Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women

Cardiothoracic Unit, Hospital for Sick Children, London.

OBJECTIVES. This study assessed whether aging is associated with progressive endothelial dysfunction, whether the pattern of any age-related decline in vascular health is different in men and women and whether any gender difference is consistent with known changes in hormonal status. BACKGROUND. Coronary and cerebrovascular disease are much less common in young and middle-aged women compared with men, although the gender difference in death from atherosclerosis is less marked after the menopause. Endothelial dysfunction is an early event in atherogenesis and is important in dynamic plaque stenosis in later life. The effect of aging on endothelial function in men and women, however, is not well known. METHODS. We used high resolution ultrasound to study endothelium-dependent and endothelium-independent vascular responses. Brachial artery physiology was investigated in 238 subjects (103 men, 135 women; mean [+/- SD] age 38 +/- 17 years, range 15 to 72) with no known risk factors for atherosclerosis. The responses to reactive hyperemia (flow-mediated dilation, which is endothelium dependent) and to glyceryl trinitrate (an endothelium-independent dilator) were assessed for all the subjects and then for men and women separately. RESULTS. On multivariate analysis for the whole group, reduced flow-mediated dilation was related to older age (r = -0.34, p < 0.0001). In men, flow-mediated dilation was preserved in subjects aged < or = 40 years but declined thereafter at 0.21%/year. In women, flow-mediated dilation was stable until the early 50s, after which it declined at 0.49%/year (p = 0.002 compared with men). In contrast, there was no significant change in the glyceryl trinitrate response with aging in either gender. CONCLUSIONS. Aging is associated with progressive endothelial dysfunction in normal humans, and this appears to occur earlier in men than in women. In women, however, a steep decline commences at around the time of the menopause. This is consistent with a protective effect of estrogens on the arterial wall.

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				C. Duvernoy, J. Martin, K. Briesmiester, A. Bargardi, O. Muzik, and L. Mosca Myocardial Blood Flow and Flow Reserve in Response to Hormone Therapy in Postmenopausal Women with Risk Factors for Coronary Disease J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2783 - 2788. [Abstract] [Full Text] [PDF]

				D. Sun, A. Huang, E. H. Yan, Z. Wu, C. Yan, P. M. Kaminski, T. D. Oury, M. S. Wolin, and G. Kaley Reduced release of nitric oxide to shear stress in mesenteric arteries of aged rats Am J Physiol Heart Circ Physiol, June 1, 2004; 286(6): H2249 - H2256. [Abstract] [Full Text] [PDF]

				D. J. Kurz, S. Decary, Y. Hong, E. Trivier, A. Akhmedov, and J. D. Erusalimsky Chronic oxidative stress compromises telomere integrity and accelerates the onset of senescence in human endothelial cells J. Cell Sci., May 1, 2004; 117(11): 2417 - 2426. [Abstract] [Full Text] [PDF]

				I. Eskurza, K. D. Monahan, J. A. Robinson, and D. R. Seals Ascorbic acid does not affect large elastic artery compliance or central blood pressure in young and older men Am J Physiol Heart Circ Physiol, April 1, 2004; 286(4): H1528 - H1534. [Abstract] [Full Text] [PDF]

				I. Eskurza, K. D. Monahan, J. A. Robinson, and D. R. Seals Effect of acute and chronic ascorbic acid on flow-mediated dilatation with sedentary and physically active human ageing J. Physiol., April 1, 2004; 556(1): 315 - 324. [Abstract] [Full Text] [PDF]

				K. F. Harris and K. A. Matthews Interactions Between Autonomic Nervous System Activity and Endothelial Function: A Model for the Development of Cardiovascular Disease Psychosom Med, March 1, 2004; 66(2): 153 - 164. [Abstract] [Full Text] [PDF]

				M. Ogami, Y. Ikura, M. Ohsawa, T. Matsuo, S. Kayo, N. Yoshimi, E. Hai, N. Shirai, S. Ehara, R. Komatsu, et al. Telomere Shortening in Human Coronary Artery Diseases Arterioscler Thromb Vasc Biol, March 1, 2004; 24(3): 546 - 550. [Abstract] [Full Text]

				E. J. Benjamin, M. G. Larson, M. J. Keyes, G. F. Mitchell, R. S. Vasan, J. F. Keaney Jr, B. T. Lehman, S. Fan, E. Osypiuk, and J. A. Vita Clinical Correlates and Heritability of Flow-Mediated Dilation in the Community: The Framingham Heart Study Circulation, February 10, 2004; 109(5): 613 - 619. [Abstract] [Full Text] [PDF]

				D. N. Proctor, D. W. Koch, S. C. Newcomer, K. U. Le, and U. A. Leuenberger Impaired leg vasodilation during dynamic exercise in healthy older women J Appl Physiol, November 1, 2003; 95(5): 1963 - 1970. [Abstract] [Full Text] [PDF]

				C. R. Woodman, E. M. Price, and M. H. Laughlin Selected Contribution: Aging impairs nitric oxide and prostacyclin mediation of endothelium-dependent dilation in soleus feed arteries J Appl Physiol, November 1, 2003; 95(5): 2164 - 2170. [Abstract] [Full Text] [PDF]

				L. G. Futterman and L. Lemberg The Effects of Aging on Arteries Am. J. Crit. Care., September 1, 2003; 12(5): 472 - 475. [Full Text] [PDF]