Rachel E.D. Climie

Validity and reliability of central blood pressure estimated by upper arm oscillometric cuff pressure

BACKGROUND Noninvasive central blood pressure (BP) independently predicts mortality, but current methods are operator-dependent, requiring skill to obtain quality recordings. The aims of this study were first, to determine the validity of an automatic, upper arm oscillometric cuff method for estimating central BP (O(CBP)) by comparison with the noninvasive reference standard of radial tonometry (T(CBP)). Second, we determined the intratest and intertest reliability of O(CBP). METHODS To assess validity, central BP was estimated by O(CBP) (Pulsecor R6.5B monitor) and compared with T(CBP) (SphygmoCor) in 47 participants free from cardiovascular disease (aged 57 ± 9 years) in supine, seated, and standing positions. Brachial mean arterial pressure (MAP) and diastolic BP (DBP) from the O(CBP) device were used to calibrate in both devices. Duplicate measures were recorded in each position on the same day to assess intratest reliability, and participants returned within 10 ± 7 days for repeat measurements to assess intertest reliability. RESULTS There was a strong intraclass correlation (ICC = 0.987, P < 0.001) and small mean difference (1.2 ± 2.2 mm Hg) for central systolic BP (SBP) determined by O(CBP) compared with T(CBP). Ninety-six percent of all comparisons (n = 495 acceptable recordings) were within 5 mm Hg. With respect to reliability, there were strong correlations but higher limits of agreement for the intratest (ICC = 0.975, P < 0.001, mean difference 0.6 ± 4.5 mm Hg) and intertest (ICC = 0.895, P < 0.001, mean difference 4.3 ± 8.0 mm Hg) comparisons. CONCLUSIONS Estimation of central SBP using cuff oscillometry is comparable to radial tonometry and has good reproducibility. As a noninvasive, relatively operator-independent method, O(CBP) may be as useful as T(CBP) for estimating central BP in clinical practice.

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.

Abdominal Obesity and Brain Atrophy in Type 2 Diabetes Mellitus.

Aim Type 2 diabetes mellitus (T2D) is associated with gray matter atrophy. Adiposity and physical inactivity are risk factors for T2D and brain atrophy. We studied whether the associations of T2D with total gray matter volume (GMV) and hippocampal volume (HV) are dependent on obesity and physical activity. Materials and Methods In this cross-sectional study, we measured waist-hip ratio (WHR), body mass index (BMI), mean steps/day and brain volumes in a community dwelling cohort of people with and without T2D. Using multivariable linear regression, we examined whether WHR, BMI and physical activity mediated or modified the association between T2D, GMV and HV. Results There were 258 participants with (mean age 67±7 years) and 302 without (mean age 72±7 years) T2D. Adjusting for age, sex and intracranial volume, T2D was independently associated with lower total GMV (p = 0.001) and HV (p<0.001), greater WHR (p<0.001) and BMI (p<0.001), and lower mean steps/day (p = 0.002). After adjusting for covariates, the inclusion of BMI and mean steps/day did not significantly affect the T2D-GMV association, but WHR attenuated it by 32% while remaining independently associated with lower GMV (p<0.01). The T2D-HV association was minimally changed by the addition of BMI, steps/day or WHR in the model. No statistical interactions were observed between T2D and measures of obesity and physical activity in explaining brain volumes. Conclusions Abdominal obesity or its downstream effects may partially mediate the adverse effect of T2D on brain atrophy. This requires confirmation in longitudinal studies.

Exercise excess pressure and exercise-induced albuminuria in patients with type 2 diabetes mellitus

Exercise-induced albuminuria is common in patients with type 2 diabetes mellitus (T2DM) in response to maximal exercise, but the response to light-moderate exercise is unclear. Patients with T2DM have abnormal central hemodynamics and greater propensity for exercise hypertension. This study sought to determine the relationship between light-moderate exercise central hemodynamics (including aortic reservoir and excess pressure) and exercise-induced albuminuria. Thirty-nine T2DM (62 ± 9 yr; 49% male) and 39 nondiabetic controls (53 ± 9 yr; 51% male) were examined at rest and during 20 min of light-moderate cycle exercise (30 W; 50 revolutions/min). Albuminuria was assessed by the albumin-creatinine ratio (ACR) at rest and 30 min postexercise. Hemodynamics recorded included brachial and central blood pressure (BP), aortic stiffness, augmented pressure (AP), aortic reservoir pressure, and excess pressure integral (Pexcess). There was no difference in ACR between groups before exercise (P > 0.05). Exercise induced a significant rise in ACR in T2DM but not controls (1.73 ± 1.43 vs. 0.53 ± 1.0 mg/mol, P = 0.002). All central hemodynamic variables were significantly higher during exercise in T2DM (i.e., Pexcess, systolic BP and AP; P < 0.01 all). In T2DM (but not controls), exercise Pexcess was associated with postexercise ACR (r = 0.51, P = 0.002), and this relationship was independent of age, sex, body mass index, heart rate, aortic stiffness, antihypertensive medication, and ambulatory daytime systolic BP (β = 0.003, P = 0.003). Light-moderate exercise induced a significant rise in ACR in T2DM, and this was independently associated with Pexcess, a potential marker of vascular dysfunction. These novel findings suggest that Pexcess could be important for appropriate renal function in T2DM.

Aortic reservoir characteristics and brain structure in people with type 2 diabetes mellitus; a cross sectional study.

BackgroundCentral hemodynamics help to maintain appropriate cerebral and other end-organ perfusion, and may be altered with ageing and type 2 diabetes mellitus (T2DM). We aimed to determine the associations between central hemodynamics and brain structure at rest and during exercise in people with and without T2DM.MethodsIn a sample of people with T2DM and healthy controls, resting and exercise measures of aortic reservoir characteristics (including excess pressure integral [Pexcess]) and other central hemodynamics (including augmentation index [AIx] and aortic pulse wave velocity [aPWV]) were recorded. Brain volumes (including gray matter volume [GMV] and white matter lesions [WML]) were derived from magnetic resonance imaging (MRI) scans. Multivariable linear regression was used to study the associations of hemodynamic variables with brain structure in the two groups adjusting for age, sex, daytime systolic BP (SBP) and heart rate.ResultsThere were 37 T2DM (63 ± 9 years; 47% male) and 37 healthy individuals (52 ± 8 years; 51% male). In T2DM, resting aPWV was inversely associated with GMV (standardized β = -0.47, p = 0.036). In healthy participants, resting Pexcess was inversely associated with GMV (β = -0.23, p = 0.043) and AIx was associated with WML volume (β = 0.52, p = 0.021). There were no associations between exercise hemodynamics and brain volumes in either group.ConclusionsBrain atrophy is associated with resting aortic stiffness in T2DM, and resting Pexcess in healthy individuals. Central vascular mechanisms underlying structural brain changes may differ between healthy individuals and T2DM.

Persistent elevation of central pulse pressure during postural stress in patients with type 2 diabetes mellitus

An abnormal increase or decrease in blood pressure (BP) in response to postural stress is associated with increased risk of developing hypertension and stroke. However, the haemodynamic responses contributing to changes in central BP with postural stress are not well characterised. We aimed to determine this in controls compared to patients with type 2 diabetes mellitus (T2DM), whom we hypothesised would have an abnormal postural response. 41 participants (20 control, 21 T2DM) underwent measurement of brachial and central BP (by radial tonometry), with simultaneous bioimpedance cardiography (to determine stroke volume (SV) and cardiac output (CO)) and heart rate variability in seated and standing postures. Systemic vascular resistance (SVR; mean arterial pressure/CO), and arterial elastance (EA; end systolic pressure/SV) were calculated. Postural changes were defined as seated minus standing values. Central pulse pressure (PP) was higher in patients with T2DM and did not change from seated-to-standing positions, whereas there was a significant decrease upon standing in controls (P<0.05). The change in central systolic BP (SBP) correlated with change in SVR and EA in controls (r=0.67 and 0.68, P<0.05, respectively), but not in patients with T2DM (r=−0.05 and r=0.03, P>0.05, respectively). SV was the only significant correlate of change in central SBP in T2DM patients (r=0.62, P<0.05) and this was not observed in controls (r=−0.08 P>0.05). We conclude that central haemodynamic responses to postural stress are altered in patients with T2DM and result in persistent elevation of central PP while standing. This may contribute to increased cardiovascular risk associated with T2DM.

Ambulatory and central haemodynamics during progressive ascent to high-altitude and associated hypoxia

High-altitude hypoxia causes major cardiovascular changes, which may result in raised resting brachial blood pressure (BP). However, the effect of high-altitude hypoxia on more sensitive measures of BP control (such as 24 h ambulatory BP and resting central BP) is largely unknown. This study aimed to assess this and compare high-altitude responses to resting brachial BP, as well as determine the haemodynamic correlates of acute mountain sickness (AMS) during a progressive trekking ascent to high-altitude. Measures of oxygen saturation (pulse oximetry), 24 h ambulatory BP, resting brachial and central BP (Pulsecor) were recorded in 10 adults (aged 27±4, 30% male) during a 9-day trek to Mount Everest base camp, Nepal. Data were recorded at sea level (stage 1; <450 m above sea level (ASL)) and at progressive ascension to 3440 m ASL (stage 2), 4350 m ASL (stage 3) and 5164 m ASL (stage 4). The Lake Louise score (LLS) was used to quantify AMS symptoms. Total LLS increased stepwise from sea level to stage 4 (0.3±0.7 vs 4.4±2.0, P=0.012), whereas oxygen saturation decreased to 77±9% (P=0.001). The highest recordings of 24 h ambulatory, daytime, night time, brachial and central systolic BP and diastolic BP were achieved at stage 3, which were significantly greater than at sea level (P<0.005 for all). Twenty-four-hour ambulatory heart rate (HR) and night HR correlated with oxygen saturation (r=−0.741 and −0.608, both P<0.001) and total LLS (r=0.648 and r=0.493, both P<0.001). We conclude that 24 h ambulatory BP, central BP and HR are elevated during high-altitude hypoxia, but AMS symptoms are only related to tachycardia.

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.

SIMPLE INTERMITTENT RESISTANCE ACTIVITY MITIGATES THE DETRIMENTAL EFFECT OF PROLONGED UNBROKEN SITTING ON ARTERIAL FUNCTION IN OVERWEIGHT AND OBESE ADULTS

Prolonged sitting contributes to cardiovascular disease (CVD) risk. The underlying mechanisms are unknown, but may include changes in arterial function and vasoactive mediators. We examined the effects of prolonged unbroken sitting, relative to regular active interruptions to sitting time, on arterial function in adults at increased CVD risk. In a randomized crossover trial, 19 sedentary overweight/obese adults (mean±SD 57±12 yrs), completed two laboratory-based conditions: five hours uninterrupted sitting (SIT) and; five hours sitting interrupted every 30 minutes by three minutes of simple resistance activities (SRA). Femoral artery function (flow mediated dilation; FMD), blood flow and shear rate were measured at zero hour, 30 minutes, one, two and five hours. Brachial FMD was assessed at zero and five hours. Plasma was collected hourly for measurement of endothelin-1 (ET-1), nitrates/nitrites, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). There was a significant decline in femoral artery FMD, averaged over five hours in the SIT condition, relative to SRA (p<0.001). Plasma ET-1 total AUC over five hours increased in the SIT condition compared to SRA (p=0.006). There was no significant difference between conditions in femoral or brachial shear rate, brachial FMD, nitrates/nitrites, VCAM-1 or ICAM-1 (p>0.05 for all). Five hours of prolonged sitting, relative to regular interruptions to sitting time, impaired femoral artery vasodilator function and increased circulating ET-1 in overweight/obese adults. There is the need to build on this evidence beyond acute observations to better understand the potential longer-term vascular-related consequences of prolonged sitting.

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.