Isolated office hypertension: are there any markers of future blood pressure status?

BACKGROUND: The introduction of ambulatory blood pressure monitoring into clinical practice has defined a clinical condition called 'isolated office hypertension'. OBJECTIVE: The aim of this study was to evaluate the long-term systolic and diastolic blood pressure changes in patients with isolated office hypertension and to identify the presence of markers capable of identifying which patients will develop sustained hypertension. METHODS: All the 407 patients enrolled had a random office systolic or/and diastolic blood pressure of over 140/90mmHg and a mean daytime ambulatory blood pressure of 130/84mmHg or less. At enrollment, each patient underwent a 'baseline examination' made up of a physical evaluation, a 24h ambulatory blood pressure monitoring, and a mental arithmetic test performed at the end of the 24h ambulatory monitoring. RESULTS: Of the 173 patients finally studied, 102 (58.9%) developed sustained hypertension with an increase in both ambulatory systolic and diastolic blood pressure. At the time of the baseline examination, the patients were divided into two groups. Group A included patients with mean ambulatory systolic and diastolic blood pressures in the first hour of 130/84mmHg or less; group B included patients with mean ambulatory systolic and diastolic pressures in the first hour of greater than 130/84mmHg. During the mental arithmetic test, the systolic and heart rate values increased significantly only in group B patients. Of the 102 patients who had become hypertensive by the time of the follow-up examination, 84 (82%) belonged to group B. CONCLUSION: These data suggest that isolated office hypertension may indeed be a transitional state towards the development of sustained hypertension. Moreover, the mean ambulatory blood pressure value during the first hour can be considered to be a marker of a higher risk of developing sustained hypertension.

Oral tramadol and buprenorphine in tumour pain. An Italian multicentre trial.

In this multicentre trial tramadol and buprenorphine were compared for the treatment of neoplastic pain no longer responsive to non-steroidal antiinflammatory drugs. A total of 131 adults (86 M, 45F) were treated with tramadol (one 100-mg slow-release tablet every 8-12 h), or buprenorphine (one sublingual 0.2-mg tablet every 6-8 h). The trial was to continue for up to six months. Most patients started treatment with 2-3 tablets/day in both groups, and the mean treatment period was 58 days for tramadol and 51 for buprenorphine. Almost all dose changes needed were made in the first fortnight in both treatment groups, and the largest number of patients dropped out because of inadequate pain relief or progression of the underlying disease. The results achieved in the first two weeks persisted throughout the rest of the trial, and the investigator's assessments on each patient's clinical chart corresponded closely with those that patients made in their own daily diaries. In the four hours after the first dose both drugs virtually halved the severity of pain (measured using a visual analogue scale), and this relief lasted throughout treatment. By the end of the first week the proportion of patients with strong/unbearable pain in the tramadol group had fallen significantly (from 98.4% to 48.1%, p < 0.05), as compared to a drop from 92% to 66.7% for buprenorphine. The quality of sleep also tended to improve in the tramadol group, with the proportion of patients enjoying good or deep sleep rising from 37% to 50%, as compared to 33% to 40-44% with buprenorphine. Karnofsky's and Spitzer's indices reflecting the quality of life did not change in the tramadol group; in the buprenorphine group the Karnofsky index dropped slightly after a fortnight (p < 0.05 between treatments). In the first two months of the trial the number of patients with no/moderate pain rose continuously in the tramadol group (71% and 80% after one and two months); the rise was less marked in the buprenorphine group (number of patients with mild/moderate pain, 45% and 65%). In both the short term and in the longer term, it was found that the levels of efficacy and acceptability were always significantly better in the tramadol group than in the buprenorphine group. General and biological safety in both drugs was good. The most typical side-effects were those characteristic of opioids (nausea and/or vomiting, drowsiness). Adverse reactions were reported in 17 patients taking tramadol (25%) and in 16 taking buprenorphine (26%). There were six drop-outs in the first group (9%) and seven in the second (11%). Serious symptoms arose more frequently in the buprenorphine group (19% cf. 10%). No signs of dependence or tolerance were noted.

Diurnal blood pressure variability in essential hypertension and vascular reactivity to isometric stress.

The present study was designed to assess the hemodynamic conditions, by means of impedance cardiography methods, and the relation existing between vascular reactivity to isometric stress (isometric handgrip test) and the day/night blood pressure variations, estimated by ABPM. Fifty unselected untreated non-obese EEH adult subjects (WHO class I) with a duration of disease not exceeding 3 years were classified as dippers or non-dippers according to commonly accepted criteria. Twenty three normotensive volunteers acted as controls. SBP, DBP, HR, CI and SVRI were assessed at rest and after IHG test. At rest dippers, non-dippers and controls showed comparable CI. SVRI were more enhanced in EEH than in controls and, although not significantly, in non-dippers than in dippers. During IHG all subjects showed a significant rise of SBP, DBP and HR; CI variations were of comparable size in all groups while SVRI increases were not. Non-dippers showed a significant SVRI rise after IHG in comparison with resting values. In dippers and in controls SVRI increment was insignificantly different in comparison with resting values. Non-dippers showed a closest correlation between BP and SVRI rise during IHG while dippers showed a less consistent association. In conclusion, our data suggest that in adults with short duration EEH the existence of non-dipper condition may be unrelated to myocardial hypertrophy. Blunted nocturnal BP fall is associated with vascular hyper-reactivity revealed by a bigger elevation of SVRI during IHG.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipid profile during antihypertensive treatment. The SLIP Study Group. Study on Lipids with Isoptin Press.

Some antihypertensive drugs adversely affect the plasma lipid profile, and this has to be taken into account when choosing treatment for hypertension because it may offset the beneficial blood pressure-lowering effect of these agents. In this study, the long term effects of verapamil sustained release (SR) 240mg daily and enalapril 20mg daily on plasma lipid levels were investigated in 931 patients with mild to moderate hypertension. Patients whose blood pressure was not effectively lowered after at least 1 month of monotherapy had either enalapril 20mg once daily added to their verapamil treatment or hydrochlorothiazide 12.5mg once daily added to their enalapril treatment. Blood pressure and lipid profile were assessed before and after 6 months of treatment. Of 864 evaluable patients, 563 patients (65.1%) were successfully treated with monotherapy and 220 patients (25.5%) required combination therapy. A total of 81 patients withdrew from the trial. Systolic and diastolic blood pressure were significantly reduced by treatment with either verapamil or enalapril, and heart rate was reduced slightly, but significantly, by both treatments. Total cholesterol, triglycerides and low density lipoprotein were significantly reduced by both treatments. High density lipoprotein levels were significantly increased in verapamil recipients, but not in enalapril recipients. Adverse effects occurred in 37 (3.9%) patients receiving verapamil SR and 25 (2.7%) patients receiving enalapril. In conclusion, long term treatment with the antihypertensive agents verapamil and enalapril, alone or in combination regimens, significantly improved the plasma lipid profile. Verapamil SR had the most beneficial effect on plasma lipid levels.

Isradipine in the treatment of peripheral occlusive vascular disease of the lower limbs: a pilot study.

The long-term effects of isradipine on peripheral occlusive vascular disease of the lower limbs were investigated in 23 normotensive patients with stable Fontaine stage IIa disease and with an absolute pain-free interval (treadmill speed 4 km/h, no incline) of 300 - 700 m, and Doppler ankle - arm arterial pressure index of less than 0.80 in at least one leg. Using a double-blind, parallel-group design, patients received either 2.5 mg isradipine twice daily or placebo for 12 months. Both isradipine (n = 11) and placebo (n = 12) increased the absolute pain-free interval mean values; the increases were not significantly different. Similar trends were observed in the mean values for relative pain-free interval and ankle--arm arterial pressure index. In a subgroup of patients with a baseline absolute pain-free interval of greater than 500 m, isradipine (n = 6) significantly (P less than 0.001) increased both the absolute and the relative pain-free intervals and increased the ankle--arm arterial pressure index compared with placebo (n = 7). The favourable effects of long-term isradipine treatment suggest that isradipine could positively interfere with factors involved in the progression of atherosclerotic lesions or improve collateral vessel flow.

Effects of treatment with verapamil SR and captopril on the lipid profile of hypertensive patients.

The potential beneficial effects of antihypertensive drugs on cardiovascular morbidity and mortality may be compromised by their adverse effects on serum lipid levels. In our study we compared verapamil and captopril and evaluated their effects on blood pressure and on serum lipid and lipoprotein levels, with particular attention to lipoprotein(a) [Lp(a)]. 20 hypertensive patients were treated with sustained release verapamil 240mg once daily or captopril 25mg twice daily for 3 months in a double-blind randomised study. Diastolic blood pressure was reduced from 100 +/- 3mm Hg to 87 +/- 6mm Hg (p < 0.01) and from 100 +/- 5mm Hg to 92 +/- 7mm Hg (p < 0.05) in the verapamil and captopril groups, respectively. Small but significant changes in serum lipid levels were noted: total cholesterol was reduced from 6 to 5.8 mmol/L (verapamil) and from 6.1 to 5.9 mmol/L (captopril); low density lipoprotein (LDL) cholesterol was reduced from 4 to 3.8 mmol/L (verapamil) and from 4.2 to 3.9 mmol/L (captopril); apolipoprotein C-III was reduced from 0.3 +/- 0.07 to 0.2 +/- 0.06 mmol/L (9.7 +/- 2.5 to 9.2 +/- 2.3 mg/dl) [verapamil] and from 0.2 +/- 0.1 to 0.2 +/- 0.09 mmol/L (9.1 +/- 3.7 to 8.3 +/- 3.4 mg/dl) [captopril]; apolipoprotein A-II increased only with verapamil (p < 0.02). Lp(a) levels showed only minor changes in individual patients. In conclusion, in our study verapamil and captopril were effective antihypertensive agents and did not adversely effect the lipid profile.

Ambulatory blood pressure normalcy: the PAMELA Study.

Although ambulatory blood pressure monitoring is gaining in popularity, it still has important limitations in clinical use, particularly for the definition and diagnosis of hypertension. Various attempts have been made to calculate 'normal' or 'reference' values for ambulatory blood pressure, mostly by 24-h non-invasive monitoring in groups of 'normal' subjects. The most appropriate approach, however, is to compare 24-h ambulatory blood pressure values and casual or clinic blood pressure values in a random sample of a suitably large population. The PAMELA Study has been planned to obtain an epidemiological evaluation of 24-h ambulatory blood pressure values, and its design is described here. In the city of Monza, 2400 subjects aged between 25 and 64 years have been randomly selected according to World Health Organization Monitoring Cardiovascular Diseases (WHO-MONICA) project criteria within sex and age strata. In these subjects, clinic blood pressure, random-zero blood pressure, ambulatory blood pressure (24-h monitoring with SpaceLabs 90207; Redmond, Washington, USA), home blood pressure, electrocardiographic and echocardiographic indices, cardiovascular risk factors and psychological variables are being measured.

Comparison of the new alpha 1-blocker alfuzosin with propranolol as first-line therapy in hypertension.

The new alpha 1-blocker alfuzosin was compared with propranolol as monotherapy for hypertension in a double-blind, parallel group study of 8-week duration in 40 patients with essential hypertension. The patients (11 males, 29 females; mean age 47.8 +/- 2.2 years in the alfuzosin group and 46.6 +/- 2.4 years in the propranolol group) randomly received either alfuzosin from 2.5 mg b.i.d. up to 10 mg b.i.d. or propranolol from 40 mg b.i.d. up to 160 mg b.i.d. according to an individualized dose-titration schedule. The two groups were comparable with respect to disease history, cardiovascular risk factors, concomitant diseases, previous treatments and end-placebo blood pressure and heart rate values. Four patients did not complete the study, two patients in the alfuzosin group: one patient because of postural hypotension and the second one because of breast cancer; and two patients in the propranolol group: one patient for inefficacy and the second one lost to follow-up. At the end of the 8-week trial the mean daily doses were 12.2 +/- 0.61 mg and 196 +/- 9.82 mg for alfuzosin and propranolol, respectively. The antihypertensive effects of the two drugs were comparable. Upright and supine blood pressures decreased significantly with both treatments from the second week on (P less than 0.001 for all BP values). At the end of the 8-week double-blind trial, 83% of alfuzosin patients and 67% of propranolol patients were normalized. The two treatments differed significantly with respect to their effect on heart rate. Alfuzosin did not induce marked changes in heart rate: only a slight increase was observed. In contrast, propranolol caused bradycardia, more marked in the upright position. Palpitations, headache, asthenia and orthostatic hypotension were reported in the alfuzosin group. Asthenia and decreased libido were reported in the propranolol group. These data prove that alfuzosin has antihypertensive effects equivalent to propranolol and it is an interesting agent for the therapy of essential hypertension. It can be used as a first agent at doses between 5 and 20 mg/day with satisfactory therapeutic response and without relevant side-effects.

Serum lipids and apolipoproteins in patients with essential hypertension.

Fifty hypertensive untreated outpatients (34 women, 16 men), with stage I and II essential hypertension, were studied in comparison to 50 age- and sex-matched controls with similar life-styles. Total cholesterol triglycerides, LDL-cholesterol, VLDL-cholesterol, and HDL-cholesterol were measured by enzymatic methods, and apolipoproteins AI, AII, B, CII, CIII and E by RID. The results showed significant differences between hypertensives and controls respectively in triglycerides (135.2 +/- 73.9 versus 90.2 +/- 33.8, P less than 0.01) and VLDL cholesterol (26.7 +/- 14.8 versus 17.7 +/- 6.6, P less than 0.01) while no significant differences were observed in total, LDL and HDL cholesterol. Significant differences between the two groups were also observed in apolipoproteins, particularly in apo AI (130.0 +/- 28.2 versus 144.9 +/- 27.9, P less than 0.05), apo AII (32.9 +/- 10.2 versus 39.6 +/- 11.4, P less than 0.01), apo CII (4.0 +/- 2.6 versus 5.4 +/- 2.9, P less than 0.05) and apo E (5.0 +/- 1.8 versus 4.3 +/- 1.8, P less than 0.05), while no significant differences were observed in apo B and CIII values. The results suggest that in untreated hypertensive patients alterations in the apolipoproteins profile are present which, in part, may be responsible for the elevated incidence of cardiovascular disease, independently from the blood pressure values.

A multicenter study of doxazosin in the treatment of patients with mild or moderate essential hypertension and concomitant intermittent claudication.

This study assessed the efficacy and safety of once-daily doxazosin in the treatment of patients (n = 19) with mild or moderate essential hypertension (sitting diastolic blood pressure [DBP] 95 to 114 mm Hg) and concomitant intermittent claudication (Doppler ankle/arm ratio of less than 0.80 and walking tolerance of less than 700 m on the treadmill). After 14 weeks of treatment with doxazosin, a significant (p less than 0.05) reduction in systolic blood pressure and DBP was observed. Mean blood pressures were reduced from 170/100 mm Hg at baseline to 161/93 mm Hg at the end of treatment. Minor changes in heart rate occurred, which with continued treatment were not statistically significant from baseline. In 12 of 16 (75.0%) efficacy-evaluable patients blood pressure was normalized (DBP to less than or equal to 90 mm Hg with an greater than or equal to 5 mm Hg reduction from baseline) with a mean daily dose of 7.6 mg/day. Doxazosin improved the hypertension severity category in 13 of 16 (81.3%) patients. The blood pressure ratios between both the thighs and arms and ankles and arms showed no statistically significant changes after treatment with doxazosin. Thigh blood flow at rest and the reactive hyperemia after 3 minutes of arterial occlusion did not change statistically. There was a tendency for pain-free distance to improve. Laboratory data were not significantly changed after treatment with doxazosin. Of the 19 patients studied, 5 reported mild or moderate side effects that were either tolerated or disappeared with continued treatment. No patient had therapy withdrawn and no patient required a dose reduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Microcirculation and hemorheology in NIDDM patients.

The authors studied 10 patients with non-insulin-dependent diabetes mellitus and 5 controls matched for age, sex, blood lipids, and smoking habit. The two groups were also comparable for hemorheologic characteristics as evaluated by viscosimetry on whole blood, plasma and serum, erythrocyte filtration and aggregation. The microcirculation was studied in the subjects of both groups by microalbuminuria determination, retinal fluorangiography, and capillaroscopic examination of the bulbar conjunctive and nail folds. None of the patients presented microalbuminuria values higher than the upper limit of normal (20mg/24h). Fluoroangiographic alterations were observed in 4 patients, and all 10 presented capillaroscopic alterations at the bulbar conjunctiva (microaneurysms, erythrocyte aggregates) and nail folds (more frequently of the fingers than toes). Similar alterations were detected in controls. Thus these abnormalities seem independent of hemorheologic values.

Placebo effect and adaptation to noninvasive monitoring of BP.

Three 24 h ambulatory monitorings of BP were performed at two-week intervals in 21 untreated hypertensives (mean age 38 +/- 10 yrs, 13 males and 9 females). After the first baseline monitoring, the patients were randomised, according to a cross-over design, to one of the following sequences: no therapy to placebo or placebo to no therapy. At the end of each period, noninvasive ambulatory monitoring was performed. Mean +/- SE 24 h systolic (SBP) and diastolic (DBP) pressures recorded at the first monitoring were 129.2 +/- 3.5 mmHg and 81.7 +/- 2.3 mmHg respectively. At the second and third monitorings, mean 24 h BP differences versus baseline levels were -2.9 +/- 1.8 and -4.7 +/- 1.7 mmHg for SBP, and -2.0 +/- 1.1 and -2.7 +/- 1.5 mmHg for DBP. Both SBP and DBP differences at repeated monitorings were significant by analysis of variance (P less than 0.05). No significant effects on BP of treatment sequence or of placebo administration were found. Analysis of covariance showed a significant relationship between initial 24 h BP and subsequent mean 24 h BP differences (SBP: beta = -0.260, DBP: beta = -0.124). ANOVA performed on waking and sleeping BP separately showed the observed differences to be significant only during waking hours. Regression analysis showed that the decrease in 24 h BP at repeated monitorings was significantly related to the extent of 'white coat'-induced BP increase only for DBP (P = 0.022). For both 24 h SBP and DBP, however, a negative correlation between the alarm reaction to the presence of the physician and 24 h BP decrease at repeated monitorings was observed. It is concluded that noninvasive ambulatory monitoring is subject to adaptative phenomena but not to placebo effect. Factors influencing the defence reactions to manual measurements and to ambulatory monitoring might be partly different.

[Blood pressure changes induced by physical exercise and tyramine infusion in hypertensive and normotensive subjects]. / Modificazioni pressorie indotte da esercizio fisico e da infusione di tiramina in soggetti ipertesi e normotesi.

The aim of our investigation was to assess blood pressure (BP) and heart rate (HR) variations in 20 essential hypertensive male inpatients (WHO class I and II) and in 20 normotensive healthy volunteers submitted to three provocation tests: isometric handgrip (IHG), bicycle ergometric exercise (BEE) and tyramine infusion (TI) given as i.v. boluses with saline in a single-blind manner. According to our data, IHG induced a comparable rise of systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate in both hypertensive and normotensive subjects. BEE, compared with IHG, caused a more significant (p less than 0.01) rise in SBP and heart rate in both groups. By contrast, DBP during BEE increased significantly in hypertensive (p less than 0.01), but decreased slightly in normotensive subjects (p = n.s.). TI caused a dose dependent SBP rise in both groups studied, while DBP and HR were unaffected. BP elevation was, however, more marked in hypertensive subjects. Confirming this finding, significantly lower tyramine doses were required to produce the same SBP increase in hypertensive patients than in the normotensive volunteers. In short, an SBP rise during TI, and a DBP rise during BEE may be the markers of enhanced cardiovascular reactivity on the part of hypertensive subjects. Our study suggests that BP reactivity to stress may be different according to the laboratory stress employed and also that BEE and TI are more useful than IHG for the assessment of enhanced cardiovascular response to stress in hypertensive subjects.

Beta-TG and plasma catecholamines levels after sympathetic stimuli in hypertensives and patients with peripheral vascular disease.

The influence of the sympathetic nervous system on platelet functions in vivo is still controversial. The aims of our study were to compare the response to various sympathetic stimuli in normal subjects and in patients with essential hypertension (HT) or peripheral vascular disease (PVD) and to evaluate any correlations among plasma levels of catecholamines, beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4). In basal conditions beta-TG and PF4 values in the HT patients were higher than those observed in the controls of the same age but lower than those of the PVD patients. Although the different sympathetic stimuli (90 degrees tilting, handgrip, treadmill test, bicycle test) caused a significant increase of the plasma epinephrine (E) and norepinephrine (NE) levels, they did not modify the beta-TG and PF4 levels in any of the groups studied. The platelet activation indices, therefore, regardless of the basal values, do not seem to be influenced by sympathetic stimulation.

[Cardiovascular reactivity to isometric stress in patients with stable and borderline hypertension and in normotensive subjects. Effects of alpha sympatholytics and beta blocking agents]. / La reattività cardiovascolare allo stress isometrico in soggetti ipertesi stabili, borderline e normotesi. Effetto in alfalitici e betabloccanti.

Aim of the study was to evaluate blood pressure (BP) and heart rate (HR) variability during isometric handgrip test (IHT) in 20 ambulant non-obese male adults affected by sustained hypertension (SH) WHO I and II, 20 borderline hypertensive (BH) and 20 normotensives (C) of comparable sex, age and BMI. SBP and DBP were assessed by "Random Zero" sphygmomanometer, HR by ECG registration. IHT was performed at 30% of maximal effort for 3 min. IHT was carried out: 1) after 7 days placebo, 2) after 7 days propranolol treatment (80 mg/day) and, following 10 days wash-out, 3) after 7 days prazosin treatment (0.5 mg/day). After placebo IHT caused increases of SBP, DBP and HR values insignificantly different in the 3 groups. After propranolol IHT induced significantly more elevated SBP and DBP increases in SH than in BH or in C. These increases were significantly more elevated in comparison with those observed, in advance, in the same group of SH subjects after placebo. After prazosin treatment SBP increase induced by IHT was, on the contrary, significantly more elevated in BH than in SH or in C. This increase is more significant in comparison with that observed in the same BH group after placebo treatment. As for DBP variations induced by IHT after alpha sympatholytic therapy we have observed that SH subjects show significantly lesser diastolic variations as compared with those obtained in BH or in C groups after this treatment. In conclusion, enhanced IHT induced SBP elevation after propranolol and dampened DBP reactivity after prazosin suggest an overriding alpha stimulation in SH subjects. SBP hyperreactivity induced by IHT after alpha sympatholytic treatment and DBP hyporeactivity after betablockers emphasize the role of beta stimulation in BH individuals. Inhibition of BP reactivity to IHT in C after prazosin suggest that this one is mediated by alpha adrenergic receptors.

Decreased fibrinolytic response to adrenergic stimulation in hypertensive patients.

The aim of this study was to assess the function of the fibrinolytic system at rest and in response to adrenergic stimulation in patients with stable essential hypertension as compared with normotensives. At rest, essential arterial hypertensives were characterized by increased levels of circulating tissue-plasminogen activator, associated with an increased activity of its specific inhibitor, the PAI-1. After stress, fibrinolytic response was impaired in essential arterial hypertensives despite a greater release of tissue plasminogen activator by endothelial cells. Therefore, the PAI-1 activity may be increased in essential arterial hypertensives not only at rest, but also after stress. This may represent a risk factor for hypertensive patients.

Comparison of a vasodilating beta-blocker and a cardioselective beta-blocker in long-term treatment of hypertension: a European multicentre study.

The therapeutic effectiveness and safety of indenolol, a vasodilating beta-blocker with beta 2-agonism, was compared with that of atenolol, a cardioselective beta-blocker, in a 1-year double-blind trial. A total of 143 hypertensive patients (diastolic blood pressure 95-115 mmHg after 1 month of placebo) were randomly allocated to either atenolol, 50 mg/day, or indenolol, 60 mg/day. If the target diastolic blood pressure (less than or equal to 90 mmHg) was not reached after 1 month, the beta-blocker was doubled. If the target was still not reached, a diuretic was added after 2 months and doubled after 4 months. There was a higher overall responsiveness and monotherapy was more effective in the atenolol group, but at the lower dose indenolol was more effective than atenolol; however, no differences between drugs were significant. Although the drop-out rate was higher with indenolol, withdrawals due to side effects were similar in both groups. Indenolol was as effective and safe as atenolol in long-term antihypertensive therapy.

Cardiovascular responses to physical exercise and tyramine infusion in hypertensive and normotensive subjects.

The aim of our investigation was to assess blood pressure and heart rate variations in 20 essential hypertensive male in-patients (WHO class I and II) and in 20 normotensive healthy volunteers submitted to three provocation tests: isometric handgrip (IHG), bicycle ergometric exercise (BEE) and tyramine infusion (TI) given as i.v. boluses alternating with saline in a single-blind fashion. According to our data IHG induced a comparable rise of systolic BP, diastolic BP and heart rate both in hypertensive and normotensive subjects. BEE, compared with IHG, caused a more significant (P less than 0.01) rise in SBP and heart rate in both groups. By contrast, DBP during BEE was significantly increased in hypertensive (P less than 0.01), but slightly decreased in normotensive subjects (P = NS). TI caused a dose dependent SBP rise in both groups studied, while DBP and HR were unaffected. BP elevation was, however, more marked in hypertensive subjects. Confirming this finding significantly lower tyramine doses were required to produce the same SBP increase in hypertensives than in the normotensive volunteers. In short, SBP rise during TI and DBP rise during BEE may be the markers of an enhanced cardiovascular reactivity of hypertensive subjects. Our study suggests that BP reactivity to stress may be different according to the laboratory stress employed and also that BEE and TI are more useful than IHG for the assessment of an enhanced cardiovascular response to stress in hypertensive subjects.

Ticlopidine in the treatment of intermittent claudication: a 21-month double-blind trial.

After a 3-month, single-blind, run-in period, 151 patients with intermittent claudication were randomly allocated to receive the antiplatelet agent ticlopidine (250 mg twice per day) or an identical placebo. One hundred and twenty patients completed the double-blind phase of the trial, which lasted 21 months. The primary analysis was performed according to the "intention-to-treat principle" in all 151 enrolled patients. There was, continuing on from the third month after randomization, a progressive and sustained improvement of the pain-free and maximum walking distances in the two treatment groups that was significantly greater in the ticlopidine group. The ankle-arm systolic blood pressure ratio at rest and after exercise increased in a significant manner in the ticlopidine group only. In a secondary analysis, with exclusion of 25 patients because of protocol violations at selection, consistently significant differences in favor of the ticlopidine group were still observed for maximum walking distance and systolic ankle-arm blood pressure ratio, both at rest and after exercise. No major side effects were reported in the treated group. It is concluded that long-term treatment with ticlopidine improves walking ability and ankle systolic blood pressure in patients with claudication.