Petitto M

Obesity and cardiac function.

We studied 10 obese volunteers, mean age 36.5 ± 10.3 years, who weighed 123.56 ± 28.7 kg and were 69.96 ± 22.5 kg overweight. The subjects did not have diabetes, arterial hypertension or signs of cardiac and respiratory failure or disease and all underwent right- and left-heart catheterization. Cardiac output and stroke volume were high, according to increased oxygen consumption and to the degree of obesity. Ventricular end-diastolic and atrial pressures ranged from normal to high and correlated with body weight, signs of volume overloading and reduced left ventricular (LV) compliance. The mean pulmonary artery pressure was elevated and correlated well with weight, pulmonary resistance being normal; mean aortic pressure did not correlate with weight, and systemic arterial resistance tended to have a negative correlation. The LV function curve showed impaired ventricular function, particularly for the heaviest subjects, in whom Vmax, and the ratio of the stroke work index to LV end-diastolic pressure were reduced. These indexes correlated well with each other and both correlated negatively with the degree of obesity. In contrast, maximal dP/dt was normal and did not correlate with excess weight. These observations show that depressed LV function is already present in relatively young obese people, even if they are free from signs of cardiopathy and other associate diseases. The degree of impairment of heart function seems to parallel the degree of obesity.

A double-blind comparison of nicorandil and metoprolol in stable effort angina pectoris

SummaryThe antianginal activities of nicorandil, 10 and 20 mg bid, and metoprolol, 100 mg bid, were compared in patients with stable effort angina pectoris in a randomized, double-blind parallel group study lasting 7 weeks. Twenty patients were enrolled into the trial and 16 patients completed the study. To evaluate the antiischemic effects of the two drugs, a treadmill exercise test was performed after a 1-week placebo run-in period and 6 weeks of treatment. On the same occasions, weekly sublingual nitroglycerine consumption and the number of anginal attacks were also recorded in the patients diary. The total duration of exercise increased significantly with both nicorandil, 10 and 20 mg, and metoprolol (p<0.01). Similar improvements were observed in the time to onset of ischemia with both treatments (p<0.01). The double product at maximal comparable workload (MAX 1) was reduced with the two drugs (p<0.05 for nicorandil and p<0.01 for metoprolol), while at the maximal exercise time (MAX 2) it was reduced with metoprolol (p<0.01) and slightly but not significantly increased with both doses of nicorandil. Weekly sublingual nitroglycerine consumption and anginal attacks were also significantly reduced a similar manner by both treatments (p<0.01). In conclusion, nicorandil, 10 and 20 mg bid, exerted an antiischemic effect comparable with that of metoprolol in patients with stable effort angina pectoris.

Blood pressure and cardiac morphology in young children of hypertensive subjects.

Our aim was to assess echocardiographic parameters and the effort blood pressure of 50 children of hypertensives with respect to 50 children of normotensives. Systolic and diastolic blood pressures at rest were comparable between the two groups. Left ventricular mass index (LVMI), interventricular septum and posterior wall thicknesses were higher in children of hypertensives (P < 0.01). Systolic blood pressure was higher in children of hypertensives at maximal effort until 5 min of recovery (P < 0.01). Similarly, diastolic blood pressure was higher at 1 and 2 min of recovery (P < 0.01). Direct correlations of mean diastolic wall thickness (r = 0.39, P < 0.01) and LVMI (r = 0.33, P < 0.05) with percentage effort systolic blood pressure increases were found in children of hypertensives but not in children of normotensives. In conclusion, we confirmed early cardiac alterations and a tendency for effort hypertension in children of hypertensives. The relationship between these data could be explained, either by effort systolic overload or by a common response to an increased adrenergic stimulus.

Effort blood pressure control in the course of antihypertensive treatment

In 30 patients with mild hypertension (diastolic blood pressure, 95 to 105 mmHg), the antihypertensive effect of rilmenidine 1 mg was compared in a double-blind study, with the effect of hydrochlorothiazide 25 mg. Patients not satisfactorily controlled received a combined therapy on the same doses of the two drugs used. Rilmenidine and hydrochlorothiazide induced a significant reduction (p = 0.01) of supine and erect systolic/diastolic blood pressure 23 hours after drug intake with no change in heart rate. This effect was due to a reduction in cardiac output (bioimpedance method) significant (p = 0.05) only for rilmenidine. Both drugs controlled the increase of effort systolic blood pressure in comparison with placebo on systemic vascular resistance treadmill exercise testing. Effort cardiac output was increased by each treatment in comparison with baseline values. Both at rest and on exertion, there was no effect on systemic vascular resistance induced by the two drugs. In a second group of 10 patients with moderate hypertension (diastolic blood pressure, 105 to 115 mmHg), rilmenidine 1 mg was administered in order to evaluate its efficacy and hemodynamic effects (bioimpedance and radionuclide ventriculography), at rest and during a lying cycloergometer effort test. The drug induced a significant decrease in blood pressure at rest and on exertion four hours after drug intake. This effect was due to a reduction (p = 0.05) in systemic vascular resistance, whereas cardiac output and heart rate remained unchanged. Our results show that the reduction in systolic/diastolic blood pressure induced by rilmenidine 1 mg is comparable with that induced by the well-known antihypertensive drug hydrochlorothiazide in mild hypertension. In moderate hypertension, the 1-mg dose appears to be insufficient in controlling the blood pressure in all patients. The drug exerts its antihypertensive effect through the normalization of the altered hemodynamic parameters of hypertension (high cardiac output and/or increased systemic vascular resistance). Rilmenidine also respects the physiologic increase in blood pressure and cardiac output on exertion.

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.

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.

Ventricular Function in Elderly Hypertensive Patients: A Radionuclide Assessment

Radionuclide ventriculography (RNV) was used to study the influences of age and the duration of hypertension on left ventricular function in 3 groups of patients: 22 normotensive adults, 126 hypertensive adults, and 53 hypertensive elderly. The elderly hypertensive patients showed, in comparison with the normotensives, an increase of SVR, end-diastolic volume (EDV) and end-systolic volume (ESV), and reduced ejection fraction (EF) with comparable change in mean ejection rate (MER), cardiac output (CO), HR, stroke volume (SV), blood volume (BV), and systolic blood pressure (SBP)/ESV. In comparison with hypertensive adults, they had increased SVR with similarly increased BV, EF, ESV, and SBP/ESV and reduced CO, SV, EDV, and MER. Hemodynamic parameters had negative correlations with age and with duration of hypertension, while a positive correlation was recorded between SVR and age. Thus, advanced age provides an additional impairment to ventricular function to that already induced by hypertension by means of a further increase of SVR and reduced ventricular distensibility as the relation of BV to EDV shows.

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.