Psychophysiological reactivity and cardiac end-organ changes in white coat hypertension.

This study aimed 1) to assess whether patients with an exaggerated blood pressure response to the doctor's presence ("white coat" effect) also display a pattern of enhanced blood pressure reactivity to mental stress and physical exercise and 2) to determine the presence of left ventricular structural and filling abnormalities in patients with white coat hypertension. We studied 56 (40 men) consecutive patients (mean [SD] age, 46.4 [9.1] years) whose clinic blood pressure was repeatedly high. Patients were classified as having white coat hypertension (n = 20) if both their mean daytime (from 7 AM to 11 PM) ambulatory systolic and diastolic blood pressures were less than 134 and 90 mm Hg, respectively. Patients were considered to have persistent hypertension (n = 36) if daytime systolic blood pressure was 134 mm Hg or more or diastolic blood pressure was 90 mm Hg or more. Eighteen subjects with clinic blood pressure lower than 140/90 mm Hg served as a normotensive control group. Blood pressure reactivity from baseline to mental arithmetic, isometric handgrip, and cycle ergometry did not display any difference among the three groups. The white coat hypertensive group had left ventricular mass index lower than the persistent hypertensive group but higher than the normotensive group. Doppler indexes of left ventricular diastolic filling displayed similar abnormalities in the white coat and persistent hypertensive groups compared with the normotensive group.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential effects of feeding on the ultradian variation of the growth hormone (GH) response to GH-releasing hormone in normal subjects and patients with obesity and anorexia nervosa.

Nutritional status and metabolic fuels are factors involved in the regulation of GH secretion and GH responses to GHRH. The effects of feeding on GHRH-induced GH release were studied in 13 normal women, 14 obese women, and 9 women with anorexia nervosa. GHRH-(1-44) (50 micrograms, iv) was administered at 0900 h after an overnight fast or at 1300 h after a normal meal at 0800 h, and at the same times 45 min after a 800-Cal meal on different days. The mean peak plasma GH responses to GHRH administered before a meal at 0900 h were 52.8 +/- 5.6 (+/- SE) micrograms/L in normal women, 8.2 +/- 1.3 micrograms/L in obese women, and 53.2 +/- 7.7 micrograms/L in anorexic women. When GHRH was administered before a meal at 1300 h, the mean peak plasma GH levels were lower than those at 0900 h; this reduction was -64.2% in normal women, -64.9% in obese women, and -55.8% in women with anorexia nervosa. After feeding, the plasma GH responses to GHRH were blunted in normal women at 0900 h (-60.9%) and 1300 h (-34.6%) compared with the fasting peak responses. In obese women the plasma GH response to GHRH after feeding was increased compared with that when these women had fasted (+60% at 0900 h and +406.9% at 1300 h). Finally, differential effects of feeding were present in anorexic women; the response was lower at 0900 h (-46.4%) and greater at 1300 h (+50.8%). We conclude that there is an ultradian variation in GHRH-stimulated GH secretion and that the responses differ according to nutritional status and body weight.

Effects of celiprolol on cardiovascular reactivity to laboratory stressors in patients with hypertension.

An ideal antihypertensive drug should reduce blood pressure not only at rest but also during stressful situations. To test whether this criterion is fulfilled by celiprolol, a new beta 1-selective adrenergic blocker drug with peripheral vasodilating activity, we examined the effects of its oral administration on cardiovascular reactivity to laboratory stressors in 18 patients with essential hypertension, according to a placebo-controlled crossover design. In the 12 patients classified as "responders," celiprolol significantly reduced resting systolic and diastolic blood pressure (p less than 0.05 for both). Compared with placebo, celiprolol induced a blood pressure reduction from 179.4 +/- 16.9/119.5 +/- 12.4 mm Hg to 160.7 +/- 12.6/109.4 +/- 3.1 mm Hg during mental arithmetic; from 200.9 +/- 20.7/139.2 +/- 11.9 mm Hg to 184.1 +/- 16.4/127.6 +/- 12.1 mm Hg during handgrip test; from 212.8 +/- 18.5/126.2 +/- 14.2 mm Hg to 185.9 +/- 18.2/117.1 +/- 15.2 mm Hg during cycle ergometry. Our data suggest that in the majority of treated patients celiprolol is effective in reducing blood pressure not only at rest but also during a variety of stressful events, thereby ameliorating the impact of recurring stress-induced increases of blood pressure on the cardiovascular system.

Platelet alpha 2-adrenoceptors and diurnal changes of platelet aggregability in hypertensive patients.

OBJECTIVE: To analyse whether platelets from hypertensive patients have an increased responsiveness to aggregating agents during morning hours and whether these changes might be related to concurrent changes in platelet membrane alpha 2-adrenoceptor characteristics, plasma catecholamine and cortisol levels, and blood pressure values. DESIGN AND METHODS: Blood samples from 14 mild-to-moderate essential hypertensive males were collected in the morning (0700-0900 h) and the evening (1900-2100 h) to determine platelet aggregability responses to adrenaline and ADP, platelet alpha 2-adrenoceptor number and binding affinity to [3H]-yohimbine, plasma catecholamines and cortisol. During the same day patients underwent 24-h ambulatory blood pressure monitoring. RESULTS: The lowest concentration of adrenaline required to induce biphasic aggregation was significantly lower in the morning than in the evening, indicating an increased morning platelet aggregability to adrenaline; the minimum ADP concentration inducing aggregation was similar in morning and evening samples. There were no significant differences between morning and evening samples in platelet alpha 2-adrenoceptor number and binding affinity. Plasma adrenaline, noradrenaline and cortisol levels were higher in the morning than in the evening, but no correlation was observed between hormonal changes and the morning increase in platelet sensitivity to adrenaline. Ambulatory blood pressure recording showed abrupt morning elevations in systolic and diastolic blood pressures over sleeping values. However, morning blood pressure readings were not significantly different from those recorded during the rest of the day and in the evening. The morning rise in mean arterial pressure displayed a significant inverse correlation with the increased platelet sensitivity to adrenaline that was observed during the same hours. CONCLUSIONS: The results indicate that the increased morning responsiveness to adrenaline that was observed in platelets obtained from hypertensive patients does not appear to be mediated by changes in the characteristics of platelet membrane alpha 2-adrenoceptors, but morning blood pressure elevations might play some role in inducing this platelet hyper-reactivity.

Effects of benazepril on stress testing blood pressure in essential hypertension.

The effects of different doses of the angiotensin-converting enzyme inhibitor benazepril on cardiovascular response to a set of standardized laboratory tasks were analyzed. Eighteen patients (15 men and 3 women) with mild-to-moderate essential hypertension were randomly allocated to receive 10 or 20 mg of benazepril, or placebo, each administered once daily for 2 weeks, according to a double-blind, 3-period design. At the end of each treatment period, patients were examined at resting baseline and while performing mental arithmetic, handgrip and cycle ergometry tests. In comparison with placebo, the average reductions in resting systolic blood pressure (BP) were 8.7 mm Hg (95% confidence intervals [CI] -15.2 to -2.1) with 10 mg of benazepril, and 7.8 mm Hg (95% CI -14.4 to -1.3) with 20 mg; the corresponding reductions in resting diastolic BP were 5.1 mm Hg (95% CI -8.7 to -1.4) and 6.8 mm Hg (95% CI -10.4 to -3.1) (all p < 0.05). During mental arithmetic, the reductions in systolic BP were 10.4 mm Hg (95% CI -17.4 to -3.4) with 10 mg of benazepril, and 13.8 mm Hg (95% CI -20.8 to -6.8) with 20 mg; diastolic BP was reduced by 4.5 mm Hg (95% CI -8.5 to -0.5) and 8.3 mm Hg (95% CI -13.2 to -4.3), respectively (all p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Relation of stress testing and ambulatory blood pressure to hypertensive cardiac damage.

In essential hypertension, the severity of cardiovascular damage is only weakly related to clinic blood pressure (BP), whereas a better relationship seems to exist with BP recorded during stressful situations. The present study compared BP levels measured during laboratory stress testing and 24-h ambulatory monitoring with regard to their relationship with cardiac end-organ involvement. BP recorded during a mental and a physical challenge and during 24-h ambulatory monitoring was related to Doppler echocardiography characteristics of left ventricular structure and filling in 63 untreated essential hypertensives and in 32 healthy subjects. In the hypertensive group, only a weak relationship was observed between left ventricular mass and clinic BP; the strength of this association was not improved by BP measured during mental task and cycle ergometry, and was slightly but not significantly higher for BP recorded during ambulatory monitoring. In multivariate analysis, left ventricular mass was independently predicted by stroke index and 24-h systolic BP. Among the different pressure measures, 24-h, daytime, and nighttime BPs bore the only significant relation to relative wall thickness. In the normotensive group, no significant relationship was observed between left ventricular mass and different measures of BP. Doppler indexes of left ventricular diastolic filling did not significantly relate to any BP measurement in the hypertensive group, and generally bore a significant inverse relationship to various BP recordings in the normotensive group. To summarize, stress testing BP does not help in identifying hypertensive patients with increased left ventricular mass.

Abnormal blood pressure response to exercise in borderline hypertension. A two year follow-up study.

Twenty-eight men with borderline hypertension according to the World Health Organization criteria underwent maximal exercise testing, and then were followed for a two year period. The prevalence of abnormal blood pressure behavior during exercise was 53.58% (n = 15). During follow-up established hypertension developed in 63.33% (n = 10) of subjects with an abnormal blood pressure response to exercise, and only in 15% (n = 2) of subjects with normal blood pressure behavior. In predicting established hypertension development in a two year follow-up, maximal exercise testing has the following statistical values: sensitivity = 83.33%, specificity = 68.75%, accuracy = 75%, positive predictive value = 66.66%, negative predictive value = 84.61%.

Corticotropin-releasing hormone inhibition of gonadotropin secretion during the menstrual cycle.

To determine whether corticotropin-releasing hormone (CRH) exerts an inhibitory action on gonadotropin secretion in normal fertile women, the effects of CRH on luteinizing hormone (LH), follicle-stimulating hormone (FSH), and cortisol secretion were studied during the menstrual cycle. CRH had no effect on LH release during the midfollicular phase of the cycle. By contrast, IV injection of 100 micrograms CRH elicited significant decreases in LH concentrations during late follicular (-50%) and midluteal (-52%) phases of the cycle. LH concentrations decreased during the four-hours following injection of CRH and returned to those observed during the control period five hours after injection. Similarly, CRH elicited a significant decrease in FSH secretion during the midluteal phase of the cycle. CRH injection induced an increase in cortisol release during all phases of the cycle. These data demonstrate that exogenous CRH administration results in inhibition of gonadotropin secretion in late follicular and midluteal phases of the cycle. These results suggest that elevated endogenous CRH levels resulting in increased cortisol secretion could contribute to decreased gonadotropin secretion and, thus, disruption of reproductive function during stressful conditions in women.

Comparison of the effects of terazosin and enalapril on laboratory stress testing blood pressure in patients with essential hypertension.

It is the current opinion that an ideal antihypertensive drug should reduce blood pressure (BP) not only at rest but also during stressful situations. The current study was aimed to compare the effects of the selective alpha 1-adrenergic blocker terazosin (5 mg once daily) and of the angiotensin-converting enzyme inhibitor enalapril (20 mg once daily) on cardiovascular response to a set of standardized laboratory stressors, such as mental arithmetic, handgrip test and cycle ergometry, in a group of 16 essential hypertensive patients. The study was a randomized, double-blind, cross-over trial preceded by a placebo run-in period. Terazosin and enalapril had a comparable effect on resting BP, reducing systolic (SBP) and diastolic (DBP) blood pressure from 159.5 +/- 13.9/101.6 +/- 8.8 mm Hg during placebo by 7.8%/6.7% and by 11.3%/10.2%, respectively. The "response" rate to the two treatments was approximately the same, being 69% and 75% after terazosin and enalapril, respectively. During mental arithmetic, from an average of 181.6 +/- 17.8/118.6 +/- 11.5 mm Hg during placebo, BP was reduced by 11.5%/7.9% after terazosin and by 13.6%/8.5% after enalapril; during handgrip test, BP decreased from 207.2 +/- 22.2/142.2 +/- 13.6 mm Hg by 7.3%/8.4% after terazosin and by 7.7%/7.1% after enalapril; finally, during cycle ergometry, terazosin and enalapril lowered BP by 5.4%/6.7% and 7%/3.1%, respectively, from a placebo value of 215.5 +/- 17.3/127.6 +/- 11.2. No significant difference in antihypertensive efficacy was observed between the two drugs, either at rest and during stress testing.(ABSTRACT TRUNCATED AT 250 WORDS)

Casual versus 24-hour ambulatory blood pressure recording in the evaluation of chronic administration of sustained-release verapamil.

Although ambulatory blood pressure monitoring has been used widely for the evaluation of antihypertensive treatment, little information is available regarding the comparison between this method and casual BP measurement during drug trials. In our study, we tested the efficacy of a new formulation of verapamil, 240 mg sustained-release tablets, and compared the degree of BP reduction as detected by casual (standard mercury manometer) and by 24-hour ambulatory recording (Spacelab ICR 5300). A statistically significant fall in casual BP was observed after verapamil with respect to placebo. Moreover, 24-hour, waking and sleeping ambulatory BPs were significantly reduced by verapamil. The mean BP reduction was similar for office (20.1/16.1 +/- 4.3/3.1 mmHg) and for day-time ambulatory monitoring (13.4/10.7 +/- 4.2/1.9 1.9 mmHg), but no correlation was found between BP fall recorded by the two techniques for individual subjects. This study suggests that sustained-release verapamil is an effective antihypertensive drug. Individual mean BP reduction outside the clinic may not be predicted from office readings and therefore ambulatory BP recording seems to provide a better basis for testing the efficacy of drugs.

Placebo effect in the treatment of angina pectoris.

The interference of placebo effect in the treatment of angina pectoris has been studied in a group of patients with stable angina pectoris, selected on the basis of normal electrocardiogram at rest and a pathologic ergometric electrocardiographic test. It was found that the patients could be divided, according to the results of the exercise test, into two groups: placebo responders and place-bo-non-responders. The anti-anginal effect of beta-blocking agents has been clearly demonstrated only in the placebo-non-responders group. No statistically significant effect of beta-blocking agents was observed in the placebo-responders group. This result shows that it is necessary, in double blind trials, at first to separate placebo-responders from placebo-non responders. Otherwise the correct evaluation of a drug can be modified by the placebo-responders group.

Latent myocardial contractile impairment in patients with angina pectoris.

Intravenous injection of Angiotensin II gives rise to a rapid and transient increase of the afterload of the left ventricle (increased peripheral resistances). In this haemodynamic setting the functional behaviour of the left ventricle, through indirect parameters such as systolic time intervals, was compared in 14 patients with angina and in 15 normal control subjects. As regards blood pressure and heart rate a similar behaviour was registered in the two groups in basal conditions; directly after the intravenous injection of Angiotensin II changes suggesting impairment of left ventricular function failure have been obsered in patients with angina pectoris.

Thallium-201 myocardial imaging in young asymptomatic subjects with "ischaemic" changes in exercise electrocardiogram.

In order to assess the significance of a positive electrocardiographic response to exercise test in 10 asymptomatic subjects with normal resting ECG, a myocardial perfusion scanning with Thallium-201 at rest and during exercise was performed. The following ECG tests were also performed on these subjects: forced hyperventilation, exercise test after nitroglycerin (TNG), exercise test after propranolol. Myocardial perfusion scans did not reveal any defect at rest nor during exercise. Hyperventilation determined abnormalities of ventricular repolarization in all subjects. TNG did not improve the response to exercise test and even decreased the ischemic threshold. After propranolol the electrocardiographic response to exercise became normal in 9 cases, while in 1 subject the ST depressions were impressively reduced. All subjects had a follow-up of 14 to 91 months. During this period none presented symptoms suggesting a coronary disease. This study suggests that combined evaluation of Thallium myocardial perfusion imaging during exercise and exercise ECG test after TNG is most useful in differentiating ischemic from nonischemic exercise ST depressions in asymptomatic population.

[The relationship between high-density lipoproteins, thromboxane B2 and arteriosclerosis in a case of primary hypoalphalipoproteinemia]. / Rapporto tra lipoproteine ad alta densità, trombossano B2 ed arteriosclerosi in un caso di ipoalfalipoproteinemia primitiva.

Data in the literature suggest that cases of hypoalphalipoproteinemia involve an increase in thromboxane B2 (TXB2) together with an increased risk of atherosclerosis. A recent detailed examination of a 32-year-old man revealed clinical and biochemical features strongly indicative of that pathology. The case presented several unusual features: marked infiltration of the skin and mesenteric lymph nodes by histiocytic lipids with sufficient hyperplasia to induce acute intestinal occlusion combined with an in vivo TXB2 generation curve, subsequently inhibited by aspirin, that was comparable to the curves of the control subjects. Furthermore there were no signs of early atherosclerotic damage so that it was possible to postulate the hypothesis that despite the 50% drop in alpha-lipoprotein levels, they were still sufficient to ensure normal turnover of the other lipoproteins so that, however complex the clinical condition, it was an incomplete expression of a phenotype.

[Evaluation of systolic intervals in Duchenne cardiomyopathy]. / Evaluation des intervalles systoliques dans la cardiomyopathie de Duchenne.

Patients with progressive muscular dystrophy rarely survive beyond the second or third decades: the commonest causes of death are respiratory failure and cardiac failure. An easily repeatable method for early recognition of cardiac dysfunction and its follow-up would therefore be valuable. We performed a polycardiographic study of systolic time intervals in 11 patients with dystrophy (each subject representing an age from 7 to 17 years) in a group comprising 10 of their mothers and in control groups matched for age and sex. The mean values of QS2, PEP and QS1 were significantly higher in patients compared to controls (QS2 : 543 +/- 26 msec compared to 519 +/- 19 msec; PEP : 142 +/- 21 msec compared to 123 +/- 18 msec, and QS1 : 105 +/- 22 msec compared to 75 +/- 12 msec) whilst mean ICT was shorter (36 +/- 11 msec, compared to 49 +/- 5 msec). Mean LVET was comparable in patients and control. These results indicate a reduction in compliance and an increase in end diastolic left ventricular tension. When the systolic time intervals were analysed in each child, an increase in PEP and reduction in LVET were characteristic of the more serious phases of the disease with cardiac failure. It is emphasized that early stages of the disease are characterised by restrictive changes resulting in a reduction in ICT whilst terminal stages with reduced cardiac output cause a reduction in LVET and an increase in PEP. No significant changes were found in the mothers of patients compared to the control group. These results indicate that systolic time intervals may be useful in following up patients with Duchenne's cardiomyopathy.

[Electro-vectorcardiographic study in Duchenne de Boulogne progressive muscular dystrophy]. / Etude électro-vectocardiographique dans la dystrophie musculaire progressive de Duchenne de Boulogne.

Electrocardiographic changes are well known in Duchenne's muscular dystrophy (DMD). Their cause is still controversial. The aim of this study was: to verify the genetic theory of these changes to improve our understanding of their pathogenesis, by studying the distribution and characteristics of the mother carriers; to determine whether electro-vectocardiography could be of value in detecting carriers of the disease. Fourteen patients aged from 7 to 17 years old with DMD underwent ECG and VCG. ECG changes were recorded in 13 of the 14 cases: increased amplitude of the R wave in the right precordial leads or deep Q waves (amplitude greater than or equal to 2 mm, duration less than 0,04 msec) in the peripheral or left precordial leads. The algebraic sum of R--S in V1 was greater than normal in 6 carriers. VCG criteria of posterior myocardial infarction were fulfilled in 11 patients. "Bites" were recorded in 4 patients and 8 carriers. Electrical changes were therefore found in both patients and carriers with equal significance: in the first group the main appearances were of pseudo-infarction, principally involving the posterior wall; in the second group, less specific changes, best recorded on VCG, suggesting foci of myocardial fibrosis were observed. We think that the "bites" recorded in 66 p. 100 of mothers, could be a useful parameter for detecting carrier subjects.

[Comparison of the efficacy of monotherapy with a beta-blocker, a diuretic, and ACE inhibitors in the control of blood pressure during stress]. / Confronto dell'efficacia delle monoterapie con beta-bloccante, diuretico, ACE-inibitore nel controllo dei valori pressori durante stress.

In order to compare the efficacy of beta-blocking, diuretics and ACE-inhibiting monotherapy in controlling the blood pressure increase to stress, a study was conducted on 30 subjects (10 treated with atenolol, 10 with hydrochlorothiazide/amiloride combination, 10 with enalapril) with mild or moderate essential hypertension whose resting blood pressures were normalised by therapy. In the 3 groups of subjects blood pressure values at rest, during mental stress, static and dynamic exercise did not significantly differ before antihypertensive therapy. Atenolol and enalapril significantly reduced systolic and diastolic pressure below pretreatment values throughout and immediately after each test, differing from diuretic therapy which did not show any significant reduction in diastolic rises at the peak of hand-grip or in both systolic and diastolic pressures at the highest work-loads during dynamic exercise. In the recovery period of the exercise cycle test diuretics also produced a later normalisation of diastolic pressure. In conclusion, beta-blockers and ACE-inhibitors seem to be more effective than diuretics in the control of the blood pressure response to stress in hypertensive patients, suggesting that these drugs are the first choice treatment of mild to moderate hypertension.

Cardiovascular reactivity, plasma markers of endothelial and platelet activity and plasma renin activity after mental stress in normals and hypertensives.

Endothelial injury and platelet activation, mechanisms known to be involved in vascular lesions, may promote the development of cardiovascular disorders possibly associated with mental stress. Plasma markers of platelet activation (beta-thromboglobulin, BTG) and of endothelium activity (factor VIII/von Willebrand factor, FVIII/vWf) and plasma renin activity (PRA) were determined in 17 healthy normotensive volunteers and in 21 hypertensives without target-organ damage before and after mental stress (a colour-word conflict test). The aim of the study was to compare cardiovascular reactivity with the stress-induced changes in platelet and endothelium activity. Individual responses in BTG and factor FVIII/vWf after the colour-word conflict test were markedly different, but significant mean increases were observed in both groups with no difference in the degree of response and in the percentage of responders. No correlations were found among the changes in plasma variables or between cardiovascular reactivity (systolic and diastolic blood pressure and heart rate) and the changes in BTG, FVIII/vWf and PRA. These findings suggest that hypertensive patients do not have an abnormal platelet or endothelium reactivity to mental stress, at least when the disease is free of vascular complications. This dissociation of stress-induced variability in BTG and FVIII/vWf and cardiovascular reactivity indicates that these indices could be used as independent markers of mental stress.

Heart rate variability and ventricular ectopic activity in hypertensive patients.

In order to investigate whether the severity of ventricular ectopic beats in hypertensive patients is influenced by the autonomic drive to the heart, we evaluated the relationship between the degree of dysrhythmias and 24-h spontaneous heart rate variability, an index of sympatho-vagal balance at cardiac level. Ambulatory 24-h ECG monitoring was used to examine 42 untreated essential hypertensives, previously scored for the presence and the extent of hypertensive target organ damage. No significant difference was found in the prevalence of complex ventricular ectopic beats in patients with a heart rate variability that was lower and higher than the arbitrary cut off points selected to divide subjects into groups. Neither heart rate variability nor the degree of arrhythmias was correlated with blood pressure levels, whereas the degree of ectopy was influenced by the presence of target organ damage and left ventricular hypertrophy (by ECG). Our results seem to exclude an association between dysrhythmias in hypertensives and autonomic outflow to the heart as detected by the analysis of heart rate variability.