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• W2083765557 abstract "Digital peripheral arterial tonometry (PAT) is an emerging, noninvasive method to assess vascular function. The physiology underlying this phenotype, however, remains unclear. Therefore, we evaluated the relation between digital PAT and established brachial artery ultrasound measures of vascular function under basal conditions and after reactive hyperemia. Using a cross-sectional study design, digital PAT and brachial artery ultrasonography with pulsed wave Doppler were simultaneously completed at baseline and after reactive hyperemia in both those with established coronary artery disease (n = 99) and healthy volunteers with low cardiovascular disease risk (n = 40). Under basal conditions, the digital pulse volume amplitude demonstrated a significant positive correlation with the brachial artery velocity-time integral that was independent of the arterial diameter, in both the healthy volunteer (rs = 0.64, p <0.001) and coronary artery disease (rs = 0.63, p <0.001) cohorts. Similar positive relations were observed with the baseline brachial artery blood flow velocity and blood flow. In contrast, no relation between the reactive hyperemia-evoked digital PAT ratio and either brachial artery flow-mediated dilation or shear stress was observed in either cohort (p = NS). In conclusion, these findings demonstrate that the digital PAT measures of vascular function more closely reflect basal blood flow in the brachial artery than reactive hyperemia-induced changes in the arterial diameter or flow velocity, and the presence of vascular disease does not modify the physiology underlying the digital PAT phenotype. Digital peripheral arterial tonometry (PAT) is an emerging, noninvasive method to assess vascular function. The physiology underlying this phenotype, however, remains unclear. Therefore, we evaluated the relation between digital PAT and established brachial artery ultrasound measures of vascular function under basal conditions and after reactive hyperemia. Using a cross-sectional study design, digital PAT and brachial artery ultrasonography with pulsed wave Doppler were simultaneously completed at baseline and after reactive hyperemia in both those with established coronary artery disease (n = 99) and healthy volunteers with low cardiovascular disease risk (n = 40). Under basal conditions, the digital pulse volume amplitude demonstrated a significant positive correlation with the brachial artery velocity-time integral that was independent of the arterial diameter, in both the healthy volunteer (rs = 0.64, p <0.001) and coronary artery disease (rs = 0.63, p <0.001) cohorts. Similar positive relations were observed with the baseline brachial artery blood flow velocity and blood flow. In contrast, no relation between the reactive hyperemia-evoked digital PAT ratio and either brachial artery flow-mediated dilation or shear stress was observed in either cohort (p = NS). In conclusion, these findings demonstrate that the digital PAT measures of vascular function more closely reflect basal blood flow in the brachial artery than reactive hyperemia-induced changes in the arterial diameter or flow velocity, and the presence of vascular disease does not modify the physiology underlying the digital PAT phenotype. Endothelial dysfunction is integral to the pathogenesis and progression of coronary artery disease (CAD).1Flammer A.J. Lüscher T.F. Three decades of endothelium research: from the detection of nitric oxide to the everyday implementation of endothelial function measurements in cardiovascular diseases.Swiss Med Wkly. 2010; 140: w13122PubMed Google Scholar Brachial artery flow-mediated dilation (FMD) is the most widely used noninvasive method to assess endothelial function; however, the technical complexity and lack of standardization limit its clinical application.2Corretti M.C. Anderson T.J. Benjamin E.J. Celermajer D. Charbonneau F. Creager M.A. Deanfield J. Drexler H. Gerhard-Herman M. Herrington D. Vallance P. Vita J. Vogel R. International Brachial Artery Reactivity Task ForceGuidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force.J Am Coll Cardiol. 2002; 39: 257-265Abstract Full Text Full Text PDF PubMed Scopus (3882) Google Scholar Digital peripheral arterial tonometry (PAT) quantifies the reactive hyperemia-induced changes in pulse volume amplitude (PVA) in the fingertip and is an emerging, automated method to noninvasively assess endothelial function.3Hamburg N.M. Benjamin E.J. Assessment of endothelial function using digital pulse amplitude tonometry.Trends Cardiovasc Med. 2009; 19: 6-11Abstract Full Text Full Text PDF PubMed Scopus (133) Google Scholar Digital PAT is predictive of the presence of cardiovascular disease risk factors,4Hamburg N.M. Keyes M.J. Larson M.G. Vasan R.S. Schnabel R. Pryde M.M. Mitchell G.F. Sheffy J. Vita J.A. Benjamin E.J. Cross-sectional relations of digital vascular function to cardiovascular risk factors in the Framingham Heart Study.Circulation. 2008; 117: 2467-2474Crossref PubMed Scopus (552) Google Scholar, 5Hamburg N.M. Palmisano J. Larson M.G. Sullivan L.M. Lehman B.T. Vasan R.S. Levy D. Mitchell G.F. Vita J.A. Benjamin E.J. Relation of brachial and digital measures of vascular function in the community: the Framingham Heart Study.Hypertension. 2011; 57: 390-396Crossref PubMed Scopus (285) Google Scholar, 6Schnabel R.B. Schulz A. Wild P.S. Sinning C.R. Wilde S. Eleftheriadis M. Herkenhoff S. Zeller T. Lubos E. Lackner K.J. Warnholtz A. Gori T. Blankenberg S. Münzel T. Noninvasive vascular function measurement in the community: cross-sectional relations and comparison of methods.Circ Cardiovasc Imaging. 2011; 4: 371-380Crossref PubMed Scopus (148) Google Scholar, 7Toggweiler S. Schoenenberger A. Urbanek N. Erne P. The prevalence of endothelial dysfunction in patients with and without coronary artery disease.Clin Cardiol. 2010; 33: 746-752Crossref PubMed Scopus (24) Google Scholar impaired vasodilator responses to acetylcholine in coronary arteries,8Bonetti P.O. Pumper G.M. Higano S.T. Holmes Jr, D.R. Kuvin J.T. Lerman A. Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia.J Am Coll Cardiol. 2004; 44: 2137-2141Abstract Full Text Full Text PDF PubMed Scopus (761) Google Scholar, 9Matsuzawa Y. Sugiyama S. Sugamura K. Nozaki T. Ohba K. Konishi M. Matsubara J. Sumida H. Kaikita K. Kojima S. Nagayoshi Y. Yamamuro M. Izumiya Y. Iwashita S. Matsui K. Jinnouchi H. Kimura K. Umemura S. Ogawa H. Digital assessment of endothelial function and ischemic heart disease in women.J Am Coll Cardiol. 2010; 55: 1688-1696Abstract Full Text Full Text PDF PubMed Scopus (179) Google Scholar and adverse cardiovascular events in a single study.10Rubinshtein R. Kuvin J.T. Soffler M. Lennon R.J. Lavi S. Nelson R.E. Pumper G.M. Lerman L.O. Lerman A. Assessment of endothelial function by non-invasive peripheral arterial tonometry predicts late cardiovascular adverse events.Eur Heart J. 2010; 31: 1142-1148Crossref PubMed Scopus (525) Google Scholar Although previous studies have demonstrated a direct contribution of nitric oxide to the brachial artery FMD11Meredith I.T. Currie K.E. Anderson T.J. Roddy M.A. Ganz P. Creager M.A. Postischemic vasodilation in human forearm is dependent on endothelium-derived nitric oxide.Am J Physiol. 1996; 270: H1435-H1440PubMed Google Scholar and the digital PAT ratio,12Nohria A. Gerhard-Herman M. Creager M.A. Hurley S. Mitra D. Ganz P. Role of nitric oxide in the regulation of digital pulse volume amplitude in humans.J Appl Physiol. 2006; 101: 545-548Crossref PubMed Scopus (357) Google Scholar conflicting results regarding their correlation have been reported.5Hamburg N.M. Palmisano J. Larson M.G. Sullivan L.M. Lehman B.T. Vasan R.S. Levy D. Mitchell G.F. Vita J.A. Benjamin E.J. Relation of brachial and digital measures of vascular function in the community: the Framingham Heart Study.Hypertension. 2011; 57: 390-396Crossref PubMed Scopus (285) Google Scholar, 6Schnabel R.B. Schulz A. Wild P.S. Sinning C.R. Wilde S. Eleftheriadis M. Herkenhoff S. Zeller T. Lubos E. Lackner K.J. Warnholtz A. Gori T. Blankenberg S. Münzel T. Noninvasive vascular function measurement in the community: cross-sectional relations and comparison of methods.Circ Cardiovasc Imaging. 2011; 4: 371-380Crossref PubMed Scopus (148) Google Scholar, 13Dhindsa M. Sommerlad S.M. DeVan A.E. Barnes J.N. Sugawara J. Ley O. Tanaka H. Interrelationships among noninvasive measures of postischemic macro- and microvascular reactivity.J Appl Physiol. 2008; 105: 427-432Crossref PubMed Scopus (141) Google Scholar, 14Heffernan K.S. Karas R.H. Mooney P.J. Patel A.R. Kuvin J.T. Pulse wave amplitude is associated with brachial artery diameter: implications for gender differences in microvascular function.Vasc Med. 2010; 15: 39-45Crossref PubMed Scopus (16) Google Scholar, 15Kuvin J.T. Patel A.R. Sliney K.A. Pandian N.G. Sheffy J. Schnall R.P. Karas R.H. Udelson J.E. Assessment of peripheral vascular endothelial function with finger arterial pulse wave amplitude.Am Heart J. 2003; 146: 168-174Abstract Full Text Full Text PDF PubMed Scopus (618) Google Scholar Despite growing interest in the utility of digital PAT, the physiology underlying the digital PVA signal and its relation with established vascular function phenotypes remains unclear. In particular, the relation between digital PVA and brachial artery blood flow velocity, and the effect of vascular disease on these phenotypes, has not been rigorously evaluated. Therefore, we characterized the relation between digital PAT and brachial artery ultrasound vascular function phenotypes, under both basal and reactive hyperemia-evoked conditions, in healthy volunteers (HVs) and patients with established CAD. Patients with established CAD (defined as ≥50% stenosis in ≥1 major epicardial coronary artery by coronary angiography) were identified in the University of North Carolina Cardiac Catheterization Laboratory (Chapel Hill, North Carolina). The exclusion criteria included pregnancy, atrial fibrillation, Raynaud's disease, left ventricular ejection fraction ≤35%, the current use of insulin or long-acting nitrates, active autoimmune disease, history of severe aortic stenosis, history of solid organ transplant or dialysis, or a history of cancer within the previous 5 years. A parallel cohort of HVs was identified by advertisement from the local Chapel Hill, North Carolina community. After a detailed history and a fasting serum chemistry and cholesterol panel, the potential participants were excluded if they had a history of cardiovascular disease, had risk factors for CAD (including physician-diagnosed hypertension or diabetes, cigarette smoking within the previous 6 months, high cholesterol [defined as total cholesterol >240 mg/dl, triglycerides >200 mg/dl, or low-density lipoprotein cholesterol >160 mg/dl), or body mass index >30 kg/m2), or were currently taking any medication for a chronic medical condition. The University of North Carolina at Chapel Hill Biomedical Institutional Review Board approved the study protocol. Eligible participants (108 with CAD and 41 HVs) provided written informed consent and returned to the clinical research unit for a single morning study visit after fasting overnight and withholding their morning medications. The participants were instructed to refrain from tobacco products, caffeine, and vigorous exercise the morning of the study visit and from the use of vitamin C, vitamin E, fish oil, niacin, or arginine supplements, oral decongestants, nonsteroidal anti-inflammatory drugs (other than low-dose aspirin), and erectile dysfunction medications for ≥7 days before the study visit. Those who experienced a respiratory tract infection within 4 weeks before the study visit were not eligible to participate. The endothelial function measurements were completed in a quiet, dimly lit, temperature-controlled room and were obtained with the participant in the supine position. After 10 minutes of rest, brachial artery reactivity was assessed by quantifying the arterial diameter and blood flow velocity at baseline and after reactive hyperemia using a 12.5-MHz linear-array transducer (Philips HDI 5000 system) with pulsed wave Doppler, as previously described.16Sherwood A. Bower J.K. McFetridge-Durdle J. Blumenthal J.A. Newby L.K. Hinderliter A.L. Age moderates the short-term effects of transdermal 17beta-estradiol on endothelium-dependent vascular function in postmenopausal women.Arterioscler Thromb Vasc Biol. 2007; 27: 1782-1787Crossref PubMed Scopus (84) Google Scholar, 17Schneider A. Neas L. Herbst M.C. Case M. Williams R.W. Cascio W. Hinderliter A. Holguin F. Buse J.B. Dungan K. Styner M. Peters A. Devlin R.B. Endothelial dysfunction: associations with exposure to ambient fine particles in diabetic individuals.Environ Health Perspect. 2008; 116: 1666-1674Crossref PubMed Scopus (108) Google Scholar Reactive hyperemia was induced by inflating a blood pressure cuff around the right forearm for 5 minutes to a pressure of ≥70 mm Hg greater than the systolic blood pressure. All images were electrocardiogram gated and obtained by the same sonographer throughout the study. The data were analyzed using Brachial Tools software (Medical Imaging Applications, Coralville, Iowa). The brachial artery diameter was measured at end-diastole from the lumen–intimal interface of the proximal and distal walls. The baseline diameter was averaged from 10 consecutive frames. The arterial diameter was assessed for 90 seconds after cuff deflation, and the diameter during peak dilation was averaged from 3 consecutive frames. The peak change in arterial dilation was observed a mean ± SD of 51 ± 12 seconds after cuff deflation. The brachial artery FMD (endothelium-dependent) was calculated as the percentage of change in brachial artery diameter from baseline [brachial artery FMD = 100 × (diameterPeak − diameterBaseline)/(diameterBaseline)]. The reproducibility of this method in our laboratory has been previously reported.16Sherwood A. Bower J.K. McFetridge-Durdle J. Blumenthal J.A. Newby L.K. Hinderliter A.L. Age moderates the short-term effects of transdermal 17beta-estradiol on endothelium-dependent vascular function in postmenopausal women.Arterioscler Thromb Vasc Biol. 2007; 27: 1782-1787Crossref PubMed Scopus (84) Google Scholar After 10 minutes of rest, a second baseline image was acquired, which correlated highly with the initial baseline measurement (r = 0.99, p <0.001). Endothelial-independent vasodilation was assessed 5 minutes after sublingual administration of nitroglycerin (0.4 mg) as the percentage of change in the arterial diameter [100 × (diameterNitroglycerin − diameterBaseline)/(diameterBaseline)]. The brachial artery blood flow velocity was measured using pulsed wave Doppler at baseline and for 15 seconds after cuff deflation. The velocity-time integral was measured by automated planimetry of the velocity profile and averaged for 3 consecutive cardiac cycles at baseline and during peak reactive hyperemia. The reactive hyperemia-induced increase in the velocity-time integral relative to baseline was calculated as a ratio (velocity-time integral following reactive hyperemia/velocity-time integral at baseline). The mean flow velocity (V) was calculated by dividing the velocity-time integral (in cm) by the duration of the cycle (in seconds). The mean flow velocity was converted to local shear stress (8 × μ × Vx/diameterBaseline) and blood flow [Vx × π × (diameterBaseline/2)2], as previously reported,18Mitchell G.F. Parise H. Vita J.A. Larson M.G. Warner E. Keaney Jr, J.F. Keyes M.J. Levy D. Vasan R.S. Benjamin E.J. Local shear stress and brachial artery flow-mediated dilation: the Framingham Heart Study.Hypertension. 2004; 44: 134-139Crossref PubMed Scopus (314) Google Scholar, 19Pyke K.E. Tschakovsky M.E. The relationship between shear stress and flow-mediated dilatation: implications for the assessment of endothelial function.J Physiol. 2005; 568: 357-369Crossref PubMed Scopus (458) Google Scholar each of which normalize the flow velocity to the arterial diameter. The subscript x indicates either baseline or peak reactive hyperemia, and μ indicates blood viscosity at an assumed value of 0.035 dyne · s/cm2. Because the reactive hyperemia-induced flow velocity changes in the conduit arteries are regulated by dilation of the distal resistance vessels, brachial shear stress after reactive hyperemia is as an index of microvascular function.18Mitchell G.F. Parise H. Vita J.A. Larson M.G. Warner E. Keaney Jr, J.F. Keyes M.J. Levy D. Vasan R.S. Benjamin E.J. Local shear stress and brachial artery flow-mediated dilation: the Framingham Heart Study.Hypertension. 2004; 44: 134-139Crossref PubMed Scopus (314) Google Scholar, 19Pyke K.E. Tschakovsky M.E. The relationship between shear stress and flow-mediated dilatation: implications for the assessment of endothelial function.J Physiol. 2005; 568: 357-369Crossref PubMed Scopus (458) Google Scholar The digital PVA was measured on the index finger of each hand using plethysmographically based probes and the Endo-PAT 2000 device (Itamar Medical, Caesarea, Israel) simultaneously with the brachial artery ultrasound measurements. The measurements were obtained continuously during baseline (5 minutes), cuff occlusion (5 minutes), and postcuff deflation (5 minutes), and the data were automatically derived using the Endo-PAT, version 3.0.4, software. The digital PAT ratio was calculated as the ratio of postcuff deflation PVA (in 30-second intervals) to the baseline PVA in the arm undergoing cuff occlusion (occluded) and then normalized to the contralateral (control) arm. The digital PAT ratio in the 90- to 120-second postcuff deflation interval [(PVAoccluded,90–120seconds/PVAoccluded,Baseline)/(PVAcontrol,90–120seconds/PVAcontrol,Baseline)] is presented, as described previously,4Hamburg N.M. Keyes M.J. Larson M.G. Vasan R.S. Schnabel R. Pryde M.M. Mitchell G.F. Sheffy J. Vita J.A. Benjamin E.J. Cross-sectional relations of digital vascular function to cardiovascular risk factors in the Framingham Heart Study.Circulation. 2008; 117: 2467-2474Crossref PubMed Scopus (552) Google Scholar unless otherwise noted. The digital PAT test was unsuccessful in 10 study participants (9 with CAD and 1 HV), consistent with previous reports.4Hamburg N.M. Keyes M.J. Larson M.G. Vasan R.S. Schnabel R. Pryde M.M. Mitchell G.F. Sheffy J. Vita J.A. Benjamin E.J. Cross-sectional relations of digital vascular function to cardiovascular risk factors in the Framingham Heart Study.Circulation. 2008; 117: 2467-2474Crossref PubMed Scopus (552) Google Scholar, 6Schnabel R.B. Schulz A. Wild P.S. Sinning C.R. Wilde S. Eleftheriadis M. Herkenhoff S. Zeller T. Lubos E. Lackner K.J. Warnholtz A. Gori T. Blankenberg S. Münzel T. Noninvasive vascular function measurement in the community: cross-sectional relations and comparison of methods.Circ Cardiovasc Imaging. 2011; 4: 371-380Crossref PubMed Scopus (148) Google Scholar The reproducibility of this automated method has been previously established.20Bonetti P.O. Holmes Jr, D.R. Lerman A. Barsness G.W. Enhanced external counterpulsation for ischemic heart disease: what's behind the curtain?.J Am Coll Cardiol. 2003; 41: 1918-1925Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar The data are presented as the mean ± SD or the median (interquartile range). The study population characteristics were compared using 1-way analysis of variance or Wilcoxon rank sum test, as appropriate. The relations between each digital PAT and brachial artery ultrasound phenotype were evaluated using Spearman's rank correlation (rs). Partial correlations were also evaluated to account for the potential effect of the demographic (age, gender, race) and vascular (baseline brachial artery diameter, baseline brachial artery velocity-time integral, baseline digital PVA, brachial shear stress after reactive hyperemia) variables on these relations. The parameters that were not normally distributed, including the digital PVA and PAT ratio, were log10-transformed before graphic presentation. Because the units of each digital PAT and brachial artery ultrasound measure were not the same, Bland-Altman plots could not be constructed to evaluate the agreement between each phenotype.21Bland J.M. Altman D.G. Applying the right statistics: analyses of measurement studies.Ultrasound Obstet Gynecol. 2003; 22: 85-93Crossref PubMed Scopus (1071) Google Scholar The analyses were performed using SAS, version 9.2 (SAS Institute, Cary, North Carolina). Statistical significance was set at p <0.05. The cohort characteristics are provided in Table 1. The participants in the CAD cohort returned for their study visit 61 ± 33 days after cardiac catheterization. High rates of statin, renin-angiotensin system inhibitor, β-blocker, aspirin, and clopidogrel use were reported, consistent with management of the CAD cohort according to current clinical practice guidelines.Table 1Study participant characteristicsCharacteristicCAD (n = 99)HV (n = 40)Age (years)59 ± 951 ± 8⁎p <0.05 versus coronary artery disease.Women33 (33%)23 (58%)⁎p <0.05 versus coronary artery disease.Black race18 (18%)7 (18%)Body mass index (kg/m2)30 ± 626 ± 3⁎p <0.05 versus coronary artery disease.Body mass index ≥30 kg/m253 (54%)0†Exclusion criteria in HV cohort.Current smoker23 (23%)0†Exclusion criteria in HV cohort.Diabetes24 (24%)0†Exclusion criteria in HV cohort.Hypertension82 (83%)0†Exclusion criteria in HV cohort.Disease severity One-vessel disease35 (35%)— Two-vessel disease36 (36%)— Three-vessel disease28 (28%)—Revascularization procedure‡In CAD cohort, 55 of 99 underwent percutaneous coronary intervention and 10 of 99 underwent coronary artery bypass grafting between screening and the study visit.65 (66%)—Systolic blood pressure (mm Hg)136 ± 17122 ± 14⁎p <0.05 versus coronary artery disease.Diastolic blood pressure (mm Hg)80 ± 1074 ± 8⁎p <0.05 versus coronary artery disease.Total cholesterol (mg/dl)159 (49)192 (30)⁎p <0.05 versus coronary artery disease.Low-density lipoprotein cholesterol (mg/dl)85 (41)117 (30)⁎p <0.05 versus coronary artery disease.High-density lipoprotein cholesterol (mg/dl)48 (17)65 (23)⁎p <0.05 versus coronary artery disease.Triglycerides (mg/dl)97 (79)69 (32)⁎p <0.05 versus coronary artery disease.Total/high-density lipoprotein cholesterol3.4 (1.6)3.1 (1.4)High-sensitivity C-reactive protein (mg/L)1.6 (3.3)0.7 (1.7)⁎p <0.05 versus coronary artery disease.Statin use92 (93%)0†Exclusion criteria in HV cohort.Renin-angiotensin system inhibitor use§Either angiotensin-converting enzyme inhibitor or angiotensin receptor blocker.61 (62%)0†Exclusion criteria in HV cohort.β-Blocker use82 (83%)0†Exclusion criteria in HV cohort.Aspirin use96 (97%)0†Exclusion criteria in HV cohort.Clopidogrel use79 (80%)0†Exclusion criteria in HV cohort.Data presented as mean ± SD, median (interquartile range), or n (%). p <0.05 versus coronary artery disease.† Exclusion criteria in HV cohort.‡ In CAD cohort, 55 of 99 underwent percutaneous coronary intervention and 10 of 99 underwent coronary artery bypass grafting between screening and the study visit.§ Either angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Open table in a new tab Data presented as mean ± SD, median (interquartile range), or n (%). Under basal conditions, the digital PVA and brachial artery diameter correlated modestly in both cohorts (Figure 1); however, these correlations were not statistically significant when adjusting for age, gender, and race (HVs, rs = 0.21, p = 0.208; CAD group, rs = 0.12, p = 0.260). The baseline digital PVA demonstrated a significant positive correlation with basal brachial artery velocity-time integral that was similar in both cohorts (Figure 1). After stratifying by gender, significant relations were observed in women (HVs, rs = 0.80, p <0.001; CAD group, rs = 0.65, p <0.001) and men (HVs, rs = 0.55, p = 0.023; CAD group, rs = 0.66, p <0.001). Similar relations were also observed after adjusting for age, gender, race, and brachial artery diameter (HVs, rs = 0.71, p <0.001; CAD group, rs = 0.72, p <0.001), and when the data were expressed as the mean flow velocity (HVs, rs = 0.56, p <0.001; CAD group, rs = 0.62, p <0.001), blood flow (HVs, rs = 0.78, p <0.001; CAD group, rs = 0.72, p <0.001), or shear stress (Figure 1), further demonstrating a positive relation between the basal digital PVA and brachial artery blood flow velocity that is independent of arterial size. A significant positive relation was observed between the brachial artery FMD and brachial shear stress after reactive hyperemia (HVs, rs = 0.64, p <0.001; CAD group, rs = 0.54, p <0.001), which serves as the stimulus for arterial dilation, in both cohorts. A significant inverse relation was also observed between the digital PAT ratio and baseline PVA (HVs, rs = −0.63, p <0.001; CAD group, rs = −0.79, p <0.001) in both cohorts. A significant inverse relation between age and the brachial artery FMD (HVs, rs = −0.33, p = 0.037; CAD group, rs = −0.33, p = 0.001), but not the digital PAT ratio (HVs, rs = 0.05, p = 0.737; CAD group, rs = 0.08, p = 0.403), was observed in both cohorts. No significant relation between the digital PAT ratio and FMD was observed in either cohort (Figure 2) . Similar results were observed after adjusting for age, gender, race, and brachial shear stress after reactive hyperemia (HVs, rs = −0.02, p = 0.925; CAD group, rs = −0.01, p = 0.930) and in each 30-second postcuff deflation interval used for the digital PAT ratio calculation (data not shown). No relation between the digital PAT ratio and nitroglycerin-mediated dilation was observed in either cohort (HVs, rs = 0.13, p = 0.454; CAD group, rs = 0.17, p = 0.092). In contrast, a significant positive relation between the digital PAT ratio and the brachial artery velocity-time integral ratio was observed in both cohorts (Figure 2). A similar correlation was also observed with the reactive hyperemia-induced increase in blood flow relative to baseline (HVs, rs = 0.41, p = 0.012; CAD group, rs = 0.65, p <0.001). Although the relation between the digital PAT and brachial artery velocity-time integral ratio persisted after adjusting for age, gender, and race (HVs, rs = 0.48, p = 0.004; CAD group, rs = 0.66, p <0.001), the correlations were substantially weakened after also adjusting for baseline digital PVA (HVs, rs = 0.19, p = 0.272; CAD group, rs = 0.34, p = 0.001) or the baseline brachial artery velocity-time integral (HVs, rs = 0.25, p = 0.145; CAD group, rs = 0.11, p = 0.295). Moreover, no significant relation between the brachial shear stress after reactive hyperemia and the digital PVA after reactive hyperemia was observed in the HVs (rs = 0.05, p = 0.748) or CAD group (rs = 0.13, p = 0.244). Similar results were observed in each 30-second postcuff deflation interval (data not shown), further demonstrating the lack of a relation between digital PAT and brachial artery ultrasound phenotypes after reactive hyperemia. After stratifying the CAD cohort by gender, disease severity, recent revascularization procedure, and the use of clopidogrel, β blockers, or renin-angiotensin system inhibitors, similar relations between each basal and reactive hyperemia-evoked digital PAT and brachial artery ultrasound phenotype were observed within all subsets of the population (data not shown). Digital PAT is an emerging, automated method to noninvasively assess endothelial function. The physiology underlying this phenotype, however, has remained unclear. In the present study, we observed a significant positive correlation between the baseline digital PVA and brachial artery blood flow velocity that was independent of the arterial diameter. In contrast, no relation was observed between the reactive hyperemia-evoked digital PAT ratio and brachial artery FMD. Furthermore, no correlation was observed between digital PVA and brachial artery brachial shear stress after reactive hyperemia, the stimulus for brachial artery vasodilation and an index of microvascular function.18Mitchell G.F. Parise H. Vita J.A. Larson M.G. Warner E. Keaney Jr, J.F. Keyes M.J. Levy D. Vasan R.S. Benjamin E.J. Local shear stress and brachial artery flow-mediated dilation: the Framingham Heart Study.Hypertension. 2004; 44: 134-139Crossref PubMed Scopus (314) Google Scholar, 19Pyke K.E. Tschakovsky M.E. The relationship between shear stress and flow-mediated dilatation: implications for the assessment of endothelial function.J Physiol. 2005; 568: 357-369Crossref PubMed Scopus (458) Google Scholar, 22Anderson T.J. Charbonneau F. Title L.M. Buithieu J. Rose M.S. Conradson H. Hildebrand K. Fung M. Verma S. Lonn E.M. Microvascular function predicts cardiovascular events in primary prevention: long-term results from the Firefighters and their Endothelium (FATE) study.Circulation. 2011; 123: 163-169Crossref PubMed Scopus (278) Google Scholar, 23Kullo I.J. Malik A.R. Santos S. Ehrsam J.E. Turner S.T. Association of cardiovascular risk factors with microvascular and conduit artery function in hypertensive subjects.Am J Hypertens. 2007; 20: 735-742Crossref PubMed Scopus (21) Google Scholar Although a significant positive relation was observed between digital PAT ratio and the reactive hyperemia-induced increase in the brachial artery velocity-time integral and blood flow, this relation was driven by the positive correlation between the baseline brachial artery blood flow velocity and baseline digital PVA. Collectively, these data demonstrate that the digital PAT measures of vascular function more closely reflect brachial artery blood flow velocity" @default.
• W2083765557 created "2016-06-24" @default.
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• W2083765557 date "2012-03-01" @default.
• W2083765557 modified "2023-10-14" @default.
• W2083765557 title "Relation Between Digital Peripheral Arterial Tonometry and Brachial Artery Ultrasound Measures of Vascular Function in Patients With Coronary Artery Disease and in Healthy Volunteers" @default.
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