Influence of tamoxifen on carotid intima-media thickness in postmenopausal women.

BACKGROUND: Intima-media thickness of the common carotid artery (IMT-CCA) is an early marker of atherosclerosis. Tamoxifen is a selective estrogen-receptor modulator with estrogen-like effects on cardiovascular risk factors but as-yet unexplored effects on carotid artery structure. The goal of this study was to determine the influence of tamoxifen on IMT-CCA in menopausal women. METHODS AND RESULTS: With a predefined calculation of the sample size, 67 menopausal women with cancer who were treated with tamoxifen for > or =1 year and 37 menopausal women with cancer who were never treated with tamoxifen were enrolled. IMT-CCA, internal diameter, and pulse pressure were determined with a high-definition echotracking device and applanation tonometry in a central core laboratory that was blinded to treatment. Both groups were similar for clinical characteristics, including cardiovascular risk factors. IMT and internal diameter were significantly lower in the tamoxifen group (mean duration of treatment, 2.4+/-0.9 years) than in the control group (609+/-117 microm versus 662+/-147 microm, P=0.04, and 4.89+/-0.60 mm versus 5.12+/-0.58 mm, P=0.03, respectively). Pulse pressure was not influenced by the use of tamoxifen. After adjustment for age, cardiovascular risk factors, carotid pulse pressure, duration of menopause, and previous use of hormone replacement therapy, IMT remained significantly lower among tamoxifen users (P<0.00001), with an impact on IMT (-70 microm) equivalent to spontaneous evolution with 12 years of aging (5 microm/y). CONCLUSION: The use of tamoxifen was associated with a significantly lower carotid IMT in menopausal women with cancer. Randomized trials are needed to confirm the cardioprotective effect of selective estrogen-receptor modulators in terms of prevention of atherosclerosis.

[Endocrine hypertension in pregnancy]. / Hypertensions artérielles endocriniennes au cours de la grossesse.

Hypertension is a frequent complication of pregnancy and may compromise fetal and maternal outcome. Hypertension may be pregnancy-induced, essential or secondary to endocrine disorders. Most cases of endocrine hypertension are the consequence of adrenal diseases. Pheochromocytoma, hypercorticism, primary aldosteronism or glucocorticoid-remediable aldosteronism can be present or diagnosed at any term and may cause severe hypertension. The most hazardous form of endocrine hypertension during pregnancy is pheochromocytoma because it may involve paroxysmal arrhythmia and/or hypertension during labor. Clinical clues and biological tests are similar to those used in non-pregnant subjects. Tests for tumor location are limited to ultrasound and magnetic resonance scans in order to avoid maternal and fetal irradiation. Medication to prepare for pheochromocytoma surgery uses alpha- and beta-blockers. The timing of surgery depends on the term of pregnancy at the diagnosis of the tumor.

Compressibility of the carotid artery in patients with pseudoxanthoma elasticum.

The arterial wall has generally been considered as noncompressible in in vitro studies. However, compressibility of the arterial wall (CAW) has never been studied in vivo in humans. Large interstitial proteoglycans play a major role in sustaining the compression generated by pulsatile forces. The aims of the present study were to develop an experimental methodology for the assessment of CAW in vivo in humans and to study CAW in patients with pseudoxanthoma elasticum (PXE), a genetic disease characterized by proteoglycan accumulation and fragmented, swollen, and calcified elastic fibers in connective tissues. We studied 19 female patients with PXE and 15 normal female control subjects matched for age and blood pressure. A high-resolution echo-tracking system was used for the continuous determination of internal diameter and wall thickness at the site of the common carotid artery. Matrices of the radiofrequency signal were analyzed with a dedicated software to measure carotid wall cross-sectional area every 4 milliseconds during 4 to 6 cardiac cycles. CAW was calculated as the stroke change in cross-sectional area. CAW was 44% higher in patients with PXE than in control subjects (6.8+/-2.6% versus 4.7+/-2.7%, respectively; P<0.05). In control subjects, CAW decreased with age in a linear manner (r=-0.75, P<0.01). In PXE patients, the relationship with age was not homogeneous: CAW tended to increase with age before 40 years (P=0.07) and significantly decreased with age in older patients (P<0.01). Carotid geometry and elastic properties did not differ between PXE patients and control subjects. In conclusion, CAW was measurable in vivo and noninvasively in humans. The higher CAW of PXE patients compared with that of control subjects suggests that proteoglycans are important determinants of compressibility.

Radial artery hypertrophy occurs in coronary atherosclerosis and is independent of blood pressure.

Endothelial dysfunction, believed to underlie the structural changes of atherosclerosis, is a systemic phenomenon. Despite this, the radial artery has been considered as devoid of atherosclerosis and is commonly used as a conduit in coronary artery bypass grafting (CABG). Recently, histological study has shown intimal hyperplasia and other structural changes consistent with early atherosclerosis in the radial artery. The objective of the present study was to determine if structural changes in the radial artery could be detected in vivo in patients with coronary atherosclerosis. Using high resolution echo-tracking, measurements of radial artery internal diameter, wall thickness and wall cross-sectional area were made in 25 patients awaiting CABG and in 20 controls. Digital and brachial blood pressures were also recorded. Mean arterial pressures did not differ between the patient and control groups. All measures of wall thickness were greater in the patient than the control group. Neither current arterial pressures nor past history of hypertension correlated with wall thickness. Using a model of analysis of covariance, coronary artery disease was the best single predictor of intima-media thickness, R(2)=48%, n=44, P<0.0005. We concluded that increased radial artery wall thickness can be demonstrated in vivo in patients with coronary atherosclerosis. This is a novel observation which seems to be independent of blood pressure, and is consistent both with the hypothesis of systemic endothelial dysfunction leading to systemic structural changes and also to the recent histological evidence for atherosclerotic changes in this vessel.

Local pulse pressure is a major determinant of large artery remodelling.

1. The aim of the present brief review is to show that the pulsatile component of blood pressure is a stronger determinant of large artery remodelling than the steady component (i.e. mean blood pressure). 2. Pulse pressure, which is a strong determinant of cardiovascular events, including coronary heart disease and stroke, is increased when large arteries stiffen. Local pulse pressure, measured with applanation tonometry in normotensives and patients with essential hypertension, explains a significant part of the variance of intima-media thickness at the site of the carotid artery, a proximal elastic artery, whereas mean blood pressure does not contribute. Local pulse pressure has no influence on intima-media thickness at the site of the radial artery, a distal muscular artery that undergoes very little stroke change in diameter. 3. The decrease in carotid pulse pressure is also a major determinant of the regression of carotid intima-media thickness after antihypertensive treatment. Local pulse pressure can influence not only intima-media thickness, but also internal diameter. Indeed, there is a significant association between the lumen enlargement of the ascending aorta in patients with Marfan syndrome and pulse pressure. In addition, carotid pulse pressure is positively correlated with carotid internal diameter in normotensives and hypertensives, and the decrease in carotid internal diameter during long-term antihypertensive treatment is influenced by the decrease in carotid pulse pressure and not by the reduction in mean blood pressure. 4. We suggest that the effects of pulse pressure on large artery remodelling may explain part of its predictive value on cardiovascular events.

[Local pulse pressure and regression of arterial wall hypertrophy during antihypertensive treatment. CELIMENE study. The Celiprolol Intima-Media Enalapril Efficacy study]. / Pression pulsée locale et régression de l'hypertrophie pariétale artérielle au cours du traitement antihypertenseur. Etude Celimene. Celiprolol Intima-Media Enalapril Efficacy.

BACKGROUND: Local Pulse Pressure (PP) is an independent determinant of carotid artery wall thickness, stronger than mean BP. The present study was designed to assess whether a beta-adrenoceptor antagonist or an ACE inhibitor-based treatment was able to reduce carotid artery wall hypertrophy through the reduction in carotid PP rather than by lowering mean BP, and whether the influence of local PP reduction could also be detected at the site of a muscular artery, the radial artery. METHODS AND RESULTS: Ninety-eight essential hypertensive patients were randomised to 9 months of double-blind treatment with either celiprolol or enalapril. Arterial parameters were determined with high resolution echotracking systems. PP was measured locally with PP applanation tonometry, and independently of mean BP. After 9 month's treatment, mean BP, carotid PP and intima-media thickness (IMT) decreased significantly, with no difference between the tow groups. The reduction in carotid pression pulsée, but not in mean BP, was a major independent determinant of the reduction in carotid IMT. Radial artery IMT and PP decreased significantly with both treatments. However, the reduction in radial artery IMT was not related to the changes in radial artery PP. CONCLUSION: The regression of carotid artery wall hypertrophy during long-term antihypertensive treatment was dependent on the reduction in local PP rather than on the lowering of mean BP. The effect of PP lowering on IMT reduction was observed at the site of an elastic artery but not at the site of a muscular artery.