Atsushi Nakagomi

Invasive validation of a novel brachial cuff-based oscillometric device (SphygmoCor XCEL) for measuring central blood pressure.

Background: Studies have established the prognostic value of central SBP and pulse pressure (PP). The SphygmoCor XCEL (AtCor Medical, Sydney, Australia) device provides practical central blood pressure (BP) measurement for daily clinical use with its easy-to-use, operator-independent procedure. However, this device has not been validated against invasive measurement. Method: Simultaneous oscillometric and high-fidelity invasive measurements of central SBP and PP were compared for 36 patients who underwent coronary arteriography. Invasive measurement of brachial BP was also performed. Oscillometrically measured brachial SBP and DBP were used for calibration. Results: The differences between the invasive and the oscillometric measurements were −4.6 ± 9.9 mmHg for central SBP and −18.5 ± 10.6 mmHg for central PP (mean ± SD). We found strong correlation between the invasive and oscillometric measurements (central SBP and central PP, respectively: r = 0.91 and 0.89; slope, 1.28 and 1.38; both P < 0.001). Although the large slopes of the regression lines indicated a systemic bias toward lower values when measuring in high pressure ranges, the bias was mainly due to calibration error rather than device-specific error because errors of the central measurements correlated well with those of brachial measurements (SBP and PP, respectively: r = 0.80 and 0.77; both P < 0.001). Conclusion: The impaired accuracy of central BP measurement was mainly due to calibration-derived, but not device-dependent, bias. Strong correlation between oscillometric and invasive measurements indicates that SphygmoCor XCEL warrants future investigations to determine the clinical validity of this device.

Comparison of invasive and brachial cuff-based noninvasive measurements for the assessment of blood pressure amplification

Our aim was to assess the discrepancy in the blood pressure amplification (BPA) value defined as the aortic-to-brachial increase in systolic BP (SBP) between invasive and noninvasive brachial cuff-based methods. In 45 patients undergoing cardiac catheterization, BP in the brachial artery and ascending aorta were measured with an invasive catheter and a brachial cuff-based oscillometric device. To calculate aortic SBP, brachial waveforms were calibrated by the brachial systolic and diastolic BP (DBP) (C1 calibration) or by the brachial mean BP and DBP (C2 calibration). C1 calibration underestimated aortic SBP (−17.7 mm Hg (95% confidence interval: −21.9 to −13.5)), whereas C2 calibration generated an approximately accurate aortic SBP (1.8 mm Hg (−2.4 to 5.9)). Regarding brachial SBP, noninvasively measured values were markedly underestimated (22.2 mm Hg (−26.4 to −18.0)), resulting in a slightly low BPA value in C1 calibration (11.9±6.3 mm Hg) and a paradoxical negative BPA value in C2 calibration (−7.6±6.7 mm Hg). Multiple linear regression analysis showed that the cuff-catheter difference of BPA was positively correlated with the cuff-catheter difference of brachial SBP in both calibrations (C1 calibration: β=0.51; C2 calibration: β=0.50; both P<0.01). Although noninvasively measured BPA was associated with invasively measured BPA only in C1 calibration (r=0.33, P=0.03), when using invasively measured brachial SBP instead of a cuff-based measurement, the BPA was well associated with invasively measured BPA in both calibrations (C1 calibration: r=0.57; C2 calibration: r=0.52; both P<0.001). In conclusion, there was a trade-off in accuracy between brachial cuff-based noninvasive aortic SBP and BPA because of the inherent inaccuracies in the cuff-based method. This finding should be fully considered in establishing standardized reference values for aortic BP.

Role of the central nervous system and adipose tissue BDNF/TrkB axes in metabolic regulation

Background/Objectives:Brain-derived neurotrophic factor (BDNF) and its receptor (tropomyosin-related kinase B: TrkB, also known as Ntrk2) have a key role in central regulation of the energy balance. BDNF and TrkB are also expressed in the peripheral tissues, including adipose tissue, but their peripheral role has been unclear. Here we report on the functional significance of the adipose tissue BDNF/TrkB axis in metabolic homeostasis.Materials and Methods:To examine the role of the BDNF/TrkB axis in the central nervous system and in adipose tissue, we generated adipocyte-specific or neuron-specific BDNF/TrkB conditional knockout (CKO) mice. Then we compared the feeding behavior and metabolic profile between each type of CKO mouse and their littermates.Results:Bdnf expression was significantly increased in the adipose tissue of mice receiving a high-calorie diet, whereas Ntrk2 expression was decreased. The Bdnf/Ntrk2 expression ratio of adipose tissue was higher in female mice than male mice. Fabp4-Cre mice are widely used to establish adipocyte-specific CKO mice. However, we found that Fabp4-Cre-induced deletion of Bdnf or Ntrk2 led to hyperphagia, obesity, and aggressiveness, presumably due to ectopic Fabp4-Cre mediated gene recombination in the brain. Next, we attempted to more specifically delete Bdnf or Ntrk2 in adipocytes using Adipoq-Cre mice. Expression of Ntrk2, but not Bdnf, in the adipose tissue was reduced by Adipoq-Cre mediated gene recombination, indicating that adipocytes only expressed TrkB. No phenotypic changes were detected when Adipoq-Cre TrkB CKO mice were fed a normal diet, whereas female CKO mice receiving a high-calorie diet showed a decrease in food intake and resistance to obesity.Conclusions:The adipose tissue BDNF/TrkB axis has a substantial influence on the feeding behavior and obesity in female mice.

Aortic pulsatility assessed by an oscillometric method is associated with coronary atherosclerosis in elderly people.

Abstract The aim of this study was to investigate the association of aortic pulsatility assessed by a non-invasive brachial cuff-based method with coronary atherosclerosis. In total, 139 patients undergoing coronary angiography were included in this cross-sectional study. Aortic blood pressure (BP) indices were recorded invasively by a fluid-filled catheter and non-invasively by a brachial cuff-based oscillometric device. Fractional pulse pressure (FPP) was defined as pulse pressure (PP)/mean BP and pulsatility index (PI) as PP/diastolic BP. Aortic FPP and PI in coronary artery disease (CAD) patients were significantly higher than in non-CAD patients in both invasive and non-invasive methods. Multivariate logistic regression analysis demonstrated that non-invasively measured aortic FPP and PI were associated with CAD risk in patients aged ≥70 years [aortic FPP per 0.1 odds ratio (OR) = 1.66, 95% confidence interval (CI) 1.05–2.64; aortic PI per 0.1 OR =1.39, 95% CI 1.02–1.88; all p < 0.05], but were not associated with CAD risk in patients aged <70 years. In linear regression analysis, non-invasively measured aortic FPP and PI correlated with SYNTAX and Gensini scores only in patients aged ≥70 years. Aortic FPP and PI measured non-invasively by a brachial cuff-based oscillometric device were associated with coronary atherosclerosis in elderly patients.

Crucial Effect of Calibration Methods on the Association Between Central Pulsatile Indices and Coronary Atherosclerosis

BACKGROUND Several studies have reported that central systolic blood pressure (SBP) estimation is affected by calibration methods. However, whether central pulsatile indices, namely pulse pressure (PP) and fractional PP (FPP) (defined as PP/mean arterial pressure (MAP)), also depend on calibration methods remains uninvestigated. This study assessed the accuracy and discriminatory ability of these indices for coronary atherosclerosis using 2 calibration methods. METHODS Post-hoc analysis of a previous cross-sectional study (n = 139) that investigated the association between central pulsatile indices and coronary atherosclerosis. A validated-oscillometric device provided PP and FPP at the brachial artery (bPP and bFPP) and central artery using 2 calibration methods: brachial SBP/diastolic BP (DBP) (cPPsd and cFPPsd) and MAP/DBP (cPPmd and cFPPmd). Accuracy was assessed against invasive measurements (cPPinv and cFPPinv). Multivariate logistic and linear regression analyses were performed to assess the association between pulsatile indices and the presence of coronary artery disease (CAD) and SYNTAX score, respectively. RESULTS cPPmd and cFPPmd were closer to invasive values than cPPsd (cPPsd: 39.6±12.6; cPPmd: 60.2±20.1; cPPinv: 71.4±22.9). cFPP exhibited similar results (cFPPsd: 0.35±0.09; cFPPmd: 0.55±0.14; cFPPinv: 0.70±0.19). In patients ≥70 years, only cFPPmd was significantly associated with CAD risk (odds ratio: 1.66 (95% confidence interval: 1.05–2.64)). SYNTAX score was significantly correlated with cPPmd, cFPPmd, and bFPP (standardized &bgr;: cPPmd 0.39, cFPPmd 0.50, bFPP 0.42, all P < 0.01). No significant association was observed in patients aged <70 years. CONCLUSIONS Central pulsatile indices calibrated with brachial MAP/DBP were more accurate and discriminatory for coronary atherosclerosis than SBP/DBP calibration.

Association between 1-h post-load plasma glucose levels and arterial stiffness in normotensive subjects with normal glucose tolerance:

Objective: To investigate the relationship between 1-h post-load plasma glucose, measured during an oral glucose tolerance test, and arterial stiffness, determined by brachial–ankle pulse-wave velocity, in normotensive subjects with normal glucose tolerance. Methods: Study subjects were non-industrial workers aged 25–55 years (n = 8381) who underwent a regular health check-up every 5 years. We included only normotensive subjects with normal glucose tolerance based on the American Diabetes Association criteria. Subjects taking medication and having an abnormal ankle–brachial index (⩽1.0 or ⩾1.3) were excluded. The final sample comprised 4970 participants (mean age: 38.8 ± 9.4 years; women: n = 2048). Results: 1-h post-load plasma glucose correlated with brachial–ankle pulse-wave velocity in men (β = 0.04, p = 0.01), but not women (β = –0.03, p = 0.13) in multivariate linear regression analysis. We found a significant interaction between 1-h post-load plasma glucose and age in men (p = 0.04); therefore, a subgroup analysis was performed in each 5-year age group. The correlation between 1-h post-load plasma glucose and brachial–ankle pulse-wave velocity was significant in the 55-year-old age group (β = 0.12, p = 0.01) and neared significant in 45-year-old (β = 0.08, p = 0.07) and 50-year-old (β = 0.09, p = 0.07) age groups. Conclusion: Elevated 1-h post-load plasma glucose levels were associated with arterial stiffness in normotensive, middle-aged men with normal glucose tolerance.

Validity of the augmentation index and pulse pressure amplification as determined by the SphygmoCor XCEL device: a comparison with invasive measurements

Augmentation index (AIx) and pulse pressure (PP) amplification can be determined by the SphygmoCor XCEL device in an operator-independent manner. This study aimed to examine its validity against invasive measurements. Simultaneous recordings of central aortic pressure waveforms were performed with oscillometric and high-fidelity invasive methods in 35 patients who underwent coronary arteriography. Brachial blood pressure was also recorded using the two methods. AIx for the aortic pressure waveform was defined as the ratio of augmentation pressure to PP. PP amplification was defined as the ratio of brachial PP to aortic PP. The differences between the invasive and oscillometric measurements were −7.7±12.7% for AIx and 0.17±0.14 for PP amplification (mean±s.d.). Strong correlations between the invasive and oscillometric measurements were found in both indices (AIx: r=0.75; PP amplification: r=0.80; both P<0.001). The Bland–Altman plot showed a proportional bias of PP amplification, but not of AIx (AIx: r=−0.21, P=0.23; PP amplification: r=−0.61; P<0.001). In conclusion, estimated AIx may be reliable considering the high correlation between the invasive and noninvasive values and the lack of proportional bias against invasive assessment. However, a substantial underestimation and a large scatter of estimated AIx were also observed. Further studies using the device to investigate associations with target organ damage or prognoses are needed to clarify its clinical validity.

Age-related change in contribution of stroke volume to central pulse pressure

ABSTRACT We investigated age-related change in the contribution of stroke volume (SV) to central PP (cPP). Eighty seven adult subjects who were free of vasoactive agents were included. Subjects were divided into three age groups: young (20–39 years, n = 26), middle (40–49 years, n = 29), and old (≥50 years, n = 32). SV was calculated by Doppler echocardiography. Hemodynamic indices were measured using a brachial cuff-based oscillometric method. The brachial and cPP showed a small decline from the young group to the middle group and a greater rise after 50 years old. SV significantly and positively correlated with brachial (r = 0.53, p < 0.01) and cPP (r = 0.57, p < 0.01) in the young group. In the middle group, the association of SV with brachial pulse pressure was significant (r = 0.38, p = 0.04) and that with cPP was bordering significant (r = 0.34, p = 0.07). No significant association was found between SV and PP in the old group. In conclusion, the contribution of SV to cPP decreases with age. Age-related changes in the determinants of cPP should be considered when investigating the clinical value of cPP.

OS 13-03 HIGH UPSTROKE TIME OF ARTERIAL PULSE WAVE IS AN INDEPENDENT PREDICTOR FOR THE PRESENCE OF CORONARY ARTERY DISEASE.

Objective: Pulse wave velocity is a non-invasive method that is useful not only for estimating arterial stiffness but also screening cardiovascular events in the general population. Upstroke time (UT) and % mean artery pressure (% MAP) are novel, adjunctive indices for arterial stiffness that are derived from morphology analysis of the pulse wave during brachial-ankle pulse wave velocity (baPWV) measurement. Several studies have shown the association between UT and coronary artery calcification score as assessed by multi-detector computed tomography (MDCT). However, there are no studies examining relationship between these markers and CAD as assessed by coronary angiography (CAG), the current gold standard for the diagnosis of CAD. The aim of this study was to determine the association between the indices for arterial stiffness such as UT and % MAP, and the presence of CAD as assessed by CAG. Design and Method: We enrolled 98 patients who underwent both baPWV measurement and elective CAG for suspected CAD. Significant coronary artery disease(sCAD) was defined as having at least one stenotic lesion over 50%. Using univariate and multivariate logistic regression analysis, we evaluated the contribution of UT and % MAP for the presence of sCAD, and determined if they served as independent, incremental risks for sCAD. Results: In univariate logistic regression analysis, UT and % MAP were associated with sCAD (UT: Odds Ratio(OR) 1.23[95% Confidence Interval (95% CI) 1.00–1.50], p = 0.015; % MAP: OR 0.81[95% CI 0.68–0.96], p = 0.018), whereas baPWV was not (OR 1.03[95% CI 0.91–1.16], p = 0.587). In multivariate analysis, only UT remained significant after adjusting traditional risk factors and other potential confounders (OR 1.29 [95% CI 1.02–1.64]; p = 0.036). Conclusions: Among indices for arterial pulse waves, only UT serves as independent, incremental risk for the presence of significant CAD.

PS 02-11 Upstroke Time Is an Independent Predictor for the Presence of Coronary Artery Disease in Patients with Chronic Kidney Disease

Objective: Pulse wave velocity is a marker for arterial stiffness, and indicative of increased cardiovascular morbidity and mortality in the general population. Upstroke time (UT) of arterial pulse, defined as time from the initial rise to the peak of the wave, is another parameter for arterial stiffness that is obtained during brachial-ankle pulse wave velocity (baPWV) measurement. Studies have shown significant association between baPWV and cardiovascular events or mortality in hemodialysis patients. However, there are few studies examining such relationship in non-hemodialysis chronic kidney disease (CKD) patients. Moreover, clinical utility of UT among these patients remains unknown. The present study aimed to examine the association between UT and the presence of coronary heart disease (CAD) in non-hemodialysis CKD patients. Design and Method: We enrolled 105 patients (35 non-hemodialytic CKD; 70 non-CKD) who measured baPWV and UT and underwent elective coronary angiography for suspected CAD. CKD was defined as estimated glomerular filtration rate below 60 ml/min/1.73m2. Significant coronary artery disease (sCAD) was defined as one or more stenosis over 50%. To examine the contribution of baPWV and UT for the presence of sCAD, multivariate logistic regression analysis with adjustment for potential confounders was performed in each patient group. Results: In non-hemodialysis CKD patients, UT but not baPWV was associated with sCAD (UT: Odds Ratio(OR) 1.62[95% Confidence Interval (95% CI) 1.05–2.50], p = 0.029; baPWV: OR 1.13[95% CI 0.90–1.42], p = 0.280) in univariate logistic regression analysis. In multivariate analysis, UT remained significant after adjusting traditional risk factors and other potential confounders (OR 12.4 [95% CI 1.02–151.3]; p = 0.036). In non-CKD patients, neither UT nor baPWV was associated with sCAD in both univariate and multivariate analysis. Conclusions: In non-hemodialysis CKD patients, UT serves as independent predictive risk for the presence of significant CAD.