S. Di Somma

Cerebral blood flow velocity and systemic vascular resistance after acute reduction of low-density lipoprotein in familial hypercholesterolemia.

Background and Purpose Low-density lipoprotein apheresis is currently used for the treatment of familial hypercholesterolemia, an inherited disorder of metabolism associated with premature development of cardiovascular disease. We wanted to evaluate cerebral blood flow velocity, cardiac output, and systemic vascular resistance in patients with familial hypercholesterolemia before and after low-density lipoprotein apheresis. Methods Ten patients (age range, 14 to 46 years; 4 males, 6 females) with familial hypercholesterolemia (8 homozygotes, 2 heterozygotes) and 10 healthy control subjects of comparable age and sex distribution participated in the study. Low-density lipoprotein apheresis by dextran sulfate was performed in 8 patients (7 homozygotes, 1 heterozygote). Six patients (4 homozygotes, 2 heterozygotes) underwent a procedure of extracorporeal erythrocyte filtration with the same extracorporeal volume as for low-density lipoprotein apheresis, but with the exclusion of the passage of plasma through the dextran sulfate column. Cerebral blood flow velocity (transcranial Doppler), cardiac output, and systemic vascular resistance (electric bioimpedance cardiography) were determined by noninvasive techniques before and 1 day and 7 days after low-density lipoprotein apheresis or extracorporeal erythrocyte filtration. Plasma and blood viscosities were measured at the same time. Results Before apheresis, mean and diastolic cerebral flow velocities were abnormally low in hypercholesterolemic patients (P<01 and P<02 vs healthy control subjects, respectively). After apheresis, low-density lipoprotein cholesterol was lowered by 40% to 60% from baseline, and cerebral blood flow velocities (mean, systolic, and diastolic velocities) were increased (P<01). Cardiac output, systemic vascular resistance, and viscosity values were not significantly modified. Extracorporeal erythrocyte nitration (without passage of plasma through the dextran sulfate column) did not modify serum lipids, hemodynamic parameters, or viscosity values. Conclusions Low-density lipoprotein apheresis produces potentially useful hemodynamic effects. They are not adequately explained by changes in blood viscosity alone and might reflect a restoration of endothelium-mediated vasodilation, which is inhibited by high concentrations of low-density lipoprotein.

Indapamide and atenolol in the treatment of hypertension: double-blind comparative and combination study

Fifteen out-patients with moderate hypertension were randomly and sequentially treated with atenolol, indapamide and a combination of the two drugs after a wash-out period of at least 1 week and a 2-week placebo run-in period. The duration of treatment was 4 weeks in each case. The dosage was 2.5 mg indapamide and 100 mg atenolol, in single tablets which were taken at 11.00 hours. All the treatment regimens produced a highly significant (p less than 0.001) reduction in systolic and diastolic, supine and standing blood pressure; these reductions were not significantly different for the single drugs but were significantly greater for the combined therapy. The number of patients reaching the end-point of a diastolic blood pressure of 95 mmHg or less was the same with either atenolol or indapamide, i.e. 7 (46.6%), but was greater with the combined therapy, i.e. 10 (66.6%). A significant (p less than 0.001) reduction in pulse rate was observed with the treatments involving atenolol. Acceptability of the treatments was very good; the number of volunteered and elicited complaints during the different treatments being less compared to the placebo period, particularly for the combined treatment. No significant difference was observed in the blood biochemistry tests. The results are discussed in light of the mechanisms of action of the two drugs, which seem well integrated with each other, and the duration of the antihypertensive effect, which allows a single administration with consequent good treatment compliance.

A comparative study of simvastatin versus pravastatin in patients with primary hypercholesterolaemia

Abstract One hundred patients with primary hypercholesterolaemia (total plasma cholesterol ⩾ 6.2 mmol/l (240 mg/dl)) were enrolled in an open, randomized, parallel comparative study of simvastatin and pravastatin. Prior to entry into a 4-week placebo baseline period, all patients started or continued a standard lipid-lowering diet for at least 6 weeks. Patients were randomized to receive either simvastatin ( n = 50) or pravastatin ( n = 50), both at the recommended starting dose of 10 mg/day, for 6 weeks. With simvastatin, plasma total cholesterol (TC) decreased from 7.59 to 5.80 mmol/l, a reduction of 24%; TC dropped from 7.48 to 6.35 mmol/l during pravastatin therapy. Low density lipoprotein (LDL)-cholesterol was reduced by 33% and 22% with simvastatin and pravastatin and high density lipoprotein (HDL)-cholesterol was increased by 10% and 7%, respectively. The level of total plasma triglycerides (TG) was reduced by 12% with simvastatin and by 6% with pravastatin. All changes were significant ( P ⩽ 0.01) except for the change in TG with pravastatin. Both drugs were well tolerated and the range and the frequency of adverse events was similar for both treatment groups. No patients were withdrawn from the study due to adverse clinical events: insomnia in one patient (a 57-year-old woman) in the pravastatin group required a reduction in dose to 5 mg/day. It is concluded that at the recommended starting dose, simvastatin had a significantly greater lipid-lowering effect than pravastatin.

Atenolol and Amiodarone: a Comparative Study of Their Anti-ischaemic Effect

A total of 10 patients with mixed angina were entered into a study to compare the anti-ischaemic efficacy of atenolol and amiodarone. The study was divided into three parts: (a) placebo for 2 weeks; (b) 100 mg atenolol given for 8 weeks; and (c) amiodarone given for 8 weeks, divided into week 1, 200 mg three times daily; week 2, 200 mg twice daily; weeks 3 and 4, 200 mg once daily; weeks 5–8, 200 mg once daily for 5 days a week. Clinical examination, basal and multi-stage effort electrocardiograms were performed at the end of each treatment. The number of anginal attacks and the amount of trinitrin taken by the patients were significantly reduced by both drugs with no significant difference between them. Compared with placebo, both drugs induced a significant increase in work capacity and in the time to decrease the ST-segment by 1 mm. At rest, atenolol reduced systolic blood pressure, heart rate and the systolic blood pressure–heart rate product compared with placebo. Systolic blood pressure was also reduced significantly compared with patients given amiodarone. Amiodarone did not influence these parameters. At maximum effort, amiodarone reduced heart rate and the systolic blood pressure–heart rate product compared with placebo. This reduction was greater for atenolol. The ST-segment depression was comparable between patients given either test drug. Amiodarone, therefore, exerts an anti-ischaemic effect similar to that shown by atenolol with different haemodynamics: atenolol reducing myocardial oxygen demand, amiodarone having an additive increase of coronary flow. Such an effect was obtained with a lower dose of amiodarone than is commonly used.

Treatment of hypertensive patients with ventricular arrhythmias: comparison and combination of β-blocker and anti-arrhythmic therapy

The effect of therapy with atenolol and tocainide, separately or in combination, was studied in 20 patients with hypertension and concomitant ventricular arrhythmias. Patients were given 400 mg tocainide, three times daily, 100 mg atenolol, once daily (plus 25 mg hydrochlorothiazide and 2.5 mg amiloride diuretics if required) and a combination of these treatments. Tocainide alone significantly reduced the incidence of ventricular arrhythmias without affecting atrial arrhythmias. It also controlled exercise-induced arrhythmias in 7/13 (54%) patients. Atenolol significantly reduced atrial arrhythmias and had a good effect on exercise-induced arrhythmias (reduced in 75% of patients), but it did not have a significant effect on ventricular arrhythmias. In 13 patients, despite normalization of blood pressure by atenolol, it was necessary to combine antihypertensive therapy (atenolol) with anti-arrhythmic therapy (tocainide) in order to reduce ventricular arrhythmias. All drugs were well tolerated. It is concluded that, in certain patients, specific anti-arrhythmic treatment may be necessary to control ventricular arrhythmias in hypertensive patients despite normalization of blood pressure by β-blockers.