Age-Related Increase in Femoral Intima-Media Thickness in Healthy Humans
To the Editor:
We read with interest the recent article by Kornet et al,1 who reported that wall shear stress of the common femoral artery did not change, whereas intima-media thickness (IMT) increased significantly with advancing age. Their findings in general are consistent with our contention that age-related increases in IMT of the common femoral artery observed in healthy humans may not be due to diffusive atherosclerosis but rather due to hypertrophy and/or hyperplasia of vascular smooth muscle cells in the medial layer of the arterial wall. Insight into this issue comes from studies in experimental animals. Arterial walls thicken with age, even in animals in which the incidence of atherosclerosis is very low.2 In other species that are known to develop atherosclerosis (eg, rabbits), the age-related arterial wall thickening is not associated with an increase in fibroatheromas or fatty streaks unless it is accompanied by experimentally induced hyperlipidemia.2 3 In this context, we recently reported that the IMT of the common femoral artery increases with age in a healthy, rigorously screened, nonsmoking population.4 Additionally, we reported that the IMT of the common femoral artery is strongly and positively related to chronic levels of efferent sympathetic nervous system activity yet not significantly related to blood pressure and metabolic risk factors.4 We concluded that the trophic influence of the sympathetic nervous system (norepinephrine) in stimulating vascular smooth muscle cell hypertrophy might be a major contributor to the increases in IMT of this muscular artery with advancing age. Thus, the data reported by Kornet et al1 complement our data and further suggest that modest increases in arterial wall thickness of the common femoral artery with advancing age in healthy humans may not be due to diffusive atherosclerosis within the intimal layer but may reflect smooth muscle hypertrophy/hyperplasia within the medial layer of the arterial wall.
Kornet L, Hoeks APG, Lambregts J, Reneman RS. In the femoral artery bifurcation, differences in mean wall shear stress within subjects are associated with different intima-media thickness. Arterioscler Thromb Vasc Biol. 1999;19:2933–2939.
Dinenno FA, Jones PP, Seals DR, Tanaka H. Age-associated arterial wall thickening is related to elevations in sympathetic activity in healthy humans. Am J Physiol. 2000;278:H1205–H1210.
We thank Dr Tanaka and his colleagues for their valuable comments to our study published in Arteriosclerosis, Thrombosis, and Vascular Biology.R1 We could not agree more that increases in intima-media thickness (IMT) are not necessarily related to atherosclerotic changes. The correlations found between increases in IMT and the occurrence of atherosclerosis, even when corrected for age, in a variety of epidemiological studiesR2 R3 could be explained by 2 independent processes developing at the same rate. It cannot be excluded, however, that very pronounced increases in IMT may be indicative of atherosclerosis,R4 but even in this situation, a causal relation has still to be established.
Arterial diameter increases with age to maintain such hemodynamic forces as wall shear stress and pulse pressure near baseline levels. We have always been in favor of the idea that the increase in arterial diameter, combined with the increase in mean arterial pressure and pulse pressure, lead to arterial wall thickening to maintain tensile stress of the arterial wall near baseline level with increasing age.R5 R6 R7
In a recent multiparametric study, it was shown that not only diastolic arterial wall diameter, mean arterial pressure, and pulse pressure but also age was an independent variable in determining IMT of the common carotid artery.R8 In this respect, the observations of Dinneno and colleaguesR9 that age-associated arterial wall thickening is related to enhanced sympathetic activity, causing hypertrophy and/or hyperplasia of smooth muscle cells, is of interest. This enhanced activity may indeed contribute to the increase in IMT with age, especially because this increase was found to be unrelated to wall shear stress.R1 However, one should keep in mind that locally, IMT is dependent on wall shear stress, being larger in areas where this stress is lower.R1 That elevated sympathetic activity may also influence arterial wall properties in the femoral artery is indicated by the observation that this artery shows a stiffer behavior with a full than with an empty bladder.R10
Kornet L, Hoeks APG, Lambregts JAC, Reneman RS. In the femoral artery bifurcation differences in mean wall shear rate are associated with different intima-media-thicknesses. Arterioscler Thromb Vasc Biol. 1999;19:2933–2940.
Salonen R, Tervahauta M, Salonen J, Pekkanen J, Nissinen A, Karvonen MJ. Ultrasonographic manifestations of common carotid atherosclerosis in elderly eastern Finnish men: prevalence and associations with cardiovascular diseases and risk factors. Arterioscler Thromb. 1994;14:1631–1640.
Chambless LE, Folsom AR, Clegg LX, Sharrett AR, Shahar E, Nieto FJ, Rosamond WD, Evans G. Carotid wall thickness is predictive of incident clinical stroke: the Atherosclerosis Risk in Communities (ARIC) study. Am J Epidemiol.. 2000;151:478–487.
Bots ML, Hofman A, Grobbee DE. Increased common carotid intima-media thickness: adaptive response or a reflection of atherosclerosis? findings from the Rotterdam Study. Stroke.. 1997;28:2442–2447.
Glagov S, Bassiouny HS, Giddens D, Zarins CK. Intimal thickening: morphogenesis, functional significance and detection. J Vasc Invest. 1995;1:2–14.
Schmidt-Trucksäss A, Grathwohl D, Schmid A, Boragk R, Upmeier C, Keul J, Huonker M. Structural, functional, and hemodynamic changes of the common carotid artery with age in male subjects. Arterioscler Thromb Vasc Biol. 1999;19:1091–1097.
Dinenno FA, Jones PP, Seals DR, Tanaka H. Age-associated arterial wall thickening is related to elevations in sympathetic activity in healthy humans. Am J Physiol.. 2000;278:H1205–H1210.