Problems in the evaluation of antihypertensive therapy using the trough/peak ratio.

In 1988, the U.S. Food and Drug Administration proposed guidelines for the clinical evaluation of new antihypertensive drugs. According to these guidelines, the drug effect at trough (measured as the difference in blood pressure values from placebo) should be no less than one half to two thirds of the peak effect. Unfortunately, calculation of the trough/peak ratio suffers the consequences of many methodological, interpretative, practical, and epidemiological problems. When taking readings at short time intervals, noninvasive ambulatory blood pressure monitoring allows evaluation of blood pressure variability by means of several statistical parameters. Blood pressure variability, measured as the standard deviation of the overall 24-hour blood pressure measurements, has been demonstrated to be significantly correlated with target-organ damage in hypertensive patients. Blood pressure variability may not change with long-acting antihypertensive agents, but it may increase with short-acting ones. Therefore, assessment of the trough/peak ratio may be overcome by the evaluation of drug-induced changes in the standard deviation of the mean 24-hour blood pressure.

Ambulatory blood pressure pattern in elderly athletes.

Indications with respect to parasympathetic nervous activity in vivo can be obtained only by means of indirect parameters. Ten elderly athletes were compared to 10 sedentary healthy peers, in order to evaluate blood pressure (BP) and heart rate (HR) circadian change and variability, as assessed by ambulatory 24-h non-invasive monitoring. Such comparison proved that the elderly athletes have a significantly lower value in: systolic 24-h BP; systolic and diastolic 24-h BP variability; systolic and diastolic day-time BP variability; systolic night-time BP variability; 24-h, day-time and night-time mean HR, as well as HR variability. Prolonged physical training improves, therefore, the parasympathetic control on the cardiovascular system in the elderly, which causes a low BP, HR, and a low related variability. Regular exercise induces a shift in the sympathetic: parasympathetic tone ratio towards a stronger parasympathetic influence. Such a neurovegetative tone seems to confer juvenile characteristics to the cardiovascular system of elderly athletes.

[Carditis associated with Mycoplasma pneumoniae infection. Clinical aspects and therapeutic problems]. / La cardite associata ad infezione da Mycoplasma pneumoniae. Peculiarità cliniche e problemi terapeutici.

A clinical case of carditis associated with Mycoplasma pneumoniae infection in a 65 year-old woman is reported in order to stress some clinical features and therapeutic problems; during a 5-year follow-up. On the basis of this experience it is possible to state that in the pathogenesis an autoimmune mechanism probably plays an important role, whereas in therapy specific antibiotics are not effective and a long-term treatment with anti-inflammatory drugs is necessary.

["White coat effect" on blood pressure]. / L'"effetto camice bianco" sulla pressioine arteriosa.

In the past few years non-invasive ambulatory blood pressure monitoring has become a widespread technology in the assessment of arterial hypertension. The "white coat effect" concept derives from comparison between "clinic" and "ambulatory" blood pressure. It consists of two opposite conditions: clinic hypertension with ambulatory normotension (the so-called "white coat hypertension") and clinic normotension with ambulatory hypertension (the so-called "white coat normotension"). Nearly 20% of unselected referred populations shows conditions that may not need medical treatment, such as the "white coat hypertensives", or that may need antihypertensive therapy, such as the "white coat normotensives".

White-coat normotension and blood pressure variability.

The objective of this study was to assess blood pressure variability in patients with clinical normotension and ambulatory hypertension (the so-called white-coat normotension). In 58 white-coat normotensives (mean age 64.2 +/- 14.9 years; male/female ratio = 1.5:1) the authors evaluated blood pressure variability using the twenty-four-hour coefficient of variability. Fifty-eight essential hypertensives with the same age and sex distribution were recruited as a control group. The coefficient of variability in white-coat normotension was greater than in the control group (14.8/16.1 +/- 4.2/3.8% vs 13.5/15.1 +/- 3.3/3.1%), but this difference was not statistically significant. These findings suggest that white-coat normotension is the result of a specific relaxing response to medical visits and not the expression of an elevated blood pressure variability. It is probably due to the reverse of the alerting response, which causes white-coat hypertension.

[Cardiovascular effects of autonomic neuropathy in insulin-dependent diabetes mellitus]. / Effetti cardiovascolari della neuropatia autonomica nel diabete mellito insulino-dipendente.

The present study was designed to evaluate whether autonomic diabetic neuropathy is a marker of severe cardiovascular disease. We recruited three groups of 12 patients each with the same age, sex and body weight distribution: Group DAN + (diabetics with neuropathy), Group DAN- (diabetics without neuropathy) and Group C (healthy control group). The patients underwent two-dimensional color Doppler echocardiography and maximal electrocardiographic exercise test by cycloergometer (multistage program with 25 W increments 3 min steps). Cardiovascular autonomic function was evaluated by Ewing's tests (heart rate and blood pressure measurement during lying to standing, deep breathing, handgrip isometric stress test and Valsalva manoeuvre). Heart rate and blood pressure proved to be significantly higher in the Group DAN+, than in the other groups, either at baseline or during stress test. Only 33% of DAN+ patients proved to reach 100 W during stress test, compared to 82% of DAN- and 87% of control subjects. No DAN+ patients reached 125 W, compared with 45% of DAN- and 58% of Group C patients. Echocardiographic examination showed normal left ventricular systolic function in all groups, without any significant difference in ventricular dimensions, and impaired left ventricular diastolic function in DAN+ patients, compared to Group C subjects (peak E 66.75 +/- 8.36 vs 73.49 +/- 12.53 cm/s; peak A 72.1 +/- 13.42 vs 59.75 +/- 13.26 cm/s; E/A 0.84 +/- 0.21 vs 1.38 +/- 0.15 and isovolumetric relaxation time 101 +/- 21 vs 70 +/- 17 ms). Our data suggest that diabetic autonomic neuropathy is a marker of reduced exercise tolerance and of diastolic left ventricular dysfunction.

Circadian changes of ambulatory blood pressure in an unselected population.

Ambulatory blood pressure monitoring does not interfere with the night-time blood pressure and heart rate reduction, typical haemodynamic effects of sleep. An unselected population of 186 subjects was split into quartiles by age to assess the age related changes in 24-h blood pressure profile. From ambulatory blood pressure monitoring data we calculated day-time and night-time blood pressure and heart rate average values, as well as their percent difference. Results show that there is no difference with regard to nocturnal heart rate reduction (on average, 15%) between age groups or sexes, whereas nocturnal blood pressure reduction (on average, 10%) is significantly lower in elderly males, but not females, when compared with young people. This flat 24-h blood pressure profile is associated with hypertension. Circadian changes of ambulatory blood pressure are very different in elderly hypertensive men and provide a marker of diffuse arterial damage.

[Therapy of arterial hypertension associated with acute stroke. Current trends and problems]. / Terapia dell'ipertensione arteriosa associata all'ictus cerebrale in fase acuta. Orientamenti e problemi attuali.

Acute stroke may cause hypertension and actually available devices for non-invasive blood pressure monitoring make it possible to study short-term variability of pressure in this condition, in order to settle a more rational diagnostic and therapeutic approach. In our experience blood pressure variability has shown to be greater in thrombo-embolic, than haemorrhagic stroke. This outcome contributes to explain literature disagreement on benefits of antihypertensive therapy and suggests the need for blood pressure monitoring in every trial, that wants to evaluate with satisfactory reliability the antihypertensive treatment in ischaemic stroke. As to antihypertensive drugs to be used in stroke patients, we prefer antiadrenergics, because hypertension in this clinical condition is due to adrenergic overactivity. Our preliminary experience with a centrally acting antiadrenergic drug (clonidine) has shown its ability not only to reduce blood pressure, but also blood pressure variability in ischaemic stroke.

[Effects of physical activity on the cardiovascular autonomic function in the aged]. / Effetti della attività fisica sulla funzione autonomica cardiovascolare nell'anziano.

The objective of this trial was to evaluate whether cardiovascular vagal-sympathetic relationship, which is expected to be decreased in the elderly, can be modified by physical activity performed in advanced age. Cardiovascular autonomic function, as assessed by heart rate and arterial blood pressure during lying to standing, deep breathing, handgrip isometric stress test and Valsalva manoeuver, was estimated through Ewing's test in 10 sedentary healthy elderly subjects (mean age 68 +/- 3.1) compared to 10 long-distance runners of the same age (mean age 69 +/- 4.6). The endurance athletes, suitable for competition, had been practicing sport activity for a long time. Moreover in order to evaluate the influence of physical activity on cardiovascular response to exertion in the elderly all subjects were submitted to maximal electrocardiographic exercise test on a cycloergometer (multistage program with 30 watt x 3 min. steps). Heart rate, arterial systolic and diastolic blood pressure were recorded; double product was calculated at baseline; furthermore, total and maximal watts were recorded. For each of the parameters, Student's "t" test for independent observations was used in order to evaluate statistical differences among the two groups. Our data exhibited better results in cardiovascular reflex response due to parasympathetic (Valsalva and deep breathing test) neurovegetative modulation in the trained subjects with respect to the sedentary controls: Valsalva ratio (VR) = 2.04 +/- 0.44 vs 1.40 +/- 0.18 p < 0.001); deep breathing test (FC) = 23.6 +/- 6.2 vs 15.1 +/- 2.5 p < 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)

[Arterial hypertension in Cushing's disease: the 24-hour pressure profile without and during treatment with beta-blockers or cyproheptadine]. / L'ipertensione arteriosa nel morbo di Cushing: profilo pressorio delle 24 ore senza e durante trattamento con betabloccanti o ciproeptadina.

Studying a patient with Cushing's disease by 24-hour indirect blood pressure monitoring, we confirmed that the normal nocturnal fall in blood pressure was absent, although the usual decrease in heart rate persisted. Thereafter we found a hypervariability in blood pressure and heart rate, which was reversed by treatment with betablockers and/or cyproheptadine. The therapy restored also the normal nocturnal fall in blood pressure. The low-dose cyproheptadine therapy normalized urinary free cortisol levels and restored a 24-hour blood pressure profile better than the low-dose beta-blocker therapy.

[Arterial pressure variability in the acute phase of a cerebral stroke]. / La variabilità della pressione arteriosa nella fase acuta dell'ictus cerebrale.

OBJECTIVE: Acute stroke may cause hypertension and recently available devices for noninvasive blood pressure monitoring make it possible to study short-term variability of pressure in this condition. DESIGN AND METHODS: Eight patients (5 males, 3 females, mean age 66 +/- 12 years) with haemorrhagic stroke and 13 male patients (mean age 73 +/- 10 years) with thrombo-embolic stroke underwent 24-hour blood pressure monitoring in the acute stage by the Takeda Medical 2420 (A&D Co., Japan), programmed to measure blood pressure every 10 min during day-time and 15 min during night-time. Blood pressure variability was measured by the variability coefficient (standard deviation/24 h mean). The diagnosis was confirmed in all cases by Computed Tomography scanning. Statistical differences between groups were evaluated by Student's "t" test for independent samples. RESULTS: In haemorrhagic stroke the mean of variability coefficient proved be 10.7% for systolic and 12.8% for diastolic blood pressure, whereas in thromboembolic stroke it was 14.1% for systolic and 17.7% for diastolic blood pressure. The difference between means was statistically significant (p < 0.02 for systolic and p < 0.01 for diastolic blood pressure). CONCLUSIONS: Blood pressure variability is greater in thrombo-embolic, than haemorrhagic stroke. The hypervariability can be misleading in judging the hypertensive state in this condition.

[The effects of treatment with atenolol and benazapril on 24-hour pressure variability]. / Effetti del trattamento con atenololo e con benazapril sulla variabilità pressoria delle 24 ore.

One of the functions of the sympathetic nervous system is to produce a short-term increase in blood pressure. It might be thought, therefore, that antihypertensive drugs which interfere with the functioning of the sympathetic nervous system (e.g. betablockers) would reduce blood pressure variability over 24 h whereas those that act independently of it (e.g. ACE inhibitors) would not. Two groups of 10 hypertensives underwent noninvasive 24-h blood pressure monitoring before and after antihypertensive treatment with a betablocker (atenolol) and an ACE inhibitor (benazepril) respectively. Blood pressure variability was measured by the variability coefficient (standard deviation/mean). Atenolol induced a non-statistically significant decrease in blood pressure variability, whereas benazepril caused a statistically significant increase in systolic blood pressure variability. Therefore, we conclude that the evaluation of ACE-inhibitor therapeutic effect on blood pressure by the "casual" measurement can be misleading in judging the efficacy of such drugs.

An idiopathic hypereosinophilic syndrome mimicking seronegative rheumatoid arthritis: 20-year follow-up with clinical and laboratory findings.

A clinical case of idiopathic hypereosinophilic syndrome mimicking seronegative rheumatoid arthritis with a twenty year follow-up is reported. The patient showed other sign of the disease, such as pericarditis, gastroenteritis and hepatomegaly. Among the laboratory findings the elevated levels of aldolase and LDH 2, never reported previously, are stressed.