Efficacy of exercise, losartan, enalapril, atenolol and rilmenidine in subjects with blood pressure hyperreactivity at treadmill stress test and left ventricular hypertrophy.

High levels of activity of the renin-angiotensin system (RAS) and sympathetic nervous system (SNS) are related to left ventricular hypertrophy (LVH). A percentage of subjects with hyperactivity to treadmill stress test show LVH to echocardiogram. This paper aims at evaluating neurohumoral influence over these subjects by comparing drugs that block both the RAS and the SNS. In a 1-year open protocol, 195 normotensive subjects, with hyperactivity to treadmill stress test and LVH, were randomly assigned to supervised physical exercise, rilmenidine 1 mg day(-1), atenolol 50 mg day(-1), enalapril 10 mg day(-1) or losartan 50 mg day(-1). Changes in left ventricular mass index (LVMI), measured by means of echocardiogram, were the primary end point. Changes in systolic blood pressure (SBP) at rest and peak effort were also evaluated. Enalapril significantly brought LVMI down in relation to the basal value (28.2%; n=36) similarly to losartan (26.9%; n=42); P>0.05. However, both were more efficient than physical exercise (2.9%; n=39), rilmenidine (5.1%; n=38) and atenolol (7.2%; n=40); P<0.001. There was no significant difference in SBP reduction at rest and peak effort in groups assigned to atenolol, enalapril and losartan; P>0.05. In such groups, reduction was greater than in groups assigned to physical exercise and rimenidine; P<0.001. In conclusion, drugs that block RAS were more efficient in reducing LVH than physical exercise and drugs that block SNS, and such reduction took place regardless of SBP level reduction at rest and peak effort.

Obesity, estrone, and coronary artery disease in postmenopausal women.

OBJECTIVES: The link between obesity and endogenous estrogen with coronary artery disease (CAD) in postmenopausal women is uncertain. In this prospective study we analyzed the association of body mass index (BMI) and blood levels of estrone in postmenopausal women with known CAD or with a high risk factor score for CAD. METHODS: Participants were 251 female clinic patients aged 50-90 years who were postmenopausal and not using estrogen therapy. Clinical and behavioral characteristics and fasting blood for estrone and heart disease risk factors were collected at baseline, and again at 1 and 2 years. Women were grouped according to their BMI (kg/m2) as normal (18.5< or =BMI<25), overweight (25< or =BMI<30) or obese (BMI > or =30), and by low and high estrone levels (<15 and > or =15pg/mL, respectively). Fatal and nonfatal events were recorded for 2 years after baseline. RESULTS: Women with a low estrone level were older, thinner, and had less hypertension, diabetes, and lower triglyceride and glucose levels. BMI was positively associated with estrone levels, hypertension, and diabetes and inversely associated with HDL cholesterol. There were 14 deaths, 8 attributed to CAD. The Kaplan-Meier survival curve showed a nonsignificant trend (p=0.074) of greater all cause mortality in women with low estrone levels (<15mL). In this model, adjusted for BMI, age [OR=1.08; p=0.03], C-reactive protein [OR=1.24; p=0.024] and hypertension [OR=6.22; p=0.003] were independent predictors of all cause mortality. CONCLUSIONS: Postmenopausal women with low estrone levels (<15pg/mL) had a trend for increased mortality over the next 2 years. Larger, longer studies are needed.

Effects of estradiol alone and combined with norethisterone acetate on pulse-wave velocity in hypertensive postmenopausal women.

BACKGROUND: Arterial hypertension and postmenopausal reduction of estrogen levels may be involved in modifications of the stiffness of large arteries. OBJECTIVES: To evaluate the pulse-wave velocity (PWV) and indirectly the arterial stiffness in hypertensive postmenopausal women submitted to hormone therapy with estradiol alone or combined with norethisterone acetate. SUBJECTS: Forty-five hypertensive postmenopausal women were double-blindly, randomly assigned to three arms of treatment: placebo (group I); estradiol 2 mg/day (group II); or estradiol 2 mg/day and norethisterone acetate 1 mg/day (group III). METHODS: Arterial stiffness was assessed from PWV measurements of the common carotid and femoral arteries (CF-PWV) and the common carotid and radial arteries (CR-PWV) obtained using the automatic Complior(R) device, taken at baseline and after 12 weeks of treatment. RESULTS: After the 12-week treatment, values of CF-PWV and CR-PWV were not significantly different (p = 0.910 and p = 0.736, respectively) among the groups. Systolic blood pressure showed a positive correlation with CF-PWV in groups II and III (p = 0.02 and p < 0.001, respectively). CONCLUSIONS: PWV and arterial stiffness in postmenopausal hypertensive women did not reduce over a 12-week treatment with estradiol alone compared with the same period of treatment with estradiol combined with norethisterone acetate.

Bioeffects of albumin-encapsulated microbubbles and real-time myocardial contrast echocardiography in an experimental canine model.

Myocardial contrast echocardiography has been used for assessing myocardial perfusion. Some concerns regarding its safety still remain, mainly regarding the induction of microvascular alterations. We sought to determine the bioeffects of microbubbles and real-time myocardial contrast echocardiography (RTMCE) in a closed-chest canine model. Eighteen mongrel dogs were randomly assigned to two groups. Nine were submitted to continuous intravenous infusion of perfluorocarbon-exposed sonicated dextrose albumin (PESDA) plus continuous imaging using power pulse inversion RTMCE for 180 min, associated with manually deflagrated high-mechanical index impulses. The control group consisted of 3 dogs submitted to continuous imaging using RTMCE without PESDA, 3 dogs received PESDA alone, and 3 dogs were sham-operated. Hemodynamics and cardiac rhythm were monitored continuously. Histological analysis was performed on cardiac and pulmonary tissues. No hemodynamic changes or cardiac arrhythmias were observed in any group. Normal left ventricular ejection fraction and myocardial perfusion were maintained throughout the protocol. Frequency of mild and focal microhemorrhage areas in myocardial and pulmonary tissue was similar in PESDA plus RTMCE and control groups. The percentages of positive microscopical fields in the myocardium were 0.4 and 0.7% (P = NS) in the PESDA plus RTMCE and control groups, respectively, and in the lungs they were 2.1 and 1.1%, respectively (P = NS). In this canine model, myocardial perfusion imaging obtained with PESDA and RTMCE was safe, with no alteration in cardiac rhythm or left ventricular function. Mild and focal myocardial and pulmonary microhemorrhages were observed in both groups, and may be attributed to surgical tissue manipulation.

Exercise stress testing before and after successful multivessel percutaneous transluminal coronary angioplasty.

Controversy exists regarding the diagnostic accuracy, optimal technique, and timing of exercise testing after percutaneous coronary intervention. The objectives of the present study were to analyze variables and the power of exercise testing to predict restenosis or a new lesion, 6 months after the procedure. Eight-four coronary multi-artery diseased patients with preserved ventricular function were studied (66 males, mean age of all patients: 59 +/- 10 years). All underwent coronary angiography and exercise testing with the Bruce protocol, before and 6 months after percutaneous coronary intervention. The following parameters were measured: heart rate, blood pressure, rate-pressure product (heart rate x systolic blood pressure), presence of angina, maximal ST-segment depression, and exercise duration. On average, 2.33 lesions/patient were treated and restenosis or progression of disease occurred in 46 (55%) patients. Significant increases in systolic blood pressure (P = 0.022), rate-pressure product (P = 0.045) and exercise duration (P = 0.003) were detected after the procedure. Twenty-seven (32%) patients presented angina during the exercise test before the procedure and 16 (19%) after the procedure. The exercise test for the detection of restenosis or new lesion presented 61% sensitivity, 63% specificity, 62% accuracy, and 67 and 57% positive and negative predictive values, respectively. In patients without restenosis, the exercise duration after percutaneous coronary intervention was significantly longer (460 +/- 154 vs 381 +/- 145 s, P = 0.008). Only the exercise duration permitted us to identify patients with and without restenosis or a new lesion.

Exercise stress testing before and after successful multivessel percutaneous transluminal coronary angioplasty

Controversy exists regarding the diagnostic accuracy, optimal technique, and timing of exercise testing after percutaneous coronary intervention. The objectives of the present study were to analyze variables and the power of exercise testing to predict restenosis or a new lesion, 6 months after the procedure. Eight-four coronary multi-artery diseased patients with preserved ventricular function were studied (66 males, mean age of all patients: 59 ± 10 years). All underwent coronary angiography and exercise testing with the Bruce protocol, before and 6 months after percutaneous coronary intervention. The following parameters were measured: heart rate, blood pressure, rate-pressure product (heart rate x systolic blood pressure), presence of angina, maximal ST-segment depression, and exercise duration. On average, 2.33 lesions/patient were treated and restenosis or progression of disease occurred in 46 (55 percent) patients. Significant increases in systolic blood pressure (P = 0.022), rate-pressure product (P = 0.045) and exercise duration (P = 0.003) were detected after the procedure. Twenty-seven (32 percent) patients presented angina during the exercise test before the procedure and 16 (19 percent) after the procedure. The exercise test for the detection of restenosis or new lesion presented 61 percent sensitivity, 63 percent specificity, 62 percent accuracy, and 67 and 57 percent positive and negative predictive values, respectively. In patients without restenosis, the exercise duration after percutaneous coronary intervention was significantly longer (460 ± 154 vs 381 ± 145 s, P = 0.008). Only the exercise duration permitted us to identify patients with and without restenosis or a new lesion.

Assessment of the cardiovascular effects of electroconvulsive therapy in individuals older than 50 years.

To evaluate the impact of electroconvulsive therapy on arterial blood pressure, heart rate, heart rate variability, and the occurrence of ischemia or arrhythmias, 38 (18 men) depressive patients free from systemic diseases, 50 to 83 years old (mean: 64.7 +/- 8.6) underwent electroconvulsive therapy. All patients were studied with simultaneous 24-h ambulatory blood pressure and Holter monitoring, starting 18 h before and continuing for 3 h after electroconvulsive therapy. Blood pressure, heart rate, heart rate variability, arrhythmias, and ischemic episodes were recorded. Before each session of electroconvulsive therapy, blood pressure and heart rate were in the normal range; supraventricular ectopic beats occurred in all patients and ventricular ectopic beats in 27/38; 2 patients had non-sustained ventricular tachycardia. After shock, systolic, mean and diastolic blood pressure increased 29, 25, and 24% (P < 0.001), respectively, and returned to baseline values within 1 h. Maximum, mean and minimum heart rate increased 56, 52, and 49% (P < 0.001), respectively, followed by a significant decrease within 5 min; heart rate gradually increased again thereafter and remained elevated for 1 h. Analysis of heart rate variability showed increased sympathetic activity during shock with a decrease in both sympathetic and parasympathetic drive afterwards. No serious adverse effects occurred; electroconvulsive therapy did not trigger any malignant arrhythmias or ischemia. In middle-aged and elderly people free from systemic diseases, electroconvulsive therapy caused transitory increases in blood pressure and heart rate and a decrease in heart rate variability but these changes were not associated with serious adverse clinical events.

Assessment of the cardiovascular effects of electroconvulsive therapy in individuals older than 50 years

To evaluate the impact of electroconvulsive therapy on arterial blood pressure, heart rate, heart rate variability, and the occurrence of ischemia or arrhythmias, 38 (18 men) depressive patients free from systemic diseases, 50 to 83 years old (mean: 64.7 ± 8.6) underwent electroconvulsive therapy. All patients were studied with simultaneous 24-h ambulatory blood pressure and Holter monitoring, starting 18 h before and continuing for 3 h after electroconvulsive therapy. Blood pressure, heart rate, heart rate variability, arrhythmias, and ischemic episodes were recorded. Before each session of electroconvulsive therapy, blood pressure and heart rate were in the normal range; supraventricular ectopic beats occurred in all patients and ventricular ectopic beats in 27/38; 2 patients had non-sustained ventricular tachycardia. After shock, systolic, mean and diastolic blood pressure increased 29, 25, and 24 percent (P < 0.001), respectively, and returned to baseline values within 1 h. Maximum, mean and minimum heart rate increased 56, 52, and 49 percent (P < 0.001), respectively, followed by a significant decrease within 5 min; heart rate gradually increased again thereafter and remained elevated for 1 h. Analysis of heart rate variability showed increased sympathetic activity during shock with a decrease in both sympathetic and parasympathetic drive afterwards. No serious adverse effects occurred; electroconvulsive therapy did not trigger any malignant arrhythmias or ischemia. In middle-aged and elderly people free from systemic diseases, electroconvulsive therapy caused transitory increases in blood pressure and heart rate and a decrease in heart rate variability but these changes were not associated with serious adverse clinical events.

Effect of sexual steroids on the calcium content of aortic atherosclerotic plaque of oophorectomized rabbits.

We determined the effect of conjugated equine estrogen plus medroxyprogesterone acetate on calcium content of aortic atherosclerotic lesions in oophorectomized adult New Zealand rabbits submitted to a cholesterol rich diet. Five groups of 10 animals each were studied: G1 = control, G2 = cholesterol diet only, G3 = diet plus conjugated equine estrogen (0.625 mg/day); G4 and G5 = diet, conjugated equine estrogen (0.625 mg/day) plus medroxyprogesterone acetate (5 and 10 mg/day, respectively). Mean weight varied from 2.7 +/- 0.27 to 3.1 +/- 0.20 kg (P = 0.38) between groups at the beginning and 3.1 +/- 0.27 to 3.5 +/- 0.20 kg (P = 0.35) at the end of the experiment. Cholesterol and triglyceride levels were determined at the time of oophorectomy, 21 days after surgery (time 0), and at the end of follow-up of 90 days. The planimetric method was used to measure plaque and caryometric method for histopathologic examination of the aorta. Calcium content was determined by the method of von Kossa. A similar increase in cholesterol occurred in all treated groups without differences between them at the end of the study. Groups G4 and G5 had smaller areas of atherosclerotic lesions (2.33 +/- 2.8 and 2.45 +/- 2.1 cm(2), respectively) than the groups receiving no progestogens (G2: 5.6 +/- 4 and G3: 4.6 +/- 2.8 cm(2); P = 0.02). The relation between lesion area and total aorta area was smaller in groups treated with combined drugs compared to the groups receiving no progesterone (G4: 14.9 +/- 13 and G5: 14.2 +/- 13.4 vs G2: 35.8 +/- 26 and G3: 25 +/- 8 cm(2), respectively; P = 0.017). Oral conjugated equine estrogen (0.625 mg/day) plus medroxyprogesterone acetate (5 or 10 mg/day) provoked a greater reduction in atherosclerotic plaque area and calcium content in treated groups, suggesting a dose-dependent effect.

Effect of sexual steroids on the calcium content of aortic atherosclerotic plaque of oophorectomized rabbits

We determined the effect of conjugated equine estrogen plus medroxyprogesterone acetate on calcium content of aortic atherosclerotic lesions in oophorectomized adult New Zealand rabbits submitted to a cholesterol rich diet. Five groups of 10 animals each were studied: G1 = control, G2 = cholesterol diet only, G3 = diet plus conjugated equine estrogen (0.625 mg/day); G4 and G5 = diet, conjugated equine estrogen (0.625 mg/day) plus medroxyprogesterone acetate (5 and 10 mg/day, respectively). Mean weight varied from 2.7 ± 0.27 to 3.1 ± 0.20 kg (P = 0.38) between groups at the beginning and 3.1 ± 0.27 to 3.5 ± 0.20 kg (P = 0.35) at the end of the experiment. Cholesterol and triglyceride levels were determined at the time of oophorectomy, 21 days after surgery (time 0), and at the end of follow-up of 90 days. The planimetric method was used to measure plaque and caryometric method for histopathologic examination of the aorta. Calcium content was determined by the method of von Kossa. A similar increase in cholesterol occurred in all treated groups without differences between them at the end of the study. Groups G4 and G5 had smaller areas of atherosclerotic lesions (2.33 ± 2.8 and 2.45 ± 2.1 cm², respectively) than the groups receiving no progestogens (G2: 5.6 ± 4 and G3: 4.6 ± 2.8 cm²; P = 0.02). The relation between lesion area and total aorta area was smaller in groups treated with combined drugs compared to the groups receiving no progesterone (G4: 14.9 ± 13 and G5: 14.2 ± 13.4 vs G2: 35.8 ± 26 and G3: 25 ± 8 cm², respectively; P = 0.017). Oral conjugated equine estrogen (0.625 mg/day) plus medroxyprogesterone acetate (5 or 10 mg/day) provoked a greater reduction in atherosclerotic plaque area and calcium content in treated groups, suggesting a dose-dependent effect.

Avaliação de reserva de fluxo coronariano e miocárdico pela ecodopplercardiografia transtorácica e ecocardiografia com contraste miocárdico em pacientes com lesão na artéria coronária descendente anterior / Detection of left anterior descending coronary artery obstruction by real time myocardial contrast echocardiography with adenosine. A head to head comparison with transthoracic doppler

Embora a ecocardiografia com perfusão miocárdica em tempo real (EPTR) permita detectar doença arterial coronária (DAC), sua correlação com reserva de fluxo coronário (RFC) obtida pelo estudo Doppler não foi demonstrada. Objetivo: Comparar a RFC obtida pela EPTR e pelo Doppler no território da artéria coronária descendente anterior (ADA) em pacientes com suspeita de DAC. Métodos: Avaliamos prospectivamente 44 pacientes (18 homens, 57 +- 13 anos) com EPTR em repouso e durante infusão de adenosi na 140 mcg/kg/min. Quantificação do pico de intensidade miocárdica (A), velocidade das microbolha (B) e RFC pela EPTR foi realizada utilizando software específico (Q-lab-Philip Medical Systems).A RFC foi obtida pelo Doppler como a relação entre a velocidade de pico diastólica durante hiperemia e no estado basal. Todos os pacientes foram submetidos à angiografia quantitativa dentro de 7 dias. Valores de 1,7 e 2,4 de RFC pela EPTR e pelo Doppler foram utilizados para identificação DAC (estenoses >50 por cento) na ADA. Resultados: A exeqüibilidade foi de 84 por cento para aquisição adequada dos fluxos Doppler da ADA e 86 por cento para a quantificação da reserva de fluxo pela EPTR. A sensibilidade e a especificidade e acurácia para de detecção de obstrução coronariana ou não no território da ADA baseado nas análises de reservas de fluxo foram respectivamente de 96 por cento,87 por cento e 93 por cento para o Doppler da ADA, de 94 por cento, 86 por cento e 89 por cento para o índice de fluxo miocárdico (AxB) e de 75 por cento, 81 por cento e 77 por cento para a velocidade de fluxo miocárdico (B). Pela análise de regressão logística, o estudo com Doppler da ADA foi o parâmetro que melhor diferenciou os pacientes com e sem lesão na ADA (Odds Ratio 0,01 - intervalo de confiança de 95 por cento de 0,001 a 0,136).Conclusão: A avaliação da RFC e miocárdio, tanto pelo Doppler da ADA quanto pela EPTR foram capazes de diferenciar precisamente os indivíduos com lesão na ADA. No entanto, a acurácia diagnóstica pelo Doppler da ADA foi superior aos outros parâmetros analisados.

Temperature, air pollution, and mortality from myocardial infarction in São Paulo, Brazil.

An increase in daily mortality from myocardial infarction has been observed in association with meteorological factors and air pollution in several cities in the world, mainly in the northern hemisphere. The objective of the present study was to analyze the independent effects of environmental variables on daily counts of death from myocardial infarction in a subtropical region in South America. We used the robust Poisson regression to investigate associations between weather (temperature, humidity and barometric pressure), air pollution (sulfur dioxide, carbon monoxide, and inhalable particulate), and the daily death counts attributed to myocardial infarction in the city of São Paulo in Brazil, where 12,007 fatal events were observed from 1996 to 1998. The model was adjusted in a linear fashion for relative humidity and day-of-week, while nonparametric smoothing factors were used for seasonal trend and temperature. We found a significant association of daily temperature with deaths due to myocardial infarction (P < 0.001), with the lowest mortality being observed at temperatures between 21.6 and 22.6 degrees C. Relative humidity appeared to exert a protective effect. Sulfur dioxide concentrations correlated linearly with myocardial infarction deaths, increasing the number of fatal events by 3.4% (relative risk of 1.03; 95% confidence interval = 1.02-1.05) for each 10 microg/m(3) increase. In conclusion, this study provides evidence of important associations between daily temperature and air pollution and mortality from myocardial infarction in a subtropical region, even after a comprehensive control for confounding factors.

Temperature, air pollution, and mortality from myocardial infarction in São Paulo, Brazil

An increase in daily mortality from myocardial infarction has been observed in association with meteorological factors and air pollution in several cities in the world, mainly in the northern hemisphere. The objective of the present study was to analyze the independent effects of environmental variables on daily counts of death from myocardial infarction in a subtropical region in South America. We used the robust Poisson regression to investigate associations between weather (temperature, humidity and barometric pressure), air pollution (sulfur dioxide, carbon monoxide, and inhalable particulate), and the daily death counts attributed to myocardial infarction in the city of São Paulo in Brazil, where 12,007 fatal events were observed from 1996 to 1998. The model was adjusted in a linear fashion for relative humidity and day-of-week, while nonparametric smoothing factors were used for seasonal trend and temperature. We found a significant association of daily temperature with deaths due to myocardial infarction (P < 0.001), with the lowest mortality being observed at temperatures between 21.6 and 22.6ºC. Relative humidity appeared to exert a protective effect. Sulfur dioxide concentrations correlated linearly with myocardial infarction deaths, increasing the number of fatal events by 3.4 percent (relative risk of 1.03; 95 percent confidence interval = 1.02-1.05) for each 10 µg/m increase. In conclusion, this study provides evidence of important associations between daily temperature and air pollution and mortality from myocardial infarction in a subtropical region, even after a comprehensive control for confounding factors.

Acute and chronic effects of oestradiol on left ventricular diastolic function in hypertensive postmenopausal women with left ventricular diastolic dysfunction.

BACKGROUND: Left ventricular function changes in the postmenopausal state. However, there are conflicting reports about the effects of oestrogen on left ventricular diastolic function in postmenopausal women. OBJECTIVE: To evaluate the acute and chronic effects of oestradiol in physiological doses on diastolic heart function in hypertensive postmenopausal women with left ventricular diastolic dysfunction. METHODS: A prospective, randomised, double blind, placebo controlled study was used to evaluate the effects of oestradiol in 34 hypertensive women with left ventricular dysfunction. The acute effects of a single 1 mg oral dose of oestradiol or placebo were determined after 90 minutes. The chronic effects of 1 mg oestradiol orally/day or placebo were determined after 12 weeks. Diastolic functional indices (mitral flow and pulmonary venous flow) were assessed by Doppler echocardiography. RESULTS: Though an appropriate serum concentration was achieved, no acute effect of oestradiol administration on left ventricular diastolic function was identified. After 12 weeks of treatment the following changes (mean (SD)) were identified in the oestradiol group: a decrease in isovolumic relaxation time from 127 (23) to 106 (16) ms (p < 0.001), and in the deceleration time of the mitral E wave from 260 (42) to 238 (20) ms (p < 0.05); and an increase in the E/A ratio from 0.8 (0.2) (basal) to 1.0 (0.2) after 12 weeks (p < 0.001). CONCLUSIONS: Hypertensive postmenopausal women who had hormone replacement therapy over a period of 12 weeks had significant improvement in left ventricular diastolic function. No changes were identified following acute administration.

Effects of estradiol on myocardial global performance index in hypertensive postmenopausal women.

The objective of this study was to assess the acute and chronic effects of estradiol on the myocardial performance index (MPI) in hypertensive postmenopausal women. There are conflicting reports on the effects of estrogen on left ventricular function in postmenopausal women, and we are unaware of any study on the myocardial performance index in the postmenopausal state. We undertook a prospective, randomized, double-blind, placebo-controlled study in 34 women, distributed into an estradiol group or a placebo group. After 90 min and at 12 weeks of administration of 1 mg of oral estradiol we evaluated, by Doppler echocardiography, its effects on the MPI. The estradiol group showed no alteration in the MPI after 90 min of the administration of estradiol. On the other hand, after 12 weeks of treatment we observed a statistically significant decrease of isovolumic relaxation time, from 127+/-23 ms to 106+/-16 ms (p < 0.001 and of the MPI from 0.63+/-0.13 to 0.48+/-0.09 (p < 0.01) and an increase in ejection time, from 297+/-32 ms to 330+/-31 ms (p < 0.01). In conclusion, estrogen replacement therapy over a period of 12 weeks showed a significant improvement in the MPI in hypertensive postmenopausal women, whereas the acute administration did not have any effect.

Antagonism of the acute hemodynamic effects of captopril in decompensated congestive heart failure by aspirin administration.

The concomitant use of angiotensin-converting enzyme inhibitors and aspirin may cause pharmacological antagonism. Hence we examined the effect of aspirin on the neurohormonal function and hemodynamic response to captopril in heart failure patients. Between April 1999 and August 2000, 40 patients were randomized into four equal groups: 1) captopril, 2) aspirin, 3) captopril-aspirin: captopril was given alone on the first day, followed by aspirin on the remaining days, and 4) aspirin-captopril: aspirin was given alone on the first day, followed by captopril on the remaining days. Hemodynamic, norepinephrine and prostaglandin measurements were performed pre- and post-medication for 4 days. Captopril (50 mg) was given orally every 8 h and 300 mg aspirin was given on the first day, and 100 mg/day thereafter. In the captopril group and only on the first day of captopril-aspirin, captopril produced increases in cardiac index (2.1 +/- 0.6 to 2.5 +/- 0.5 l min-1 m-2, P<0.0001), and reduced peripheral vascular resistance (1980 +/- 580 to 1545 +/- 506 dyn s-1 cm-5/m , P<0.0001) and pulmonary wedge pressure (20 +/- 4 to 15 +/- 4 mmHg, P<0.0001). In contrast, aspirin alone or associated with captopril showed no significant hemodynamic changes. Norepinephrine decreased (P<0.02) only in the captopril group. Prostaglandin levels did not differ significantly among groups. Thus, aspirin compromises the short-term hemodynamic and neurohormonal effects of captopril in patients with acute decompensated heart failure.

Antagonism of the acute hemodynamic effects of captopril in decompensated congestive heart failure by aspirin administration

The concomitant use of angiotensin-converting enzyme inhibitors and aspirin may cause pharmacological antagonism. Hence we examined the effect of aspirin on the neurohormonal function and hemodynamic response to captopril in heart failure patients. Between April 1999 and August 2000, 40 patients were randomized into four equal groups: 1) captopril, 2) aspirin, 3) captopril-aspirin: captopril was given alone on the first day, followed by aspirin on the remaining days, and 4) aspirin-captopril: aspirin was given alone on the first day, followed by captopril on the remaining days. Hemodynamic, norepinephrine and prostaglandin measurements were performed pre- and post-medication for 4 days. Captopril (50 mg) was given orally every 8 h and 300 mg aspirin was given on the first day, and 100 mg/day thereafter. In the captopril group and only on the first day of captopril-aspirin, captopril produced increases in cardiac index (2.1 + or - 0.6 to 2.5 + or - 0.5 l min-1 m-2, P<0.0001), and reduced peripheral vascular resistance (1980 + or - 580 to 1545 + or - 506 dyn s-1 cm-5/m2, P<0.0001) and pulmonary wedge pressure (20 + or - 4 to 15 + or - 4 mmHg, P<0.0001). In contrast, aspirin alone or associated with captopril showed no significant hemodynamic changes. Norepinephrine decreased (P<0.02) only in the captopril group. Prostaglandin levels did not differ significantly among groups. Thus, aspirin compromises the short-term hemodynamic and neurohormonal effects of captopril in patients with acute decompensated heart failure

Etofibrate but not controlled-release niacin decreases LDL cholesterol and lipoprotein (a) in type IIb dyslipidemic subjects

Etofibrate is a hybrid drug which combines niacin with clofibrate. After contact with plasma hydrolases, both constituents are gradually released in a controlled-release manner. In this study, we compared the effects of etofibrate and controlled-release niacin on lipid profile and plasma lipoprotein (a) (Lp(a)) levels of patients with triglyceride levels of 200 to 400 mg/dl, total cholesterol above 240 mg/dl and Lp(a) above 40 mg/dl. These patients were randomly assigned to a double-blind 16-week treatment period with etofibrate (500 mg twice daily, N = 14) or niacin (500 mg twice daily, N = 11). In both treatment groups total cholesterol, VLDL cholesterol and triglycerides were equally reduced and high-density lipoprotein cholesterol was increased. Etofibrate, but not niacin, reduced Lp(a) by 26 percent and low-density lipoprotein (LDL) cholesterol by 23 percent. The hybrid compound etofibrate produced a more effective reduction in plasma LDL cholesterol and Lp(a) levels than controlled-release niacin in type IIb dyslipidemic subjects