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CLINICAL RESEARCH: HORMONE THERAPY IN CORONARY ARTERY DISEASE

Effects of raloxifene on endothelium-dependent dilation, lipoproteins, and markers of vascular function in postmenopausal women with coronary artery disease

Kaye A. Griffiths, DMU^*, Mark A. Sader, MBBS, FRACP, Michael R. Skilton, BSc^*, Jason A. Harmer, BSc^* and David S. Celermajer, MBBS, PhD, FRACP^*,*

^* Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia
Heart Research Institute, Sydney, Australia
Department of Medicine, University of Sydney, Sydney, Australia

Manuscript received April 3, 2003; accepted April 24, 2003.

^* Reprint requests and correspondence: Prof. David S. Celermajer, Department of Cardiology, Royal Prince Alfred Hospital, Missenden Road, Camperdown, New South Wales 2050, Australia.
david.celermajer{at}email.cs.nsw.gov.au

OBJECTIVES: We sought to assess the effects of raloxifene, a selective estrogen receptor modulator, on arterial physiology and biology in postmenopausal women with coronary artery disease (CAD).

BACKGROUND: Raloxifene improves endothelial function and markers of vascular health in vitro in experimental animals and in healthy postmenopausal women. In women whose arteries are affected by advanced atherosclerosis, however, the vascular effects of estrogen receptor modulation are unknown.

METHODS: We conducted a prospective, randomized, double-blinded, placebo-controlled, crossover trial of raloxifene, 60 mg/day for 8 weeks, in 33 consecutively eligible and consenting postmenopausal women age 50 to 75 years with known CAD. Parameters measured at the beginning and end of each treatment period included brachial artery flow-mediated dilation (FMD), the primary end point, as well as nitroglycerin-induced dilation, peripheral artery tonometry, serum lipoprotein levels, and markers of vascular function, including urinary prostaglandin, serum endothelin-1, and fibrinogen levels.

RESULTS: Baseline FMD was impaired in these women, as expected (2.84 ± 0.60%), but there was no significant difference between the effect of raloxifene (0.26 ± 0.66% increase) and placebo (0.01 ± 0.63% decrease) on this marker of endothelial function (p = 0.82). No significant raloxifene-related effects were observed on derived aortic pressure, pulse pressure, augmentation index, total cholesterol or low- and high-density lipoprotein subfractions, markers of thrombosis, or vasoconstrictor or vasodilator substances.

CONCLUSIONS: In postmenopausal women with treated CAD, selective estrogen receptor modulation with raloxifene does not improve a comprehensive set of parameters examining vascular function and serum lipoprotein levels.

Abbreviations and Acronyms   AT III   antithrombin III   CAD   coronary artery disease   eNOS   endothelial nitric oxide synthase   FMD   flow-mediated dilation   GTN   glyceryl trinitrate   HDL   high-density lipoprotein   HRT   hormone replacement therapy   LDL   low-density lipoprotein   NO   nitric oxide   PGF1   2,3-dinor-6-keto-prostaglandin F1

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