O. de Divitiis

Cardiac abnormalities in young women with anorexia nervosa.

OBJECTIVE--To identify the characteristics of cardiac involvement in the self-induced starvation phase of anorexia nervosa. METHODS--Doppler echocardiographic indices of left ventricular geometry, function, and filling were examined in 21 white women (mean (SD) 22 (5) years) with anorexia nervosa according to the DSMIII (Diagnostic and Statistical Manual of Mental Disorders) criteria, 19 women (23 (2) years) of normal weight, and 22 constitutionally thin women (21 (4) years) with body mass index < 20. RESULTS--13 patients (62%) had abnormalities of mitral valve motion compared with one normal weight woman and two thin women (p < 0.001) v both control groups). Left ventricular chamber dimension and mass were significantly less in women with anorexia nervosa than in either the women of normal weight or the thin women, even after standardisation for body size or after controlling for blood pressure. There were no substantial changes in left ventricular shape. Midwall shortening as a percentage of the values predicted from end systolic stress was significantly lower in the starving patients than in women of normal weight: when endocardial shortening was used as the index this difference was overestimated. The cardiac index was also significantly reduced in anorexia nervosa because of a low stroke index and heart rate. The total peripheral resistance was significantly higher in starving patients than in both control groups. The left atrial dimension was significantly smaller in anorexia than in the women of normal weight and the thin women, independently of body size. The transmitral flow velocity E/A ratio was significantly higher in anorexia than in both the control groups because of the reduction of peak velocity A. When data from all three groups were pooled the flow velocity E/A ratio was inversely related to left atrial dimension (r = -0.43, p < 0.0001) and cardiac output (r = -0.64, p < 0.0001) independently of body size. CONCLUSIONS--Anorexia nervosa caused demonstrable abnormalities of mitral valve motion and reduced left ventricular mass and filling associated with systolic dysfunction.

Supernormal contractility in primary hypertension without left ventricular hypertrophy.

Forty-three subjects with uncomplicated primary hypertension and without echocardiographic left ventricular hypertrophy and 54 normotensive volunteers were studied by two-dimensional targeted M-mode echocardiography to evaluate systolic function and contractility before the development of compensatory hypertrophy. The ratio of peak systolic pressure to end-systolic dimension was used to assess left ventricular performance and was divided for either posterior wall thickness or cross-sectional area to generate hypertrophy-independent indices of inotropic state. Fractional shortening was normal in the hypertensive group, despite the increase in end-systolic stress. Systolic pressure/dimension ratio was higher in hypertensive subjects (p less than 0.001), as were hypertrophy-independent indices of inotropic state (p less than 0.005), which were inversely correlated to left ventricular mass (p less than 0.001). Values in 11 hypertensive subjects were above the upper confidence limit of the normal shortening/stress relation, which provides a load-independent measure of inotropic state. They showed high hypertrophy-independent indices of inotropic state (p less than 0.01), while the other hypertensive subjects did not. High fractional shortening, wall stress, and systolic pressure (p less than 0.01) were found in the subgroup with supernormal performance, while left ventricular mass was not different from that of other subgroups, depicting inadequate left ventricular hypertrophy. The duration of hypertension was the same in the subgroups. Supernormal inotropic state could be considered one form of primary adaptation to high wall stress that serves to maintain systolic ventricular performance.

Desmin‐free cardiomyocytes and myocardial dysfunction in end stage heart failure

Our aim was to evaluate the desmin content in the myocardial tissue of patients with end‐stage heart failure of ischaemic origin and to assess its role on cardiac function. We studied 18 explanted hearts from patients transplanted for end‐stage heart failure due to ischaemic cardiomyopathy (ICM). Control myocardial tissue was obtained from the cardiac biopsies of six women with breast cancer taken prior to commencing chemotherapy with anthracyclines, four male donors for heart transplantation and two autoptic hearts from patients who died due to non‐cardiac events. Myocardial tissue, obtained from the left ventricle (remote zone from infarcted area), was analyzed by light and confocal immunochemistry (desmin) microscopy. The desmin content of myocardial tissue was obtained by real‐time PCR. Cardiac function was evaluated by echocardiographic and right heart catheterization data, obtained before heart transplantation. Confocal microscopy evaluation showed a significant decrease in the number of desmin‐positive myocytes (P<0.01) in ICM hearts compared to controls. At real‐time PCR evaluation, there was a reduction (P<0.01) in desmin content in the ICM patients compared to controls. A negative correlation was found between desmin‐free cardiomyocytes and ejection fraction (EF) (r=−0.834; P<0.02) on echocardiogram. A negative relationship (r=−0.688) was also found between desmin‐negative myocytes and capillary wedge pressure. In conclusion, the myocardial tissue of patients with end‐stage heart failure of ischaemic origin, shows a decreased number in desmin‐positive myocytes at immunochemistry evaluation compared to normal individuals. This deficiency in cytoskeletal intermediate filament content is associated with reduced cardiac function.

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.

Comparative evaluation of the antihypertensive efficacy of once-daily sustained-release isradipine and lacidipine using 24-hour ambulatory blood-pressure monitoring

In this single-blind crossover study the antihypertensive efficacies of two dihydropyridine calcium antagonists, sustained-release isradipine and lacidipine, were compared using clinic and ambulatory blood-pressure measurements. After a 2-week placebo wash-out, 34 patients (19 men, 15 women, mean age 49 years) with mild to moderate hypertension (diastolic blood pressure range 95 – 110 mmHg) were treated with 5 mg sustained-release isradipine for 4 weeks and 4 mg lacidipine for 4 weeks in a random order. Medications were taken once daily at 08.00 h. Clinic and ambulatory blood pressures were recorded at the end of each placebo or treatment period. Two patients stopped isradipine and six lacidipine because of severe adverse effects. Clinic systolic and diastolic blood pressures decreased by an average of 17/14 mmHg with isradipine and 17/13 mmHg with lacidipine, compared with placebo (P < 0.01 in both cases), without a change in heart rate. Mean ambulatory 24-h and daytime systolic and diastolic blood pressure were significantly reduced by sustained-release isradipine and lacidipine (P < 0.05 and P < 0.01, respectively). At night systolic blood pressure fell compared with placebo (P < 0.05 with both drugs) whereas the reduction in diastolic blood pressure was not statistically significant. Mean 24-h heart rate remained unchanged. Blood-pressure variability did not differ significantly between the two drugs or between either drug and the placebo. The antihypertensive effects of sustained-release isradipine and lacidipine were similar, but the tolerability of isradipine appears to be greater since it caused fewer withdrawals.

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.

Left ventricular hypertrophy, compliance and ventricular filling.

A total of 20 untreated hypertensive patients were divided into two equal groups matched for sex, age and blood pressure but with [mean diastolic wall thickness (MDWT) > 1.2 cm] or without (MDWT > 1.2 cm) left ventricular hypertrophy (LVH). All patients underwent pulsed doppler echocardiography and 99Tc radionuclide ventriculography at rest to assess diastolic and systolic abnormalities. In hypertensives with LVH the interventricular wall thickness, posterior wall thickness and relative diastolic wall thickness were significantly (P < 0.01) higher and peak filling rate was significantly (P < 0.01) lower than in hypertensives without LVH. The indices of systolic function, however, were not significantly different in the two patient groups. In hypertensives without LVH peak filling rate directly correlated with heart rate, whereas in those with LVH peak filling rate directly correlated with heart rate and the ratio of peak velocity of early left ventricular filling: peak velocity of late left ventricular filling due to atrial contraction. It is concluded that diastolic parameters may be useful tools for assessing myocardial compliance and may be effective markers of diastolic dysfunction.

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.

Coronary vasoreactivity is not altered in young people with type 1 diabetes

BACKGROUND AND AIM Abnormal coronary microvascular circulation has been demonstrated in diabetes and is associated with increased rate of cardiovascular events. Our objective was to evaluate coronary vasoreactivity in young people with type 1 diabetes with and without microvascular complications. METHODS AND RESULTS Twenty-five type 1 diabetic patients without microvascular complications (DC-), 23 with microvascular complications (DC+), and 18 control subjects (C) were studied. Coronary vasoreactivity was assessed by means of coronary flow reserve (CFR). Blood flow velocity in the left anterior descending coronary artery was measured at rest and after high-dose dipyridamole using transthoracic color-guided pulsed Doppler echocardiography. CFR was defined as the ratio of hyperaemic to resting diastolic peak flow velocities. The three groups had similar cardiac function parameters, and also systolic and diastolic blood pressure at rest, which remained unchanged during dipyridamole infusion. Resting coronary flow velocity was comparable in C, DC-, and DC+ (p=ns). Dipyridamole infusion produced a threefold increase in coronary diastolic peak velocity, which reached similar values in C (0.69±0.16 m/s), DC- (0.69±0.18 m/s), and DC+ (0.66±0.11 m/s). Mean CFR ratio was similar in C (3.33±0.66), DC- (3.30±0.51), and DC+ (3.24±0.60). At multiple linear regression analysis, no association was found between CFR and age, sex, HbA(1c), duration of diabetes, and complications. CONCLUSION Coronary vasodilatory function is preserved in young D patients, even those with early microvascular complications, suggesting that coronary vasoreactivity deteriorates at more advanced stages of microvascular complications and/or in the presence of other cardiovascular risk factors.