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Aortic stiffening, cerebral resistance vessel function and structure, and cerebral perfusion

Izzard, Ashley S.

doi: 10.1097/HJH.0000000000000004
Editorial Commentaries

Institute of Cardiovascular Sciences, University of Manchester, Manchester, UK

Correspondence to Ashley S. Izzard, PhD, Institute of Cardiovascular Sciences, Core technology Facility (3rd Floor), University of Manchester, 46 Grafton St, Manchester M13 9NT, UK. Tel: +44 161 275 1227; fax: +44 161 275 1183; e-mail:

Increased stiffening of the aorta relative to the carotid arteries results in increased carotid arterial pressure and flow pulsatility, and this is associated with diffuse microvascular brain lesions (including increased white matter hyper-intensity volume and sub-cortical infarcts) and cognitive impairment [1]. Thus, the aforementioned study provides an important link between previous studies that have shown that increased aortic stiffness is associated with microvascular brain lesions in hypertensive patients [2] and that arterial stiffness is an independent predictor of longitudinal changes in cognitive function in the older individual [3]. It has also been shown that stiffening of the aorta is associated with reduced cerebral perfusion in deep sub-cortical frontal and parietal white matter, regions of the brain predisposed to microvascular damage [4,5].

Regular exercise is associated with an attenuation of age-related arterial stiffening [6] and has a beneficial effect on cognition [7]. In the current issue of the Journal, Tarumi et al. [8] have taken the next step forward and examined associations between cardiopulmonary fitness, cognitive function, central artery stiffness (aortic pulse wave velocity and carotid ultrasound) and, in a sub-set, cerebral perfusion in sedentary and endurance-trained middle-aged adults. Although, by necessity, certain aspects of this study are confirmatory, this is the first time that associations between all the aforementioned parameters have been measured in the same study. The authors observed lower central artery stiffness, greater cognitive function and greater regional cerebral perfusion in endurance-trained middle-aged adults compared with the sedentary group, and conclude ‘These results suggest that habitual aerobic exercise and the maintenance of a lower central artery stiffness in midlife may attenuate the pathological process leading to cognitive decline in later life’.

It has been suggested that increased pulse pressure in the cerebral circulation due to stiffening of the aorta results in cerebral hyoperfusion (or the consequences thereof) [1,8–11]. If this is the case the question is as to what is the mechanism. O’Rourke and Safar [9] proposed that because the brain (and kidney) receives a high blood flow, the arteries are exposed to higher pulsatile circumferential stress and shear stress compared with the other vascular beds, hence the cerebral (and renal) circulation is particularly vulnerable to microvascular damage when pulsatility is increased further due to stiffening of the large arteries. As to the nature of the microvascular damage, the authors discuss the findings of Byrom [12], which are based to a large extent on his observations of rats with experimentally induced (Goldblatt) hypertension. In this study, where arterial spasm (which in fact is probably protective) and arterial necrosis are major findings, the hypertension was quite severe and the findings may be, at least in part, a consequence of the high mean arterial pressure (MAP) than the pulse pressure alone.

On the contrary, it has been suggested that functional and structural mechanisms which are employed in the cerebral circulation to protect the distal microcirculation from pressure/flow pulsatilty increase cerebral resistance resulting in hypoperfusion and eventual cognitive decline [11]. Regarding functional mechanisms, it has been suggested that arterial/arteriolar myogenic tone may be more sensitive to alterations in pulse pressure than MAP; thus an increase in aortic stiffness, enhancing pulsatility in the cerebral circulation, may increase myogenic constriction resulting in cerebral hypoperfusion [11]. This concept is based primarily on observations in the renal vasculature; however, it is important to note that renal afferent arteriolar constriction has been shown to be determined by systolic rather than pulse pressure. Furthermore, the above pertains to the kidney because of the unique kinetics of the afferent arteriolar myogenic response where the onset of constriction to an increase in pressure is much more rapid than the dilation to a reduction in pressure, so that at physiological pulse rates, the level tone is determined by the highest (systolic) pressure [13]. Structural changes in the cerebral resistance vessels due to an increased pulse pressure have also been considered to increase basal cerebral resistance [4,11]. Elegant studies in rats have shown that pulse pressure, rather than mean, systolic or diastolic pressure, is a major determinant of growth (hypertrophy) in the cerebral resistance vessels [14,15]. Growth, defined by an increase in vessel wall cross-sectional area of the vessel wall, has sometimes been shown to contribute to the increased wall thickness-to-lumen diameter ratio (w/l) observed in the cerebral arteries in hypertension [16]. The structurally determined increased w/l is generally considered to contribute to the increased cerebral resistance in hypertension, protecting the distal microcirculation (capillaries and venules) from the raised arterial pressure; although if this is so, exactly how is uncertain given the evidence against an increased w/l acting as an amplifier of resistance to flow [17]. However, in an aforementioned study, higher arteriolar wall cross-sectional area is not accompanied by a reduced lumen diameter in the presence of basal tone or at maximal dilation, and vice versa [15]. Thus, the functional consequence of cerebral arterial growth, if any, is unclear. Nevertheless, it is important to note that alterations in cerebral arterial structure, which result in a reduced lumen diameter, are of potential pathological significance as it may limit the ability of the cerebral circulation to increase flow if the normal pressure to a cerebral vascular territory is reduced, for example distal to a stenosis. Cerebral reserve in the spontaneously hypertensive rat or stroke-prone hypertensive rat is normal in the control condition, but impaired following ligation of the carotid or middle cerebral artery resulting in infarction [18–20].

Although the functional consequences of arterial growth in the cerebral circulation are uncertain, arterial growth in the retinal arterioles, which are thought to mirror the cerebral circulation, may be of prognostic significance in relation to cognitive impairment. A recent study has shown central pulse pressure to be an independent determinant of the w/l in the retinal circulation in humans [21]; it is important to note that in these studies the w/l will be influenced by the level of arteriolar tone as well as vascular structure. This group has also shown the retinal w/l is increased in hypertension, compared with normotensive controls, and increased further in patients with cerebrovascular disease. Intriguingly, retinal arteriolar wall cross-sectional area was only increased in the cerebrovascular disease patient group [22]. This is somewhat reminiscent of the findings, albeit in subcutaneous small arteries, where an increase in w/l predicts cardiovascular morbidity and mortality [23] and growth is of even greater prognostic value [24].

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Conflicts of interest

There are no conflicts of interest.

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