Reactive Hyperemia and Cardiovascular Risk
2007; Lippincott Williams & Wilkins; Volume: 27; Issue: 10 Linguagem: Inglês
10.1161/atvbaha.107.149740
ISSN1524-4636
AutoresAndrew C. Philpott, Todd J. Anderson,
Tópico(s)Cerebrovascular and Carotid Artery Diseases
ResumoHomeArteriosclerosis, Thrombosis, and Vascular BiologyVol. 27, No. 10Reactive Hyperemia and Cardiovascular Risk Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBReactive Hyperemia and Cardiovascular Risk Andrew Philpott and Todd J. Anderson Andrew PhilpottAndrew Philpott From the Department of Cardiovascular Sciences and the Libin Cardiovascular Institute, University of Calgary, Alberta, Canada. and Todd J. AndersonTodd J. Anderson From the Department of Cardiovascular Sciences and the Libin Cardiovascular Institute, University of Calgary, Alberta, Canada. Originally published1 Oct 2007https://doi.org/10.1161/ATVBAHA.107.149740Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:2065–2067Since the description of the classical cardiovascular risk factors by the Framingham group some 50 years ago,1 more recent efforts have explored the utility of biomarkers to further refine risk stratification. Although vascular imaging and biochemical markers have shown considerable promise,2 assessment of vascular function has particular appeal. Endothelial dysfunction is an attendant feature of established atherosclerosis3 and a precursor when only risk factors for atherosclerosis are present.4 It is thought in large part to reflect decreased nitric oxide bioavailability in the vasculature. As such it has been suggested that endothelial dysfunction plays a central pathophysiological role in the development and clinical expression of cardiovascular disease, making it well suited as a surrogate marker of risk.See p 2113Assessment of Endothelial FunctionEndothelial function has been generally assessed by measuring vasomotion of conduit vessels or regional increases in blood flow, reflecting microvascular/resistance vessel function, in the coronary or peripheral circulation. Although coronary endothelial function remains a "gold standard," its complexity and invasive requirements do not permit extensive use. Flow-mediated dilation of the peripheral circulation (FMD) has evolved as a popular marker because of the relative simplicity, a belief that it largely reflects nitric oxide–dependent endothelial function, its correlation with coronary reactivity, and modulation by risk factors or their treatment. What is often underappreciated, however, is that the relationship between vascular risk factors and FMD is rather poor. In addition, the correlation between measures of conduit vessel and microvascular function is weak and ultimately it is microvascular function that controls blood flow and oxygen transport.Can Endothelial Function Testing Predict Outcomes?Impaired coronary reactivity has been shown to predict subsequent cardiac events in several small studies.5,6 Attenuated FMD has been associated with complications after coronary angioplasty7 and vascular surgery,8 long term events in subjects with atherosclerosis,9,10 and in patients without overt cardiovascular disease.11–13 In the recently published Cardiovascular Health Study the association was weak but was maintained independent of traditional cardiovascular risk factors.13 Finally, microvascular dysfunction assessed by forearm plethysmography predicts long term outcomes in patients with cardiovascular disease.14,15Mechanism of Endothelial Function TestingAssessment of FMD in humans typically involves the induction of a shear stress stimulus in the conduit brachial artery after ischemia induced by occlusion of the forearm vessels for 5 minutes.16 This shear stress is generated by dilation of the microvasculature, thereby producing increased flow (reactive hyperemia) in the conduit vessel. This can be measured by Doppler ultrasound after the release of the blood pressure cuff. FMD has been shown to produce a largely NO-dependent FMD response,17 depending on study conditions.18 Pyke et al also suggest that the FMD measure could be improved if corrected for variability in the shear stimulus.19As part of the exploration of the appropriate vascular end point, components of FMD, namely shear stress20 and reactive hyperaemia,20 were compared with traditional risk factors. Risk factors were more closely related to diastolic shear stress and hyperaemic velocity than FMD. This suggested that endothelial dysfunction detected by FMD may be in greater part attributable to a reduced microvascular stimulus (via reduced reactive hyperemia) rather than impaired conduit vessel response (via brachial artery dilatation).20 The prognostic importance of these measures of microvascular function had not been previously evaluated.Current StudyIn the current issue, Huang and colleagues report data providing support for the hypothesis that the stimulus for FMD, reactive hyperemia, as well as FMD itself both provide prognostic information. This was the first study to associate reactive hyperaemia velocity with cardiovascular outcomes. The study involved 267 stable patients with peripheral vascular disease in whom an assessment of vascular function was undertaken within the month before vascular surgery. The group included the cohort (n=199) that were originally reported to demonstrate an association between FMD and perioperative events.8After a median follow-up of nearly 1 year and 50 cardiovascular events (representing 19% of the study population), lower hyperemic flow velocity (75±39 versus 95±50 cm/s, P=0.009) and lower FMD (4.5±3.0 versus 6.9±4.6%, P<0.001) predicted patients with an event. Cox proportional hazards models including both reactive hyperemia and FMD revealed that both predicted cardiovascular events (OR 2.7, 95% CI 1.2 to 5.9, P=0.018, and OR 4.2, 95% CI: 1.8 to 9.8, P=0.001, respectively) after adjusting for other risk factors. It should be noted that although a subanalysis revealed that this association remained significant for events occurring after 30 days, the majority of the events occurred during or soon after surgery, and as such it could be argued that the principal message from the study pertains to the link between reactive hyperemia and perioperative risk.Interestingly, despite the independent association of reactive hyperemia with outcomes, FMD remained a stronger measure of risk in this population. This may suggest that conduit function is more important than microvascular stimulus in this population with advanced disease. In light of the recent Framingham data, which showed a stronger association between cardiovascular risk factors and reactive hyperemia or diastolic shear stress than with FMD, it could be speculated that microvascular dysfunction may be more sensitive to the early stages of atherosclerosis, whereas conduit function may better reflect overt cardiovascular disease. Comparative analysis of these 2 markers in upcoming large population studies with more diverse risk may provide some clarification.Mechanism of Reactive HyperemiaReactive hyperemia is a consequence of the reduction in vascular resistance after temporary interruption of blood flow, and likely results from the combined effects of flow and ischemia induced vasodilators as well as a local myogenic response.21 The relative contribution of these factors to reactive hyperemia, particularly NO, but also ATP-sensitive potassium channels, adenosine, and endothelium-derived hyperpolarizing factor has been the source of some debate and may depend to some extent on the testing conditions and vascular territory.22 Several authors have described diminution of reactive hyperemia in the presence of the nitric oxide synthase inhibitor L-NMMA suggesting a role for NO in this process,23,24 although this result is not replicated in all studies.22 It would be fair to say, however, that peak hyperaemic velocity is at best partially dependent on endothelium-derived nitric oxide. The time course of hyperaemic velocity or flow changes after occlusion release may be more endothelium-dependent but is generally not measured simultaneously with diameter changes. Peak hyperaemic velocity likely provides an integrated measure of vascular function not confined to endothelium-derived products.Recent analysis of data from the Framingham study found that reactive hyperemia and the related measure shear stress were more strongly related to cardiovascular risk factors in that population than was FMD.20 Previously, small studies have shown that reactive hyperemia is impaired in the presence of hypertension, and the nitric oxide dependency of reactive hyperemia indicated by L-NMMA has been shown to be diminished in this setting, suggesting a causative role for NO in reduced RH in the presence of this cardiovascular risk factor. With the current study of Huang et al, we perhaps see the translation of this microvascular dysfunction into long term cardiovascular outcomes.Conclusions and Future PerspectivesThis study is the first to investigate and report an independent association between impaired reactive hyperemia and subsequent cardiovascular outcomes. It is in agreement with 2 previous studies that assessed outcomes related to a different measure of microvascular function using the more invasive technique of forearm plethysmography.14,15 The results speak to the importance of the microvascular stimulus in addition to the conduit response and provide impetus for further exploration of the mechanisms of vascular dysfunction and its assessment. The most appropriate measure of vascular health has yet to be established. As the hyperaemic velocity measure should be relatively easily derived from existing data within the several large population studies investigating long-term outcomes and FMD, answers on general applicability of these results may not be far away. Download figureDownload PowerPointFigure In healthy endothelium, 5-minute occlusion of the conduit artery induces release of vasodilators from the microvasculature. When occlusion is released the reduced microvascular resistance results in increased conduit artery velocity and flow, causing shear stress to the endothelium and culminating in vasodilation of the conduit artery mainly via nitric oxide.Sources of FundingT.J.A. is a Senior Scholar of the Alberta Heritage Foundation for Medical Research (Edmonton, AB, Canada).DisclosuresNone.FootnotesCorrespondence to T.J. Anderson, MD, 1403 29th Street NW, Calgary, AB, T2N 2T9. E-mail [email protected] References 1 Dawber TR, Kannel WB. The Framingham study. An epidemiological approach to coronary heart disease. Circulation. 1966; 34: 553–555.CrossrefMedlineGoogle Scholar2 Tsimikas S, Willerson JT, Ridker PM. C-reactive protein and other emerging blood biomarkers to optimize risk stratification of vulnerable patients. J Am Coll Cardiol. 2006; 47: C19–C31.CrossrefMedlineGoogle Scholar3 Ludmer PL, Selwyn AP, Shook TL, Wayne RR, Mudge GH, Alexander RW, Ganz P. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med. 1986; 315: 1046–1051.CrossrefMedlineGoogle Scholar4 Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992; 340: 1111–1115.CrossrefMedlineGoogle Scholar5 Schachinger V, Britten MB, Zeiher AM. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation. 2000; 101: 1899–1906.CrossrefMedlineGoogle Scholar6 Suwaidi JA, Hamasaki S, Higano ST, Nishimura RA, Holmes DR Jr, Lerman A. Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation. 2000; 101: 948–954.CrossrefMedlineGoogle Scholar7 Patti G, Pasceri V, Melfi R, Goffredo C, Chello M, D'Ambrosio A, Montesanti R, Di Sciascio G. Impaired flow-mediated dilation and risk of restenosis in patients undergoing coronary stent implantation. Circulation. 2005; 111: 70–75.LinkGoogle Scholar8 Gokce N, Keaney JF Jr, Hunter LM, Watkins MT, Nedeljkovic ZS, Menzoian JO, Vita JA. Predictive value of noninvasively determined endothelial dysfunction for long-term cardiovascular events in patients with peripheral vascular disease. J Am Coll Cardiol. 2003; 41: 1769–1775.CrossrefMedlineGoogle Scholar9 Brevetti G, Silvestro A, Schiano V, Chiariello M. Endothelial dysfunction and cardiovascular risk prediction in peripheral arterial disease: additive value of flow-mediated dilation to ankle-brachial pressure index. Circulation. 2003; 108: 2093–2098.LinkGoogle Scholar10 Chan SY, Mancini GB, Kuramoto L, Schulzer M, Frohlich J, Ignaszewski A. The prognostic importance of endothelial dysfunction and carotid atheroma burden in patients with coronary artery disease. J Am Coll Cardiol. 2003; 42: 1037–1043.CrossrefMedlineGoogle Scholar11 Fathi R, Haluska B, Isbel N, Short L, Marwick TH. The relative importance of vascular structure and function in predicting cardiovascular events. J Am Coll Cardiol. 2004; 43: 616–623.CrossrefMedlineGoogle Scholar12 Shimbo D, Grahame-Clarke C, Miyake Y, Rodriguez C, Sciacca R, Di Tullio M, Boden-Albala B, Sacco R, Homma S. The association between endothelial dysfunction and cardiovascular outcomes in a population-based multi-ethnic cohort. Atherosclerosis. 2007; 192: 197–203.CrossrefMedlineGoogle Scholar13 Yeboah J, Crouse JR, Hsu FC, Burke GL, Herrington DM. Brachial flow-mediated dilation predicts incident cardiovascular events in older adults: the Cardiovascular Health Study. Circulation. 2007; 115: 2390–2397.LinkGoogle Scholar14 Heitzer T, Schlinzig T, Krohn K, Meinertz T, Munzel T. Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation. 2001; 104: 2673–2678.CrossrefMedlineGoogle Scholar15 Perticone F, Ceravolo R, Pujia A, Ventura G, Iacopino S, Scozzafava A, Ferraro A, Chello M, Mastroroberto P, Verdecchia P, Schillaci G. Prognostic significance of endothelial dysfunction in hypertensive patients. Circulation. 2001; 104: 191–196.CrossrefMedlineGoogle Scholar16 Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, Herrington D, Vallance P, Vita J, Vogel R. 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 Scholar17 Joannides R, Haefeli WE, Linder L, Richard V, Bakkali EH, Thuillez C, Luscher TF. Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo. Circulation. 1995; 91: 1314–1319.CrossrefMedlineGoogle Scholar18 Mullen MJ, Kharbanda RK, Cross J, Donald AE, Taylor M, Vallance P, Deanfield JE, MacAllister RJ. Heterogenous nature of flow-mediated dilatation in human conduit arteries in vivo: relevance to endothelial dysfunction in hypercholesterolemia. Circ Res. 2001; 88: 145–151.CrossrefMedlineGoogle Scholar19 Pyke KE, Tschakovsky ME. Peak vs. total reactive hyperemia: which determines the magnitude of flow-mediated dilation? J Appl Physiol. 2007; 102: 1510–1519.CrossrefMedlineGoogle Scholar20 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 Scholar21 Hayoz D, Weber R, Rutschmann B, Darioli R, Burnier M, Waeber B, Brunner HR. Postischemic blood flow response in hypercholesterolemic patients. Hypertension. 1995; 26: 497–502.CrossrefMedlineGoogle Scholar22 Tagawa T, Imaizumi T, Endo T, Shiramoto M, Harasawa Y, Takeshita A. Role of nitric oxide in reactive hyperemia in human forearm vessels. Circulation. 1994; 90: 2285–2290.CrossrefMedlineGoogle Scholar23 Meredith IT, Currie KE, Anderson TJ, Roddy MA, Ganz P, Creager MA. Postischemic vasodilation in human forearm is dependent on endothelium-derived nitric oxide. Am J Physiol. 1996; 270: H1435–H1440.MedlineGoogle Scholar24 Higashi Y, Sasaki S, Nakagawa K, Matsuura H, Kajiyama G, Oshima T. A noninvasive measurement of reactive hyperemia that can be used to assess resistance artery endothelial function in humans. Am J Cardiol. 2001; 87: 121–125, A129.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Ahn J, Kim J, Choi W and Kim C (2021) High-resolution functional photoacoustic monitoring of vascular dynamics in human fingers, Photoacoustics, 10.1016/j.pacs.2021.100282, 23, (100282), Online publication date: 1-Sep-2021. D'Agata M, Hoopes E, Berube F, Hirt A, Kuczmarski A, Ranadive S, Wenner M and Witman M (2021) Evidence of reduced peripheral microvascular function in young Black women across the menstrual cycle, Journal of Applied Physiology, 10.1152/japplphysiol.00452.2021, 131:6, (1783-1791), Online publication date: 1-Dec-2021. D'Agata M, Hoopes E, Berube F, Hirt A and Witman M (2021) Young black women demonstrate impaired microvascular but preserved macrovascular function compared to white women, Experimental Physiology, 10.1113/EP089702, 106:10, (2031-2037), Online publication date: 1-Oct-2021. Junqueira C, Ferreira E, Junqueira A, Cyrino F, Maranhão P, Kraemer-Aguiar L, Bottino D, de Souza M and Bouskela E Peripheral microvascular dysfunction is also present in patients with ischemia and no obstructive coronary artery disease (INOCA), Clinical Hemorheology and Microcirculation, 10.3233/CH-201065, 79:3, (381-393) Langham M, Caporale A, Wehrli F, Parry S and Schwartz N (2020) Evaluation of Vascular Reactivity of Maternal Vascular Adaptations of Pregnancy With Quantitative MRI : Pilot Study , Journal of Magnetic Resonance Imaging, 10.1002/jmri.27342, 53:2, (447-455), Online publication date: 1-Feb-2021. Haptonstall K, Choroomi Y, Moheimani R, Nguyen K, Tran E, Lakhani K, Ruedisueli I, Gornbein J and Middlekauff H (2020) Differential effects of tobacco cigarettes and electronic cigarettes on endothelial function in healthy young people, American Journal of Physiology-Heart and Circulatory Physiology, 10.1152/ajpheart.00307.2020, 319:3, (H547-H556), Online publication date: 1-Sep-2020. Hanson B, Proffit M and Gifford J (2020) Vascular function is related to blood flow during high-intensity, but not low-intensity, knee extension exercise, Journal of Applied Physiology, 10.1152/japplphysiol.00671.2019, 128:3, (698-708), Online publication date: 1-Mar-2020. Dass N, Kilakkathi S, Obi B, Moosreiner A, Krishnaswami S, Widlansky M and Kidambi S (2017) Effect of gender and adiposity on in vivo vascular function in young African Americans, Journal of the American Society of Hypertension, 10.1016/j.jash.2017.03.002, 11:5, (246-257), Online publication date: 1-May-2017. Soares R, Reimer R and Murias J (2017) Changes in vascular responsiveness during a hyperglycemia challenge measured by near-infrared spectroscopy vascular occlusion test, Microvascular Research, 10.1016/j.mvr.2017.01.003, 111, (67-71), Online publication date: 1-May-2017. Nuffer Z, Rupasov A, Bekal N, Murtha J and Bhatt S (2017) Spectral Doppler ultrasound of peripheral arteries: a pictorial review, Clinical Imaging, 10.1016/j.clinimag.2017.07.007, 46, (91-97), Online publication date: 1-Nov-2017. Bretón-Romero R, Wang N, Palmisano J, Larson M, Vasan R, Mitchell G, Benjamin E, Vita J and Hamburg N (2016) Cross-Sectional Associations of Flow Reversal, Vascular Function, and Arterial Stiffness in the Framingham Heart Study, Arteriosclerosis, Thrombosis, and Vascular Biology, 36:12, (2452-2459), Online publication date: 1-Dec-2016. Tuchin V, Larin K, Leahy M, Wang R, Young A and Vishwanath K (2016) Quantitative assessment of reactive hyperemia using laser speckle contrast imaging at multiple wavelengths SPIE BiOS, 10.1117/12.2213179, , (97071H), Online publication date: 17-Mar-2016. Gerber R, Vita J, Ganz P, Wager C, Araujo A, Rosen R and Kupelian V (2015) Association of Peripheral Microvascular Dysfunction and Erectile Dysfunction, Journal of Urology, 10.1016/j.juro.2014.08.108, 193:2, (612-617), Online publication date: 1-Feb-2015. Vetter M, Martin B, Fung M, Pajevic M, Anderson T and Raedler T (2015) Microvascular dysfunction in schizophrenia: a case–control study, npj Schizophrenia, 10.1038/npjschz.2015.23, 1:1, Online publication date: 1-Dec-2015. Anderson T and Phillips S (2015) Assessment and Prognosis of Peripheral Artery Measures of Vascular Function, Progress in Cardiovascular Diseases, 10.1016/j.pcad.2014.11.005, 57:5, (497-509), Online publication date: 1-Mar-2015. Martin J, Beck D and Braith R (2014) Peripheral resistance artery blood flow in subjects with abnormal glucose tolerance is improved following enhanced external counterpulsation therapy, Applied Physiology, Nutrition, and Metabolism, 10.1139/apnm-2013-0497, 39:5, (596-599), Online publication date: 1-May-2014. Beck D, Martin J, Casey D and Braith R (2013) Exercise training improves endothelial function in resistance arteries of young prehypertensives, Journal of Human Hypertension, 10.1038/jhh.2013.109, 28:5, (303-309), Online publication date: 1-May-2014. Edwards-Richards A, DeFreitas M, Katsoufis C, Seeherunvong W, Sasaki N, Freundlich M, Zilleruelo G and Abitbol C (2014) Capillary rarefaction: an early marker of microvascular disease in young hemodialysis patients, Clinical Kidney Journal, 10.1093/ckj/sfu106, 7:6, (569-574), Online publication date: 1-Dec-2014. Brewster S, Floras J, Zinman B and Retnakaran R (2013) Endothelial Function in Women with and without a History of Glucose Intolerance in Pregnancy, Journal of Diabetes Research, 10.1155/2013/382670, 2013, (1-9), . Martin B, Verma S, Charbonneau F, Title L, Lonn E and Anderson T (2013) The relationship between anthropometric indexes of adiposity and vascular function in the FATE cohort, Obesity, 10.1002/oby.20266, 21:2, (266-273), Online publication date: 1-Feb-2013. Langham M, Englund E, Mohler E, Li C, Rodgers Z, Floyd T and Wehrli F (2013) Quantitative CMR markers of impaired vascular reactivity associated with age and peripheral artery disease, Journal of Cardiovascular Magnetic Resonance, 10.1186/1532-429X-15-17, 15:1, Online publication date: 1-Dec-2013. Wexler O, M Morgan M, Gough M, Steinmetz S, Mack C, Darling D, Doolin K, Apostolakos M, Graves B, Frampton M, Chen X and Pietropaoli A (2012) Brachial artery reactivity in patients with severe sepsis: an observational study, Critical Care, 10.1186/cc11223, 16:2, (R38), . Cunningham S, Rush J and Freeman L (2012) Systemic Inflammation and Endothelial Dysfunction in Dogs with Congestive Heart Failure, Journal of Veterinary Internal Medicine, 10.1111/j.1939-1676.2012.00923.x, 26:3, (547-557), Online publication date: 1-May-2012. McCall D, McKinley M, Noad R, McKeown P, McCance D, Young I and Woodside J (2011) The assessment of vascular function during dietary intervention trials in human subjects, British Journal of Nutrition, 10.1017/S0007114511002996, 106:7, (981-994), Online publication date: 14-Oct-2011. Corretti M, Panjrath G and Jones S (2011) Endothelial Function and Dysfunction Preventive Cardiology: Companion to Braunwald's Heart Disease, 10.1016/B978-1-4377-1366-4.00032-9, (526-539), . Lockhart C, Agnew C, McCann A, Hamilton P, Quinn C, McCall D, Plumb R, McClenaghan V, McGivern R, Harbinson M and McVeigh G (2011) Impaired flow-mediated dilatation response in uncomplicated Type 1 diabetes mellitus: influence of shear stress and microvascular reactivity, Clinical Science, 10.1042/CS20100448, 121:3, (129-139), Online publication date: 1-Aug-2011. GALARRAGA B, BELCH J, PULLAR T, OGSTON S and KHAN F (2010) Clinical Improvement in Rheumatoid Arthritis Is Associated with Healthier Microvascular Function in Patients Who Respond to Antirheumatic Therapy, The Journal of Rheumatology, 10.3899/jrheum.090417, 37:3, (521-528), Online publication date: 1-Mar-2010. Schnorbus B, Schiewe R, Ostad M, Medler C, Wachtlin D, Wenzel P, Daiber A, Münzel T and Warnholtz A (2009) Effects of pentaerythritol tetranitrate on endothelial function in coronary artery disease: results of the PENTA study, Clinical Research in Cardiology, 10.1007/s00392-009-0096-z, 99:2, (115-124), Online publication date: 1-Feb-2010. Langham M, Floyd T, Mohler E, Magland J and Wehrli F (2010) Evaluation of Cuff-Induced Ischemia in the Lower Extremity by Magnetic Resonance Oximetry, Journal of the American College of Cardiology, 10.1016/j.jacc.2009.08.068, 55:6, (598-606), Online publication date: 1-Feb-2010. Langham M, Jain V, Magland J and Wehrli F (2010) Time-resolved absolute velocity quantification with projections, Magnetic Resonance in Medicine, 10.1002/mrm.22559, 64:6, (1599-1606), Online publication date: 1-Dec-2010. Akhtar M, Kleis S, Metcalfe R and Naghavi M (2010) Sensitivity of Digital Thermal Monitoring Parameters to Reactive Hyperemia, Journal of Biomechanical Engineering, 10.1115/1.4001137, 132:5, Online publication date: 1-May-2010. Matsuoka H (2009) Postprandial Microvascular Dysfunction, Circulation Journal, 10.1253/circj.CJ-09-0445, 73:8, (1399-1400), . Lockhart C, Hamilton P, Quinn C and McVeigh G (2009) End-organ dysfunction and cardiovascular outcomes: the role of the microcirculation, Clinical Science, 10.1042/CS20080069, 116:3, (175-190), Online publication date: 1-Feb-2009. Markopoulou P, Papanikolaou E, Loukopoulou S, Galina P, Papassotiriou I and Siahanidou T (2021) Elevated circulating endothelial microparticles (EMPs) in prepubertal children born preterm, Pediatric Research, 10.1038/s41390-021-01655-8 Martin B, Verma S, Charbonneau F, Title L, Lonn E and Anderson T (2012) The Relationship Between Anthropometric Indexes of Adiposity and Vascular Function in the FATE Cohort, Obesity, 10.1038/oby.2012.113 Galarraga B, Khan F, Kumar P, Pullar T and Belch J (2008) C-reactive protein: the underlying cause of microvascular dysfunction in rheumatoid arthritis, Rheumatology, 10.1093/rheumatology/ken386, 47:12, (1780-1784) October 2007Vol 27, Issue 10 Advertisement Article InformationMetrics https://doi.org/10.1161/ATVBAHA.107.149740PMID: 17881738 Originally publishedOctober 1, 2007 Keywordsatherosclerosisendothelial functionrisk factormicrovesselsPDF download Advertisement
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