Background Brachial artery ultrasound has been proposed as an inexpensive, accurate way to assess cardiovascular risk in populations. However, analysis and interpretation of these data are not uniform. Methods We analysed the relationship between relative and absolute changes in brachial artery diameter in response to flow-mediated dilation and age, gender and baseline diameter among 4040 ultrasound examinations from subjects aged 14 to 98 years. Results Reproducibility studies demonstrated intra- and interreader and intrasubject correlations from 0.67 to 0.84 for repeated measures of per cent change in diameter. Per cent change in diameter after flow stimulus was 3.58 ± 0.10% (mean ± standard deviation). Corresponding values for baseline diameter and absolute change in diameter were 4.43 ± 0.87 mm and 0.15 ± 0.01 mm, respectively. Baseline diameter and its variance were inversely related to per cent change in diameter (P < 0.001). In contrast, absolute change in diameter was more uniform throughout the range of baseline diameters. Baseline diameter was directly related, and per cent change in diameter inversely related, to age (P < 0.001 for all three measures). Time to maximum vasodilator response increased with age (P < 0.001). Women (n=2315) had significantly larger per cent change in diameter than men (n=1725) (P < 0.001). However, after adjustment for age and baseline diameter, per cent and absolute change were 5% smaller in women than men (P < 0.05 for both). In multivariate analysis, age was overwhelmingly the most important determinant of absolute change in diameter (P < 0.001). Conclusions Automated analysis of brachial flow-mediated vasodilator responses is both feasible and reproducible in large-scale clinical and population-based research.

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In postmenopausal women with coronary disease and hyperlipidemia, conjugated equine estrogen produced significant improvements in lipids and vasodilator responses despite the concurrent administration of low dose medroxyprogesterone acetate. Low dose lovastatin produced greater reductions in LDL, but less dramatic improvements in vasodilator responses. Estrogen/progestin plus lovastatin may provide additional benefits via a greater reduction in the LDL/HDL ratio and attenuation of estrogen-associated hypertriglyceridemia. More information is needed about the safety and efficacy of such combinations of hormone replacement and reductase inhibitor therapy.

Abstract-Selective estrogen receptor modulators, like tamoxifen and related compounds, have mixed estrogen agonistic/ antagonistic effects. Tamoxifen may confer significant cardiovascular benefits without the estrogen-associated risks of endometrial and breast cancer. Droloxifene, a structural analogue of tamoxifen, has estrogen agonistic effects on bone and antagonistic effects on endometrial and breast tissue. Its cardiovascular effects in women are unknown. We enrolled 24 healthy postmenopausal women in a randomized, double-blind, 2-period crossover trial comparing the effects of droloxifene (60 mg/d) with conjugated estrogen (0.625 mg/d). Plasma lipids, coagulation and fibrinolytic factors, and brachial flow-mediated vasodilator responses were measured at the beginning and end of each treatment period. Droloxifene and estrogen resulted in 16.6% and 12.0% reductions, respectively, in low density lipoprotein cholesterol (PϽ0.001) and 13.2% and 9.5% reductions, respectively, in lipoprotein(a) (PϽ0.05). In contrast, estrogen, but not droloxifene, increased high density lipoprotein (18.5%, PϽ0.001). Droloxifene also reduced fibrinogen by 17.8% versus a 7.3% reduction with estrogen (Pϭ0.004) but produced no estrogen-like changes in plasminogen, plasminogen activator inhibitor-1, or tissue plasminogen activator. Droloxifene and estrogen produced 36.4% and 27.3% increases, respectively, in flow-mediated vasodilation (percent change from baseline, PϽ0.05 for both). Droloxifene has estrogen agonistic properties regarding low density lipoprotein and lipoprotein(a) metabolism, certain coagulation factors, and endothelium-dependent vasodilation but, unlike estrogen, has no effect on high density lipoprotein/triglyceride metabolism and the fibrinolytic cascade. It remains unknown whether droloxifene can confer a true cardiovascular benefit. Key words: droloxifene Ⅲ hormone replacement therapy Ⅲ women Ⅲ estrogen Ⅲ cardiovascular disease E strogen replacement therapy favorably influences several domains of vascular health, including lipid metabolism, endothelial function, and aspects of hemostasis. 1 However, estrogen replacement also carries an increased risk of endometrial 2 and possibly breast 3 carcinoma. The recent Heart and Estrogen/Progestin Study trial 4 also raises questions about whether the favorable effects of estrogen on the cardiovascular system may be offset by other, previously unrecognized, adverse cardiovascular effects, resulting in no overall clinical cardiovascular benefit.Selective estrogen receptor modulators (SERMs), like tamoxifen, are compounds with mixed estrogen agonistic/antagonistic effects. Other benzothiophene derivatives, such as raloxifene, and other structurally unrelated compounds, such as soy phytoestrogens and tibolone, have variable degrees of estrogen agonistic and antagonistic effects. 5 Tamoxifen lowers cholesterol, 6 and in trials in women with breast cancer, it was associated with 15% to 63% fewer cardiovascular events. 7 However, tamoxifen also increases the risk for endometrial ...