EDITORIALHypertension and cardiovascular disease: Is arterial stiffness the heart of the matter?

EDITORIALHypertension and cardiovascular disease: Is arterial stiffness the heart of the matter?

In the previous issue of Blood Pressure, we presented the 2007 ESH/ESC hypertension guidelines [1]. For the first time, the measurement of pulse wave velocity (PWV), a comprehensive non‐invasive assessment of arterial stiffness, was recognized as a diagnostic procedure for cardiovascular risk stratification. The current issue of Blood Pressure presents further research and evidence pertaining to the clinical importance of large artery dysfunction in pathogenesis of hypertension, target organ damage and cardiovascular disease. We should nurture this growth of interest in measuring arterial stiffness and wave reflection so that it can evolve beyond the province of researchers and spread outward to practicing physicians. There are several reasons for this belief.

First, a major reason for assessing large artery function in hypertensive patients derives from the demonstration that arterial stiffness and central pulse pressure have a predictive value for cardiovascular events. Aortic stiffness has been shown to independently predict all‐cause and cardiovascular mortality, fatal and non‐fatal coronary events, and fatal strokes in patients with uncomplicated essential hypertension [2].

Second, in a milestone document, recently published, we have a consensus that unifies terminology and clarifies methodological issues [2], which might serve as a “guided tour” for newcomers in the field of arterial stiffness and wave reflection. We have reliable non‐invasive tools to measure large artery function and they are likely to become cheaper because of increased usage since the publication of the 2007 ESH/ESC guidelines. As is the case with most devices coming out these days, further progress in technical aspects can also be expected.

Third, arterial stiffness should be considered as an impending sign of early cardiovascular damage, which might be attributed to both hemodynamic and non‐hemodynamic factors. Increased arterial stiffness may precede and predispose to more advanced damage of other target organs, like the heart, brain or kidneys [3]. Traditionally, arterial stiffness was regarded as the result of hypertension rather than its cause. However, there is emerging evidence that the relationship between hypertension and arterial stiffness is bi‐directional [4], [5]. Arterial stiffness has been associated with an increased risk of future hypertension, independent of established risk factors and level of blood pressure [6]. In subjects with high normal blood pressure, increased arterial stiffness clearly predicts the progression to established hypertension [7]. Thus, early detection of arterial stiffness before the development of overt hypertension or advanced target organ damage may identify persons at high cardiovascular risk.

Fourth, there is a growing interest in the differential effects of various medications on large artery function. Tropeano et al. [8] have recently shown a blood pressure‐independent effect from a high angiotensin‐converting enzyme inhibitor dose on arterial stiffness. Furthermore, drugs having a more potent effect on central hemodynamics seem to provide superior cardiovascular protection [9].

The rapidly growing field of arterial research represents one of the most exciting and progressive fields of cardiovascular medicine. Previous concepts linking arterial stiffness and wave reflections to hypertension and cardiovascular disease are continuously evolving, and new ones are emerging. In untreated patients with essential hypertension, aortic stiffness is significantly related to high‐sensitivity C‐reactive protein (hs‐CRP) and interleukin‐6 [10], [11]. In normotensive subjects, hs‐CRP correlates with augmentation index and central pulse pressure [12]. Interestingly, baseline hs‐CRP was not only an independent predictor of pulse wave velocity and central augmentation index but also of the peripheral pulse pressure reduction after antihypertensive treatment in the REASON study [8]. In the current issue of Blood Pressure, Tsai et al. describe association of increased arterial stiffness and inflammation with proteinuria and left ventricular hypertrophy in non‐diabetic hypertensive patients [13]. Taken together, these studies indicate that the inflammation process might be implicated in the stiffening of large arteries and contribute to development and progression of hypertension and its complications. Several other mechanisms might be implicated. These include changes in production of contractile proteins in smooth muscle cells [14], endothelial dysfunction and cell release of inducible matrix metalloproteinases (including matrix metalloproteinase‐9) [2]. Finally, there might be a specific genetic predisposition to the development of premature arterial stiffening. This concept is supported by a recent study showing that matrix metalloproteinase‐9 gene polymorphism contributes to arterial stiffness in patients with hypertension [15].

While it is generally accepted that arterial stiffness is an intermediate endpoint for cardiovascular events, data are less consistent with respect to the predictive value augmentation index, central pulse pressure and other central blood pressure‐derived indices.

In the current issue of Blood Pressure, Jankowski et al. [16] review the evidence linking the pulsatile component of blood pressure to the pathogenesis of atherosclerosis. This review examines, first, the potential importance of steady and pulsatile components of blood pressure; second, the mechanisms by which pulsatile component of blood pressure might contribute to the pathogenesis of atherosclerosis; third, predictive value of central pulse pressure; and fourth, new treatment strategies that might reduce pulsatile blood pressure parameters and potentially improve prognosis of high risk patients. The review is accompanied by an original paper by the same group of investigators [17] demonstrating that ascending aortic pulsatility is related to the extent of coronary atherosclerosis irrespective of the presence of hypertension. A list of papers dealing with large artery function in the current issue of the journal is completed by a study of Crilly et al. [18] who evaluated reproducibility of central aortic blood pressures measured non‐invasively using radial artery applanation tonometry and peripheral pulse wave analysis.

Despite recent advances, there is no doubt that further studies focusing on the predictive value of treatment‐related changes in arterial stiffness and wave reflection are needed, particularly in younger subjects. Furthermore, the question of reduction in arterial stiffness is a desirable therapeutic goal per se in terms of clinical endpoints such as morbidity or mortality remains to be determined. Better understanding of the mechanism underlying arterial stiffness might ultimately lead to the development of new drugs providing earlier and more effective cardiovascular protection than the standard hypertensive treatments currently in use.