Dean Picone

Brachial-to-radial SBP amplification: implications of age and estimated central blood pressure from radial tonometry.

Objectives: The reference standard for noninvasive estimation of central blood pressure (BP) is radial tonometry calibrated using brachial SBP and DBP. Brachial-to-radial-SBP amplification (B-R-SBPAmp) may introduce error into central BP estimation, but the magnitude of such amplification is uncertain. This study aimed to determine the magnitude and effect of ageing on B-R-SBPAmp; the effect of B-R-SBPAmp on radial tonometry estimated central SBP; and correlates of B-R-SBPAmp. Methods: Forty young (28 ± 5 years) and 20 older (60 ± 8 years) healthy participants underwent brachial and radial artery ultrasound to identify SBP from the first Doppler flow inflection during BP cuff deflation (first Korotkoff sound). Impedance cardiography, ultrasound, tonometry and anthropometric data were collected to explore B-R-SBPAmp correlates. Results: Radial SBP was significantly higher than brachial SBP in younger (118 ± 12 versus 110 ± 10 mmHg; P < 0.001) and older (135 ± 12 versus 121 ± 11 mmHg; P < 0.001) participants. The magnitude of B-R-SBPAmp (radial minus brachial SBP) was higher in older than younger participants (14 ± 7 versus 8 ± 7 mmHg; P = 0.002), independent of sex and heart rate. Estimated central SBP was higher in both age groups when radial waveforms were recalibrated using radial (versus brachial) SBP (P < 0.001). The central SBP change relative to B-R-SBPAmp was associated with augmentation index (r = 0.739, P < 0.001), independent of age, sex and heart rate. Age, male sex and high-density lipoprotein each positively related to B-R-SBPAmp in multiple regression analysis (P < 0.05). Conclusion: Major B-R-SBPAmp occurs in healthy people and is higher with increasing age. Furthermore, B-R-SBPAmp contributes to underestimation of radial tonometry derived central SBP.

Exaggerated blood pressure response to early stages of exercise stress testing and presence of hypertension.

OBJECTIVES Exaggerated exercise blood pressure (EEBP) recorded during exercise testing at moderate-intensity is independently associated with cardiovascular mortality. It is hypothesized that EEBP may be indicative of underlying hypertension unnoticed by standard clinic (resting) BP measures (thus explaining increased mortality risk), but this has never been confirmed by association with hypertension defined using ambulatory BP monitoring, which was the aim of this study. DESIGN Cross-sectional study. METHODS 100 consecutive patients free from coronary artery disease (aged 56±9 years, 72% male) underwent clinically indicated exercise stress testing. Exercise BP was recorded at each stage of the Bruce protocol. Presence of hypertension was defined as 24-hour systolic BP ≥130mmHg or daytime systolic BP ≥135mmHg. RESULTS Exercise systolic BP at stage 1 and 2 of the test was significantly associated with the presence of hypertension (P<0.05), with the strongest association observed between stage 1 exercise systolic BP and 24-h systolic BP >130mmHg (AUC=0.752, 95% CIs 0.649-0.846, P<0.001). 79% of participants achieving systolic BP ≥150mmHg at stage 1 of the test were classified as having hypertension, with systolic BP >150mmHg predicting hypertension independently of age, sex and in-clinic hypertension status (OR=4.83, 95% CIs 1.62-14.39, P=0.005). CONCLUSIONS Irrespective of resting BP, systolic BP ≥150mmHg during early stages of the Bruce exercise stress test is associated with presence of hypertension. EEBP should be a warning signal to health/exercise professionals on the presence of hypertension and the need to provide follow up care to reduce cardiovascular risk.

Arterial reservoir characteristics and central-to-peripheral blood pressure amplification in the human upper limb

Background: Arterial reservoir characteristics are related to blood pressure (BP) and independently predict cardiovascular events. It is unknown if arterial reservoir characteristics are modified from the central-to-peripheral large arteries and whether there is a contributory role to BP amplification. The aim of this study was to assess central-to-peripheral changes in arterial reservoir characteristics and determine associations with BP. Methods: Reservoir pressure (RP) and excess pressure (XSP) were derived from intra-arterial BP waveforms among 51 participants (aged 63 ± 13 years, 63% men) undergoing clinically indicated cardiac angiography. BP waveforms were recorded in the ascending aorta, brachial (mid-humerus) and radial (wrist) arteries via catheter pull-back. Results: There was no significant difference in RP between arterial sites (54 ± 15, 53 ± 15 and 52 ± 17 mmHg for the aorta, brachial and radial artery, respectively; P = 0.68). Conversely, XSP increased stepwise from the aorta to the brachial and radial arteries (24 ± 11, 42 ± 14 and 53 ± 16 mmHg; P < 0.001), as did SBP (134 ± 18, 141 ± 16 and 146 ± 19 mmHg; P = 0.004). There were highly significant associations between RP and SBP at all arterial sites (r = 0.821, 0.649 and 0.708; P < 0.001 for all), but the strength of associations between peak XSP and SBP increased significantly from the aorta to the radial artery (r = 0.121 and 0.508; z = 3.04; P = 0.004). Conclusion: Arterial reservoir characteristics are modified through the large arteries of the upper limb. Although RP remains relatively constant, XSP increases significantly and is highly related to BP (SBP and pulse pressure) amplification. These data provide a new understanding on arterial reservoir characteristics and large-artery BP physiology.

Aortic-to-brachial stiffness gradient and kidney function in type 2 diabetes

Objectives: A reversed aortic-to-brachial stiffness gradient (ab-SG), defined as aortic pulse wave velocity (aPWV) greater than brachial PWV (bPWV), was recently shown to predict mortality independent of aPWV in dialysis patients. Patients with type 2 diabetes mellitus (T2DM) have increased risk of renal damage and exhibit haemodynamic abnormalities at rest and during exercise that may alter the ab-SG. This study aimed to examine ab-SG in patients with T2DM by comparison with nondiabetic controls during rest and exercise, and to determine associations between ab-SG, aPWV, and kidney function. Methods: Study participants were 60 patients with T2DM and 60 age and sex-matched nondiabetic controls (58 ± 8 years, 55% male both). ab-SG was defined as the quotient of bPWV (carotid-to-radial) and aPWV (carotid-to-femoral) recorded via applanation tonometry. Kidney function was assessed using estimated glomerular filtration rate (eGFR). The exercise substudy was undertaken in 21 patients with T2DM and 21 matched nondiabetic controls during semirecumbent exercise. Results: ab-SG was significantly lower in patients with T2DM (0.99 ± 0.2 vs. 1.2 ± 0.3, P < 0.001) and aPWV, but not bPWV, was significantly higher (P < 0.001 and P = 0.25). A total of 58% of patients with T2DM vs. 27% of nondiabetic controls (&khgr;2 = 11.0, P < 0.001) had a reversed ab-SG (aPWV ≥ bPWV). ab-SG predicted eGFR independent of age, sex, T2DM status, and cardiovascular risk factors (&bgr; = 13.2, P = 0.024), whereas aPWV did not (&bgr; = −0.88, P = 0.30). Exercise ab-SG was significantly lower in patients with T2DM (0.97 ± 0.2 vs. 1.2 ± 0.2, P < 0.001), but did not predict eGFR. Conclusions: Patients with T2DM have a reversed ab-SG during rest and exercise. Resting ab-SG predicts kidney function independent of aPWV, implying a reversed ab-SG may have a pathophysiological function.

Discovery of New Blood Pressure Phenotypes and Relation to Accuracy of Cuff Devices Used in Daily Clinical Practice.

Cuff blood pressure (BP) is the reference standard for management of high BP, but the method is inaccurate and can lead to BP misclassification. The aims of this study were to determine whether distinctive BP phenotypes exist based on BP transmission (amplification) variability from central-to-peripheral arteries and whether applying one standard cuff BP measurement approach (eg, oscillometry) to all people could discriminate the BP phenotypes. Intra-arterial BP was measured at the ascending aorta and brachial and radial arteries in 126 participants (61±10 years; 69% male) after coronary angiography. Central-to-peripheral systolic BP (SBP) transmission (SBP amplification) was defined by ≥5 mm Hg SBP increase between the aorta-to-brachial or brachial-to-radial arteries. Standard cuff BP was measured 4 different times using 3 different devices. Three independent investigators also provided data (n=255 from 4 studies) using another 3 separate cuff BP devices. Four distinct BP phenotypes were discovered based on variability in SBP amplification: phenotype 1, both aortic-to-brachial and brachial-to-radial SBP amplification; phenotype 2, only aortic-to-brachial SBP amplification; phenotype 3, only brachial-to-radial SBP amplification; and phenotype 4, neither aortic-to-brachial nor brachial-to-radial SBP amplification. Aortic SBP was significantly higher among phenotypes 3 and 4 compared with phenotypes 1 and 2 (P=0.00074), but this was not discriminated using any standard cuff BP measures (P=0.31). Data from independent investigators confirmed the key findings. This is the first-in-human discovery of BP phenotypes that have significantly different BPs, but which are not discriminated by standard cuff BP devices used in daily clinical practice. Improved BP device accuracy may be achieved by considering individual phenotypic BP differences.

Longitudinal Changes in Excess Pressure Independently Predict Declining Renal Function Among Healthy Individuals—A Pilot Study

BACKGROUND Aortic reservoir function independently predicts end-organ damage in cross-sectional analyses. However, longitudinal associations are more important regarding causation, but this has never been examined at rest or in response to light-moderate intensity exercise. The aim of this study was to determine the association between the change in aortic reservoir characteristics, in particular excess pressure integral (Pexcess) at rest and in response to exercise and the change in kidney function among healthy individuals followed over time. METHODS Aortic reservoir function (Pexcess and reservoir pressure), aortic stiffness, brachial and central blood pressure (BP), and renal function (estimated glomerular filtration rate [eGFR]) were recorded among 33 healthy individuals (57 ± 9 years; 55% male) at baseline and after an average 3.0 ± 0.3 years. RESULTS Over the follow up period, there was a significant increase in resting brachial BP, central BP, Pexcess, and aortic stiffness (P < 0.05 all). The change over time in resting Pexcess (but not aortic stiffness) was significantly related to the change in eGFR (r = -0.38, P = 0.038) and remained independent of age at follow up, change in 24-hour ambulatory systolic BP and body mass index (β = -0.0300, P = 0.043). There was no association between the change in aortic pulse wave velocity and the change eGFR (P = 0.46) nor were there any associations with exercising hemodynamics. CONCLUSIONS Pexcess is independently associated with a decline in renal function among healthy people followed over 3 years. These novel findings indicate the need to determine the underlying physiological determinants of aortic reservoir function.

Brachial-to-radial systolic blood pressure amplification in patients with type 2 diabetes mellitus.

Brachial-to-radial-systolic blood pressure amplification (Bra-Rad-SBPAmp) can affect central SBP estimated by radial tonometry. Patients with type 2 diabetes mellitus (T2DM) have vascular irregularities that may alter Bra-Rad-SBPAmp. By comparing T2DM with non-diabetic controls, we aimed to determine the (1) magnitude of Bra-Rad-SBPAmp; (2) haemodynamic factors related to Bra-Rad-SBPAmp; and (3) effect of Bra-Rad-SBPAmp on estimated central SBP. Twenty T2DM (64±8 years) and 20 non-diabetic controls (60±8 years; 50% male both) underwent simultaneous cuff deflation and two-dimensional ultrasound imaging of the brachial and radial arteries. The first Korotkoff sound (denoting SBP) was identified from the first inflection point of Doppler flow during cuff deflation. Bra-Rad-SBPAmp was calculated by radial minus brachial SBP. Upper limb and systemic haemodynamics were recorded by tonometry and ultrasound. Radial SBP was higher than brachial SBP for T2DM (136±19 vs 127±17 mm Hg; P<0.001) and non-diabetic controls (135±12 vs 121±11 mm Hg; P<0.001), but Bra-Rad-SBPAmp was significantly lower in T2DM (9±8 vs 14±7 mm Hg; P=0.042). The product of brachial mean flow velocity × brachial diameter was inversely and independently correlated with Bra-Rad-SBPAmp in T2DM (β=−0.033 95% confidence interval −0.063 to −0.004, P=0.030). When radial waveforms were calibrated using radial, compared with brachial SBP, central SBP was significantly higher in both groups (T2DM, 116±13 vs 125±15 mm Hg; and controls, 112±10 vs 124±11 mm Hg; P<0.001 both) and there was a significant increase in the number of participants classified with ‘central hypertension’ (SBP⩾130 mm Hg; P=0.004). Compared with non-diabetic controls, Bra-Rad-SBPAmp is significantly lower in T2DM. Regardless of disease status, radial SBP is higher than brachial SBP and this results in underestimation of central SBP using brachial-BP-calibrated radial tonometry.

Identification of the optimal protocol for automated office blood pressure measurement among patients with treated hypertension

BACKGROUND Automated office blood pressure (AOBP) involving repeated, unobserved blood pressure (BP) readings during one clinic visit is recommended for in-office diagnosis and assessment of hypertension. However, the optimal AOBP protocol to determine BP control in the least amount of time with the fewest BP readings is yet to be determined and was the aim of this study. METHODS One hundred and eighty-nine patients (mean age 62.8 ± 12.1 years; 50.3% female) with treated hypertension referred to specialist clinics at 2 sites underwent AOBP in a quiet room alone. Eight BP measurements were taken starting immediately after sitting and then at 2-minute intervals (15 minutes total). The optimal AOBP protocol was defined by the smallest mean difference and highest intraclass correlation coefficient (ICC) compared with daytime ambulatory BP (ABP). The same BP device (Mobil-o-graph, IEM) was used for both AOBP and daytime ABP. RESULTS Average 15-minute AOBP and daytime ABP were 134 ± 22/82 ± 13 and 137 ± 17/83 ± 11 mm Hg, respectively. The optimal AOBP protocol was derived within a total duration of 6 minutes from the average of 2 measures started after 2 and 4 minutes of seated rest (systolic BP: mean difference (95% confidence interval) 0.004(-2.21, 2.21) mm Hg, P = 1.0; ICC = 0.81; diastolic BP: mean difference 0.37(-0.90, 1.63) mm Hg, P = 0.57; ICC = 0.86). AOBP measures taken after 8 minutes tended to underestimate daytime ABP (whether as a single BP or the average of more than 1 BP reading). CONCLUSIONS Only 2 AOBP readings taken over 6 minutes (excluding an initial reading immediately after sitting) may be needed to be comparable with daytime ABP.

PS 17-22 SIX MONTHS EXERCISE INTERVENTION SIGNIFICANTLY IMPROVES ALBUMIN-CREATININE RATIO IN PATIENTS WITH TYPE 2 DIABETES: A RANDOMISED CONTROLLED TRIAL

Objective: Patients with type 2 diabetes (T2DM) are at increased risk of elevated albumin creatinine ratio (ACR), a marker of kidney damage. Cross-sectional data suggests an inverse relationship between ACR and physical activity, however it is unclear whether a structured exercise intervention can improve ACR in patients with T2DM. We sought to test this in the current study. Design and method: Fifty previously sedentary patients with T2DM (aged 55–75 years) were randomised to a six-month structured aerobic and resistance exercise program (n = 26, mean age 65 ± 5 years, 63% male) or control (n = 24, 67 ± 5 years, 42% male). Measurements taken pre- and post-intervention included: ACR (using standard laboratory techniques); aortic stiffness, clinic BP, 24-hour ambulatory (24-ABPM); and cardiorespiratory fitness via gas analysis (VO2 peak) during Bruce protocol treadmill testing. Results: There were no differences between groups at baseline for any measured variable. Compared with controls, there was a significant reduction in ACR (−0.9 ± 1.6 versus 0.6 ± 1.5, p = 0.011) with exercise intervention. However, there was no between group difference for the change in aortic stiffness, clinic BP or 24-ABPM. Exercise intervention significantly increased time on treadmill (85 ± 97 versus 17 ± 69 s, p = 0.018) and achieved borderline improvements in weight (−0.5 ± 2.5 versus 1.0 ± 2.1 kg, p = 0.051) and VO2 peak (0.9 ± 2.5 versus -0.7 ± 4.3 ml/min/kg, p = 0.21). The change in ACR with intervention remained significant after multiple adjustment including sex, weight, aortic stiffness, clinic BP, 24-ABPM or baseline ACR (p < 0.05). Conclusions: A six-month exercise intervention program significantly improved ACR in patients with T2DM, independent of BP and other variables associated with kidney function. Regular exercise should be advocated for kidney health in patients with T2DM.

LBPS 02-10 DISCOVERY OF A NEW BLOOD PRESSURE PHENOTYPE FROM INTRA-ARTERIAL CENTRAL-TO-PERIPHERAL RECORDINGS: IMPLICATIONS FOR BRACHIAL CUFF MEASUREMENTS AND CARDIOVASCULAR RISK ASSESSMENT

Objective: Brachial cuff blood pressure (BP) accuracy could be influenced by variability in central-to-peripheral systolic BP (SBP)-amplification. However, this has never been determined and we aimed to achieve this by characterising SBP-amplification phenotypes and examining associations with cuff BP accuracy. Design and Method: Intra-arterial BP was measured at the ascending aorta, brachial and radial arteries in 86 patients (61.6 ± 9.8 years; 66% male) following coronary angiography. Cuff BP was measured bilaterally by oscillometric devices before catheterisation, and then simultaneously with intra-arterial brachial BP. SBP-amplification between arterial segments was defined as ≥5 mmHg SBP increase between the aorta-to-brachial or brachial-to-radial arteries. Results: Average aortic-to-brachial and brachial-to-radial SBP-amplification were 8.3 ± 9.5 mmHg and 6.4 ± 9.1 mmHg. Four distinct SBP-amplification phenotypes were observed: 1) both aortic-to-brachial and brachial-to-radial SBP-amplification; 2) only aortic-to-brachial SBP-amplification; 3) only brachial-to-radial SBP-amplification; 4) no aortic-to-brachial or brachial-to-radial SBP-amplification. Patients with no SBP-amplification had significantly elevated aortic SBP compared with all other phenotypes (Table, p = 0.037). When measured simultaneously, aortic SBP was significantly underestimated by brachial cuff BP only in the patients with no SBP-amplification (Table 1), despite no differences between phenotypes in clinical characteristics or cuff SBP measured before or simultaneous to catheterisation (p > 0.1 all). Conclusions: These are the first data to describe distinctive variability in central-to-peripheral SBP-amplification, and includes discovery of a phenotype in which cardiovascular risk may be elevated because of significantly increased aortic SBP that is not detected by conventional cuff BP methods.