been reported to improve prediction of hypertension-mediated organ damage (HMOD) compared with conventional clinic BP. However, clinic BP is often confounded by poor measurement technique and 'white-coat hypertension' (WCH). We compared prediction of cardiac MRI (cMRI)-derived left ventricular mass index (LVMI) by differing BP measurement modalities in young men with elevated BP, confirmed by ABPM. METHODS: One hundred and forty-three treatment-naive men (<55 years) with hypertension confirmed by ABPM and no clinical evidence of HMOD or cardiovascular disease (37% with masked hypertension) were enrolled. Relationships between BP modalities and cMRI-LVMI were evaluated. RESULTS: Men with higher LVMI (upper quintile) had higher clinic, central and ambulatory SBP compared with men with lower LVMI. Regression coefficients for SBP with LVMI did not differ across BP modalities ( r  = 0.32; 0.3; 0.31, for clinic SBP, CASP and 24-h ABPM, respectively, P  < 0.01 all). Prediction for high LVMI using receiver-operated curve analyses was similar between measurement modalities. No relationship between DBP and LVMI was seen across measurement modalities. CONCLUSION: In younger men with hypertension confirmed by ABPM and low cardiovascular risk, clinic SBP and CASP, measured under research conditions, that is, with strict adherence to guideline recommendations, performs as well as ABPM in predicting LVMI. Prior reports of inferiority for clinic BP in predicting HMOD and potentially, clinical outcomes, may be due to poor measurement technique and/or failure to exclude WCH.

The impact of pre-existing hypertension and its treatment on outcomes in patients admitted to hospital with COVID-19.

The impact of pre-existing hypertension on outcomes in patients with the novel corona virus (SARS-CoV-2) remains controversial. To address this, we examined the impact of pre-existing hypertension and its treatment on in-hospital mortality in patients admitted to hospital with Covid-19. Using the CAPACITY-COVID patient registry we examined the impact of pre-existing hypertension and guideline-recommended treatments for hypertension on in-hospital mortality in unadjusted and multi-variate-adjusted analyses using logistic regression. Data from 9197 hospitalised patients with Covid-19 (median age 69 [IQR 57-78] years, 60.6% male, n = 5573) was analysed. Of these, 48.3% (n = 4443) had documented pre-existing hypertension. Patients with pre-existing hypertension were older (73 vs. 62 years, p < 0.001) and had twice the occurrence of any cardiac disease (49.3 vs. 21.8%; p < 0.001) when compared to patients without hypertension. The most documented class of anti-hypertensive drugs were angiotensin receptor blockers (ARB) or angiotensin converting enzyme inhibitors (ACEi) (n = 2499, 27.2%). In-hospital mortality occurred in (n = 2020, 22.0%), with more deaths occurring in those with pre-existing hypertension (26.0 vs. 18.2%, p < 0.001). Pre-existing hypertension was associated with in-hospital mortality in unadjusted analyses (OR 1.57, 95% CI 1.42,1.74), no significant association was found following multivariable adjustment for age and other hypertension-related covariates (OR 0.97, 95% CI 0.87,1.10). Use of ACEi or ARB tended to have a protective effect for in-hospital mortality in fully adjusted models (OR 0.88, 95% CI 0.78,0.99). After appropriate adjustment for confounding, pre-existing hypertension, or treatment for hypertension, does not independently confer an increased risk of in-hospital mortality patients hospitalized with Covid-19.

Pulse Wave Calibration and Implications for Blood Pressure Measurement: Systematic Review and Meta-Analysis.

[Figure: see text].

Identifying Isolated Systolic Hypertension From Upper-Arm Cuff Blood Pressure Compared With Invasive Measurements.

Isolated systolic hypertension (ISH) is the most common form of hypertension and is highly prevalent in older people. We recently showed differences between upper-arm cuff and invasive blood pressure (BP) become greater with increasing age, which could influence correct identification of ISH. This study sought to determine the difference between identification of ISH by cuff BP compared with invasive BP. Cuff BP and invasive aortic BP were measured in 1695 subjects (median 64 years, interquartile range [55-72], 68% male) from the INSPECT (Invasive Blood Pressure Consortium) database. Data were recorded during coronary angiography among 29 studies, using 21 different cuff BP devices. ISH was defined as ≥130/<80 mm Hg using cuff BP compared with invasive aortic BP as the reference. The prevalence of ISH was 24% (n=407) according to cuff BP but 38% (n=642) according to invasive aortic BP. There was fair agreement (Cohen κ, 0.36) and 72% concordance between cuff and invasive aortic BP for identifying ISH. Among the 28% of subjects (n=471) with misclassification of ISH status by cuff BP, 20% (n=96) of the difference was due to lower cuff systolic BP compared with invasive aortic systolic BP (mean, -16.4 mm Hg [95% CI, -18.7 to -14.1]), whereas 49% (n=231) was from higher cuff diastolic BP compared with invasive aortic diastolic BP (+14.2 mm Hg [95% CI, 11.5-16.9]). In conclusion, compared with invasive BP, cuff BP fails to identify ISH in a sizeable portion of older people and demonstrates the need to improve cuff BP measurements.

Impact of statin therapy on central aortic pressures and hemodynamics: principal results of the Conduit Artery Function Evaluation-Lipid-Lowering Arm (CAFE-LLA) Study.

BACKGROUND: Statins reduce the risk of cardiovascular events in people with hypertension. This benefit could arise from a beneficial effect of statins on central aortic pressures and hemodynamics. The Conduit Artery Function Evaluation-Lipid-Lowering Arm (CAFE-LLA) study, an Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) substudy, investigated this hypothesis in a prospective placebo-controlled study of treated patients with hypertension. METHODS AND RESULTS: CAFE-LLA recruited 891 patients randomized to atorvastatin 10 mg/d or placebo from 5 centers in the United Kingdom and Ireland. Radial artery applanation tonometry and pulse-wave analysis were used to derive central aortic pressures and hemodynamic indices at repeated visits over 3.5 years of follow-up. Atorvastatin lowered low-density lipoprotein cholesterol by 32.4 mg/dL (95% confidence interval [CI], 28.6 to 36.3) and total cholesterol by 35.1 mg/dL (95% confidence interval, 30.9 to 39.4) relative to placebo. Time-averaged brachial blood pressure was similar in CAFE-LLA patients randomized to atorvastatin or placebo (change in brachial systolic blood pressure, -0.1 mm Hg [95% CI, -1.8 to 1.6], P=0.9; change in brachial pulse pressure, -0.02 mm Hg [95% CI, -1.6 to 1.6], P=0.9). Atorvastatin did not influence central aortic pressures (change in aortic systolic blood pressure, -0.5 mm Hg [95% CI, -2.3 to 1.2], P=0.5; change in aortic pulse pressure, -0.4 mm Hg [95% CI, -1.9 to 1.0], P=0.6) and had no influence on augmentation index (change in augmentation index, -0.4%; 95% CI, -1.7 to 0.8; P=0.5) or heart rate (change in heart rate, 0.25 bpm; 95% CI, -1.3 to 1.8; P=0.7) compared with placebo. The effect of statin or placebo therapy was not modified by the blood pressure-lowering treatment strategy in the factorial design. CONCLUSIONS: Statin therapy sufficient to significantly reduce cardiovascular events in treated hypertensive patients in ASCOT did not influence central aortic blood pressure or hemodynamics in a large representative cohort of ASCOT patients in CAFE-LLA.

Influence of Age on Upper Arm Cuff Blood Pressure Measurement.

Blood pressure (BP) is a leading global risk factor. Increasing age is related to changes in cardiovascular physiology that could influence cuff BP measurement, but this has never been examined systematically and was the aim of this study. Cuff BP was compared with invasive aortic BP across decades of age (from 40 to 89 years) using individual-level data from 31 studies (1674 patients undergoing coronary angiography) and 22 different cuff BP devices (19 oscillometric, 1 automated auscultation, 2 mercury sphygmomanometry) from the Invasive Blood Pressure Consortium. Subjects were aged 64±11 years, and 32% female. Cuff systolic BP overestimated invasive aortic systolic BP in those aged 40 to 49 years, but with each older decade of age, there was a progressive shift toward increasing underestimation of aortic systolic BP (P<0.0001). Conversely, cuff diastolic BP overestimated invasive aortic diastolic BP, and this progressively increased with increasing age (P<0.0001). Thus, there was a progressive increase in cuff pulse pressure underestimation of invasive aortic PP with increasing decades of age (P<0.0001). These age-related trends were observed across all categories of BP control. We conclude that cuff BP as an estimate of aortic BP was substantially influenced by increasing age, thus potentially exposing older people to greater chance for misdiagnosis of the true risk related to BP.

Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study.

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 substudy of the Anglo-Scandinavian 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.

Accuracy of Cuff-Measured Blood Pressure: Systematic Reviews and Meta-Analyses.

BACKGROUND: Hypertension (HTN) is the single greatest cardiovascular risk factor worldwide. HTN management is usually guided by brachial cuff blood pressure (BP), but questions have been raised regarding accuracy. OBJECTIVES: This comprehensive analysis determined the accuracy of cuff BP and the consequent effect on BP classification compared with intra-arterial BP reference standards. METHODS: Three individual participant data meta-analyses were conducted among studies (from the 1950s to 2016) that measured intra-arterial aortic BP, intra-arterial brachial BP, and cuff BP. RESULTS: A total of 74 studies with 3,073 participants were included. Intra-arterial brachial systolic blood pressure (SBP) was higher than aortic values (8.0 mm Hg; 95% confidence interval [CI]: 5.9 to 10.1 mm Hg; p < 0.0001) and intra-arterial brachial diastolic BP was lower than aortic values (-1.0 mm Hg; 95% CI: -2.0 to -0.1 mm Hg; p = 0.038). Cuff BP underestimated intra-arterial brachial SBP (-5.7 mm Hg; 95% CI: -8.0 to -3.5 mm Hg; p < 0.0001) but overestimated intra-arterial diastolic BP (5.5 mm Hg; 95% CI: 3.5 to 7.5 mm Hg; p < 0.0001). Cuff and intra-arterial aortic SBP showed a small mean difference (0.3 mm Hg; 95% CI: -1.5 to 2.1 mm Hg; p = 0.77) but poor agreement (mean absolute difference 8.0 mm Hg; 95% CI: 7.1 to 8.9 mm Hg). Concordance between BP classification using the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure cuff BP (normal, pre-HTN, and HTN stages 1 and 2) compared with intra-arterial brachial BP was 60%, 50%, 53%, and 80%, and using intra-arterial aortic BP was 79%, 57%, 52%, and 76%, respectively. Using revised intra-arterial thresholds based on cuff BP percentile rank, concordance between BP classification using cuff BP compared with intra-arterial brachial BP was 71%, 66%, 52%, and 76%, and using intra-arterial aortic BP was 74%, 61%, 56%, and 65%, respectively. CONCLUSIONS: Cuff BP has variable accuracy for measuring either brachial or aortic intra-arterial BP, and this adversely influences correct BP classification. These findings indicate that stronger accuracy standards for BP devices may improve cardiovascular risk management.

Effects of exercise on central aortic pressure before and after treatment with renin-angiotensin system blockade in patients with hypertension.

INTRODUCTION: Brachial blood pressure increases with exercise and an excessive rise predicts increased cardiovascular risk. Measurement of brachial blood pressure alone may exaggerate the true blood pressure elevation due to exercise-induced change to pressure amplification. Whether blood pressure-lowering treatment modulates pressure amplification during exercise is unknown. METHODS: Thirty-two participants with stage 1-2 hypertension (mean age 59.2 years) received eight weeks' blood pressure lowering with either aliskiren (300mg, n=16) or valsartan (320mg, n=16). Brachial and central aortic pressure (CASP) were measured non-invasively during treadmill exercise (Bruce protocol) at baseline, after eight weeks' treatment and 48 hours following treatment withdrawal. RESULTS: The rise in brachial blood pressure with exercise exceeded the rise in CASP, indicative of enhanced pressure amplification. Eight weeks' treatment elicited similar reductions in brachial blood pressure and CASP which did not differ between rest and peak exercise (p>0.05). The exercise-induced increase in systolic pressure amplification did not differ between baseline and following eight weeks' treatment (p>0.05). These effects remained unchanged following treatment withdrawal. CONCLUSION: Blood pressure lowering does not directly influence the relationship between aortic and brachial pressure either at rest or during exercise in patients with hypertension, other than through proportionate lowering of both pressures. These effects remained unchanged 48 hours after a simulated missed medication dose.

Effects of treatment withdrawal on brachial and central aortic pressure after direct renin inhibition or angiotensin receptor blockade.

INTRODUCTION: Whilst sustained lowering of brachial systolic blood pressure (Br-SBP) and central aortic systolic pressure (CASP) have been demonstrated in patients with hypertension, effects of treatment withdrawal on these parameters have not been investigated. The ASSERTIVE study previously reported more sustained control of Br-SBP with aliskiren versus telmisartan in patients with hypertension, following 7-days treatment withdrawal. In this ASSERTIVE sub-study, we hypothesised that aliskiren would similarly exert more sustained control of CASP than telmisartan during treatment withdrawal. METHODS: We investigated the effects of treatment withdrawal on both Br-SBP and CASP following 12-weeks treatment with either aliskiren (300 mg) or telmisartan (80 mg). Br-SBP and CASP were measured at the end of treatment, and at days 2 and 7 following treatment withdrawal in 303 patients (CASP randomised set). RESULTS: Of the CASP randomised set, 94 patients completed CASP measurements at all time points (CASP completer set). After 7 days of treatment withdrawal, aliskiren demonstrated lesser increases in both Br-SBP and CASP than telmisartan; Br-SBP change: -2.0±1.6 vs. +5.6±1.7 mmHg, p = 0.001; CASP change: -0.4±1.6 vs. +4.6±1.7 mmHg, p = 0.041, n = 94. Similar findings were obtained for the CASP randomised set. CONCLUSIONS: Following treatment withdrawal, aliskiren demonstrated more sustained control of both brachial and central SBP than telmisartan.

Increased pulse wave velocity is not associated with elevated augmentation index in patients with diabetes.

OBJECTIVE: Increased arterial stiffness is a risk factor for cardiovascular disease and is a feature associated with diabetes. Pulse wave velocity (PWV) is an accepted index of arterial stiffness and augmentation index (AI) derived from radial applanation tonometry has been advocated as a measurement of arterial stiffness. This study compares the relationship between PWV and AI in people with and without diabetes. DESIGN AND METHODS: A total of 66 people with diabetes and 66 age-matched non-diabetic controls were studied. Central aortic pressure waves were generated using applanation tonometry over the radial artery and used to calculate AI. Carotid-femoral PWV (PWVcf) was measured simultaneously. RESULTS: Relative to controls, diabetes was associated with increased pulse pressure (PP) and PWVcf (P < 0.01). In contrast, AI did not differ between groups even after adjustment for heart rate. This observation remained consistent irrespective of diabetes type, arterial site, and the presence or absence of antihypertensive therapy. Multiple regression analysis revealed diabetes to be a significant determinant of PWVcf, but not AI. CONCLUSIONS: PP and PWVcf are increased in people with diabetes, but this is not associated with increased AI. These findings conclusively demonstrate that AI is not a reliable measure of arterial stiffness in people with diabetes.

Rapid telomere attrition in cardiac tissue of the ageing Wistar rat.

Many studies show an association between ageing and mean telomere length in DNA isolated from peripheral blood mononuclear cells, few studies have examined less accessible tissues. This study has two objectives: (i) to define the best method to prepare rodent DNA for telomere length measurement by Southern blotting and (ii) to determine whether there are differential rates of telomere attrition in different rodent tissues. We found that the use of agarose plugs for DNA isolation was essential for the accurate measurement of rodent telomere length. Tissue was collected from neonatal (3 days) or aged (18-24 months) male Wistar rats and terminal restriction fragment (TRF) length was measured by Southern blotting. Cardiac tissue from aged rats showed a 38% loss of TRF length compared with newborn animals (p<0.001, n=13), this contrasts with much smaller reductions in brain (1.6%), liver (14.2%), kidney (8.9%) and lung (9.7%). This study demonstrates that the methods of DNA preparation are critical for accurate measurement of telomeres in rodent tissues. Moreover, we show differential rates of telomere attrition in rat tissues, the heart being most susceptible to telomere loss. These observations could have important implications for the study of age-specific changes in tissue function.

Blood pressure and plasma renin activity responses to different strategies to inhibit the renin-angiotensin-aldosterone system during exercise.

OBJECTIVE: The effect of two different strategies for renin-angiotensin-aldosterone system (RAAS) blockade; direct renin inhibition (DRI) versus angiotensin receptor blockade (ARB) on blood pressure (BP) and plasma renin activity (PRA) was compared during exercise. METHODS: Hypertensive adults were randomised to aliskiren (300 mg once daily, n=33) or valsartan (320 mg once daily, n=35). BP and PRA were measured during treadmill exercise (Bruce protocol), at baseline, end of treatment (eight weeks), and after treatment withdrawal (48 hours after last dose). RESULTS: After eight weeks treatment, Aliskiren inhibited PRA (>80%) at rest and during exercise, with inhibition remaining undiminished 48 hours after treatment withdrawal. In contrast, valsartan increased PRA at rest, and more-so during exercise (>400%). Angiotensin receptor blockade, as indicated by PRA increase, was reduced, 48 hours after valsartan treatment withdrawal, suggesting more sustained RAAS blockade with aliskiren. Despite divergent effects on PRA, similar exercise-induced changes in BP were seen. The primary outcome, the rise in systolic BP from rest to peak exercise (baseline to after treatment withdrawal) did not differ between treatments (p=0.25). CONCLUSION: Measurement of PRA is a more sensitive index of RAAS blockade than the BP response during exercise. Furthermore, after treatment withdrawal, aliskiren provides more sustained RAAS inhibition than valsartan at rest and during exercise.

Novel description of the 24-hour circadian rhythms of brachial versus central aortic blood pressure and the impact of blood pressure treatment in a randomized controlled clinical trial: The Ambulatory Central Aortic Pressure (AmCAP) Study.

Elevated brachial blood pressure (BP) is associated with increased cardiovascular risk and predicts morbidity and mortality in humans. Recently, 24-hour ambulatory BP monitoring and assessment of central aortic BP have been introduced to improve BP phenotyping. The Ambulatory Central Aortic Pressure (AmCAP) study combines these approaches and describes, for the first time, the diurnal patterns of simultaneously measured 24-hour ambulatory brachial and central pressures in a prespecified substudy embedded within a clinical trial of BP lowering in patients with hypertension. Twenty-four-hour ambulatory brachial and central pressure measurements were acquired using a tonometer mounted into the articulating strap of a wristwatch-like device (BPro) in 171 participants with hypertension recruited into the ASSERTIVE (AliSkiren Study of profound antihypERtensive efficacy in hyperTensIVE patients) trial. Participants were randomly assigned to BP lowering with either aliskiren 300 mg QD or telmisartan 80 mg QD for 12 weeks. Ambulatory brachial and central BP was measured in all participants both at baseline and at study end. Brachial and central BP both demonstrated typical diurnal patterns with lower pressures at night. However, night time was associated with smaller reductions in central relative to brachial pressure and decreased pulse pressure amplification (P<0.0001 for both). These effects were not modulated after BP lowering and were maintained after adjustment for day and night-time BP and heart rate (P=0.02). This study demonstrates that brachial and central pressure show different diurnal patterns, which are not modulated by BP-lowering therapy, with relatively higher night-time central pressures. These novel data indicate that night-time central BP may provide prognostic importance and warrants further investigation. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00865020.

Development and validation of a novel method to derive central aortic systolic pressure from the radial pressure waveform using an n-point moving average method.

OBJECTIVES: The purpose of this study was to develop and validate the novel application of a simple n-point moving average (NPMA)--a mathematical low pass filter--to noninvasively derive central aortic systolic pressure (CASP) from the radial artery pressure waveform (RAPWF) in humans. BACKGROUND: CASP may be an important independent determinant of clinical outcomes. Development of simple, well-validated methods to noninvasively derive CASP is necessary to facilitate the routine clinical measurement of CASP. METHODS: Three studies in different population cohorts were used to develop and validate the NPMA method to derive CASP in humans: 1) a development study (n = 217), describing the optimal application of the NPMA to derive CASP; 2) a validation study comparing NPMA-CASP with CASP derived using a generalized transfer function (GTF-CASP [SphygmoCor system, AtCor, Sydney, Australia]) using 5,349 RAPWFs from the CAFE (Conduit Artery Function Evaluation) study; and 3) an invasive validation study (n = 20) comparing NPMA-CASP with direct aortic root pressure measurements during cardiac catheterization. RESULTS: In the development study, when using the NPMA, a denominator of n/4 (where n = tonometer sampling frequency) most accurately defined CASP relative to GTF-CASP. Validation of NPMA-CASP using RAPWFs from the CAFE study revealed excellent correlation and agreement (r(2) = 0.993, mean difference 0.3 ± 1.0 mm Hg). The agreement remained robust after stratification by sex, age, treatment, and diabetes status. There was also excellent correlation and agreement (r(2) = 0.98, p < 0.001) between directly measured aortic root systolic pressures (Millar's catheter) at cardiac catheterization versus NPMA-CASP, derived simultaneously from noninvasive RAPWFs. CONCLUSIONS: We show that an NPMA with a denominator of one-quarter of the tonometer sampling frequency accurately defines CASP when applied to noninvasively acquired RAPWFs in man. These novel findings have important implications for the simplification of noninvasive CASP measurement and its wider application in clinical trials and clinical practice.

Impact of heart rate on central aortic pressures and hemodynamics: analysis from the CAFE (Conduit Artery Function Evaluation) study: CAFE-Heart Rate.

OBJECTIVES: The CAFE (Conduit Artery Function Evaluation) study showed less effective central aortic pressure lowering with atenolol-based therapy versus amlodipine-based therapy in people with hypertension. The present study examined the importance of heart rate (HR) as a determinant of this effect. BACKGROUND: Recent analyses have suggested that beta-blockers are less effective at reducing cardiovascular events than alternative blood pressure (BP)-lowering therapies. There has been much debate about the mechanism for this shortfall in benefit and specifically the role of HR lowering by beta-blockers. METHODS: Central pressures were derived from brachial pressure and radial pulse wave analysis in 2,073 patients, and 7,146 measurements were recorded and analyzed over follow-up for up to 4 years. RESULTS: There was no impact of HR on brachial systolic or pulse pressures; however, there was a highly significant inverse relationship between HR and central aortic systolic and pulse pressures (p < 0.001). This was dependent on a strong inverse relationship between HR and augmentation index, indicative of increased wave reflection at lower HRs. Multiple regression, adjusted for brachial BP, showed HR to be the major determinant of central pressures. Moreover, HR and brachial BP accounted for 92% of the variability in central systolic and pulse pressures. Consequently, drug-related differences in central aortic pressures were markedly attenuated after adjustment for HR. CONCLUSIONS: When comparing beta-blocker-based treatments with other BP-lowering strategies, HR reduction with beta-blockers is a major mechanism accounting for less effective central aortic pressure reduction per unit change in brachial pressure.