Impact of heart rate on arterial stiffness: virtual vs. real assessment

A large amount of data collected in the past few years supports the notion that heart rate (HR) is an important determinant of the mechanical properties of the arterial vessels and thus potentially participates at the development and progression of their abnormalities in several conditions and diseases. High HR has been shown in experimental animals to be related to the development of vascular atherosclerotic lesions favoring an impairment of the endothelial-dependent vasodilation and an increase in oxidative stress [1,2]. In addition, elevated HR values may promote smooth muscle cell growth and collagen deposition with a consequent reduction in arterial distensibility by increasing oscillatory shear stress [1]. Finally, animal as well as human studies have shown that acute or chronic elevations in HR are almost invariably accompanied by an increase in sympathetic cardiovascular influences and these may have additional deleterious effect on arterial stiffness. These relationships have been recently confirmed by the results of a study performed in essential hypertensive patients in which clinic HR values greater than 80 bpm were associated with a pronounced sympathetic activation, as directly assessed via the microneurographic technique, which was significantly greater for magnitude than the one detected in patients with lower HR [3]. It is likely that the HR increase modulates arterial distensibility by inducing a reduction in stroke and cardiac volume, leading to an unloading of arterial baroreceptors and cardiac receptors and thus reflexly increasing sympathetic vascular drive [4]. Several are the mechanisms through which an increase in sympathetic activity as documented by elevated HR may reduce arterial distensibility. First, the well known trophic effect of sympathetic influences on arterial wall tissue modifies the arterial wall structure in a way that favors its less extensible components and increases its thickness, as shown in animal studies in which chronic denervation of the carotid artery was accompanied by reduction of its thickness compared with the value of the contralateral intact vessel [1,2]. Second adrenergic activation may trigger contraction of vascular smooth muscle because the elastic modulus of contracted muscle tissue is greater than that of the relaxed one [5,6]. A contracted vascular smooth muscle may also have greater viscous properties, that is it may more prominently oppose resistance to vessel distension in relation to tissue. The potential importance of this factor is exemplified by the marked reduction of carotid and femoral artery distensibility that occurs in rats when HR is increased, even after sympathectomy. Finally, augmenting sympathetic vascular drive may trigger significant increases in pulse wave velocity, that is the gold standard measure of arterial distensibility [7]. In the study published in the current issue of the Journal[8], the complex relationships between HR, sympathetic activation and arterial stiffness have been reproduced as computer simulations with models reflecting the real word. In about 60 ‘simulated’ patients arterial waveforms were provided and analyzed according to different HR values. The simulated pulse wave velocity was calculated by an algorithm and computed between the ‘in-silico’ carotid and femoral arteries. Results can be summarized as follows. A progressive HR increase from 60 to 100 bpm determines a progressive elevation in carotid–femoral pulse wave velocity, which achieves a maximum of about 26%. Furthermore, the HR changes were accompanied by concomitant marked changes in blood pressure (BP) values, their maximal increase amounting to about 32 mmHg for mean arterial pressure with a predominant marked alteration in the diastolic component. Finally when corrections for BP alterations were performed the increase in pulse wave velocity were attenuated but still significant present, thereby ruling out any potential effect of the BP increase on the observed changes. The virtual ‘in silico’ model used in the study by Bikia et al.[8] has a number of advantages compared to the real assessment approach. These include the high precision and quality of the experimental data, the use of sophisticated models, the possibility to control the influence of specific variables, the greater reproducibility of the data obtained both in the short-term and in the long-term period and shorter period of time needed for each experimental session. These advantages should be counterbalanced against a number of potential limitations. First the virtual ‘in silico’ model examines the impact of HR as an ‘isolated’ force, without taking into account the presence of structural vascular modifications such as those determined by the aging process [9]. Indeed the age factor, similarly to body weight, does not appear to be present among the parameters taken into account in the virtual study population. Second, the approach fails to take into account the relationships with other determinants of arterial stiffness, such as humoral factors, angiotensin II, circulating levels of norepinephrine, sodium and calcium content within the arterial wall, etc [10]. Furthermore, the analysis allows to draw a ‘static’ rather than a ‘dynamic’ picture of the HR/vessels relationships. Finally, the approach does not take into account that the arterial ‘in-silico’ model cannot be indifferently applied to large, medium size or small arteries, given the profound intrinsic differences existing in the dynamic properties of these vessels. Despite the limitations, the ‘in-silico’ method employed in the current study allows to obtain results similar to the ones previously reported in experimental animal models and in humans. In rats, an atrial pacing-induced HR increase has been shown to cause a progressive reduction in arterial distensibility [11,12]. Similarly, a positive relationship between HR and arterial stiffness has been reported in humans [13], in which pacing induced HR increases produced marked reduction in arterial distensibility [14–16]. It thus appears that the virtual and real assessment of the vascular effects of HR may provide homogeneous and complementary results. ACKNOWLEDGEMENTS Conflicts of interest There are no conflicts of interest.