Tamoxifen improves endothelial function and reduces carotid intima-media thickness in postmenopausal women

Stamatelopoulos, Kimon; Lekakis, John; Poulakaki, Nikiforita; Papamichael, Christos; Venetsanou, Kyriaki; Aznaouridis, Konstantinos; Protogerou, Athanase D.; Παπαϊωάννου, Θεόδωρος; Kumar, Sanjay; Stamatelopoulos, Stamatios

doi:10.1016/j.ahj.2003.12.029

Cited by 64 publications

(46 citation statements)

References 42 publications

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“…No effect of one-month treatment with tamoxifen on FMD was demonstrated in another small study (only 21 patients of median age 61 years - [17]). In another very small study (14 overweight pts of the median age of 63 years) FMD did not differ between patients with breast cancer and age-matched controls [18]. FMD increased after 6 month of tamoxifen treatment in patients with breast cancer and remained unchanged in untreated controls.…”

Section: Discussionmentioning

confidence: 99%

Endotelial activation and flow-mediated vasodilation in young patients with breast cancer

Tesařová¹,

Kalousová²,

Zima³

et al. 2014

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Endothelial activation and dysfunction may play a significant role in the progression of breast cancer. In our study we examined markers of endothelial activation (soluble ICAM-1, P-selectin, E-selectin) in 98 young patients with breast cancer (< 40 years). In 50 of them (and 20 age-matched controls) we also measured flow mediated vasodilation. Patients with breast cancer had significantly higher serum levels of soluble E-selectin, P-selectin and ICAM-1, P-selectin was higher in patients with larger tumors, node involvement and seemed to be a predictor of poor outcome. We were unable to find significant difference in the parameters of flow mediated vasodilation between patients with breast cancer and healthy subjects, although both peak blood flow (PBF) and flow mediated vasodilation (FMD) seemed to be skewed compared to healthy subjects toward mean and lower levels. Cluster analysis enabled us to distinguish several larger groups of patients with different degree of endothelial activation and function and different outcome. Group of patients with high E-selectin, high ICAM-1 (higher endothelial activation) and low VEGF (putative endothelial damage) had more frequently negative estrogen receptors and had worse outcome compared to the group of patients with lower E-selectin, lower ICAM-1 and mostly positive estrogen receptors. Further studies of larger groups of patients should help to identify the pannel of endothelial markers which could help in predicting the outcome of young patients with breast cancer.

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Section: Discussionmentioning

confidence: 99%

Endotelial activation and flow-mediated vasodilation in young patients with breast cancer

Tesařová¹,

Kalousová²,

Zima³

et al. 2014

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“…The cardiovascular effects of raloxifene and other SERMs were evaluated in both basic and clinical studies. These drugs were shown to improve endothelial dysfunction, increase coronary dilatation, and improve lipid profiles (35). Although raloxifene decreased cardiovascular events in osteoporotic women with prior established atherosclerotic disease (5), major clinical studies, such as the Raloxifene Use for the Heart study, did not show a significant reduction in cardiovascular morbidity and mortality in the healthy population (6).…”

Section: Raloxifene Effects On Avcmentioning

confidence: 99%

Raloxifene attenuates Gas6 and apoptosis in experimental aortic valve disease in renal failure

Shuvy

Abedat

Beeri

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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failure is associated with aortic valve calcification. Using our rat model of uremiainduced reversible aortic valve calcification, we assessed the role of apoptosis and survival pathways in that disease. We also explored the effects of raloxifene, an estrogen receptor modulator, on valvular calcification. Gene array analysis was performed in aortic valves obtained from three groups of rats (n ϭ 7 rats/group): calcified valves obtained from rats fed with uremic diet, valves after calcification resolution following diet cessation, and control. In addition, four groups of rats (n ϭ 10 rats/group) were used to evaluate the effect of raloxifene in aortic valve calcification: three groups as mentioned above and a fourth group fed with the uremic diet that also received daily raloxifene. Evaluation included imaging, histology, and antigen expression analysis. Gene array results showed that the majority of the altered expressed genes were in diet group valves. Most apoptosisrelated genes were changed in a proapoptotic direction in calcified valves. Apoptosis and decreases in several survival pathways were confirmed in calcified valves. Resolution of aortic valve calcification was accompanied by decreased apoptosis and upregulation of survival pathways. Imaging and histology demonstrated that raloxifene significantly decreased aortic valve calcification. In conclusion, downregulation of several survival pathways and apoptosis are involved in the pathogenesis of aortic valve calcification. The beneficial effect of raloxifene in valve calcification is related to apoptosis modulation. This novel observation is important for developing remedies for aortic valve calcification in patients with renal failure.growth arrest-specific 6; uremia CARDIOVASCULAR CALCIFICATION is one of the highest causes of morbidities and mortalities in patients with end-stage renal disease. These patients develop aortic valve calcification (AVC) and coronary calcification at an accelerated rate. Associated with this cardiovascular calcification are increased rates of myocardial infarctions and valvular heart disease. The pathogenesis of AVC in renal failure (RF) is not fully elucidated. It has been suggested that the process involves active osteoblast transformation of valve tissue, which results in increased formation of bone matrix (4, 25). Most of the data regarding the pathogenesis of AVC were obtained from animal models based on various components of the metabolic syndrome, emphasizing the role of atherogenesis in AVC (26, 37). In patients with RF, AVC and aortic stenosis are common and progress especially rapidly (18). The prevalence and extent of AVC in this population is poorly explained by traditional cardiovascular risk factors; abnormalities of mineral metabolism are likely to contribute to its development and progression. Current models of RF and accelerated calcification have demonstrated that calcium phosphate metabolism is critical for disease development (13), and inhibitors of calcification (fetuin A) are important in its prevention...

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“…It would, however, be premature to interpret our data as a clear promise of such a benefit. Longerterm clinical outcome data on this subject for tamoxifen, which is assumed to exert its effects on lipids through similar mechanisms [21,[23][24][25][26][27][28], are not consistent or conclusive. Moreover, to the extent that these effects are attributable to oestrogenic actions, experience with HRT in postmenopausal women emphasises the need for caution in the interpretation of surrogate endpoints [29][30][31][32].…”

Section: Discussionmentioning

confidence: 93%

Bone Mineral Density and Lipid Changes During 5 Years of Follow-up in a Study of Prevention of Breast Cancer with Toremifene in Healthy, High-risk Pre- and Post-menopausal Women

Erkkola

Mattila

Powles

et al. 2005

Breast Cancer Res Treat

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A double-blind, randomised, placebo-controlled pilot study was initiated to evaluate the feasibility of chemoprevention with toremifene 60 mg/day in healthy women at high risk for breast cancer. Enrolment in the study was terminated earlier than planned because of slow patient accrual, although 13% of patients continued for 5 years. The revised efficacy outcomes were change in bone mineral density (BMD) from baseline at four skeletal sites, plus effects on serum lipids. In premenopausal women there was a trend for sustained increase in BMD during toremifene therapy after year 1 in lumbar spine. In postmenopausal women, toremifene had little or no effect on BMD trends. Levels of total and low-density lipoprotein (LDL) cholesterol were largely unchanged from baseline in premenopausal women treated with toremifene but were often slightly lower than in the placebo group during follow-up. Total and LDL cholesterol levels declined slightly from baseline in the postmenopausal women and were, at several points during the first 3 years, significantly lower than in the corresponding placebo group (p < 0.01). We conclude that: (a) assessment of toremifene 60 mg/day in chemoprevention will require further clinical trials; (b) toremifene 60 mg/day has no substantive negative effects on BMD in pre- or postmenopausal women and may exert a minor favourable influence (in particular, the effects of toremifene 60 mg/day on BMD in premenopausal women may make the drug an attractive alternative to tamoxifen 20 mg/day for that patient subset); (c) lipid effects of toremifene 60 mg/day are, at minimum, neutral and may be modestly favourable for reducing cardiovascular risk.

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Tamoxifen improves endothelial function and reduces carotid intima-media thickness in postmenopausal women

Cited by 64 publications

References 42 publications

Endotelial activation and flow-mediated vasodilation in young patients with breast cancer

Endotelial activation and flow-mediated vasodilation in young patients with breast cancer

Raloxifene attenuates Gas6 and apoptosis in experimental aortic valve disease in renal failure

Bone Mineral Density and Lipid Changes During 5 Years of Follow-up in a Study of Prevention of Breast Cancer with Toremifene in Healthy, High-risk Pre- and Post-menopausal Women

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