Abstract-The extent of target-organ damage has been positively associated with the magnitude of blood pressure (BP) variability in essential hypertension. However, the clinical implications of the rate of BP changes have never been investigated. We evaluated the association between the rate of systolic BP (SBP) variation derived from ambulatory BP monitoring (ABPM) data analysis and the extent of common carotid artery (CCA) intima-media thickness (IMT) in normotensive (nϭ280) and in uncomplicated hypertensive subjects (nϭ234 Key Words: blood pressure Ⅲ carotid arteries Ⅲ blood pressure monitoring Ⅲ baroreflex Ⅲ ultrasonography P rospective studies in treated and untreated hypertensive patients and in the general population have demonstrated that even after adjusting for established risk factors, the incidence of cardiovascular events is correlated with blood pressure (BP) on conventional as well as ambulatory measurements. 1,2 However, ambulatory BP monitoring (ABPM) significantly refines the prediction already provided by office recordings because target-organ damage is more closely associated with ambulatory than clinic BP. 1,2 Intra-arterial beat-to-beat monitoring has shown that BP is highly variable. 3 Despite difficulties in the assessment of BP variability, particularly with noninvasive techniques, 4 evidence from cross-sectional 5-9 and longitudinal studies 10 -12 has suggested an independent and positive relationship between the extent of target-organ damage (measured by left ventricular mass, early carotid atherosclerosis, subcortical brain lesions, or a comprehensive end-organ damage score) and the magnitude of BP variability in essential hypertension. Besides, BP variability was an independent predictor for cardiovascular mortality in the general population. 13 Interestingly, Mancia et al reported recently that hypertensive patients compared with normotensive subjects present steeper fast-and short-duration beat-to-beat BP changes, documented by means of intra-arterial BP monitoring. 14 Furthermore, experimental studies have suggested that the traumatic effect of intravascular pressure on the vessel wall, which results in vascular remodeling and atherosclerosis, may be more closely associated to oscillatory than to steady laminar shear stress. [15][16][17] This evidence raises the issue of whether a hypertensive patient's prognosis depends not only on average BP level but, to some extent, also on the degree and rate of BP variation.However, the clinical implications of the time rate of noninvasive ambulatory BP changes have never been investigated in essential hypertension. Quantitative B-mode ultrasound imaging offers the opportunity to assess the intimamedia thickness (IMT) of the common carotid artery (CCA), which is considered a reliable marker for the extent of early atherosclerosis 18 and an indicator of the risk of cardiovascular diseases. 19 Moreover, Zanchetti et al reported that CCA-IMT

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The 24-h rate of SBP variation is independently associated with impaired renal function. Target-organ damage in hypertensive patients, in addition to BP levels, dipping status and BP variability, may also be related to a steeper rate of BP fluctuations.

Steeper BP variations may produce a greater stress on the left ventricular wall and may have an additive role to body habitus, BP and HR levels in the detection of cardiac hypertrophy. Target-organ damage in hypertensive patients, in addition to BP levels, dipping status and BP variability, may also be related to a steeper rate of BP oscillations.

Steeper BP variations may produce a greater stress on the arterial wall and may have an additive role to vascular risk factors and BP parameters in the detection of the severity of coronary artery lesions in normotensive individuals with suspected coronary artery disease.

Noninvasive automatic oscillometric BP measurements underestimate direct SBP recordings and overestimate direct DBP readings in acute stroke. The magnitude of the discrepancy between intra-arterial and oscillometric SBP recordings is even more prominent in patients with critically elevated SBP levels.

These findings indicate that time rate of BP variation is superior to central hemodynamics as an associate of carotid intima-media thickness in hypertensive and normotensive individuals.

Short-term beat-to-beat TR of BP variation is associated independently with CCA-IMT values and presents a better predictor of target organ damage involvement than BP variability indexes derived from ABPM.