Hormone Replacement Therapy and Cardiovascular Disease

Dubey, Raghvendra K.; Imthurn, Bruno; Zacharia, Lefteris C.; Jackson, Edwin K.

doi:10.1161/01.hyp.0000145988.95551.28

Cited by 74 publications

(47 citation statements)

References 105 publications

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“…32,33 Epidemiological studies indicate that development of HTN and CVD may not occur until 5 to 10 years after menopause. 37,38 Therefore, we surmise that the loss of ovarian hormones may unmask a population of women predisposed to SS that, with aging and its associated loss of vascular compliance, would subsequently be at higher risk for the development of HTN and CVD.…”

Section: Discussionmentioning

confidence: 99%

Surgical Menopause Increases Salt Sensitivity of Blood Pressure

et al. 2006

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Abstract-Salt sensitivity of blood pressure is associated with an elevated risk of developing hypertension (HTN) and is an independent risk factor for cardiovascular disease. The prevalence of HTN increases after menopause. The aim of this study was to investigate prospectively whether the loss of ovarian hormones increases the occurrence of salt sensitivity among healthy premenopausal women. We enrolled 40 normotensive, nondiabetic women (age 47.2Ϯ3.5), undergoing hysterectomy-oophorectomy for nonneoplastic processes and not on hormone replacement, to determine the effect of changes in sodium intake on blood pressure the day before and subsequently 4 months after surgical menopause. Salt loading was achieved using a 2-L normal saline infusion and salt depletion produced by 40 mg of intravenous furosemide. A decrease Ͼ10 mm Hg in systolic blood pressure between salt loading and salt depletion was used to define salt sensitivity. Before and after menopause, salt-sensitive women exhibited higher waist/hip and waist/thigh ratios (PϽ0.01). Although all of the women remained normotensive, the prevalence of salt sensitivity was significantly higher after surgical menopause (21 women; 52.5%) than before (9 women; 22.5%; Pϭ0.01), because 12 (38.7%) salt-resistant women developed salt sensitivity after menopause. In summary, we demonstrated that the prevalence of salt sensitivity doubled as early as 4 months after surgical menopause, without an associated increase in blood pressure. Epidemiological studies indicate that development of HTN may not occur until 5 to 10 years after menopause. The loss of ovarian hormones may unmask a population of women prone to salt sensitivity who, with aging, would be at higher risk for the subsequent development of HTN and cardiovascular disease.

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Section: Discussionmentioning

confidence: 99%

Surgical Menopause Increases Salt Sensitivity of Blood Pressure

et al. 2006

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“…Estrogen (E 2 ) levels also increase during pregnancy (23,74). E 2 induces long-term genomic vascular effects, such as stimulation of endothelial cell growth, upregulation of endothelial NO synthase and NO production, increased cyclooxygenase (COX) activity and PGI 2 production (19,53,64,77), inhibition of vascular smooth muscle (VSM) proliferation, and downregulation of VSM Ca 2ϩ channels and PKC (33,61). E 2 also causes rapid nongenomic vasodilator effects via activation of endotheliumdependent NO, PGI 2 , and hyperpolarization pathways (24,29) and inhibition of Ca 2ϩ -dependent mechanisms of VSM contraction (13,31,64).…”

Section: The Present Study Describes Pregnancy-associated Increases Imentioning

confidence: 99%

Adaptive increases in expression and vasodilator activity of estrogen receptor subtypes in a blood vessel-specific pattern during pregnancy

Mata

Reslan

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

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RA. Adaptive increases in expression and vasodilator activity of estrogen receptor subtypes in a blood vessel-specific pattern during pregnancy. Am J Physiol Heart Circ Physiol 309: H1679 -H1696, 2015. First published September 25, 2015 doi:10.1152/ajpheart.00532.2015.-Normal pregnancy is associated with adaptive hemodynamic, hormonal, and vascular changes, and estrogen (E 2) may promote vasodilation during pregnancy; however, the specific E 2 receptor (ER) subtype, post-ER signaling mechanism, and vascular bed involved are unclear. We tested whether pregnancy-associated vascular adaptations involve changes in the expression/ distribution/activity of distinct ER subtypes in a blood vessel-specific manner. Blood pressure (BP) and plasma E 2 were measured in virgin and pregnant (day 19) rats, and the thoracic aorta, carotid artery, mesenteric artery, and renal artery were isolated for measurements of ER␣, ER␤, and G protein-coupled receptor 30 [G protein-coupled ER (GPER)] expression and tissue distribution in parallel with relaxation responses to E 2 (all ERs) and the specific ER agonist 4,4=,4Љ-(4-propyl-[1H]-pyrazole-1,3,5-triyl)-tris-phenol (PPT; ER␣), diarylpropionitrile (DPN; ER␤), and G1 (GPER). BP was slightly lower and plasma E 2 was higher in pregnant versus virgin rats. Western blots revealed increased ER␣ and ER␤ in the aorta and mesenteric artery and GPER in the aorta of pregnant versus virgin rats. Immunohistochemistry revealed that the increases in ERs were mainly in the intima and media. In phenylephrineprecontracted vessels, E 2 and PPT caused relaxation that was greater in the aorta and mesenteric artery but similar in the carotid and renal artery of pregnant versus virgin rats. DPN-and G1-induced relaxation was greater in the mesenteric and renal artery than in the aorta and carotid artery, and aortic relaxation to G1 was greater in pregnant versus virgin rats. The nitric oxide synthase inhibitor N -nitro-L-arginine methyl ester with or without the cyclooxygenase inhibitor indomethacin with or without the EDHF blocker tetraethylammonium or endothelium removal reduced E 2, PPT, and G1-induced relaxation in the aorta of pregnant rats, suggesting an endothelium-dependent mechanism, but did not affect E 2-, PPT-, DPN-, or G1-induced relaxation in other vessels, suggesting endothelium-independent mechanisms. E 2, PPT, DPN, and G1 caused relaxation of Ca 2ϩ entry-dependent KCl contraction, and the effect of PPT was greater in the mesenteric artery of pregnant versus virgin rats. Thus, during pregnancy, an increase in ER␣ expression in endothelial and vascular smooth muscle layers of the aorta and mesenteric artery is associated with increased ER␣-mediated relaxation via endothelium-derived vasodilators and inhibition of Ca 2ϩ entry into vascular smooth muscle, supporting a role of aortic and mesenteric arterial ER␣ in pregnancyassociated vasodilation. GPER may contribute to aortic relaxation while enhanced ER␤ expression could mediate other genomic vascular effects during pregnancy.

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“…(Hersh et al, 2004) Transdermal hormone preparations were less affected, and transvaginal and low-dose preparations gained somewhat, reflecting caution in the use of the full-dose oral regimens that had been used in WHI and HERS. Attempts to explain the unanticipated deleterious effects of HRT gave consideration to whether the formulation, dose and route of administration of HRT might play a role (Dubey et al, 2004;Turgeon et al, 2004;Phillips & Langer, 2005). In particular, the progestin MPA was identified as having potential deleterious effects on the vasculature.…”

Section: Clinical Trialsmentioning

confidence: 99%