Friday, December 16, 2011

Why atherosclerosis is milder or non-existent in individuals with Down syndrome?

Different necropsy studies have shown that the occurrence of atherosclerosis is milder or non-existent in subjects with Down syndrome (1, 2, 3, 4). Indeed, a study have suggested that women with Down syndrome (DS) may be less likely to express the insulin resistance syndrome*, and men and women with Down syndrome may possess fewer atherosclerotic risk factors than the comparison groups (5)
Confirming the results that DS individuals possess low levels of atherosclerosis a recent study have examined the relation between cardiovascular disease risk factors and intima-media thickness (IMT), a measure for atherosclerosis, in 52 adults with DS. The adults with DS possessed lower IMT, systolic blood pressure and diastolic blood pressure, than controls. The study’s conclusion was that the adults with DS may be protected against atherosclerosis despite elevated body fat and elevated cardiovascular risk factors (6).
It is interesting to note about the results from some studies demonstrating that at lower degrees of IMT, the thickening appears to reflect an equilibrium state in which the effects of pressure and flow on the arteries are in balance, given a characteristic relation between shear stress and local transmural pressure (7, 8).
A reasonable explanation for the reduced incidence of atherosclerosis is the altered autonomic regulation in individuals with DS, with effects of smaller changes in baroreflex sensitivity and in sympatho-excitation response (9, 10, 11). The reduced sympathetic response to stress in DS is supported by the low circulating catecholamines levels in response to incremental cycle ergometer exercise in individuals with DS (12).
In the acidity theory of atherosclerosis the sympathetic predominance is the primary step and shear stress is the last step in the cascade of events leading to the atherogenic process (13, 14)
Carlos Monteiro
Insulin resistance may contribute to enhanced SNS activity (15) and SNS activity may similarly increase insulin resistance (16)

1. Ylä-Herttuala S, Luoma J, Nikkari T, Kivimäki T. Down's syndrome and atherosclerosis. Atherosclerosis. 1989 Apr;76(2-3):269-72.
2. Murdoch JC, Rodger JC, Rao SS, Fletcher CD, Dunnigan MG. Down's syndrome: an atheroma-free model? Br Med J. 1977 Jul 23;2(6081):226-8.
3. Moss TJ, Austin GE. Pre-atherosclerotic lesions in Down syndrome. J Ment Defic Res. 1980 Jun;24(2):137-41.
4. Chaney RH. Neurogenic atherosclerosis in mentally retarded persons. J Ment Defic Res. 1987 Sep;31 ( Pt 3):235-40
5. Draheim CC, McCubbin JA, Williams DP. Differences in cardiovascular disease risk between nondiabetic adults with mental retardation with and without Down syndrome. Am J Ment Retard. 2002 May;107(3):201-11
6. Draheim CC, Geijer JR, Dengel DR. Comparison of intima-media thickness of the carotid artery and cardiovascular disease risk factors in adults with versus without the Down syndrome. Am J Cardiol. 2010 Nov 15;106(10):1512-6
7. Gnasso A, et al. Association Between Intima-Media Thickness and Wall Shear Stress in Common Carotid Arteries in Healthy Male Subjects. Circulation. 1996;94:3257-3262
8. Bots M. L, et al. Increased Common Carotid Intima-Media Thickness. Adaptive Response or a Reflection of Atherosclerosis? Findings From the Rotterdam Study. Stroke. 1997;282442 .
9. Agiovlasitis S, Collier SR, et al. Autonomic response to upright tilt in people with and without Down syndrome. Res Dev Disabil. 2010 May-Jun;31(3):857-63.
10. Iellamo F, Galante A, et al. Altered autonomic cardiac regulation in individuals with Down syndrome. Am J Physiol Heart Circ Physiol. 2005 Dec;289(6):H2387-91.
11. Bo Fernhall and Mari Otterstetter. Attenuated responses to sympathoexcitation in individuals with Down syndrome. J Appl Physiol 94: 2158–2165, 2003.
12. Eberhard Y, Etarradossi J and Terminarias A. Biochemical changes and catecholamine response in Down’s syndrome adolescents in relation to incremental maximal exercise. J Ment Defic Res 35: 140-146, 1991
13. Carlos ETB Monteiro, Acidic environment evoked by chronic stress: A novel mechanism to explain atherogenesis. Available from Infarct Combat Project, January 28, 2008 at
14. Sympathetic predominance: a primary factor in the cascade of events leading to the atherogenic spiraling, Carlos Monteiro, Monday, February 22, 2010 at
15. Pikkujamsa SM, Huikuri HV, Airaksinen KE, Rantala AO, Kauma H, Lilja M, Savolainen MJ, Kesaniemi YA. Heart rate variability and baroreflex sensitivity in hypertensive subjects with and without metabolic features of insulin resistance syndrome. Am J Hypertens 1998;11:523–31
16. Moan A, Nordby G, Rostrup M, Eide I, Kjeldsen SE. Insulin sensitivity, sympathetic activity, and cardiovascular reactivity in young men. Am J Hypertens 1995;8:268–75

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