Estado actual de la hemodinamia no invasiva en hipertensión arterial / Current status of noninvasive hemodynamics in hypertension

La hipertensión arterial es un trastorno hemodinámico que resulta de un desajuste persistente entre el volumen minuto cardíaco y la resistencia periférica. La hipertensión arterial experimenta una progresión hemodinámica durante su historia natural. La cardiografía por impedancia es un método de evaluación del aparato cardiovascular que obtiene información hemodinámica latido a latido a través del análisis de las variaciones de la impedancia del tórax al paso de una corriente eléctrica. La cardiografía de impedancia desenmascara el deterioro hemodinámico subyacente al incremento de la presión arterial conforme aumenta la edad y la presión arterial sistólica. Este método puede ayudar a mejorar el control tensional a través del tratamiento individualizado con reducción de la resistencia periférica, el mantenimiento del volumen minuto cardíaco o su aumento, de encontrarse bajo, la mejoría de la complacencia arterial y la preservación de la perfusión órgano-tisular. Es útil en el manejo de los pacientes con hipertensión resistente, dado que se logra un mayor porcentaje de pacientes controlados con cambios en el tratamiento con relación a las mediciones hemodinámicas. La cardiografía por impedancia tiene importancia y utilidad pronóstica en relación con el patrón de deterioro hemodinámico y el incremento de eventos cardiovasculares (AU)

Hypertension is a haemodynamic disorder resulting from a persistent mismatch between cardiac output and peripheral resistance. Hypertension undergoes haemodynamic progression during its natural history. Impedance cardiography is a method of evaluating the cardiovascular system that obtains haemodynamic information from beat to beat through the analysis of variations in the impedance of the thorax on the passage of an electric current. Impedance cardiography unmasks the haemodynamic deterioration underlying the increase in blood pressure as age and systolic blood pressure increases. This method may help to improve blood pressure control through individualized treatment with reduction of peripheral resistance, maintenance of cardiac output or its increase, improvement of arterial compliance and preservation of organ-tissue perfusion. It is useful in the management of patients with resistant hypertension, since a greater percentage of patients controlled with changes in the treatment in relation to the haemodynamic measurements are obtained. Impedance cardiography is important and has prognostic utility in relation to a haemodynamic deterioration pattern and increased cardiovascular events (AU)

[Current status of noninvasive hemodynamics in hypertension]. / Estado actual de la hemodinamia no invasiva en hipertensión arterial.

Hypertension is a haemodynamic disorder resulting from a persistent mismatch between cardiac output and peripheral resistance. Hypertension undergoes haemodynamic progression during its natural history. Impedance cardiography is a method of evaluating the cardiovascular system that obtains haemodynamic information from beat to beat through the analysis of variations in the impedance of the thorax on the passage of an electric current. Impedance cardiography unmasks the haemodynamic deterioration underlying the increase in blood pressure as age and systolic blood pressure increases. This method may help to improve blood pressure control through individualized treatment with reduction of peripheral resistance, maintenance of cardiac output or its increase, improvement of arterial compliance and preservation of organ-tissue perfusion. It is useful in the management of patients with resistant hypertension, since a greater percentage of patients controlled with changes in the treatment in relation to the haemodynamic measurements are obtained. Impedance cardiography is important and has prognostic utility in relation to a haemodynamic deterioration pattern and increased cardiovascular events.

Hipertensión arterial en el anciano / Arterial hypertension in the elderly

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Orthostatic hypotension in treated hypertensive patients.

INTRODUCTION: Orthostatic hypotension (OH) is a risk factor for morbidity and mortality and one of the causes of non compliance to treatment among medicated hypertensive subjects. Our objective was to assess the prevalence of OH among treated hypertensive patients and its association with clinical characteristics and antihypertensive drug class. METHODS: This was a cross-sectional study in which we assessed the prevalence of OH, defined according to the American Autonomic Society and American Academy of Neurology guidelines, among adult treated hypertensive patients who performed a home blood pressure monitoring at our institution. We also determined the prevalence of OH according to age group (< 65, 65-79 and > 80), antihypertensive drug class, office and home hypertension control status. RESULTS: We included 302 medicated patients in the study. Mean age was 66.6 (+13.8), 67% were women. We found a 9.7% global prevalence of OH, which was significantly higher among older individuals (3.6% among patients < 65 years-old, 12.2% in the 65-79 year-old group and 16.7% among octogenarians, p = 0.02) and those who consumed alpha-blockers (75 vs. 8.5%, p < 0.01). Uncontrolled hypertensive patients at office and/or at home had also a significantly higher prevalence of OH: uncontrolled vs. controlled office blood pressure (BP), 14.3 vs. 6.5%, p = 0.03 and uncontrolled vs. controlled home BP, 15.1 vs. 6.6%, p = 0.02. Remarkably, 64% of patients with OH had their BP under control when considering office-standing BP. CONCLUSION: OH is a prevalent entity among treated hypertensive patients and systematic measurement of standing BP should be mandatory in the evaluation of these patients.

Current strategies to achieve further cardiac and renal protection through enhanced renin-angiotensin-aldosterone system inhibition.

An incomplete inhibition of the renin angiotensin aldosterone system (RAAS) may be responsible for the residual organ damage and event rate that still occur in spite of an apparent blood pressure control in patients with hypertension, diabetes, chronic kidney disease and heart failure treated with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Additional antiproteinuric effect in diabetic and non diabetic chronic kidney disease, and reduction in hospitalizations in patients with heart failure already receiving a single RAAS antagonist, has been achieved by incremental inhibition of the RAAS with dual therapy or uptitration of an individual agent above conventional dosages. However, the synergistic increase in plasma renin activity (PRA) and the angiotensin II escape could reduce the expected benefit obtained with dual therapy. Results from ONTARGET showing a lack of additional outcome benefit over monotherapy, with a concomitant increase risk of hyperkalemia, renal impairment, and hypotension, discourage the use of the ACEI/ARB combination in patients at high risk of cardiovascular events. This occured despite a lower albumin excretion in dual versus single RAAS blockade, indicating that an incremental antiproteinuric effect is not automatically translated into clinical outcome benefits. The efficacy and safety of ACEI/ARB combination versus monotherapy in patients with overt proteinuria is currently evaluated by LIRICO and VA NEPHRON-D clinical trials. The long lasting direct renin inhibitor aliskiren, acting at the first and rate limiting step of the RAAS cascade, prevents the reactive increase in PRA when combined with ACEIs, ARBs or diuretics. The ASPIRE HIGHER programme, involving more than 35,000 patients with hypertension, heart failure, kidney disease and diabetes, is currently evaluating the efficacy and safety of aliskiren on top of standard therapy. The clinical benefit of adding mineralocorticoid receptor blockers (MRBs) in the control of resistant hypertension, proteinuric kidney diseases, and prevention of mortality in patients with heart failure on top of conventional treatment, evidences the pathogenic role of inadequately suppressed aldosterone as a cause of suboptimal response to conventional RAAS inhibition. The present review will focus on the pathophysiological ground, and the evidence provided by clinical trials assessing the efficacy and safety of recent strategies for the prevention of cardiovascular events and target organ damage progression via enhanced RAAS inhibition.

Combination of oral activated charcoal plus low protein diet as a new alternative for handling in the old end-stage renal disease patients.

Chronic dialysis is a valid therapeutic option in very elderly ESRD patients, even though the decision to dialyze or not has little impact on survival. Additionally, very old patients usually do not agree with starting chronic dialysis. Even though, activated charcoal is a cheap treatment for working as adsorbent for nitrogenous products its utility is very limited. We studied the combination of a low protein diet and oral activated charcoal to reduce serum urea and creatinine levels in very old ESRD patients who had refused to start chronic dialysis. Nine lucid, very old > 80 years, ESRD patients who had refused to start dialysis were prescribed a treatment based on a combination of a very low protein diet and oral activated charcoal (30 gram/day). None of the patients had anuria, oliguria, edema, significant metabolic acidosis or hyperkalemia. None of them had significant gastrointestinal symptoms. After one week and ten months of charcoal use significant decrease in blood urea and creatinine levels was observed and none of them required emergency dialysis during this time. In conclusion, in patients more than 80 years of age low protein diet and oral activated charcoal may control the uremic symptoms effectively.

Recomendaciones para la detección y el tratamiento del anciano con hipertensión arterial / Recommendations for diagnosis and treatment of aged hypertensives

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[Prevention of cardiovascular diseases by an antihypertensive program in the elderly, a cohort study]. / Prevención de eventos cardiovasculares en hipertensos mayores de 65 años bajo el cuidado de un programa de control. Estudio de cohorte.

INTRODUCTION: We started on year 2000 a Complex Intervention Program addressed at hypertension control among our patients. AIM: To compare the risk of cardiovascular events and of dying in hypertensive patients under Program care. METHOD: We started follow-up of a cohort of 1922 patients over 65 years in August 2000. Hipertension diagnosis was ascertained if patient reported to be hypertensive, or was under anti hypertensive treatment or if he/she had two blood pressure measurements = 140/90 mm Hg. Cardiovascular events were considered to be admissions due to coronary disease, cardiac insufficiency or stroke. Incidence is reported by 100 person years follow-up. Relative risks between hypertensive and normotensive patients were calculated and Cox regresión was used to adjust for potential confounders. We compared time to first cardiovascular event and to death with Log Rank Test. RESULTS: Fourty eight point three percent of patients were hypertensive and differed from normotensive patients as to age (79 (5) years vs. 77 (5) p < 0.001), proportion of diabetic patients (16.1% vs. 7.6% p < 0.001). Mean follow-up time was 28 months. Mortality RR was 1.04 (95% CI 0.69-1.58). As to incidence of cardiovascular events it was 1.86 in normotensive vs. 3.02 (RR 1.62 95% CI 1.09-2.42). When adjusted by age, sex, smoking, dislipemia and diabetes, OR was 1.3 (95% CI 0.86-1.98). CONCLUSIONS: Hypertension did not increase the risk in cardiovascular events among our hypertensive patients at 2.3 years follow-up.

Prevención de eventos cardiovasculares en hipertensos mayores de 65 años bajo el cuidado de un programa de control. Estudio de cohorte / Prevention of cardiovascular diseases by an antihypertensive program in the elderly. Cohort study

Introducción: Iniciamos en el 2000 un programa de control para la hipertensión arterial. Objetivo: Conocer el riesgo de morir y de presentar eventos cardiovasculares en los hipertensos bajo el cuidado del programa. Método: Se conformó una cohorte de 1.922 mayores de 65 años en agosto del 2000. Se consideró hipertenso si se conocía como tal, si recibía fármacos antihipertensivos o si tenía dos tomas de presión ≥ 140/90mmHg. Evento cardiovascular a las internaciones por enfermedad coronaria, insuficiencia cardiaca y accidente cerebrovascular. Expresamos densidad de incidencia (DI) de mortalidad y de eventos cardiovasculares cada100 persona-años en hipertensos y en no hipertensos y practicamos regresión de cox para ajustar por factores de riesgo en estudio. Se compara el tiempo al primer evento cardiovascular y a la muerte con Log Rank Test. Resultados: Edad 77,6 (± 5,4) años, 73,9% mujeres, el 48,3% eran hipertensos, diferentes significativamente con respecto a los normotensos en edad 79 (± 5) vs. 77 (± 5) p < 0,001, porcentaje de diabéticos (16,1 vs. 7,6%) p < 0,001. La DI del total de eventos fue de 1,86 vs. 3,02 (RR1,62, IC95% 1,09-2,42) La DI de mortalidad fue de 2,2 vs. 2,1 (RR 1.04,IC95% 0,69-1,58) Tiempo promedio de seguimiento 28 meses, el porcentaje de pacientes libre de eventos a este tiempo fue de 93% (hta) vs.96% (no hta) (p < 0,001). En el multivariado fueron significativas: diabetes,dislipidemia, tabaquismo, edad y sexo, perdiendo peso la hipertensión arterial, OR 1.30 (IC95% 0,86-1,98). Conclusiones: La hipertensión no incrementó el riesgo de presentar eventos cardiovasculares en nuestros hipertensos a 2,3 años

Introduction: We started on year 2000 a Complex Intervention Program addressed at hypertension control among our patients. Aim: To compare the risk of cardiovascular events and of dying inhypertensive patients under Program care. Method: We started follow-up of a cohort of 1922 patients over 65 years in August 2000. Hipertension diagnosis was ascertained if patient reported to be hypertensive, or was under anti hypertensive treatment or if he/she had two blood pressure measurements ≥ 140/90 mm Hg. Cardiovascular events were considered to be admissions due to coronary disease, cardiac insufficiency or stroke. Incidence is reported by 100 person years follow-up. Relative risks between hypertensive and normotensive patients were calculated and Cox regresión was used to adjust for potential confounders. We compared time to first cardiovascular event and to death with Log Rank Test. Results: Fourty eight point three percent of patients were hypertensiveand differed from normotensive patients as to age (79 (5) years vs. 77 (5) p< 0.001), proportion of diabetic patients (16.1% vs. 7.6% p < 0.001). Mean follow-up time was 28 months. Mortality RR was 1.04 (95% CI 0.69-1.58). As to incidence of cardiovascular events it was 1.86 in normotensive vs. 3.02 (RR 1.62 95% CI 1.09-2.42). When adjusted by age, sex, smoking,dislipemia and diabetes, OR was 1.3 (95% CI 0.86-1.98) Conclusions: Hypertension did not increase the risk in cardiovascular events among our hypertensive patients at 2.3 years follow-up

Ambulatory blood pressure monitoring after recovery from hemolytic uremic syndrome.

The outcome of acute renal failure due to diarrhea-associated hemolytic uremic syndrome (D+ HUS) is generally predicted to be good. However, there are only a few long-term observations with detailed reports on long-term sequelae. Specifically, adequate long-term blood pressure (BP) evaluations are scarce. The present study evaluated BP in pediatric patients after childhood D+ HUS. The study group comprised 28 patients (20 males) aged 6-23.5 years (median 10.1 years). All patients had a history of D+ HUS at a median age of 1.1 years (range 0.5-6 years). Based on the duration of oliguria and/or anuria, the primary disease was classified as mild (n=6), moderate (n=6), or severe (n=16). The BP in these patients was studied at a median time of 8.4 years (range 2.3-22.9 years) after manifestation of D+ HUS by means of office BP measurements and 24-h ambulatory BP monitoring (ABPM) using a Spacelabs 90207 oscillometric monitor. Measurements were compared with normal values of published standards for healthy children and adolescents. Conventional office BP measurements were above the 95th percentile in 1 patient. By ABPM, 2 patients were diagnosed to have mean systolic daytime and nighttime values in the hypertensive range, and systolic and diastolic hypertension was confirmed in the first patient. All these patients had a severe form of D+ HUS in the past. By applying ABPM, BP anomalies were detected in 5 additional patients. Elevated systolic BP loads were found in 4 patients, and daytime systolic and diastolic hypertension in the other 1. At the time of the study, 2 of them were classified as "recovered." The late outcome of D+ HUS may be worse than anticipated. BP anomalies as long-term sequelae of D+ HUS could be identified by ABPM but not by office BP measurements. These findings may represent an isolated sign of residual renal disturbance.

Hyperhomocysteinemia in stable pediatric, adolescents, and young adult renal transplant recipients.

BACKGROUND: High total plasma homocysteine (tHcy) levels are accompanied by an increased risk for premature development of atherosclerosis and atherothrombosis. Adult renal transplant recipients have elevated tHcy levels. Corresponding data in pediatric, adolescent, and young adult renal transplant recipients are scarce. We investigated whether tHcy levels were elevated in stable renal transplant recipients who received kidney grafts before age 18. METHODS: This cross-sectional study was conducted during routine posttransplantation follow-up. Fasting tHcy levels, serum creatinine, and lipoprotein profile were measured in 38 clinically stable renal transplant recipients with different degrees of renal function. No patient was receiving B vitamin or folic acid supplementation. Estimated glomerular filtration rate (GFR) was assessed according to Schwartz's formula. All patients followed a triple-drug immunosuppressive regimen, with the exception of three patients (deflazacort and azathioprine). Forty-one apparently healthy subjects constituted the control group. tHcy levels were determined by fluorescence polarization immunoassay in an IMx analyzer. RESULTS: Mean tHcy levels in transplant recipients were significantly higher than in controls (16.8+/-8.7 micromol/L and 9.5+/-2.3 micromol/L, respectively; P<0.01). A significant positive correlation between tHcy and serum creatinine levels was observed for both transplant recipients (rS=0.70, P<0.01) and controls (rS=0.54, P<0.01). In transplant recipients, tHcy correlated negatively with estimated GFR (rS=[minus]0.47, P<0.05). Fasting tHcy levels in excess of 14.6 micromol/L (>95th percentile in controls) were present in 19 (50%) patients; 14 of these patients had an estimated GFR<60 ml/min per 1.73 m2. When the renal transplant recipients were analyzed by renal function, mean tHcy was significantly higher in patients with an estimated GFR<60 ml/min per 1.73 m2 compared with patients with an estimated GFR> or =60 ml/min per 1.73 m2 (20.5+/-9.9 vs. 13.2+/-5.8 micromol/L, P<0.01). Both groups were significantly different from controls (P<0.01). No relationship was found between tHcy level and either cumulative cyclosporine or cumulative methylprednisone doses. No differences were observed in tHcy levels or lipoprotein profile between patients who were receiving deflazacort and those on methylprednisone. CONCLUSIONS: Hyperhomocysteinemia in renal transplant recipients is a common condition. Testing for fasting tHcy level might be a useful tool to identify patients at increased risk for development of vascular disease.

MOTRICS en Artritis Reumatoidea y Sindrome de Sjögren / Body therapy for patients with Rheumatoid Arthritis and Sjörgren Sindrome

En el Servicio de REumatologia del Hospital Rivadavia de la Ciudad de Buenos Aires se realizan, complementariamente a las actividades regulares del Servicio, talleres semanales de trabajo corporal para pacientes con Artritis Reumatoidea y con Sindrome de Sjögren, basados en los sistemas de Movimiento Vital Expresivo y Gimnasia Consciente con elementos de Eutonia. Los objetivos generales de este trabajo son: Recuperar la capacidad articular y muscular, estimular el desarrollo de la propiocepcion, brindar un espacio grupal ludico y una red corporal de contencion, y mejorar el estado animico. Se utiliza una concepcion integradora de los aspectos bio-psico-sociales del paciente. Las tecnicas incluyen movimiento con música, distintas modalidades de respiracion para el alivio del dolor y las tensiones, trabajos de relajacion, la practica del "movimiento anticipado", y el uso del tacto y el contacto como sosten mutuo. En pacientes con Artritis Reumatoidea se apunta principalmente a la ampliacion de la capacidad de movimiento, y a la recuperacion de la vitalidad y de sensaciones corporales distintas del dolor. En pacientes con Sindrome de Sjögren se trabaja en la superacion de la fatiga cronica diferencial de bajo estado de animo, la recuperacion de un cuerpo disfrutable y la afirmacion de actitudes vitales diferentes a la tendencia melancolica, y se investiga la incidencia de los ejerecicios de relajacion de las musculaturas bucal y peribucal, oftalmica y perioftalmica, en el aumento de la secrecion de lagrimas y saliva

MOTRICS en Artritis Reumatoidea y Sindrome de Sj÷gren / Body therapy for patients with Rheumatoid Arthritis and Sj÷rgren Sindrome

En el Servicio de REumatologia del Hospital Rivadavia de la Ciudad de Buenos Aires se realizan, complementariamente a las actividades regulares del Servicio, talleres semanales de trabajo corporal para pacientes con Artritis Reumatoidea y con Sindrome de Sj÷gren, basados en los sistemas de Movimiento Vital Expresivo y Gimnasia Consciente con elementos de Eutonia. Los objetivos generales de este trabajo son: Recuperar la capacidad articular y muscular, estimular el desarrollo de la propiocepcion, brindar un espacio grupal ludico y una red corporal de contencion, y mejorar el estado animico. Se utiliza una concepcion integradora de los aspectos bio-psico-sociales del paciente. Las tecnicas incluyen movimiento con música, distintas modalidades de respiracion para el alivio del dolor y las tensiones, trabajos de relajacion, la practica del "movimiento anticipado", y el uso del tacto y el contacto como sosten mutuo. En pacientes con Artritis Reumatoidea se apunta principalmente a la ampliacion de la capacidad de movimiento, y a la recuperacion de la vitalidad y de sensaciones corporales distintas del dolor. En pacientes con Sindrome de Sj÷gren se trabaja en la superacion de la fatiga cronica diferencial de bajo estado de animo, la recuperacion de un cuerpo disfrutable y la afirmacion de actitudes vitales diferentes a la tendencia melancolica, y se investiga la incidencia de los ejerecicios de relajacion de las musculaturas bucal y peribucal, oftalmica y perioftalmica, en el aumento de la secrecion de lagrimas y saliva (AU)

Contribution of stroke volume to the change in pulse pressure pattern with age.

This study investigated the effect of age on pulse pressure and its underlying mechanisms in unmedicated hypertensive men with the same level of mean arterial pressure. We included 77 men 17 to 76 years old with daytime mean arterial pressure between 95 and 114 mm Hg. In the supine position, pulse pressure showed a significant widening in young (<30 years) and older (>/=60 years) patients. Pulse pressure decreased in parallel with stroke index from age >30 to 40 to 49 years. Upright posture, however, eliminated this difference through a larger orthostatic fall in stroke index and pulse pressure in the youngest patients. After age 50 years, pulse pressure exhibited a progressive widening despite the further age-related decrease in stroke index. Supine, upright, and 24-hour pulse pressure fitted a curvilinear correlation with age (r=0.55, 0.56, and 0.68, respectively, P<0.001), with a transition at age 50 years. Before age 50 years, 24-hour pulse pressure correlated positively with stroke volume (r=0.5, P<0.001) and negatively with arterial compliance (SV/PP ratio, r=-0.37, P<0.01). In contrast, in men >/=50 years old, 24-hour pulse pressure correlated negatively with the SV/PP ratio (r=-0.5; P<0.01), without significant influence of stroke volume. Thus, in hypertensive men, the age-related change in stroke volume significantly accounted for the change in clinic and ambulatory pulse pressure during young adulthood, but its contribution decreased after the fifth decade.

Lack of effective blood pressure control among an elder hypertensive population in Buenos Aires.

Our purpose was to determine the level of awareness, treatment, and control of hypertension in a population of subjects aged 65 or more. We studied a random sample from the national health care program in Buenos Aires. Letters were mailed to 1000 selected individuals. Among those eligible, 41.4% (n = 414) were enrolled. The mean age was 73.8 years and 68% were women. Prevalence of hypertension in our sample was 77.5% (n = 321). Awareness of hypertension was 60.7% (n = 195). Fifty-four percent (n = 173) of the hypertensive subjects were receiving pharmacologic treatment and only 18.5% (n = 32) of them were controlled. These results show that there is a low level of awareness, pharmacologic treatment, and control of hypertension in the studied elderly subjects.

Diastolic pressure underestimates age-related hemodynamic impairment.

It has been hypothesized that as large arteries become more rigid with age, the pattern of hypertension changes from diastolic to systolic. Thus, diastolic blood pressure (DBP) may lose its ability to reflect the increase in vascular resistance with age. To assess this, we studied the age-related changes in blood pressure pattern and its steady-state and pulsatile determinants. We performed an epidemiological analysis based on a national survey of 10,462 subjects from Argentina. A hemodynamic analysis (impedance cardiography) was then carried out in 636 consecutive hypertensive patients (age, 25 to 74 years). Whereas the rate of increment in the prevalence of mild to moderate hypertension (MMH) reached a plateau after the sixth decade, isolated and borderline systolic forms of hypertension began a steep and sustained rise. Among patients with MMH, DBP remained stable from the third to the seventh decade, whereas SBP maintained a sustained increase. Despite similar DBP, the systemic vascular resistance index increased 47% (P<.01) and the cardiac index decreased 27% (P<.01), whereas the ratio of stroke volume to pulse pressure, an index of arterial compliance, decreased 45% (P<.01). However, there were no significant differences between older patients with MMH and those with isolated systolic hypertension in the level of SBP, vascular resistance, stroke volume, and cardiac index. Compared with age-matched normotensive control subjects, the ratio of stroke volume to pulse pressure was much more reduced in isolated systolic hypertension (48%) than in MMH (30%). In summary, the present study, carried out in a large sample of hypertensive subjects with a wide age range, showed a simultaneous impairment in vascular resistance and arterial compliance associated with aging in different patterns of hypertension. The magnitude of these changes, with opposite effects on DBP but additive effects on SBP, suggests that a hemodynamic mechanism could determine the transition in the prevalence of diastolic hypertension toward a systolic pattern of hypertension with aging. Also, the results suggest that SBP, but not DBP, is a reliable indicator of the underlying hemodynamic abnormalities (high resistance and low arterial compliance) in the elderly.

Hemodynamic effects of transdermal estradiol alone and combined with norethisterone acetate.

A 24 weeks, randomized, two-period, placebo controlled study was conducted to compare the effects of continuous transdermal 17 beta-estradiol replacement therapy (0.05 mg/day once a week) with placebo on systemic hemodynamics and blood pressure in postmenopausal women. Twenty-nine postmenopausal women (47-62 years) free of hormone replacement therapy were randomized in two groups; group 1 received estradiol patches for the first 12 weeks and placebo patches for the second, and group 2 received the same treatments in the reverse order. The effect of combined estradiol plus oral norethisterone acetate (NETA) 1 mg was also evaluated in the subset of women with intact uteri (n = 24). Crossover analysis showed that stroke volume and cardiac output were significantly higher (P < 0.05) and blood pressure was significantly lower (P < 0.05) with estradiol, irrespective of the order in which the treatments were administered. Although correlations between plasma estradiol levels during active treatment and hemodynamic changes were not significant, hemodynamic changes were significantly greater above 63 pg/ml than below this level (P < 0.05). Oral norethisterone acetate administration either during transdermal placebo or estradiol arms tended to modify systemic hemodynamics in the same direction than estradiol but the changes did not attained statistical significance. In summary compared with placebo, transdermal 17 beta-estradiol, replacement to postmenopausal women, increased cardiac output and decreased blood pressure. Although the average magnitude of changes was small, the results suggest that plasma estradiol levels could be a source of individual variability in the hemodynamic response. Oral NETA administration tended to enhance rather than reverse the estradiol-induced changes.