Arnold P.G. Hoeks

BACKGROUND: Arterial stiffness has been associated with the risk of cardiovascular disease in selected groups of patients. We evaluated whether arterial stiffness is a predictor of coronary heart disease and stroke in a population-based study among apparently healthy subjects. METHODS AND RESULTS: The present study included 2835 subjects participating in the third examination phase of the Rotterdam Study. Arterial stiffness was measured as aortic pulse wave velocity and carotid distensibility. Cox proportional hazards regression analysis was performed to compute hazard ratios. During follow-up, 101 subjects developed coronary heart disease (mean follow-up period, 4.1 years), and 63 subjects developed a stroke (mean follow-up period, 3.2 years). The risk of cardiovascular disease increased with increasing aortic pulse wave velocity index. Hazard ratios and corresponding 95% CIs of coronary heart disease for subjects in the second and third tertiles of the aortic pulse wave velocity index compared with subjects in the reference category were 1.72 (0.91 to 3.24) and 2.45 (1.29 to 4.66), respectively, after adjustment for age, gender, mean arterial pressure, and heart rate. Corresponding estimates for stroke were 1.22 (0.55 to 2.70) and 2.28 (1.05 to 4.96). Estimates decreased only slightly after adjustment for cardiovascular risk factors, carotid intima-media thickness, the ankle-arm index, and pulse pressure. The aortic pulse wave velocity index provided additional predictive value above cardiovascular risk factors, measures of atherosclerosis, and pulse pressure. Carotid distensibility as measured in this study was not independently associated with cardiovascular disease. CONCLUSIONS: Aortic pulse wave velocity is an independent predictor of coronary heart disease and stroke in apparently healthy subjects.

BACKGROUND AND PURPOSE: Studies of the association between arterial stiffness and atherosclerosis are contradictory. We studied stiffness of the aorta and the common carotid artery in relation to several indicators of atherosclerosis. METHODS: This study was conducted within the Rotterdam Study in >3000 elderly subjects aged 60 to 101 years. Aortic stiffness was assessed by measuring carotid-femoral pulse wave velocity, and common carotid artery stiffness was assessed by measuring common carotid distensibility. Atherosclerosis was assessed by common carotid intima-media thickness, plaques in the carotid artery and in the aorta, and the presence of peripheral arterial disease. Data were analyzed by ANCOVA with adjustment for age, sex, mean arterial pressure, and heart rate. RESULTS: Both aortic and common carotid artery stiffness were found to have a strong positive association with common carotid intima-media thickness, severity of plaques in the carotid artery, and severity of plaques in the aorta (P: for trend <0.01 for all associations). Subjects with peripheral arterial disease had significantly increased aortic stiffness (P:=0.001) and borderline significantly increased common carotid artery stiffness (P:=0.08) compared with subjects without peripheral arterial disease. Results were similar after additional adjustment for cardiovascular risk factors and after exclusion of subjects with prevalent cardiovascular disease. CONCLUSIONS: This population-based study shows that arterial stiffness is strongly associated with atherosclerosis at various sites in the vascular tree.

It has been well established that wall shear stress is an important determinant of endothelial cell function and gene expression as well as of its structure. There is increasing evidence that low wall shear stress, as present in artery bifurcations opposite to the flow divider where atherosclerotic lesions preferentially originate, expresses an atherogenic endothelial gene profile. Besides, wall shear stress regulates arterial diameter by modifying the release of vasoactive mediators by endothelial cells. Most of the studies on the influence of wall shear stress on endothelial cell function and structure have been performed in vitro, generally exposing endothelial cells from different vascular regions to an average wall shear stress level calculated according to Poiseuille's law, which does not hold for the in vivo situation, assuming wall shear stress to be constant along the arterial tree. Also in vivo wall shear stress has been determined based upon theory, assuming the velocity profile in arteries to be parabolic, which is generally not the case. Wall shear stress has been calculated, because of the lack of techniques to assess wall shear stress in vivo. In recent years, techniques have been developed to accurately assess velocity profiles in arterioles, using fluorescently labeled particles as flow tracers, and non-invasively in large arteries by means of ultrasound or magnetic resonance imaging. Wall shear rate is derived from the in vivo recorded velocity profiles and wall shear stress is estimated as the product of wall shear rate and plasma viscosity in arterioles and whole blood viscosity in large arteries. In this review, we will discuss wall shear stress in vivo, paying attention to its assessment and especially to the results obtained in both arterioles and large arteries. The limitations of the methods currently in use are discussed as well. The data obtained in the arterial system in vivo are compared with the theoretically predicted ones, and the consequences of values deviating from theory for in vitro studies are considered. Applications of wall shear stress as in flow-mediated arterial dilation, clinically in use to assess endothelial cell (dys)function, are also addressed. This review starts with some background considerations and some theoretical aspects.

Compliance and distensibility are wall properties of large arteries, which may play a role in cardiovascular disease. The purpose of this study was to investigate whether the influence of age on these vessel wall properties differs between vascular territories and is gender-dependent. In a population sample of 498 men and women 20 to 79 years of age, diameter, distensibility, and compliance coefficient of the muscular brachial artery were measured with an echo-tracking device. Distensibility of the aorta was measured with the use of pulse-wave velocity. The effects of age and gender were assessed and adjusted for confounding factors such as mean blood pressure, pulse rate, body mass index, smoking, alcohol intake, and antihypertensive treatment. Covariance analysis showed no relation between gender and distensibility of the elastic aorta. Distensibility of the muscular brachial artery was lower in men, whereas men had a larger diameter and larger compliance of the brachial artery. With age, distensibility of the aorta decreased in both sexes to the same extent, whereas distensibility of the brachial artery did not change significantly. With age, brachial artery diameter increased; this increase was more pronounced in women. In men brachial artery compliance did not change with age, whereas in women compliance of the brachial artery increased with age. This study (1) confirms that distensibility of the aorta, an elastic artery, decreases with age. (2) In contrast to the aorta, after adjustment for confounding factors, in both men and women, no relation exists between age and distensibility of the muscular brachial artery. (3) Brachial artery diameter increase with age is more pronounced in women than in men. (4) In contrast to the well-known decrease in arterial compliance of elastic arteries with age, brachial artery compliance is not decreased with age and is increased in women. In conclusion, the effect of age on large-artery wall properties is not uniform but depends on gender and vascular territory.

OBJECTIVES: Pulse pressure is not constant throughout the arterial tree. Use of pulse pressure at one arterial site as surrogate for pulse pressure at another arterial site may be erroneous. The present study compares three non-invasive techniques to measure local pulse pressure: (i) internally calibrated readings from applanation tonometry, (ii) alternative calibration of pressure waves obtained with applanation tonometry and (iii) alternative calibration of arterial distension waves obtained with echo-tracking. Alternative calibration assumes mean and diastolic blood pressure constant throughout the large artery tree. DESIGN AND METHODS: Study 1 used invasive measurements in the ascending aorta as a reference method and internally calibrated tonometer readings and alternatively calibrated pressure waves at the common carotid artery as test methods. Study 2 used alternatively calibrated pressure waves as a reference method and alternatively calibrated distension waves and internally calibrated applanation tonometer readings as test methods. RESULTS: In study 1, pulse pressure from internally calibrated tonometer readings was 10.2+/-14.3 mmHg lower and pulse pressure from alternatively calibrated pressure waves was 1.8+/-5.2 mmHg higher than invasive pulse pressure. Pulse pressure from calibrated distension waves was 3.4+/-6.9 mmHg lower than pulse pressure from alternatively calibrated pressure waves. According to British Hypertension Society criteria, pulse pressure from the internally calibrated tonometer achieved grade D and pulse pressure from alternatively calibrated pressure waves achieved grade A. Pulse pressure from calibrated distension waves achieved grade B when alternatively calibrated pressure waves were used as a reference method. CONCLUSIONS: Pulse pressure obtained from alternatively calibrated tonometer-derived pressure waves and echo-tracking-derived distension waves demonstrates good accuracy. Accuracy of pulse pressure from internally calibrated applanation tonometer readings at the carotid artery is poor.