Mark A. Sader

Endothelial function, vascular reactivity and gender differences in the cardiovascular system

Time for primary review 40 days. A marked gender difference exists in the prevalence and severity of cardiovascular disease, even after adjustment for traditional vascular risk factors, which are more prevalent in males [1]. This has led to an interest in the role of sex steroids themselves in the promotion or inhibition of atherogenic events. As endothelial dysfunction is an early and important event in atherogenesis [2] and appears to predict adverse coronary outcomes [3], gender differences in endothelial function and the effects of hormonal therapy on vascular function have been the focus of considerable research interest. The normal vascular endothelium regulates arterial tone, platelet and leukocyte interactions, coagulation, fibrinolysis and vascular growth [4]. Measurement of endothelial function in the systemic arteries has become established as an important method for the detection of early (pre-symptomatic) arterial abnormalities in humans [5]. Ultrasound-detected endothelial dysfunction in peripheral arteries correlates significantly with coronary endothelial dysfunction [6], as well as with the extent and severity of coronary atherosclerosis [7]. The availability of a non-invasive method for the reproducible measurement of endothelium-dependent dilatation has facilitated the study of the interactions between sex hormones and arterial function, in both males and females. The normal vascular endothelium is only one cell layer thick, separating the blood and vascular smooth muscle. The endothelium responds to physical and chemical stimuli via the synthesis and/or release of regulatory substances affecting vascular tone and growth, thrombosis and thrombolysis and platelet and leukocyte interactions with the endothelium. Substances released by the endothelium include nitric oxide (NO), prostacyclin, endothelins, interleukins, endothelial growth factors, adhesion molecules, plasminogen inhibitors and von Willebrand factor [4,8–10]. The pivotal role of the endothelium in regulating vascular smooth muscle tone has only recently been appreciated [11]. The existence of an endothelium-derived … * Corresponding author. Tel.: +61-2-9515-6519; fax: +61-2-9550-6262 davidc{at}card.rpa.cs.nsw.gov.au

Androgenic anabolic steroids and arterial structure and function in male bodybuilders.

OBJECTIVES The study examined arterial and cardiac structure and function in bodybuilders using androgenic anabolic steroids (AAS), compared to non-steroid-using bodybuilder controls. BACKGROUND Adverse cardiovascular events have been reported in bodybuilders taking anabolic steroids. The cardiovascular effects of AAS, however, have not been investigated in detail. METHODS We recruited 20 male bodybuilders (aged 35 +/- 3 years), 10 actively using AAS and 10 who denied ever using steroids. Serum lipid and hormone levels, carotid intima-media thickness (IMT), arterial reactivity, and left ventricular (LV) dimensions were measured. Vessel diameter was measured by ultrasound at rest, during reactive hyperemia (an endothelium-dependent response, leading to flow-mediated dilation, FMD), and after sublingual nitroglycerin (GTN, an endothelium-independent dilator). Arterial reactivity was also measured in 10 age-matched non-bodybuilding sedentary controls. RESULTS Use of AAS was associated with significant decreases in high density lipoprotein cholesterol, sex hormone binding globulin, testosterone and gonadotrophin levels, and significant increases in LV mass and self-reported physical strength (p < 0.05). Carotid IMT (0.60 +/- 0.04 mm vs. 0.63 +/- 0.07 mm), arterial FMD (4.7 +/- 1.4% vs. 4.1 +/- 0.7%) and GTN responses (11.0 +/- 1.9% vs. 14.4 +/- 1.7%) were similar in both bodybuilding groups (p > 0.2). The GTN responses were significantly lower and carotid IMT significantly higher in both bodybuilding groups, however, compared with the non-bodybuilding sedentary controls (p = 0.01). CONCLUSIONS Although high-level bodybuilding is associated with impaired vascular reactivity and increased arterial thickening, the use of AAS per se is not associated with significant abnormalities of arterial structure or function.

Physiological testosterone replacement and arterial endothelial function in men

objective The vascular effects of fluctuations in testosterone levels within the physiological range in otherwise healthy men are not known. We therefore aimed to study arterial function in hypogonadal men receiving long‐term physiological androgen replacement therapy, at trough and peak testosterone levels.

Androgen receptor gene expression in leucocytes is hormonally regulated: implications for gender differences in disease pathogenesis

Objective  There is evidence that male sex hormones influence the rate of progression of inflammatory and cardiovascular diseases. We have previously shown that human leucocytes and arterial cells isolated from male donors express more androgen receptor (AR) than those from female cells, with potentially pro‐atherogenic effects. We now investigate whether the gender difference in AR expression is due to genetic or hormonal regulation.

Oestradiol improves arterial endothelial function in healthy men receiving testosterone

To assess prospectively the effects of low dose oestradiol on arterial endothelial and smooth muscle function in healthy men. Oestrogen use is associated with reduced cardiovascular disease in oestrogen‐deficient women, however, the vascular effects of low‐dose oestradiol in healthy men have not been investigated previously.

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

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.

Percutaneous transcatheter patent foramen ovale closure using the right internal jugular venous approach.

Percutaneous transcatheter closure of a patent foramen ovale (PFO) is a therapeutic option in patients with paradoxical embolism. For patients in whom PFO closure is indicated when a femoral venous approach is not possible, we describe the successful closure of two PFOs using the right internal jugular venous approach. Catheter Cardiovasc Interv 2003;60:536–539.