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.

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)

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)

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)

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.

Sublingual nicardipine versus nifedipine to treat hypertensive urgencies.

Hypertensive urgencies are clinical settings in which a steady therapeutic intervention is needed, but this may be safely stretched over some hours. An appropriate antihypertensive drug to use in an urgency should show a potent but gradual effect: it should reduce BP in a short time and it should be easy to modulate the antihypertensive effect, according to individual needs. Sublingual administration is the easiest way for a therapeutical intervention in an urgency. The use of nicardipine administered sublingually was tested in comparison with nifedipine, during a hypertensive urgency, in 24 hypertensive subjects. The peak effect of nifedipine occurred within 10-20 minutes after the administration, whereas that of nicardipine occurred after 45-50 minutes; nevertheless a significant decrease both in systolic and diastolic blood pressure was already observed 20 min after nicardipine administration. The hypotensive effect of nicardipine was longer lasting than that of nifedipine. Some adverse effects were observed in the group receiving nifedipine, whereas no side effects were described by patients receiving nicardipine.

Relationship of stress testing blood pressure with electrocardiographic and fundoscopy indices of hypertensive end-organ damage.

In our study we tested firstly, whether BP changes induced by laboratory stress testing could be better related than resting blood pressure (BP) to hypertensive target-organ damage (TOD) and secondly, whether an exaggerated reactivity to stress testing might be associated with an increased prevalence of TOD. In 49 untreated essential hypertensives, BP measured at sitting rest and during a variety of stressful situations was related to the presence of TOD, assessed by electrocardiography (ECG) and fundoscopy examination. The degree of TOD was significantly correlated to resting SBP; neither SBP at peak of isometric or dynamic exercise, nor SBP during mental test showed a greater correlation with TOD than resting SBP (NS). A large variability of individual's level of BP reactivity across the different laboratory tests was observed. Patients were arbitrarily dichotomised into groups according to a hyperreactive or normoreactive response to each stress testing; patients classified as hyperreactive (SBP increase greater than upper 95% confidence limit) did not disclose a greater rate of cardiac and ocular damage than normoreactors (NS). In conclusion, stress BP does not increase the strength of relationship with TOD compared to resting BP. Cardiovascular reactivity differs according to the laboratory stimulus employed and an exaggerated BP rise during stress testing is not associated with an increased rate of TOD.

Calcium antagonists and hormone release. VIII. Effects of verapamil infusion on C-peptide to insulin molar ratio in normal subjects and obese subjects with normal glucose tolerance.

It is known that calcium-antagonist drugs can modify the insulin response to various secretagogues. In order to clarify whether calcium-antagonist effect was directed at the level of pancreatic insulin secretion or hepatic insulin extraction and further investigate the pathogenesis of hyperinsulinemia in obesity, an oral glucose tolerance test (OGTT) was performed in basal conditions and during a Verapamil infusion (VE, 5 mg/h x 3.5 h) in 12 normal subjects and 14 obese patients with normal glucose tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute complications in the course of "mild" hyperparathyroidism.

It is generally accepted that some patients affected by mild asymptomatic primary hyperparathyroidism need not be treated with surgery, but may be medically managed without risk. However, our experience regarding 5 of these cases observed in the last two years, suggests a different approach. These patients, initially diagnosed as having mild hyperparathyroidism based on only moderately elevated serum concentrations of calcium and followed medically for years, were referred to us for a sudden worsening of their clinical course. One 35-year-old man presented hemorrhagic gastritis with severe anemia and type II AV block with syncopal attacks. Three women, aged 51, 64 and 65 years, presented with severe hypercalcemia associated with renal failure in two and with marked bone disease in another. In all these cases parathyroid neoplasms were preoperatively localized (by ultrasonography, CT scan and radioactive 201-Tl 99-Tc scan) and surgically removed. Histological examination showed a parathyroid carcinoma in the male patient and single gland enlargements in the three females. A fifth patient, a 65-year-old woman, was referred to us in critical condition: severe hypercalcemia, osteopenia with femur fracture, myocardial infarction and renal failure. She died in a few days, in spite of intensive medical care. These cases suggest that patients with hyperparathyroidism initially diagnosed as "mild" need close medical observation and preferably, in our opinion, should undergo surgery.

Calcium antagonists and hormone release. VII. Effects of gallopamil infusion on insulin and C peptide release in normal subjects.

It is known that insulin release is calcium-dependent and that calcium-antagonists, blocking calcium transport across cell membranes, inhibit it, especially interfering with the second phase of insulin secretion. Gallopamil (GAL) is a new calcium-antagonist that, although structurally similar to verapamil, has more potency. It blocks slow calcium channels and fast sodium channels. Even if it has been demonstrated in vitro, there is no evidence that GAL is able to impair the glucose-induced insulin release in humans. We have submitted five normal subjects (24-36 yr old) to oral glucose tolerance test (OGTT, 75 g of glucose p.o.) and OGTT plus GAL infusion test (1 mg i.v. as a bolus, followed by a 2 mg/hr infusion for 2.5 hr, starting 30 min before glucose load), in two different days, to determine the effects of GAL on insulin and C peptide release after oral glucose load. In opposite with verapamil effects, we found that GAL did not reduce the peak levels of insulin and C peptide, but the peak response was delayed and the incremental areas tended to increase during GAL infusion, so that an impairment of glucose tolerance was equally obtained. This study indicates that different calcium-antagonist drugs exert differential effects on insulin release and their action on glucose homeostasis should be kept in mind because of the large use of these drugs in cardiac patients.

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%.

[Evaluation of the predictive stable hypertension validity during the ergometric test in borderline hypertension]. / Valutazione della validità predittiva di ipertensione stabile del test ergometrico nell'ipertensione borderline.

Aim of this study was to assess blood pressure (BP) response to exercise in borderline hypertensive subjects and to evaluate its predictive value for subsequent established hypertension development: 74 male subjects (28 borderline subjects, 26 normotensive subjects and 20 subjects with established hypertension) underwent a maximal exercise testing in the sitting position with a bicycle ergometer at the beginning of the study and then after 1 and 2 years; besides casual BP was controlled every 3 months for 2 years. Systolic BP exceeding 220 and/or diastolic BP exceeding 105 mmHg at maximal exercise and/or diastolic BP exceeding 100 mmHg at th fifth min of recovery were considered as abnormal. On the basis of BP response to exercise we divided our study group in: normotensive subjects with a normal BP response (Group A: 88%); normotensive subjects with an abnormal BP response (Group B: 12%); borderline subjects with a normal BP response (Group C: 46%); borderline subjects with an abnormal BP response (Group D:56%). At the end of a 2-year follow-up established hypertension developed in 1 subject of Group B (33%), in 2 subjects of Group C (15%) and in 10 subjects of Group D (67%); 7 subjects of Group C returned to normotension (54%). The incidence of established hypertension is significantly higher in borderline subjects with an abnormal BP response to exercise. This finding is probably due to both functional and organic factors and stresses the predictive value of exercise testing in borderline hypertension.

A discrepancy between platelet alpha 2-receptor density and functional circulatory changes in hypertensives.

To investigate whether differences exist in peripheral alpha 2-adrenoceptors between normotensive and hypertensive subjects, we determined platelet alpha 2-adrenoceptor density in 10 (7 males) untreated essential hypertensives (mean age of 51.1 years, range of 44-59 years) and in 10 age- and sex-matched normotensive controls. Moreover, in hypertensive patients, we examined the relationship between receptor density and cardiovascular reactivity to mental arithmetic, static handgrip, and bicycle exercise, to verify the hypothesis that alpha 2-adrenoceptors might play a role in modulation of hemodynamic response to sympathetic stimuli. alpha 2-Adrenoceptor density, as calculated by binding of [3H]yohimbine to platelets, was significantly higher in essential hypertensives (314.8 +/- 38.7 fmol/mg) than in normotensive subjects (213.6 +/- 34.7 fmol/mg) (p less than 0.05), whereas receptor affinity was similar in both groups (4.0 +/- 0.5 nM hypertensives, 4.3 +/- 0.5 nM normotensives; p greater than 0.05). Mental arithmetic increased mean arterial pressure (MAP) by 21.5% from basal values and heart rate (HR) by 13.2%. During isometric exercise, MAP increased by 38.1% and HR by 24.7%, while during bicycle ergometry, mean increases in MAP and HR from baseline were of 27.2 and 54.3%, respectively. No correlation was found between platelet alpha 2-adrenoceptor density and percent changes in MAP induced by all tests, or between adrenoceptors and absolute basal and peak MAP values. Our findings suggest that in hypertensive patients, peripheral alpha 2-adrenoceptors are increased with respect to matched normotensives, but these receptors seem not to be involved in the modulation of cardiovascular adaptation to enhanced sympathetic activity.

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.

[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.

Naloxone inhibition of postprandial growth hormone releasing hormone-induced growth hormone release in obesity.

The effects of opiate receptor antagonist naloxone on growth hormone (GH) release after growth hormone-releasing hormone (GHRH) administration were investigated, before or after feeding, at 13.00 h, in 20 obese women and in 10 normal women. When GHRH was administered to obese women before a meal at lunch time, the mean peak plasma GH levels were very low, while plasma GH responses significantly increased after feeding. Naloxone, infused at a rate of 1.6 mg/h starting 1 h before GHRH administration (50 micrograms i.v. as a bolus), was capable of inhibiting GH release induced by administration of GHRH after feeding. On the contrary, naloxone did not induce significant variations on the fasting GHRH-induced GH release. In normal women, naloxone did not significantly modify the GH response to GHRH, both before and after lunch. The inhibitory effect of naloxone indicates that in obese women there is an increased opioid activity, which could represent an abnormal response of the gastrointestinal tract to food ingestion.

[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.

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.