Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction

Cardiothoracic Unit, Hospital for Sick Children, London, England, United Kingdom.

OBJECTIVES. This study attempted to assess whether coronary risk factors are associated with endothelial dysfunction in the systemic arteries of asymptomatic men and women. BACKGROUND. Endothelial dysfunction is present in adults with established atherosclerosis. It is not known whether risk factors interact to produce endothelial dysfunction in clinically well subjects early in the natural history. METHODS. Using high resolution ultrasound, we measured arterial diameter at rest, after reactive hyperemia (with increased flow causing endothelium-dependent dilation) and after sublingual nitroglycerin (an endothelium-independent dilator). Arterial responses were studied noninvasively in 500 clinically well, nonhypertensive subjects (252 men, 248 women; mean [+/- SD] age 36 +/- 15 years, range 5 to 73), including 179 current and former smokers. The superficial femoral artery was studied in 46 subjects and the brachial artery in 454. RESULTS. Flow-mediated dilation ranged from -1% to +17%. All arteries dilated in response to administration of nitroglycerin (17 +/- 6%), suggesting an abnormality of endothelial function in subjects with impaired flow-mediated dilation. On univariate analysis, reduced flow-mediated dilation was significantly related to hypercholesterolemia, cigarette smoking, higher blood pressure, male gender, older age, family history of premature vascular disease and larger vessel size (p < 0.01). By multiple stepwise regression analysis, reduced flow-mediated dilation was independently associated with cigarette smoking, older age, male gender and larger vessel size (p < 0.005) but not with total cholesterol level, blood pressure or family history. A composite risk factor score was independently related to flow-mediated dilation (r = -0.30, p < 0.0001), suggesting risk factor interaction. CONCLUSIONS. Loss of endothelium-dependent dilation in the systemic arteries occurs in the preclinical phase of vascular disease and is associated with interaction of the same risk factors known to predispose to atherosclerosis and its complications in later life.

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				L. W. Lissin, R. Oka, S. Lakshmi, and J. P Cooke Isoflavones improve vascular reactivity in post-menopausal women with hypercholesterolemia Vascular Medicine, February 1, 2004; 9(1): 26 - 30. [Abstract] [PDF]

				D. R. Kaiser, K. Billups, C. Mason, R. Wetterling, J. L. Lundberg, and A. J. Bank Impaired brachial artery endothelium-dependent and -independent vasodilation in men with erectile dysfunction and no other clinical cardiovascular disease J. Am. Coll. Cardiol., January 21, 2004; 43(2): 179 - 184. [Abstract] [Full Text] [PDF]

				M. D. Cheitlin Erectile dysfunction: the earliest sign of generalized vascular disease? J. Am. Coll. Cardiol., January 21, 2004; 43(2): 185 - 186. [Full Text] [PDF]

				U. Campia, G. Sullivan, M. B. Bryant, M. A. Waclawiw, M. J. Quon, and J. A. Panza Insulin impairs endothelium-dependent vasodilation independent of insulin sensitivity or lipid profile Am J Physiol Heart Circ Physiol, January 1, 2004; 286(1): H76 - H82. [Abstract] [Full Text] [PDF]

				D. J. Green, J. H. Walsh, A. Maiorana, M. J. Best, R. R. Taylor, and J. G. O'Driscoll Exercise-induced improvement in endothelial dysfunction is not mediated by changes in CV risk factors: pooled analysis of diverse patient populations Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2679 - H2687. [Abstract] [Full Text] [PDF]

				A. Silvestro, F. Scopacasa, A. Ruocco, G. Oliva, V. Schiano, C. Zincarelli, and G. Brevetti Inflammatory status and endothelial function in asymptomatic and symptomatic peripheral arterial disease Vascular Medicine, November 1, 2003; 8(4): 225 - 232. [Abstract] [PDF]

				P. Ganz and J. A. Vita Testing Endothelial Vasomotor Function: Nitric Oxide, a Multipotent Molecule Circulation, October 28, 2003; 108(17): 2049 - 2053. [Full Text] [PDF]

				G. Brevetti, A. Silvestro, V. Schiano, and M. Chiariello Endothelial Dysfunction and Cardiovascular Risk Prediction in Peripheral Arterial Disease: Additive Value of Flow-Mediated Dilation to Ankle-Brachial Pressure Index Circulation, October 28, 2003; 108(17): 2093 - 2098. [Abstract] [Full Text] [PDF]

				J. H. Walsh, G. Yong, C. Cheetham, G. F. Watts, G. J. O'Driscoll, R. R. Taylor, and D. J. Green Effects of exercise training on conduit and resistance vessel function in treated and untreated hypercholesterolaemic subjects Eur. Heart J., September 2, 2003; 24(18): 1681 - 1689. [Abstract] [Full Text] [PDF]

				J. H. Walsh, W. Bilsborough, A. Maiorana, M. Best, G. J. O'Driscoll, R. R. Taylor, and D. J. Green Exercise training improves conduit vessel function in patients with coronary artery disease J Appl Physiol, July 1, 2003; 95(1): 20 - 25. [Abstract] [Full Text] [PDF]

				H. Kawano, H. Yasue, A. Kitagawa, N. Hirai, T. Yoshida, H. Soejima, S. Miyamoto, M. Nakano, and H. Ogawa Dehydroepiandrosterone Supplementation Improves Endothelial Function and Insulin Sensitivity in Men J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3190 - 3195. [Abstract] [Full Text] [PDF]

				G. D. Plotnick, M. C. Corretti, R. A. Vogel, R. Hesslink Jr, and J. A. Wise Effect of supplemental phytonutrients on impairment of the flow-mediated brachialartery vasoactivity after a single high-fat meal J. Am. Coll. Cardiol., May 21, 2003; 41(10): 1744 - 1749. [Abstract] [Full Text] [PDF]

				R. S. Barua, J. A. Ambrose, S. Srivastava, M. C. DeVoe, and L.-J. Eales-Reynolds Reactive Oxygen Species Are Involved in Smoking-Induced Dysfunction of Nitric Oxide Biosynthesis and Upregulation of Endothelial Nitric Oxide Synthase: An In Vitro Demonstration in Human Coronary Artery Endothelial Cells Circulation, May 13, 2003; 107(18): 2342 - 2347. [Abstract] [Full Text] [PDF]

				S. M Bode-Boger, J. Muke, A. Surdacki, G. Brabant, R. H Boger, and J. C Frolich Oral L-arginine improves endothelial function in healthy individuals older than 70 years Vascular Medicine, May 1, 2003; 8(2): 77 - 81. [Abstract] [PDF]

				M. Kimura, Y. Higashi, K. Hara, K. Noma, S. Sasaki, K. Nakagawa, C. Goto, T. Oshima, M. Yoshizumi, and K. Chayama PDE5 Inhibitor Sildenafil Citrate Augments Endothelium-Dependent Vasodilation in Smokers Hypertension, May 1, 2003; 41(5): 1106 - 1110. [Abstract] [Full Text] [PDF]