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Showing papers by "Suzanne Oparil published in 2007"



Journal ArticleDOI
TL;DR: The optimal choice of antihypertensive agents remains controversial, and there are only partial answers to important questions in the treatment of hypertension in the prevention and management of ischemic heart disease (IHD).
Abstract: Epidemiological studies have established a strong association between hypertension and coronary artery disease (CAD). Hypertension is a major independent risk factor for the development of CAD, stroke, and renal failure. The optimal choice of antihypertensive agents remains controversial, and there are only partial answers to important questions in the treatment of hypertension in the prevention and management of ischemic heart disease (IHD), such as: ● What are the appropriate systolic blood pressure (SBP) and diastolic blood pressure (DBP) targets in patients at high risk of developing CAD or in those with established CAD? ● Are the beneficial effects of treatment simply a function of blood pressure (BP) lowering, or do particular classes of drugs have uniquely protective actions in addition to lowering BP? ● Are there antihypertensive drugs that have shown particular efficacy in the primary and secondary prevention of IHD? ● Which antihypertensive drugs should be used in patients who have established CAD with stable or unstable angina pectoris, in those with non–ST-elevation myocardial infarction (NSTEMI), and in those with ST-elevation myocardial infarction (STEMI)?

768 citations


Journal ArticleDOI
TL;DR: The combination of aliskiren and valsartan at maximum recommended doses provides significantly greater reductions in blood pressure than does monotherapy with either agent in patients with hypertension, with a tolerability profile similar to that with aliskirens and valartan alone.

435 citations


01 Jan 2007
TL;DR: In the wake of the reports of the Women’s Health Initiative and the Heart and Estrogen/Progestin Replacement Study (HERS), which unexpectedly showed that combination hormone therapy was associated with adverse CVD effects, there is a heightened need to critically review and document strategies to prevent CVD in women.
Abstract: Significant advances in our knowledge about interventions to prevent cardiovascular disease (CVD) have occurred since publication of the first female-specific recommendations for preventive cardiology in 1999.1 Despite research-based gains in the treatment of CVD, it remains the leading killer of women in the United States and in most developed areas of the world.2–3⇓ In the United States alone, more than one half million women die of CVD each year, exceeding the number of deaths in men and the next 7 causes of death in women combined. This translates into approximately 1 death every minute.2 Coronary heart disease (CHD) accounts for the majority of CVD deaths in women, disproportionately afflicts racial and ethnic minorities, and is a prime target for prevention.1–2⇓ Because CHD is often fatal, and because nearly two thirds of women who die suddenly have no previously recognized symptoms, it is essential to prevent CHD.2 Other forms of atherosclerotic/thrombotic CVD, such as cerebrovascular disease and peripheral arterial disease, are critically important in women. Strategies known to reduce the burden of CHD may have substantial benefits for the prevention of noncoronary atherosclerosis, although they have been studied less extensively in some of these settings. In the wake of the reports of the Women’s Health Initiative and the Heart and Estrogen/Progestin Replacement Study (HERS), which unexpectedly showed that combination hormone therapy was associated with adverse CVD effects, there is a heightened need to critically review and document strategies to prevent CVD in women.4–7⇓⇓⇓ These studies underscore the importance of evidence-based practice for chronic disease prevention. Optimal translation and implementation of science to improve preventive care should include a rigorous process of evaluation and clear communication about the quantity and quality of evidence used to support clinical recommendations. Recently, there has …

340 citations


Journal ArticleDOI
TL;DR: This data indicates that 17β-estradiol attenuates responses to endoluminal injury of the rat carotid artery, at least in part, by decreasing inflammatory mediator expression and neutrophi...
Abstract: We have previously shown that 17β-estradiol (E2) attenuates responses to endoluminal injury of the rat carotid artery, at least in part, by decreasing inflammatory mediator expression and neutrophi...

113 citations


Journal ArticleDOI
TL;DR: This 12‐week, randomized, double‐blind, forced‐titration study compared the efficacy of 3 angiotensin receptor blockers to reduce blood pressure equivalently.
Abstract: This 12-week, randomized, double-blind, forced-titration study compared the efficacy of 3 angiotensin receptor blockers. Patients received olmesartan medoxomil 20 mg, losartan potassium 50 mg, valsartan 80 mg, or placebo once daily. At week 4, doses were titrated to 40, 100, and 160 mg once daily for olmesartan, losartan, and valsartan, respectively. At week 8, losartan was increased to 50 mg twice daily and valsartan increased to 320 mg once daily (olmesartan remained at 40 mg once daily). The primary end point was mean change from baseline in seated diastolic blood pressure (SeDBP) at week 8. All 3 medications significantly reduced mean SeDBP from baseline compared with placebo at weeks 4, 8, and 12 (P<.001). At week 8, olmesartan reduced mean SeDBP more than losartan (P<.001); more patients in the olmesartan medoxomil group achieved a blood pressure goal of <140/90 mm Hg (P<.001). Olmesartan did not reduce mean SeDBP significantly compared with valsartan, although more patients attained blood pressure goal with olmesartan (P=.031). At week 12, all agents lowered blood pressure equivalently.

81 citations


Journal ArticleDOI
TL;DR: Results reveal for the first time a precise site at which ANP-cGMP-PKG signaling exerts its antifibrogenic effect on the profibrogenics TGF-beta1 signaling pathway: by blocking T GF- beta1-induced p Smad2 and pSmad3 nuclear translocation and ECM expression in PASMCs.
Abstract: Atrial natriuretic peptide (ANP) and transforming growth factor (TGF)-β play important counterregulatory roles in pulmonary vascular adaptation to chronic hypoxia. To define the molecular mechanism...

62 citations


Journal ArticleDOI
TL;DR: Aged OVX rats lose the vasoprotective and anti-inflammatory responses to exogenous E2 seen in younger animals, which may be relevant to the lack of vasoprotsection observed in outcome trials of estrogen therapy in postmenopausal women.
Abstract: Objective: 17β-Estradiol (E 2 ) negatively modulates neointima formation, leukocyte infiltration, and proinflammatory mediator expression after vascular injury in young (10-wk-old) ovariectomized (OVX) rats. Trials of E 2 in elderly postmenopausal women have not confirmed a vasoprotective effect. This study tested the hypothesis that responsiveness to E 2 is lost in injured arteries of aged (12-mo-old) OVX rats. Design: E 2 - or vehicle-treated OVX rats underwent balloon injury of the carotid artery and were killed after 2 weeks for morphometric examination of arteries, after 24 hours for assessment of leukocyte infiltration, and after 2 hours for quantification of proinflammatory mediator mRNA expression. Results: Neointima formation was significantly reduced in aged compared with young vehicle-treated rats. E 2 treatment had directionally opposite effects on intima/media ratios in aged (+75%) and young (-40%) rats. Injury induced increases in infiltrating total leukocytes, neutrophils, monocytes/macrophages, and expression of proinflammatory mediators in arteries of aged rats; E 2 had no effect on these inflammatory responses to injury. Estrogen receptor a and β protein expression were similar in carotid arteries of young and aged rats on immunofluorescence testing. Conclusions: Aged OVX rats lose the vasoprotective and anti-inflammatory responses to exogenous E 2 seen in younger animals. These results may be relevant to the lack of vasoprotection observed in outcome trials of estrogen therapy in postmenopausal women.

54 citations


Journal ArticleDOI
TL;DR: In spite of similar office BP, ABPM levels were higher in resistant hypertensive patients with H-Aldo, suggesting that high aldosterone levels impart increased cardiovascular risk not reflected by office BP measurements.
Abstract: BackgroundAldosterone excess has been reported to be a common cause of resistant hypertension. To what degree this represents true treatment resistance is unknown.ObjectiveThe present study aimed to compare the 24-h ambulatory blood pressure monitoring (ABPM) levels in resistant hypertensive patient

38 citations


Journal Article
TL;DR: Endothelin-1 (ET-1) is a powerful vasoconstrictor and mitogen that contributes to blood pressure elevation and related vascular remodeling and target organ damage, thus elevating blood pressure and increasing vascular tone.
Abstract: Endothelin-1 (ET-1) is a powerful vasoconstrictor and mitogen that contributes to blood pressure elevation and related vascular remodeling and target organ damage. ET-1 also influences salt and water homeostasis through effects on the renin-angiotensin-aldosterone system and vasopressin, thus elevating blood pressure and increasing vascular tone. Circulating ET-1 levels are elevated in a variety of animal models of hypertension, particularly those that are salt-dependent, and in a subset of human hypertensives, i.e. African-Americans and those with renal dysfunction. ET type B receptors, which normally have vasodilator functions, mediate vasoconstriction in some hypertensives, and hypertensive African-American patients may have increased numbers of vasoconstrictor ET-B receptors in their vascular smooth muscle. Whether selective ET-A or combined ET-A/ET-B receptor antagonists are more efficacious in treating hypertension and related cardiovascular disease is controversial. ET antagonists have only modest BP lowering effects in the general population of essential hypertensives, but show promise in patients with severe, treatment resistant hypertension.

33 citations



Journal Article
TL;DR: In this article, the 24-hour ambulatory blood pressure monitoring (ABPM) levels in resistant hypertensive patients with or without hyperaldosteronism were compared with normal aldosterone status (N-Aldo) patients.
Abstract: Background Aldosterone excess has been reported to be a common cause of resistant hypertension. To what degree this represents true treatment resistance is unknown. Objective The present study aimed to compare the 24-h ambulatory blood pressure monitoring (ABPM) levels in resistant hypertensive patients with or without hyperaldosteronism. Methods Two hundred and fifty-one patients with resistant hypertension were prospectively evaluated with an early-morning plasma renin activity (PRA), 24-h urinary aldosterone and sodium, and 24-h ABPM. Daytime, night-time, and 24-h blood pressure (BP) and nocturnal BP decline were determined. Hyperaldosteronism (H-Aldo) was defined as suppressed PRA (<1.0 ng/ml per h or <1.0 μg/l per h) and elevated 24-h urinary aldosterone excretion (≥12 μg/24-h or ≥33.2 nmol/day) during ingestion of the patient's routine diet. Results In all patients, the mean office BP was 160.0 ± 25.2/89.4 ± 15.3 mmHg on an average of 4.2 medications. There was no difference in mean office BP between H-Aldo and normal aldosterone status (N-Aldo) patients. Daytime, night-time, and 24-h systolic and diastolic BP were significantly higher in H-Aldo compared to N-Aldo males. Daytime, night-time, and 24-h systolic BP were significantly higher in H-Aldo compared to N-Aldo females. Multivariate analysis indicated a significant interaction between age and aldosterone status such that the effects of aldosterone on ambulatory BP levels were more pronounced with increasing age. Conclusions In spite of similar office BP, ABPM levels were higher in resistant hypertensive patients with H-Aldo. These results suggest that high aldosterone levels impart increased cardiovascular risk not reflected by office BP measurements.

Journal ArticleDOI
TL;DR: Hyperaldosteronism is now recognized as the most common cause of resistant hypertension, and all patients with resistant hypertension should be screened with a plasma aldosterone/renin ratio even if the serum potassium level is normal.
Abstract: Correspondencia: Eduardo Pimenta • 933 19th Street South, Room 115 Birmigham, AL, 35294 EUA E-mail: eduardo.pimenta@ccc.uab.edu Artigo recebido em 3/4/07; revisado recebido em 3/4/07; aceito em 10/4/07. Definicao e prevalencia A hipertensao arterial refrataria (HAR) e definida como pressao arterial (PA) que permanece acima da meta apesar do uso de tres classes de farmacos anti-hipertensivos e em doses eficazes, incluindo um diuretico1. Os pacientes intolerantes a diureticos e com PA nao-controlada, apesar do uso de tres medicacoes anti-hipertensivas de outras classes, tambem sao considerados portadores de HAR. A meta pressorica na populacao geral e inferior a 140/90 mmHg, e em pacientes diabeticos ou com doenca renal cronica (DRC) (taxa de filtracao glomerular 1,5 mg/dl em homens ou >1,3 mg/dl em mulheres; albuminuria >300 mg/24h ou >200 mg/g de creatinina) a meta a ser atingida e inferior a 130/80 mmHg1. Os pacientes com PA controlada com quatro ou mais classes de medicamentos anti-hipertensivos tambem devem ser considerados portadores de HAR. Os fatores que predispoem a refratariedade ao tratamento anti-hipertensivo incluem mudancas na populacao, como maior expectativa de vida, maior incidencia de obesidade e menor nivel de atividade fisica, bem como fatores relacionados ao profissional de saude, como menor atencao a hipertensao sistolica isolada e as metas pressoricas mais agressivas recomendadas pelas diretrizes recentes. Esta revisao analisa os diversos fatores que contribuem para o desenvolvimento de HAR (tab. 1) e suas causas secundarias (tab. 2).

Journal ArticleDOI
TL;DR: This scientific statement summarizes the published data relating to the treatment of hypertension in the context of CAD prevention and management and attempts to develop recommendations that will be appropriate for both BP reduction and the management of CAD in its various manifestations.
Abstract: Epidemiological studies have established a strong association between hypertension and coronary artery disease (CAD). Hypertension is a major independent risk factor for the development of CAD, stroke, and renal failure. The optimal choice of antihypertensive agents remains controversial, and there are only partial answers to important questions in the treatment of hypertension in the prevention and management of ischemic heart disease (IHD), such as: This scientific statement summarizes the published data relating to the treatment of hypertension in the context of CAD prevention and management and attempts, on the basis of the best available evidence, to develop recommendations that will be appropriate for both BP reduction and the management of CAD in its various manifestations. Where data are meager or lacking, the writing group has proposed consensus recommendations, with all of the reservations that that term implies and with the hope that large gaps in our knowledge base will be filled in the near future by data from well-designed prospective clinical trials. All of the discussion and recommendations refer to adults. The writing committee has not addressed hypertension or IHD in the pediatric age group. Also, there is no discussion of the different …

Journal ArticleDOI
TL;DR: It is concluded that, in neonatal mice, hypoxia attenuates normal postnatal decreases in ET-1, vascular collagen, and elastin, and ET-AR blockade reduces collagen fiber area but not mRNA, and does not decreaseElastin despite reducing its expression.
Abstract: Endothelin-1 (ET-1) mediates hypoxia-mediated pulmonary vascular remodeling (HPVR), and endothelin-A receptor (ET-AR) blockade prevents HPVR in newborn mice. Our objective was to determine postnatal effects of chronic hypoxia and/or ET-AR blockade on lung ET-1, ET-AR, ET-BR, and vascular collagen and elastin. Newborn C57BL/6 mice (n = 6–8/gp) given either BQ610 (ET-AR blocker) or vehicle were exposed to air or hypoxia (12% O2) from birth for 1, 3, or 14 d. Lung ET-1 was assessed by ELISA, and ET-AR and ET-BR by immunohistochemistry. Vascular collagen and elastin were assessed by quantitative image analysis. ET-1, ET-AR, ET-BR, collagen I and III, and tropoelastin mRNA levels were assessed by real-time quantitative RT-PCR. We observed that: 1) hypoxia attenuated the normal postnatal decrease in ET-1 and collagen content; 2) ET-AR blockade reduced collagen independent of O2; 3) hypoxia increased elastin mRNA expression and attenuated the normal postnatal decrease in elastin content; and 4) BQ610 reduced elastin mRNA but not elastin content. We conclude that, in neonatal mice, hypoxia attenuates normal postnatal decreases in ET-1, vascular collagen, and elastin. ET-AR blockade reduces collagen fiber area but not mRNA, and does not decrease elastin despite reducing its expression.

Journal ArticleDOI
TL;DR: Differences in blood pressure or distribution of add-on medications between treatment groups were not evident in the LIFE trial and, thus, cannot account for the observed outcome difference in the primary endpoint of risk reduction of the composite of cardiovascular death, stroke and MI favoring losartan.
Abstract: Blood pressure reduction and antihypertensive medication use in the losartan intervention for endpoint reduction in hypertension (LIFE) study in patients with hypertension and left ventricular hypertrophy.


Journal Article
TL;DR: The efficacy, tolerability, and convenience of losartan/HCTZ combination therapy may increase patient compliance and lower risk for stroke, a devastating outcome in patients with hypertension.
Abstract: A fixed-dose combination of losartan/hydrochlorothiazide (HCTZ) therapy may be a logical choice for antihypertensive treatment, including for initial therapy in patients with blood pressure elevation >20/10 mmHg above treatment target. The renin–angiotensin– aldosterone–system-activating effect of hydrochlorothiazide augments the efficacy of blocking the angiotensin II type 1 (AT1) receptor with losartan. Some adverse effects associated with hydrochlorothiazide, including increased risk for new-onset diabetes mellitus, may be offset by losartan. Losartan was frequently administered with hydrochlorothiazide in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, in which there was a 25% risk reduction for stroke in the losartan-based compared with the atenolol-based treatment group. The efficacy, tolerability, and convenience of losartan/HCTZ combination therapy may increase patient compliance and lower risk for stroke, a devastating outcome in patients with hypertension.

Journal ArticleDOI
TL;DR: Arterial stiffness has been associated with an increased risk of future hypertension, independent of established risk factors and level of blood pressure, and there is emerging evidence that the relationship between hypertension and arterial stiffness is bi-directional.
Abstract: In the previous issue of Blood Pressure, we presented the 2007 ESH/ESC hypertension guidelines [1]. For the first time, the measurement of pulse wave velocity (PWV), a comprehensive non‐invasive as...

Journal ArticleDOI
TL;DR: The updated and recently released 2007 ESC Guidelines for the Management of Arterial Hypertension emphasize the assessment of total cardiovascular risk, along with proper measurement of blood pressure (BP), and novel recommendations to appropriately guide treatment strategies.
Abstract: The updated and recently released 2007 European Society of Hypertension (ESH)/European Society of Cardiology (ESC) Guidelines for the Management of Arterial Hypertension (1), emphasize the assessment of total cardiovascular (CV) risk, along with proper measurement of blood pressure (BP) and novel recommendations to appropriately guide treatment strategies. The information from both is needed to improve patient management. Importantly, the BP threshold for initiating treatment and the treatment targets are lowered. In highrisk patients, the treatment target is v130/ 80 mmHg, and treatment strategies should include consideration of prescribing aspirin and a statin.

Journal ArticleDOI
TL;DR: This new Strategic Vision calls for the Society to leverage its past successes as a ecognized and respected forum for hypertension research and education of hypertension pecialists and to reach out to new constituencies, including primary care providers, ealth care policy makers, managed care providers/payers, and, most of all, the authors' patients.
Abstract: 933-1711/07/$ – se oi:10.1016/j.jash.20 Recognizing that the challenges and opportunities facing the Society today are haning rapidly, ASH has initiated a comprehensive and extensive strategic review of its ission, goals, programs, and organizational structure. This review included a critical ook at the needs of hypertensive patients, their healthcare givers, and the scientists who rovide the fundamental basis for advances in prevention and treatment. Thus, ASH has ndertaken a sweeping Strategic Planning Initiative to define its core values and purpose nd frame its vision for the future. From these core values and this vision, the Society ill derive a consistent and cohesive strategic plan to find the path that we will follow o reach our goal, reducing the burden of disease attributable to hypertension and related isk conditions. In order for the Society to fulfill its responsibilities and realize its potential as the eading voice in the fight against hypertension and its cardiovascular consequences, there s a compelling need for a major paradigm shift in the vision, mission, and goals of the ociety. This new Strategic Vision builds on the current mission and purpose of the Society to romote and encourage the development, advancement, and exchange of scientific nformation in all aspects of research, awareness, prevention, detection, treatment, and ontrol of hypertension, and related cardiovascular diseases. The Society serves as a forum for the discussion, debate, and dissemination of cientific information and clinical treatment strategies for hypertension and cardiovasular health for the broadest possible array of scientific disciplines. This new Strategic Vision calls for the Society to leverage its past successes as a ecognized and respected forum for hypertension research and education of hypertension pecialists and to reach out to new constituencies, including primary care providers, ealth care policy makers, managed care providers/payers, and, most of all, our patients. The initial review and evaluation phase of the Strategic Planning Initiative has been ompleted. The focus now is implementation of the Strategic Plan. This will require ontinuing development of programs to further these new goals, as well as efforts to estructure organizational components where necessary, and regular review and evalution of this entire effort.


Journal ArticleDOI
TL;DR: Interest in studying the fundamental biology of the raas has burgeoned, and recent findings may help to elucidate the ultimate therapeutic role of direct renin inhibitors.
Abstract: Vol. 9 no. 9 sEpTEmbEr 2007 706 The availability of an effective orally active direct renin inhibitor is a milestone in the long journey of scientists and clinicians interested in exploring how the renin-angiotensin-aldosterone system (raas) works and in exploiting this new knowledge for the possible benefit of patients. The developers of the new direct renin inhibitor should be commended on their perseverance. The search for such a compound had gone on for at least 3 decades, with little success. Everything involved in the development of this drug had to be studied in primates at great cost and with some questions regarding applicability to humans. The direct renin inhibitor that has just been approved by the us food and Drug administration has many positive attributes: placebo-like tolerability at clinically recommended doses (although the game is in the early innings, and problems could emerge later), additive efficacy with most other antihypertensive drug classes, and a long duration of action, which is important for patients who skip doses. This persistence of effect correlates with good 24-hour blood pressure (bp) control, which may result in target organ protection. only randomized controlled trials will tell for sure. Having a direct renin inhibitor is also important because it gives the clinician and the patient an additional choice for therapy. some patients cannot or will not tolerate presently available antihypertensive agents in doses and combinations sufficient to achieve adequate bp control. While the new direct renin inhibitor produces only modest bp reduction when administered as monotherapy, it lowers bp further when combined with antihypertensive agents from most other classes. it is intriguing that this additional bp lowering occurs even when the renin inhibitor is combined with the maximal recommended dose of a downstream raas blocker, specifically, an angiotensin ii receptor blocker (arb). Whether this means that neither the renin inhibitor nor the arb alone fully shuts down the raas cascade or that the renin inhibitor acts by mechanisms in addition to shutting down angiotensin ii production is unknown and is actively being studied. There is also an important bedside-to-bench aspect of having this agent available for clinical use: interest in studying the fundamental biology of the raas has burgeoned, and recent findings may help to elucidate the ultimate therapeutic role of direct renin inhibitors. inhibition of renin activity reduces angiotensin generation, resulting in loss of the normal angiotensin-mediated feedback inhibition of renin synthesis and release. Thus, in hypertensive patients receiving aliskiren treatment, circulating levels of renin and its catalytically inactive precursor prorenin, which circulates in 10to 100-fold excess of active renin, are actually elevated, while renin activity is suppressed. Conventional wisdom dictates that these elevated plasma renin and prorenin levels are without biologic significance, since renin has no function beyond its catalytic activity (ie, angiotensin generation). recent findings have challenged that concept. some observations suggest that human prorenin is potentially biologically active and can have vasculotoxic effects. C o m m e n t a r y

Journal ArticleDOI
TL;DR: Based on new data and information from other trials, the expert panel addressed the questions, “Is it time for a new Joint National Committee report?” and “Should the 2003 hypertension treatment recommendations be updated or are they still valid?’
Abstract: Following a hypertension symposium in Washington, DC, in November 2006, a panel was convened to discuss new data from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) and to revisit the significance of this trial in the management of hypertension. Based on these data and information from other trials, the expert panel also addressed the questions, “Is it time for a new Joint National Committee report?” and “Should the 2003 hypertension treatment recommendations be updated or are they still valid?” The panel was moderated by Marvin Moser, MD, Clinical Professor of Medicine, Yale University School of Medicine, New Haven, CT. On the panel were Suzanne Oparil, MD, Professor of Medicine at the University of Alabama in Birmingham, and President of the American Society of Hypertension (ASH); William Cushman, MD, Professor of Preventive Medicine and Medicine at the University of Tennessee in Memphis and attending physician at the Washington, DC, VA Medical Center; and Vasilios Papademetriou, MD, Professor of Medicine at Georgetown University in Washington, DC, and attending physician at the Washington, DC, VA Medical Center. This expert panel discussion was supported by Pfizer Inc and each author received an honorarium from Pfizer Inc for time and effort spent participating in the discussion and reviewing the transcript for important intellectual content prior to publication. The authors maintained full control of the discussion and the resulting content of this article; Pfizer had no input in the choice of topic, speakers, or content. (Please note that Dr Oparil's comments herein do not represent the official opinion of ASH.)

Journal ArticleDOI
TL;DR: It is demonstrated for the first time in humans that spironolactone improves BP control and reduces LVH in patients with resistant hypertension who are receiving optimal doses of thiazide diuretics.
Abstract: Background: Hyperaldosteronism is being recognized to be increasingly prevalent particularly in patients with resistant hypertension and is believed in addition to raising blood pressure (BP) to induce cardiac fibrosis and LVH. We hypothesize that spironolactone a mineralocorticoid receptor antagonist, could improve blood pressure control and LVH in this high risk population. Methods: Patients with resistant hypertension (defined as requiring 4 or more antihypertensive agents) were treated with spironolactone 25mg once daily and up titrated to 50mg daily. Clinic BP, 24-hr ambulatory BP, cardiac MRI, plasma renin activity (PRA), brain natriuretic peptide (BNP) were measured before and 6 months after treatment with spironolactone. Results: Eleven subjects with a mean age 54.5_7.2 years and BMI 36.1_6.2 kg/m2 were evaluated. Ten of 11 subjects were receiving optimal doses of a thiazide diuretic as part of their treatment regimen. Clinic BP (134_13/81_7 vs. 120_11/76_7 mm Hg; p _ 0.015, p_ns), ambulatory daytime BP (142_15/83_10 vs. 132_16/76_12 mm Hg; p_ns), nighttime BP (132_16/ 74_14 vs. 121_14/65_11 mm Hg; p_0.05), 24-hr ABPM (139_15/80_11 vs. 129_15/ 73_12 mm Hg; p_ns), BNP (44.1_52.0 vs. 16.1_18.1 pg/ml; p _ 0.02), left ventricular (LV) end diastolic volume (170.0_43.9 vs. 160.9_46.4 ml; p_ns), end diastolic LV mass (178.4_48.6 vs. 148.5_33.4 gm; p _ 0.006), end systolic LV mass (195.2_55.6 vs. 155.5_34.6 gm; p _ 0.003), mean LV mass (186.8_51.9 vs. 151.9_33.8 gm; p _ 0.004), LV posterior wall thickness (10_1.9 vs. 9_1.8 mm; p_ns), interventricular septal thickness (11.3_2.4 vs. 9.6_2.2 mm; p _ 0.008) were lower at the end of six months following spiranolactone treatment compared to baseline. Serum potassium (3.7_0.4 vs. 4.3_0.5 mEq/L; p _ 0.006), serum creatinine (0.99_0.2 vs. 1.2_0.3 mg/dl; p_0.02) and PRA (1.7_2.2 vs. 12.2_16.1 ng/ml/hr; p_0.002) were higher. Conclusion: Our findings demonstrate for the first time in humans that spironolactone improves BP control and reduces LVH in patients with resistant hypertension who are receiving optimal doses of thiazide diuretics. These results suggest that mineralocorticoid receptor blockade specifically benefits patients with resistant hypertension beyond conventional diuretic therapy.

Book ChapterDOI
01 Jan 2007
TL;DR: Because large randomized controlled trials of menopausal hormone therapy have demonstrated no cardiovascular benefit and some evidence of harm (increased CHD, stroke, and thromboembolic events in women assigned to some hormone treatments), this concept of estrogenic vasoprotection has been called into question.
Abstract: There is a sexual dimorphism in the development of cardiovascular disease (CVD) in humans (1,2). The prevalence of total CVD, defined as coronary heart disease (CHD), congestive heart failure, stroke, and hypertension, is much lower in premenopausal women than in age-matched men, but rises quickly in women after the fifth decade to surpass that of men at later ages (2). Epidemiologic and observational studies of menopausal hormone therapy associate a lower risk of CHD development and CVD mortality with hormone treatment (3, 4, 5, 6, 7, 8, 9). Based on this evidence and an extensive volume of mechanistic studies from in vitro and animal research, it was thought that ovarian hormones, principally estrogens, were vasoprotective. However, because large randomized controlled trials of menopausal hormone therapy have demonstrated no cardiovascular benefit and some evidence of harm (increased CHD, stroke, and thromboembolic events in women assigned to some hormone treatments), this concept of estrogenic vasoprotection has been called into question (10, 11, 12, 13).


Journal ArticleDOI
TL;DR: On August 15, 2007, a panel discussion was held to discuss hypertension, where Suzanne Oparil,MD, University of Alabama at Birmingham, Birmingham, AL, and Thomas G. Pickering, MD, DPhil, Columbia Presbyterian Medical Center, New York, NY, spoke.
Abstract: On August 15, 2007, a panel discussion was held to discuss hypertension. The panel was moderated by Thomas D. Giles, MD, Tulane University School of Medicine, New Orleans, LA. Discussants included Suzanne Oparil, MD, University of Alabama at Birmingham, Birmingham, AL, and Thomas G. Pickering, MD, DPhil, Columbia Presbyterian Medical Center, New York, NY.

Journal ArticleDOI
TL;DR: There is a strong rationale to use combinations of an ACE inhibitor or ARB plus a diuretic for management of hypertension, based on substantially increased percentages of patients achieving target BP reductions, compared with component mono-therapies.
Abstract: Fixed‐dose combinations have a number of potential advantages compared with monotherapy or free combinations in the treatment of hypertension. Use of a fixed‐dose combination may increase patient c...