(Circulation. 2004;109:613-619.)
© 2004 American Heart Association, Inc.
Clinical Investigation and Reports |
From the Evans Department of Medicine (E.J.B., J.F.K., J.A.V.), Whitaker Cardiovascular Institute (E.J.B., R.S.V., J.F.K., J.A.V.), and Preventive Medicine Section (E.J.B., M.G.L., R.S.V.), Boston University School of Medicine, Boston, Mass; Cardiovascular Engineering, Inc (G.F.M.), Holliston, Mass; and the Framingham Study (E.J.B., M.G.L., M.J.K., R.S.V., B.T.L., S.F., E.O.), National Heart, Lung and Blood Institute, Framingham, Mass.
Correspondence to Emelia J. Benjamin, MD, ScM, Associate Professor of Medicine, Boston University, Framingham Study, 73 Mt Wayte Avenue No. 2, Framingham, MA 01702-5827. E-mail emelia{at}bu.edu
Received May 6, 2003; de novo received August 27, 2003; revision received October 28, 2003; accepted October 30, 2003.
Background Studies in selected samples have linked impaired endothelial function with cardiovascular disease and its risk factors. The clinical correlates and heritability of endothelial function in the community have not been described.
Methods and Results We examined a measure of endothelial function, brachial artery flow-mediated dilation (FMD), expressed as both percent (FMD%) and actual dilation by ultrasound with the occlusion cuff below the elbow in 2883 Framingham Study participants (52.9% women; mean age, 61 years). A subset of 1096 participants performed a 6-minute walk test before FMD determination. Mean FMD% was 3.3±3.0% in women and 2.4±2.4% in men. In stepwise multivariable linear regression models, FMD% was inversely related to age, systolic blood pressure, body mass index (BMI), lipid-lowering medication, and smoking, whereas it was positively related to female gender, heart rate, and prior walk test. The estimated heritability of FMD% was 0.14. FMD actual dilation findings were similar, except that female sex and BMI were not significantly associated.
Conclusions Increasing age, systolic blood pressure, BMI, and smoking were associated with lower FMD% in our community-based sample, whereas prior exercise and increasing heart rate were associated with higher FMD%. The estimated heritability of FMD was modest. Future research will permit more complete characterization of the genetic and environmental determinants of endothelial function and its prognostic value in the community.
Key Words: endothelium epidemiology risk factors genetics
This article has been cited by other articles:
![]() |
H. A Chami, M. J Keyes, J. A Vita, G. F Mitchell, M. G Larson, S. Fan, R. S Vasan, G. T O'Connor, E. J Benjamin, and D. J Gottlieb Brachial artery diameter, blood flow and flow-mediated dilation in sleep-disordered breathing Vascular Medicine, November 1, 2009; 14(4): 351 - 360. [Abstract] [PDF] |
||||
![]() |
M. M. Dohadwala and J. A. Vita Grapes and Cardiovascular Disease J. Nutr., September 1, 2009; 139(9): 1788S - 1793S. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. B. Chung, N. M. Hamburg, M. Holbrook, S. M. Shenouda, M. M. Dohadwala, D. F. Terry, N. Gokce, and J. A. Vita The Brachial Artery Remodels to Maintain Local Shear Stress Despite the Presence of Cardiovascular Risk Factors Arterioscler Thromb Vasc Biol, April 1, 2009; 29(4): 606 - 612. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Versari, E. Daghini, A. Virdis, L. Ghiadoni, and S. Taddei The ageing endothelium, cardiovascular risk and disease in man Exp Physiol, March 1, 2009; 94(3): 317 - 321. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Ganz and P. Y. Hsue Individualized approach to the management of coronary heart disease identifying the nonresponders before it is too late. J. Am. Coll. Cardiol., January 27, 2009; 53(4): 331 - 333. [Full Text] [PDF] |
||||
![]() |
P. Eickhoff, A. Valipour, D. Kiss, M. Schreder, L. Cekici, K. Geyer, R. Kohansal, and O. C. Burghuber Determinants of Systemic Vascular Function in Patients with Stable Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., December 15, 2008; 178(12): 1211 - 1218. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. F. Mitchell Effects of central arterial aging on the structure and function of the peripheral vasculature: implications for end-organ damage J Appl Physiol, November 1, 2008; 105(5): 1652 - 1660. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Romualdi, B. Costantini, L. Selvaggi, M. Giuliani, F. Cristello, F. Macri, A. Bompiani, A. Lanzone, and M. Guido Metformin improves endothelial function in normoinsulinemic PCOS patients: a new prospective Hum. Reprod., September 1, 2008; 23(9): 2127 - 2133. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. M. Apovian, S. Bigornia, M. Mott, M. R. Meyers, J. Ulloor, M. Gagua, M. McDonnell, D. Hess, L. Joseph, and N. Gokce Adipose Macrophage Infiltration Is Associated With Insulin Resistance and Vascular Endothelial Dysfunction in Obese Subjects Arterioscler Thromb Vasc Biol, September 1, 2008; 28(9): 1654 - 1659. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Vogel Listening to the Endothelium: A Story of Signal and Noise J. Am. Coll. Cardiol., May 20, 2008; 51(20): 1965 - 1966. [Full Text] [PDF] |
||||
![]() |
N. M. Hamburg, M. J. Keyes, M. G. Larson, R. S. Vasan, R. Schnabel, M. M. Pryde, G. F. Mitchell, J. Sheffy, J. A. Vita, and E. J. Benjamin Cross-Sectional Relations of Digital Vascular Function to Cardiovascular Risk Factors in the Framingham Heart Study Circulation, May 13, 2008; 117(19): 2467 - 2474. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Juonala, M. Kahonen, T. Laitinen, N. Hutri-Kahonen, E. Jokinen, L. Taittonen, M. Pietikainen, H. Helenius, J. S.A. Viikari, and O. T. Raitakari Effect of age and sex on carotid intima-media thickness, elasticity and brachial endothelial function in healthy adults: The Cardiovascular Risk in Young Finns Study Eur. Heart J., May 1, 2008; 29(9): 1198 - 1206. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Maas, E. Schwedhelm, L. Kahl, H. Li, R. Benndorf, N. Luneburg, U. Forstermann, and R. H. Boger Simultaneous Assessment of Endothelial Function, Nitric Oxide Synthase Activity, Nitric Oxide-Mediated Signaling, and Oxidative Stress in Individuals with and without Hypercholesterolemia Clin. Chem., February 1, 2008; 54(2): 292 - 300. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. G. Barr, S. Mesia-Vela, J. H. M. Austin, R. C. Basner, B. M. Keller, A. P. Reeves, D. Shimbo, and L. Stevenson Impaired Flow-mediated Dilation Is Associated with Low Pulmonary Function and Emphysema in Ex-smokers: The Emphysema and Cancer Action Project (EMCAP) Study Am. J. Respir. Crit. Care Med., December 15, 2007; 176(12): 1200 - 1207. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. M. Hamburg, C. J. McMackin, A. L. Huang, S. M. Shenouda, M. E. Widlansky, E. Schulz, N. Gokce, N. B. Ruderman, J. F. Keaney Jr, and J. A. Vita Physical Inactivity Rapidly Induces Insulin Resistance and Microvascular Dysfunction in Healthy Volunteers Arterioscler Thromb Vasc Biol, December 1, 2007; 27(12): 2650 - 2656. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Melikian, M. T. Kearney, M. R. Thomas, B. De Bruyne, A. M. Shah, and P. A. MacCarthy A simple thermodilution technique to assess coronary endothelium-dependent microvascular function in humans: validation and comparison with coronary flow reserve Eur. Heart J., September 2, 2007; 28(18): 2188 - 2194. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Frick, A. Suessenbacher, H. F. Alber, and O. Pachinger Endothelial dysfunction and peripheral arterial disease Eur. Heart J., August 1, 2007; 28(15): 1910 - 1910. [Full Text] [PDF] |
||||
![]() |
F. Violi, L. Loffredo, and P. Pignatelli Endothelial dysfunction and peripheral arterial disease: reply Eur. Heart J., August 1, 2007; 28(15): 1910 - 1911. [Full Text] [PDF] |
||||
![]() |
R. Migliacci, C. Becattini, R. Pesavento, G. Davi, M. C. Vedovati, G. Guglielmini, E. Falcinelli, G. Ciabattoni, F. Dalla Valle, P. Prandoni, et al. Endothelial dysfunction in patients with spontaneous venous thromboembolism Haematologica, June 1, 2007; 92(6): 812 - 818. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. A. Phillips Effects of low-carbohydrate diet on vascular health: more than just weight loss Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2037 - H2039. [Full Text] [PDF] |
||||
![]() |
B. A. Parker, S. J. Ridout, and D. N. Proctor Age and flow-mediated dilation: a comparison of dilatory responsiveness in the brachial and popliteal arteries Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H3043 - H3049. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. E. Donald, M. Charakida, T. J. Cole, P. Friberg, P. J. Chowienczyk, S. C. Millasseau, J. E. Deanfield, and J. P. Halcox Non-Invasive Assessment of Endothelial Function: Which Technique? J. Am. Coll. Cardiol., November 7, 2006; 48(9): 1846 - 1850. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. S. Pena, E. Wiltshire, K. MacKenzie, R. Gent, L. Piotto, C. Hirte, and J. Couper Vascular Endothelial and Smooth Muscle Function Relates to Body Mass Index and Glucose in Obese and Nonobese Children J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4467 - 4471. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Juonala, J. S.A. Viikari, T. Ronnemaa, H. Helenius, L. Taittonen, and O. T. Raitakari Elevated Blood Pressure in Adolescent Boys Predicts Endothelial Dysfunction: The Cardiovascular Risk in Young Finns Study Hypertension, September 1, 2006; 48(3): 424 - 430. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Iida, H. Luo, K. Hagisawa, T. Akima, P. K. Shah, T. Z. Naqvi, and R. J. Siegel Noninvasive Low-Frequency Ultrasound Energy Causes Vasodilation in Humans J. Am. Coll. Cardiol., August 1, 2006; 48(3): 532 - 537. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Taddei, D. Versari, A. Cipriano, L. Ghiadoni, F. Galetta, F. Franzoni, A. Magagna, A. Virdis, and A. Salvetti Identification of a Cytochrome P450 2C9-Derived Endothelium-Derived Hyperpolarizing Factor in Essential Hypertensive Patients J. Am. Coll. Cardiol., August 1, 2006; 48(3): 508 - 515. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. B. Meigs, P. W. F. Wilson, C. S. Fox, R. S. Vasan, D. M. Nathan, L. M. Sullivan, and R. B. D'Agostino Body Mass Index, Metabolic Syndrome, and Risk of Type 2 Diabetes or Cardiovascular Disease J. Clin. Endocrinol. Metab., August 1, 2006; 91(8): 2906 - 2912. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Juonala, J. S. A. Viikari, L. Rasanen, H. Helenius, M. Pietikainen, and O. T. Raitakari Young Adults With Family History of Coronary Heart Disease Have Increased Arterial Vulnerability to Metabolic Risk Factors: The Cardiovascular Risk in Young Finns Study Arterioscler Thromb Vasc Biol, June 1, 2006; 26(6): 1376 - 1382. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Grebe, H. J. Eisele, N. Weissmann, C. Schaefer, H. Tillmanns, W. Seeger, and R. Schulz Antioxidant Vitamin C Improves Endothelial Function in Obstructive Sleep Apnea Am. J. Respir. Crit. Care Med., April 15, 2006; 173(8): 897 - 901. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. M. van Asselt, H. S. Kok, Y. T. van der Schouw, P. H.M. Peeters, P. L. Pearson, and D. E. Grobbee Role of Genetic Analyses in Cardiology: Part II: Heritability Estimation for Gene Searching in Multifactorial Diseases Circulation, February 28, 2006; 113(8): 1136 - 1139. [Full Text] [PDF] |
||||
![]() |
S. Kathiresan, P. Gona, M. G. Larson, J. A. Vita, G. F. Mitchell, G. H. Tofler, D. Levy, C. Newton-Cheh, T. J. Wang, E. J. Benjamin, et al. Cross-Sectional Relations of Multiple Biomarkers From Distinct Biological Pathways to Brachial Artery Endothelial Function Circulation, February 21, 2006; 113(7): 938 - 945. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. K. Jacobs Women, Ischemic Heart Disease, Revascularization, and the Gender Gap: What Are We Missing? J. Am. Coll. Cardiol., February 7, 2006; 47(3_Suppl_S): S63 - S65. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. B. Meigs, C. J. O'Donnell, G. H. Tofler, E. J. Benjamin, C. S. Fox, I. Lipinska, D. M. Nathan, L. M. Sullivan, R. B. D'Agostino, and P. W.F. Wilson Hemostatic Markers of Endothelial Dysfunction and Risk of Incident Type 2 Diabetes: The Framingham Offspring Study Diabetes, February 1, 2006; 55(2): 530 - 537. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. J. Donato, A. Uberoi, D. W. Wray, S. Nishiyama, L. Lawrenson, and R. S. Richardson Differential effects of aging on limb blood flow in humans Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H272 - H278. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. F. Mitchell, J. A. Vita, M. G. Larson, H. Parise, M. J. Keyes, E. Warner, R. S. Vasan, D. Levy, and E. J. Benjamin Cross-Sectional Relations of Peripheral Microvascular Function, Cardiovascular Disease Risk Factors, and Aortic Stiffness: The Framingham Heart Study Circulation, December 13, 2005; 112(24): 3722 - 3728. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. Nair, R. K Oka, L. D Waring, E. M Umoh, C B. Taylor, and J. P Cooke Vascular compliance versus flow-mediated vasodilation: correlation with cardiovascular risk factors Vascular Medicine, November 1, 2005; 10(4): 275 - 283. [Abstract] [PDF] |
||||
![]() |
L. Lind, N. Fors, J. Hall, K. Marttala, and A. Stenborg A Comparison of Three Different Methods to Evaluate Endothelium-Dependent Vasodilation in the Elderly: The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) Study Arterioscler Thromb Vasc Biol, November 1, 2005; 25(11): 2368 - 2375. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. R. Witte, J. Westerink, E. J. de Koning, Y. van der Graaf, D. E. Grobbee, and M. L. Bots Is the Association Between Flow-Mediated Dilation and Cardiovascular Risk Limited to Low-Risk Populations? J. Am. Coll. Cardiol., June 21, 2005; 45(12): 1987 - 1993. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. L. Moens, I. Goovaerts, M. J. Claeys, and C. J. Vrints Flow-Mediated Vasodilation: A Diagnostic Instrument, or an Experimental Tool? Chest, June 1, 2005; 127(6): 2254 - 2263. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. G. Brown and J. Crowley Is There Any Hope for Vitamin E? JAMA, March 16, 2005; 293(11): 1387 - 1390. [Full Text] [PDF] |
||||
![]() |
M. Laclaustra, J. C. Kaski, A. F. Frangi, G. F. Mitchell, E. Warner, H. Parise, J. A. Vita, J. F. Keaney Jr, M. J. Keyes, D. Levy, et al. Flow-Mediated Dilation: Just a Marker of Local Shear Stress? * Response: Hypertension, March 1, 2005; 45(3): e11 - e12. [Full Text] [PDF] |
||||
![]() |
X. Zhang, X. O. Shu, G. Yang, H. L. Li, Y. B. Xiang, Y.-T. Gao, Q. Li, and W. Zheng Association of Passive Smoking by Husbands with Prevalence of Stroke among Chinese Women Nonsmokers Am. J. Epidemiol., February 1, 2005; 161(3): 213 - 218. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. A. Vita, J. F. Keaney Jr, M. G. Larson, M. J. Keyes, J. M. Massaro, I. Lipinska, B. T. Lehman, S. Fan, E. Osypiuk, P. W.F. Wilson, et al. Brachial Artery Vasodilator Function and Systemic Inflammation in the Framingham Offspring Study Circulation, December 7, 2004; 110(23): 3604 - 3609. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Juonala, J. S.A. Viikari, T. Laitinen, J. Marniemi, H. Helenius, T. Ronnemaa, and O. T. Raitakari Interrelations Between Brachial Endothelial Function and Carotid Intima-Media Thickness in Young Adults: The Cardiovascular Risk in Young Finns Study Circulation, November 2, 2004; 110(18): 2918 - 2923. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. A. Vita, M.-L. Brennan, N. Gokce, S. A. Mann, M. Goormastic, M. H. Shishehbor, M. S. Penn, J. F. Keaney Jr, and S. L. Hazen Serum Myeloperoxidase Levels Independently Predict Endothelial Dysfunction in Humans Circulation, August 31, 2004; 110(9): 1134 - 1139. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. F. O'Rourke and W. W. Nichols Shear Stress and Flow-Mediated Dilation Hypertension, August 1, 2004; 44(2): 119 - 120. [Full Text] [PDF] |
||||
![]() |
G. F. Mitchell, H. Parise, J. A. Vita, M. G. Larson, E. Warner, J. F. Keaney Jr, M. J. Keyes, D. Levy, R. S. Vasan, and E. J. Benjamin Local Shear Stress and Brachial Artery Flow-Mediated Dilation: The Framingham Heart Study Hypertension, August 1, 2004; 44(2): 134 - 139. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Frick, H. F. Alber, F. Weidinger, E. J. Benjamin, M. G. Larson, M. J. Keyes, G. F. Mitchell, R. S. Vasan, J. F. Keaney Jr, and J. A. Vita Endothelial Function in a Large Community * Response Circulation, July 20, 2004; 110(3): e24 - e24. [Full Text] [PDF] |
||||
|
Circulation Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search Copyright © 2004 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited. |