
Reactive Hyperemia Revisited
2008; Lippincott Williams & Wilkins; Volume: 28; Issue: 4 Linguagem: Inglês
10.1161/atvbaha.107.158931
ISSN1524-4636
AutoresDaniela Calderaro, Maristela Monachini, Carolina L. Zilli Vieira, Pai Ching Yu, Danielle Menosi Gualandro, André Coelho Marques, Bruno Caramelli,
Tópico(s)Antioxidant Activity and Oxidative Stress
ResumoHomeArteriosclerosis, Thrombosis, and Vascular BiologyVol. 28, No. 4Reactive Hyperemia Revisited Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBReactive Hyperemia Revisited Daniela Calderaro, Maristela C. Monachini, Carolina L.Z. Vieira, Pai Ching Yu, Danielle M. Gualandro, Andre C. Marques and Bruno Caramelli Daniela CalderaroDaniela Calderaro Heart Institute (InCor) – Hospital das Clínicas da Faculdade de Medicina da USP, São Paulo, Brazil , Maristela C. MonachiniMaristela C. Monachini Heart Institute (InCor) – Hospital das Clínicas da Faculdade de Medicina da USP, São Paulo, Brazil , Carolina L.Z. VieiraCarolina L.Z. Vieira Heart Institute (InCor) – Hospital das Clínicas da Faculdade de Medicina da USP, São Paulo, Brazil , Pai Ching YuPai Ching Yu Heart Institute (InCor) – Hospital das Clínicas da Faculdade de Medicina da USP, São Paulo, Brazil , Danielle M. GualandroDanielle M. Gualandro Heart Institute (InCor) – Hospital das Clínicas da Faculdade de Medicina da USP, São Paulo, Brazil , Andre C. MarquesAndre C. Marques Heart Institute (InCor) – Hospital das Clínicas da Faculdade de Medicina da USP, São Paulo, Brazil and Bruno CaramelliBruno Caramelli Heart Institute (InCor) – Hospital das Clínicas da Faculdade de Medicina da USP, São Paulo, Brazil Originally published1 Apr 2008https://doi.org/10.1161/ATVBAHA.107.158931Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:e23–e24To the Editor:We read with great interest Dr Huang's study, published in Arteriosclerosis, Thrombosis, and Vascular Biology.1 We are in total agreement with the authors about the clinical relevance in the perioperative setting of the hyperemic flow velocity, measured by brachial artery Doppler ultrasound. Dr Huang suggests that reactive hyperemia increases the accuracy of the noninvasive vascular reactivity test, namely the brachial artery flow-mediated dilation, in predicting cardiovascular events after major vascular surgery, even though in his patients the strongest isolated predictor was flow-mediated dilation.In a population of 96 vascular surgical patients, we assessed brachial artery flow-mediated dilation and reactive hyperemia with the same technique as Dr Huang's before major vascular surgery was performed, with a Siemens ultrasound system (Sequoia), equipped with a 7.5-mHz vascular transducer. The brachial artery ultrasound was always performed in the morning, after a 6-hour fast and at least 12 hours without smoking. Patients received all medications, including statins, and remained resting in supine position 15 minutes before the beginning until the end of the examination. We acquired 2-dimensional ultrasound images of the brachial artery and pulsed Doppler signals above the antecubital crease at baseline and during a period of reactive hyperemia induced by 5-minute cuff occlusion of the upper arm, at a 250-mm Hg pressure. After at least a 10-minute rest period, for restoration of baseline conditions, we reassessed the brachial artery image and blood flow, before and 3 minutes after administration of sublingual isosorbide dinitrate (5 mg). Images of the brachial artery were recorded at baseline and during the first 2 minutes after relief of the upper-arm occlusion for assessment of the flow-mediated response and before and 3 minutes after nitrate administration. Flows were recorded at baseline and during the first 15 seconds after cuff release, for assessment of the peak reactive hyperemia. Analysis were performed offline, by the same investigator, who was blinded to clinical outcomes. He used an automatized software that calculated for each phase of the examination, the mean diameter of 6 images of the brachial artery. Images were acquired with simultaneous record of ECG and the diameter was measured at the end-diastole (peak R, on the EKG). Hyperemic blood flow velocity was measured online by ultrasound. Flow mediated dilation (FMD) was calculated as the difference between diameters before and after reactive hyperemia in relation to the baseline artery diameter, expressed as percentage.Although Huang et al did not report cardiac risk estimation according to some specific algorithm, we consider that our population risk profile is comparable to theirs, as the mean ages are very similar and the prevalence of coronary artery disease is the same in both populations: 38%. Moreover, if we dichotomize the flow mediated dilation response, defining as normal FMD >8.0%,2 we have 67% of Huang's patients and 70% of ours with endothelial dysfunction, almost the same. The prevalence of hypertension, history of smoking, and aspirin therapy are high in both studies. We believe that a significant difference that has to be emphasized resides in the lipid lowering therapy: 54% in Huang's patients and 98% in ours (Table). Table. Baseline Characteristics and Brachial Ultrasound ResultsCharacteristicNo Event (n=69)Event (n=27)PData are mean±SD or No. and percentage, as indicated. Sample size is 96 for all characteristics, except for nitrate-mediated dilation (n=91). NA indicates not applicable. The vascular operation could be either aortic repair or peripheral revascularization, and this characteristic was statistically evaluated by Fisher exact test.Age, y65.32±9.5968.30±8.340.160Gender, n (%) female17 (25%)10 (37%)0.312Diabetes mellitus, n (%)9 (13%)5 (18%)0.528Hypertension, n (%)64 (93%)27 (100%)0.317Coronary artery disease, n (%)26 (38%)10 (37%)1.000History of heart failure, n (%)19 (27%)6 (22%)0.796History of smoking, n (%)63 (91%)24 (89%)0.180 Ex-smoker, n (%)46 (67%)17 (63%)0.812 Current smoker, n (%)17 (24%)7 (26%)1.000Hypercholesterolemia, n (%)63 (91%)25 (93%)1.000Hemoglobin, mg/dl14.05±1.5813.86±1.550.600Creatinine, mg/dl1.17±0.391.17±0.270.970Vascular operation0.818 Aortic repair, n (%)43 (62%)16 (59%) Peripheral revascularization, n (%)26 (38%)11 (41%)Lipid lowering therapy, n (%)67 (97%)27 (100%)NABeta-blocker therapy, n (%)63 (91%)22 (81%)0.282Aspirin, n (%)49 (71%)16 (59%)0.333Baseline brachial artery diameter, mm4.36±0.654.29±0.720.632Hyperemic flow velocity in the brachial artery, cm/s95.04±27.6980.71±19.780.02Change from baseline in the brachial artery Flow mediated dilation, mm0.25±0.260.20±0.280.355 Flow mediated dilation, %5.88±6.004.83±6.810.457 Nitrate-mediated dilation, % (n=91)10.4±8.4111.98±8.710.211We detected events in 27 patients during 1-month follow-up period: 4 cardiovascular deaths, 5 myocardial infarctions, 2 isolated troponin elevations, 2 ischemic strokes, 1 pulmonary embolism, 2 reoperations, and 11 noncardiac deaths (3 hemorrhagic shock, 4 sepsis, 4 seconds SIRS). Differently from Huang's study, we did not find significant difference in the flow-mediated dilation between patients with and without events: 5.88±6.00%×4.83±6.81% (P=0.46), respectively. Excluding noncardiovascular events from the analysis, the nonsignificant difference in the flow-mediated dilation of the brachial artery persisted (P=0.96). Interesting however, we found that lower hyperemic flow velocity predicted perioperative events: 81 cm/s ±20×95 cm/s ±28 (P=0.02). When we analyzed the association between hyperemic flow velocity and cardiovascular events, we found: 80 cm/s ±22×95 cm/s ±28 (P=0.09), for patients with and without events, respectively, possibly because of the lower number of events analyzed.The lower hyperemic flow velocity observed in our patients with events could not be attributed to age, sex, diabetes, hypertension, or congestive heart failure (unpublished data, Calderaro D, Monachini MC, Vieira CLZ, Yu PC, Gualandro DM, Marques AC, Caramelli B, 2007).We believe that statin therapy prescribed for the majority of our patients might have altered the vascular reactivity and might have decreased the association of flow-mediated dilation to cardiovascular events, justifying at least partially why we did not reproduce this association. Mitchell et al3 have already shown that lipid lowering therapy lost its association to FMD when reactive hyperemia was considered in the stepwise regression analysis. We hypothesized that lipid lowering therapy modifies the parameter of vascular reactivity mostly related to cardiovascular risk factors from FMD to reactive hyperemia.In addition to Dr Huang's study, our findings indicate that hyperemic flow velocity, as a marker of the vascular shear stress and directly related to the microvascular function, should be reported and analyzed routinely whenever this vascular reactivity test is performed. Actually, more than a simple stimulus for endothelial function evaluation, reactive hyperemia provides a better understanding of the vascular biology and pathophysiology of atherosclerosis.4 Moreover, differently from Dr Huang's findings, our data suggest that reactive hyperemia could be even a better predictor of cardiovascular events in specific populations or particular settings.DisclosuresNone.1 Huang AL, Silver AE, Shvenke E, Schopfer DW, Jahangir E, Titas MA, Shpilman A, Menzoian JO, Watkins MT, Raffetto JD, Gibbons G, Woodson J, Shaw PM, Dhadly M, Eberhardt RT, Keaney JF Jr, Gokce N, Vita JA. Predictive value of reactive hyperemia for cardiovascular events in patients with peripheral arterial disease undergoing vascular surgery. Arterioscler Thromb Vasc Biol. 2007; 27: 2113–2119.LinkGoogle Scholar2 Coretti MC, Anderson T, Benjamin E, Celermajer D. Guidelines 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: 257–265.CrossrefMedlineGoogle Scholar3 Mitchell GF, Parise H, Vita JA, Larson MG, Warner E, Keaney JF Jr, Keyes MJ, Levy D, Vasan RS, Benjamin EJ. Local shear stress and brachial artery flow-mediated dilation: the Framingham Heart Study. Hypertension. 2004; 44: 134–139.LinkGoogle Scholar4 Pyke KE, Tschakovsky ME. The relationship between shear stress and flow-mediated dilatation: implications for the assessment of endothelial function. J Physiol. 2005; 568 (Pt 2): 357–369.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Sun H, Yang M, Fung M, Chan S, Jawi M, Anderson T, Poon M and Jackson S (2017) Adult males with haemophilia have a different macrovascular and microvascular endothelial function profile compared with healthy controls, Haemophilia, 10.1111/hae.13278, 23:5, (777-783), Online publication date: 1-Sep-2017. Paine N, Hinderliter A, Blumenthal J, Adams K, Sueta C, Chang P, O'Connor C and Sherwood A (2016) Reactive hyperemia is associated with adverse clinical outcomes in heart failure, American Heart Journal, 10.1016/j.ahj.2016.05.008, 178, (108-114), Online publication date: 1-Aug-2016. Calderaro D, Pastana A, Flores da Rocha T, Yu P, Gualandro D, DeLuccia N, D`Amico É and Caramelli B (2013) Aspirin responsiveness safely lowers perioperative cardiovascular risk, Journal of Vascular Surgery, 10.1016/j.jvs.2013.06.061, 58:6, (1593-1599), Online publication date: 1-Dec-2013. Macas A, Bakšytė G, Šilinskytė L and Petrauskaitė J (2013) PERIOPERACINIS MIOKARDO INFARKTAS, Sveikatos mokslai, 10.5200/sm-hs.2013.129, 23:6, (29-34), Online publication date: 21-Dec-2013. Carmo G, Calderaro D, Yu P, Gualandro D, Marques A, Bittar C, Pastana A and Caramelli B (2012) Perioperative cardiovascular evaluation: heads or tails?, Revista da Associação Médica Brasileira (English Edition), 10.1016/S2255-4823(12)70237-0, 58:4, (505-512), Online publication date: 1-Jul-2012. Carmo G, Calderaro D, Yu P, Gualandro D, Marques A, Bittar C, Pastana A and Caramelli B (2012) Perioperative cardiovascular evaluation: heads or tails?, Revista da Associação Médica Brasileira, 10.1016/S0104-4230(12)70237-3, 58:4, (505-512), Online publication date: 1-Jul-2012. Gualandro D, Campos C, Calderaro D, Yu P, Marques A, Pastana A, Lemos P and Caramelli B (2012) Coronary plaque rupture in patients with myocardial infarction after noncardiac surgery: Frequent and dangerous, Atherosclerosis, 10.1016/j.atherosclerosis.2012.02.021, 222:1, (191-195), Online publication date: 1-May-2012. Carmo G, Calderaro D, Yu P, Gualandro D, Marques A, Bittar C, Pastana A and Caramelli B (2012) Perioperative cardiovascular evaluation: heads or tails?, Revista da Associação Médica Brasileira, 10.1590/S0104-42302012000400025, 58:4, (505-512), Online publication date: 1-Jul-2012. April 2008Vol 28, Issue 4 Advertisement Article InformationMetrics https://doi.org/10.1161/ATVBAHA.107.158931PMID: 18354086 Originally publishedApril 1, 2008 PDF download Advertisement
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