Evaluation of the effects of a new fermented milk product (Gaio) on primary hypercholesterolemia.

OBJECTIVE: To verify the effects on the lipid profile of a product of fermented milk (Gaio) in patients with mild to moderate primary hypercholesterolemia. DESIGN: The study was prospective, randomized, double-blinded and placebo controlled, with a crossover design. SUBJECTS: Thirty-two patients (21 women and 11 men) with ages ranging between 36 and 65 years old were included in the study. All of them were on a controlled diet for at least 8 weeks. INTERVENTION: Patients began, after clinical and laboratory analysis, in a randomized and double-blind manner to take 200 g daily of Gaio or its placebo. After 8 weeks blood was collected again for lipid profile evaluation and the crossover was made. After an additional 8 weeks blood was collected for another lipid profile determination. RESULTS: All patients included completed the study. Comparisons were made between means of lipid profile constituents after the placebo and active product periods. These showed significant mean reduction of 5.3% (P = 0.004) for total cholesterol, 6.15% (P = 0.012) for LDL-cholesterol and no significant variation for HDL-cholesterol and triglycerides. The majority of patients presented no variation or had a decrease in their total cholesterol level. However, during the active product period, three patients showed an increase in cholesterol level by more than 5%. CONCLUSION: The fermented milk (Gaio) produced a small but statistically significant decrease in total and LDL-cholesterol mean. However, not all subjects seem to respond to the product, and a few subjects showed a cholesterol increment. Further investigations are necessary to clarify this aspect.

[Impact of new knowledge about physiopathology on the treatment of myocardial ischemia]. / Impacto dos novos conhecimentos de fisiopatologia na terapêutica da isquemia miocárdica.

Unstable coronary syndromes-unstable angina, acute myocardial infarction and sudden death-share a common pathophysiology, characterized by the rupture or fissure of an atherosclerotic plaque in the ischemic event related artery. This change marks the transitions from chronic, stable to acute, unstable coronary artery disease. The events that follow plaque rupture, namely platelet adhesion and aggregation, are largely responsible for endothelial injury and the interaction of the plaque components with the blood cells. Such phenoma are not isolated or self contained, but rather dynamic and inter-related. Advances in the knowledge of unstable acute syndromes had a major impact on the therapy of these conditions, particularly on the clinical approach. Besides alleviating and preventing the onset of symptoms reducing total ischemic burden, myocardial protection and preventing or improving left ventricular dysfunction, the new management of unstable coronary syndromes highlights the use of antithrombotic drugs and measures, pharmacological or not, aimed at the protection of the endothelium, stabilization of the plaque and control or even regression of atherosclerosis. Such an approach yields significant coronary event reduction, improved quality of life and increased survival.

Beta-adrenergic blocking agents in heart failure.

Cardiac dysfunction in heart failure is widely recognized as a progressive process, regardless of the clinical signs and symptoms. An increase in cardiac sympathetic drive is one of the earliest neurohormonal responses occurring in patients with heart failure and may be one of the major causes of the progressive remodeling leading to the decline in myocardial function, and responsible for the poor prognosis of patients with heart failure. Therefore, recent data provided by several appropriately designed clinical trials clearly indicate the benefits of beta-adrenoceptor blocking agents, combined with diuretics, ACE inhibitors, and digoxin in chronic heart failure class II to IV due to systolic ventricular dysfunction. The benefits are related to symptoms, functional capacity, remodeling, and improvement in left ventricular function, reduction in cardiovascular hospitalization, a decrease in the overall and sudden cardiac death rate, and are similar in patients with ischemic or nonischemic cardiomyopathy, independent of age, gender, or functional class. In this review we describe the cardiovascular effects of the increase in sympathetic drive, the pharmacological properties of the beta-blockers most evaluated in heart failure therapy (metoprolol, bisoprolol, and carvedilol), the major clinical trials related to these agents in heart failure, the recommendations for their appropriate use in clinical practice, the precautions to be adopted, and how to handle the more common adverse reactions.

[Effects of enalapril on left ventricular hypertrophy in patients with mild or moderate essential hypertension]. / Efeitos do enalapril na hipertrofia ventricular esquerda em pacientes com hipertensão essencial leve ou moderada.

PURPOSE: To evaluate the effects of enalapril maleate on the regression of left ventricular hypertrophy (LVH) associated to hypertension. PATIENTS AND METHODS: Fifteen male, age between 45 and 65 years (mean age = 56 y) with diagnosis of mild-to-moderate essential hypertension (greater than diastolic blood pressure [DBP] less than between 90 and 114 mmHg) and LHV at the echocardiogram. The administration of enalapril maleate was initiated with a 20 mg daily dosage and titrated up to a maximum of 40 mg daily, whenever DBP was maintained above 90 mmHg and no adverse experience occurred. RESULTS: Fourteen patients completed the clinical trial and all of them achieved satisfactory blood pressure (BP) control. The dosage of enalapril was 20 mg/day for 11 patients and 40 mg/day for the other three. The mean systolic blood pressure in supine position decreased from an initial value of 151.4 +/- 9.5 to 126.4 +/- 9.4 mmHg at the end of treatment and the mean diastolic blood pressure from 100.0 +/- 5.0 to 80.4 +/- 1.5 mmHg (p less than 0.001). There was a reduction of mean diastolic septal wall thickness from 11.5 +/- 0.05 to 10.1 +/- 0.05 mm and left ventricular posterior wall thickness from 11.2 +/- 0.7 to 9.8 +/- 0.6 mm (p less than 0.05). The diastolic dimension and left ventricular volume did not show significant changes. The mean of calculated left ventricular mass showed a decrease from 263.6 +/- 32.9 to 231.3 +/- 34.7 g at the end of treatment (p less than 0.05). Mean ejection fraction and fractional fiber shortening showed light, but non significant increase. The tolerability to the drug was satisfactory. Two patients complained of transient palpitations and two other, irritative cough, that determined the treatment discontinuation in one case. CONCLUSION: Enalapril maleate 20 to 40 mg daily, besides the satisfactory control of BP in patients with mild-to-moderate essential hypertension, promoted regression of left ventricular hypertrophy, without impairment of left ventricular function.

[Antihypertensive effect of urapidil in mild to moderate arterial hypertension. Randomized, double-blind versus placebo study]. / Efeito anti-hipertensivo de urapidil em hipertensão arterial leve a moderada. Estudo randomizado, duplo-cego, contra placebo.

PURPOSE: To evaluate the efficacy and tolerability of urapidil (a new central and peripheral antihypertensive agent) in patients with mild to moderate essential hypertension. METHODS: Thirty-one patients were randomized, double-blindly, to receive either placebo (15 patients) or urapidil (16 patients) for 3 months. The initial dose of urapidil was 30mg twice daily, per oral. The dose was increased progressively till achievement of good blood pressure control or the dose of 60mg three times a day. RESULTS: Seventy percent of the patients on urapidil group responded to therapy against 30% on the placebo group. There were 3 cases of hypertensive crises (2 on urapidil and 1 on placebo) on the early therapy. The adverse events with urapidil were unfrequent and the most common were headache and dizziness. There were no modification on blood sugar and lipids level. CONCLUSION: Urapidil appears to be a safe antihypertensive agent in the treatment of mild to moderate essential hypertension. It also did not demonstrate any clinical effect on the carbohydrates and lipids profile.

[Brazilian study with alteplase in acute myocardial infarction--EBRALT]. / Estudo Brasileiro com alteplase no infarto agudo do miocárdio--EBRALT.

PURPOSE: Prospective evaluation of the effects of the intravenous administration of rt-PA (Alteplase) up to 6 hours after the pain onset on the patency of the AMI related artery, mortality, adverse reactions and complications. METHODS: Open, multicenter, non-comparative study involving 139 patients with diagnosis of AMI, with less than 6h of duration. The rt-PA was intravenously administered, in a dose of 100mg, as follows: 10mg in the 1st 2min, 50mg in 58min and 40mg in 120min. In addition, the patients received intravenous heparin (5000 IU at first and then, 1000 IU/hour, for 24h), aspirin (500mg in the 1st day and then, 100mg/day) and dipyridamole (75mg, three times a day), during the hospitalization period. The angiographic study was performed in 129 (93%) patients, within the 1st week of AMI. RESULTS: The age of the patients ranged from 29 to 85 (mean 56.6 +/- 10.3) years. The related artery for the AMI was patent (TIMI II and III flow) in 92/129 (71%) patients, with a mean ejection fraction of 50 +/- 14%, a value higher than that exhibited by patients with TIMI 0 and I flow (average ejection fraction = 44 +/- 14%). Reinfarction was diagnosed in 9 (6.4%) patients during the hospitalization period. During this period, there were 9 (6.4%) deaths. Minor hemorrhages were observed in 19 (12%) patients and major hemorrhages in 3 (2%) cases. No patient experienced stroke. CONCLUSION: The administration of the rt-PA therapy in the AMI was associated to a high reperfusion index of the related artery for the infarction, with improved left ventricular function and low incidence of reinfarction and in-hospital mortality, as well as, complications.

[Blood pressure variability and left ventricular hypertrophy in arterial hypertension]. / Variabilidade da pressão arterial e hipertrofia ventricular esquerda na hipertensão arterial.

PURPOSE: To evaluate the left ventricular hypertrophy correlation with blood pressure variability during day and night time as well as throughout the 24h period. METHODS: Fifteen patients with mild to moderate essential hypertension underwent to bi-dimensional echocardiographic study and to 24h ambulatory blood pressure monitorization. Left ventricular mass was calculated according to previous validated formulas. The standard deviation of the mean blood pressures during day-time, night-time and 24h period was taken as blood pressure variability indices. The mean age of the group was 42 years old; 9 patients were male and all were white. RESULTS: This study showed that only the systolic and diastolic blood pressure variability during the 24h period correlated significantly with left ventricular mass, (r = 0.53 and p < 0.05; r = 0.58 and p < 0.05 respectively). There was no significant correlation of the day-time and night-time pressures variability with left ventricular mass. CONCLUSION: The systolic and diastolic blood pressure variability during the 24h period may be one of the many determinants of left ventricular hypertrophy in patients with mild to moderate hypertension.

[Evaluation of the effects of macerated oral dipyridamole on the ergometric test]. / Avaliação dos efeitos do dipiridamol oral macerado no teste ergométrico.

Eighteen male patients with ages varying from 42 to 72 years (average 60.6), with coronary heart disease confirmed by angiography, on regular rehabilitation program and on regular use of dipyridamole were submitted to three exercise stress tests: a control test (TE1) and forty minutes after oral administration of macerated dipyridamole in doses of 150 mg (TE2) and 300 mg (TE3), respectively. The comparison between the data of TE2 and TE1 demonstrated that in TE2 the ST depression was more accentuated in the smallest maximal load attained and in the effort peak as well. The comparison between the data of TE3 and TE1 showed that in TE3: 1) the ST depression was more evident in the effort peak and in the smallest attained load; 2) the heart rate and the product heart rate x blood pressure were smaller in the effort peak; 3) the total time of angina and the time for its relief after effort, were longer. The other exercise stress test parameters did not show any significant changes. These data, suggest that the physical effort overload, after dipyridamole administration, produced a more marked myocardial ischemia, whose degree was proportional to the dose.

[Visualization of coronary artery obstructions by echocardiography]. / Visibilização de obstruções em artérias coronárias pela ecocardiografia.

PURPOSE: The purpose of this study was to determine the sensitivity and specificity of 2D ECO in identifying proximal and medial obstruction of the coronary artery. PATIENTS AND METHOD: Sixty five patients with coronary artery disease were studied. In thirty three patients with previous coronary angiography the echocardiographer had knowledge of the topography and the degree of the coronary obstruction (group I) but in thirty two patients he didn't (group II). The mean age of group I was 54.4 years (44 to 76) and the mean age of the group II was 58 years (42 to 74). Two-dimensional echocardiography was performed at short-axis cross-sectional of aortic valve and images were frozen at end-diastole and reject settings were used to best visualize the coronary artery. RESULTS: It was possible to observe by 2D ECO the left main coronary artery in all patients. It was also possible to identify the proximal segment of the three main arteries. The detection of obstruction was overestimated by 2D ECO when it was in the left main coronary artery. In the proximal segment, in group I, the detection of obstruction in LAD, RCA and CXA was 87.5%, 66.6% and 50% and in group II, 77.7%, 100% and 50% respectively. In the medial segment, in group I, the detection of obstruction in LAD and CXA was respectively 100% and 33.3% and in group II, 60% and 75%. These results show that the sensitivity and specificity to detect obstruction was highest in the LAD. The method overestimated the presence of obstruction in the medial segment of RCA in both groups. CONCLUSION: These findings indicate that 2D ECO is a feasible noninvasive method in assessing obstruction of the main coronary arteries with good sensitivity and specificity.

[Transdermal nitroglycerin in patients with stable angina]. / Nitroglicerina transdérmica em portadores de angina estável.

PURPOSE: To evaluate the nitroglycerin patches efficacy and tolerability in patients with stable angina pectoris. METHODS: One thousand and five hundred and thirty nine patients with stable angina pectoris, mean age 61.0 +/- 10.3, 891 men and 648 women were prospectively evaluated by five hundred and thirty five specialists after 5 mg or, posteriorly, if clinical necessary, 10 mg of nitroglycerin patches during 12 weeks. Clinical evaluation, electrocardiogram (ECG) and treadmill exercise were obtained on study entry and at weeks 2, 4, 8 and 12 for clinical evaluation, and at week 12 for ECG and treadmill exercise. RESULTS: A significative reduction was observed in the number of angina crisis, sublingual nitrates consumption, arterial blood pressure and on the percentage of positive treadmill exercise tests. The heart rate and nitroglycerin patches dose did not show statistical differences. The compliance of transdermal administration was excellent. CONCLUSION: The nitroglycerin patches administration was effective for stable angina pectoris with excellent patient's compliance.

[Comparison between lovastatin and gemfibrozil in treatment of primary hyperlipidemias]. / Comparação entre a lovastatina e o gemfibrozil no tratamento de hiperlipidemias primárias.

PURPOSE: To compare the effects of lovastatin and gemfibrozil in patients with primary hyperlipidemias. PATIENTS AND METHODS: Forty patients with cholesterolemia over 200 mg/dl and triglyceridemia not higher than 350 mg/dl, excluded secondary causes, were selected. Twenty patients received lovastatin and 20 gemfibrozil. In order to establish the lipid profile, blood samples were taken after 2 months without medication, after 4 weeks of diet and placebo and after 6 and 12 weeks of active treatment. Biochemical profile was determined before and after the treatment with active drug. RESULTS: Thirty nine patients completed the study. Total and LDL-cholesterol were significantly reduced (p less than 0.05) by both drugs but lovastatin had greater effect. Only gemfibrozil reduced triglycerides significantly. Neither drug had significant effects on HDL-cholesterol. The tolerance was satisfactory; only one patient (using gemfibrozil) needed to stop the treatment due to gastrointestinal side effects. The biochemical profile did not present any significant alteration. CONCLUSION: Both drugs produced useful effects on the lipid profile. Lovastatin produced greater reductions of total and LDL-cholesterol, while gemfibrozil was more active reducing triglycerides. Neither drug changed significantly the HDL-cholesterol.

[Treatment of mild and moderate cardiac failure with captopril. A multicenter study]. / Tratamento da insuficiência cardíaca leve e moderada com captopril. Estudo multicêntrico.

PURPOSE: Evaluation of the clinical effects of captopril addition to the conventional therapy of functional class II and III (NYHA) congestive heart failure (CHF). METHODS: One hundred and fifteen patients with CHF, 46 (40%) class II and 69 (60%) class III, on conventional treatment (digitalis and diuretic) were the subject of this study. The age ranged from 22 to 75 years (mean 56.6 +/- 11); 67 were male and 66 were caucasians. The etiologies of the heart failure were: hypertensive heart disease 47 (40.9%), ischemic heart disease 27 (23.5%), Chagas cardiomyopathy 20 (17.4%), idiopathic cardiomyopathy 15 (13.0%), and other causes 6 (5.2%). Diuretic and digitalis were maintained in the same dosage during all the treatment. Captopril therapy was started with 6.25 mg b.i.d. or t.i.d., and the dosage was increased gradually to 25 mg b.i.d. or t.i.d. The duration of the study was 12 weeks. Clinical visits occurred every four weeks and laboratory tests were performed in the beginning and at the end of the study. RESULTS: The dosage of captopril ranged from 12.5 to 75 mg (mean 28.5 +/- 13.1 mg/day). The addition of captopril to the conventional therapy of CHF was associated with significant reduction (p < 0.01) of heart rate, systolic and diastolic blood pressure. In the end of the study 13 patients (11.3%) were in functional class III, 50 (43.5%) in class II and 52 (45.2%) in class I. Globally, functional class was improved in 98 (85.2%) patients and remained unchanged in 17 (14.8%) (p < 0.01). The side effects (dizziness, cough, hypotension and headache) were moderate and uncommon and did not need interruption of the treatment. CONCLUSION: The addition of captopril to the conventional therapy of class II and III CHF was associated with significant improvement of functional class and with good tolerability.

[Multicenter comparative study of felodipine-ER and nifedipine-OROS in the treatment of mild-to-moderate arterial hypertension]. / Estudo multicêntrico comparativo da felodipina-ER e nifedipina-OROS no tratamento da hipertensão arterial leve e moderada.

PURPOSE: To compare the efficacy and tolerance of felodipine-ER and nifedipine OROS, both once daily, in the treatment of mild-to-moderate uncomplicated arterial hypertension (AH). METHODS: This was a multicentric, opened, randomized, paralled trial, that selected 121 patients with uncomplicated, mild to moderate essential AH (diastolic blood pressure (DBP) > or = 95 and < or = 110 mmHg; not under anti-hypertensive medication. All patients received placebo for two weeks. After that period, they would take either 5mg/day of felodipine, or 30mg/day of nifedipine OROS, both once daily, in a randomized fashion. Patients underwent laboratory tests and electrocardiogram (ECG) at the begining and at the end of the study, and heart rate and blood pressure (BP) measurements, nearly 24 hours after the last active drug dose. RESULTS: Completed the study 111 patients, 60 in the felodipine group and 51 in the nifedipine group. Compared to baseline, the average of systolic BP and DBP decreased from 162.5 +/- 14.3mmHg and from 102.2 +/- 5.1mmHg to 143.3 +/- 14.6 and 87.9 +/- 7.2mmHg, respectively, at the end of the treatment in the felodipine group; and from 160.5 +/- 16.3mmHg and 102.5 +/- 6.2mmHg to 136.1 +/- 14.2 and 86.7 +/- 7.0mmHg, respectively in nifedipine group (p < 0.0001 for all diferences). Adequate BP response to the treatment (DBP normalization or reduction > 10mmHg from baseline) occured in 47/60 (78.3%) patients in the felodipine group and in 38/51 (74.5%) in the nifedipine group (NS). Side effects, occured in approximately 15% of the cases, and were similar in both groups. These were usually moderate and transient, but were responsible for the withdrawal from the study of two cases in the felodipine group and of three cases in the nifedipine group. CONCLUSION: Felodipine-ER and nifedipine OROS, are similarly effective and generally well tolerated in patients with mild-to-moderate essential hypertension.

[Efficacy and tolerance of the bisoprolol/hydrochlorothiazide combination in arterial hypertension]. / Eficácia e tolerabilidade da associação bisoprolol/ hidroclorotiazida na hipertensão arterial.

PURPOSE: Multicenter, open and non-controlled study to evaluated the efficacy and the tolerability of a low-dose combination of two anti-hypertensive agents: a cardioselective beta-blocker, bisoprolol (2.5 and 5.0 mg) with 6.25 mg of hydrochlorothiazide. METHODS: One hundred and six patients in the stage I and stage II of the systemic hypertension (mild to moderate) were given the bisoprolol/hydrochlorothiazide combination once daily and the diastolic and systolic blood pressures were monitored during the 8-week trial. RESULTS: The bisoprolol/hydrochlorothiazide combination reduced the initial mean values of systolic and diastolic blood pressures, respectively, from the 157.4 mmHg and 98.8 mmHg to 137.3 mmHg and 87.4 mmHg. At the end of the treatment period, 61% of the patients normalized blood pressure values (< 90 mmHg) and 22.9% of them had responded to the treatment, resulting in a total response rate (normalized + responsive) of 83.9% of cases. Adverse events were described only in 18.9% of the patients and dizziness and headache were the most common. There were no clinically significant changes on plasma levels of potassium, uric acid, glucose, or in the lipid profile. CONCLUSION: The combination of low dosages of bisoprolol and hydrochlorothiazide may be considered an effective, well tolerated and rational alternative for the initial treatment of the patients with mild to moderate hypertension.