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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Iodized oil (1 ml im) was given to 58 goitrous patients from a mildly iodine-deficient area in Greece. Goiter size, urinary iodine, and serum T4, T3RU, T3, rT3, TSH, thyroxine-binding globulin (TBG), and thyroid autoantibodies were measured before and 1, 3, and 6 months after the injection. Goiter size decreased. Serum T4 remained relatively constant, but TBG decreased and therefore T3RU and FTI increased. Serum T3 and rT3 initially decreased (P less than 0.001) and then increased at the sixth month (P less than 0.001), both showing roughly parallel changes. Serum TSH, initially normal (1.42 +/- 0.11 (SEM) mU/liter), decreased to 0.65 +/- 0.01 and 0.76 +/- 0.05 mU/liter at the third and sixth month (difference from baseline P less than 0.001). Thyroid autoantibodies, both against thyroglobulin and the microsomal antigen, were undetectable before treatment, but became positive in 42.8% of the patients 3 and 6 months later. Three patients developed transient hyperthyroidism. This occurred 3 or 6 months after treatment, and was associated with high titers of thyroid autoantibodies. These results indicate that: 1) transient hyperthyroidism may occur after the administration of iodized oil, possibly because of thyroid tissue necrosis and leakage of hormones, and 2) serum TBG decreases after iodized oil, a finding not previously reported and one whose cause is not known.

The intraaortic balloon counterpulsation is performed today on the same principles that were described in its first experimental use in 1962. Experimental studies have shown significant increase of the mean aortic diastolic pressure, the diastolic pressure-time index, endocardial viability ratio, cardiac output, ejection fraction, coronary cerebral and renal blood flow, lactate utilization and myocardial oxygen supply and significant decrease of the systolic aortic pressure, left-ventricular end-diastolic pressure, left-ventricular work, tension time index, myocardial oxygen consumption and lactate production. In similar studies, intraaortic balloon pump (IABP) decreases the size of myocardial infarction. New IABP driving systems, small size sheaths and balloon catheters for percutaneous insertion made the use of the IABP easier and safer. The paraaortic counterpulsation device is suitable for chronic mechanical assistance. It is more effective than the IABP and shows excellent biocompatibility in chronic experiments. Its clinical application in 3 patients showed excellent biocompatibility and promising hemodynamic effects. In conclusion, the salutary hemodynamic effects of the IABP have been shown in several experimental studies. The technical improvements and the development and use of new devices suggest that we still need to learn more about the usefulness of the counterpulsation technique.

These findings suggest that endothelial dysfunction in microvascular angina is a generalized process that also involves the peripheral conduit arteries and is similar to that observed in atherosclerotic disease. IMT could be helpful in discriminating patients with microvascular angina and atherosclerotic coronary artery disease.

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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.

No significant differences were found in survival and clinical and hemodynamic variables between patients receiving standard and those receiving high doses of enalapril.