Valsartan, a new angiotensin II antagonist: antihypertensive effects over 24 hours

This study was done to assess the antihypertensive efficacy of once-daily valsartan 20 mg, 80 mg, 160 mg, and 320 mg over 24 hours using ambulatory blood pressure monitoring (ABPM). A total of 217 adult outpatients with uncomplicated essential hypertension (office mean sitting diastolic blood pressure [DBP] of > or = 95 to < or = 115 mm Hg) participated in this multicenter, double-masked, placebo-controlled study. Patients were randomized to receive valsartan 20 mg, 80 mg, 160 mg, 320 mg, or placebo for 8 weeks. Twenty-four-hour ABPM was done at baseline and after 8 weeks of treatment. All valsartan doses produced significant decreases in average ambulatory systolic blood pressure (SBP) and DBP over 24 hours compared with placebo. A trend to greater reductions compared with placebo was observed for doses of valsartan 80 mg and greater (80 mg, -6.61 mm Hg DBP, -11.04 mm Hg SBP; 160 mg, -5.51 mm Hg DBP, -10.61 mm Hg SBP; 320 mg, -8.44 mm Hg DBP, -14.34 mm Hg SBP) compared with valsartan 20 mg (-3.52 mm Hg DBP, -5.92 mm Hg SBP). Valsartan produced consistent reductions compared with placebo during both day (> 6 AM to < or = 10 PM) and night (> 10 PM to < or = 6 AM). However, in all groups, the circadian pattern of blood pressure over 24 hours was preserved and was similar to that observed at baseline (but shifted into the normotensive range in a parallel fashion). The data show that single daily doses of valsartan 80 mg and greater provide effective control of both DBP and SBP over a 24-hour period without loss of diurnal variation.     

A case report of two siblings with familial leukoencephalopathy in normotensive male adults with alopecia and lumbago

The aim of the study was to examine the hypotensive efficacy and tolerance of bisoprolol in elderly patients. Sixty patients (40 <65 years and 20 >65 years) with mild-to-moderate essential hypertension (diastolic blood pressure (DBP) between 95 and 109 mm Hg) were included in the study. After a 2-week run-in period on placebo, patients began bisoprolol therapy (5 mg/d) for 12 weeks. After 4 weeks the dose was increased to 10 mg/d in those with a DBP > or =95 mm Hg. Additionally, in 10 patients over 65 years old, 24-h ambulatory BP monitoring (ABPM) was performed, after placebo and after bisoprolol (5 mg) administration. The hypotensive efficacy of bisoprolol in the elderly and younger patients was similar. Before and after treatment the mean difference of systolic BP (SBP) was 19.6 +/- 12.5 mm Hg and DBP 9.6 +/- 6.2 mm Hg in the younger patients and 16.1 +/- 13.6 mmHg and 9.5 +/- 6.0 mmHg in the elderly patients. Bisoprolol produced a similar reduction in heart rate (23.1% vs 17.1%) in the estimated groups. The tolerance of bisoprolol was good in both groups. There were no significant differences in adverse drug reactions between the groups.     

Low dosages of felodipine ER once daily as monotherapy in elderly hypertensive patients: effect on ambulatory blood pressure and quality of life

OBJECTIVE: To establish the efficacy of 24-h ambulatory and casual blood pressure (BP) reduction, and the tolerability of once daily felodipine extended release (ER) 2.5 mg and felodipine ER 5 mg as monotherapy. DESIGN: Randomised, double-blind placebo controlled 6 weeks parallel study. SETTING: From 15 general practices centres (with 19 GPs) in the region of the University of Maastricht, The Netherlands. SUBJECTS: A total of 129 subjects aged 50-80 years with primary hypertension were screened; 27 men and 61 women with a casual diastolic BP of 100-115 mm Hg and/or a systolic BP of less than 200 mm Hg entered the study. MAIN OUTCOME MEASURES: Casual and 24-h ambulatory BP and a subjective symptom assessment (SSA) questionnaire after 6 weeks of therapy. RESULTS: After correlation for placebo response the mean casual systolic/diastolic BP (SBP/DBP) reduction was 10/5 mm Hg (NS) and 12/10 mm Hg (P < 0.05) for felodipine ER 2.5 and 5 mg, respectively. By using 24-h ambulatory BP measurements these reduction were 6/4 mm Hg (NS) and 13/8 mm Hg (P < 0.05), respectively. No significant difference for SBP and DBP was found during the night time between felodipine 2.5 and placebo (-1/0). Felodipine ER 5 mg lowered the BP load significantly during both daytime and night time but felodipine ER 2.5 mg only for DBP during the daytime. There was a significant difference for the number of responders between placebo (28%) vs felodipine ER 2.5 mg (55%) and ER 5.0 mg (59%). Both felodipine dosages and placebo were comparable in (a low) number of adverse events and results of the SSA. CONCLUSIONS: During daytime felodipine ER 2.5 mg and 5 mg are effective in BP lowering in elderly hypertensive patients. However, only felodipine ER mg is effective in reducing BP during night time (22.00-7.00). Only felodipine ER 5 mg has a significant reducing effect on BP load during day and night time. Both felodipine ER 2.5 and ER 5.0 have a significant effect on the responder rate. It appeared from this study that compared to placebo, and in contrast with felodipine ER 5 mg, the ER form of felodipine 2.5 mg has no BP lowering effect during night time in elderly patients. To assess the effectivity during night time of felodipine ER 2.5 mg in an individual patient it is recommendable to measure the BP at the end of the dose interval.     

Diurnal blood pressure patterns in normotensive and hypertensive children and adolescents

As abnormalities in diurnal ambulatory blood pressure (BP) have been associated with hypertensive target organ damage in adults, we investigated the diurnal systolic BP (SBP) and diastolic BP (DBP) patterns of 54 normotensive children, age 13.4 +/- 3.0 years, and 45 untreated borderline and mildly hypertensive children, age 14.4 +/- 2.6 years. Subjects wore the SpaceLabs 90207 ambulatory BP monitor for 24 h. BP was measured q 15 min from 08.00-21.00 h then q 30 min from 21.00-08.00 h. Nocturnal BP fall, the night-day ratio and cusum derived measures were calculated from time-weighted daytime and night-time SBP and DBP. The groups were compared using analysis of covariance with adjustment for age, race, gender and body mass index. The influence of age, gender and race on the diurnal BP profile was also examined. Nocturnal SBP fall was greater in hypertensive compared to normotensive subjects (17.1 +/- 6.7 vs 14.6 +/- 7.1 mm Hg; unadjusted mean +/- s.d., P = 0.022). Normotensive and hypertensive groups did not differ in nocturnal DBP fall or SBP or DBP night-day ratio. Race appeared to influence the diurnal BP pattern as black subjects had less nocturnal SBP fall (12.9 +/- 6.9 vs 17.1 +/- 6.5 mm Hg; P < 0.005) and a higher night-day SBP ratio (90.1 +/- 5.3 vs 86.7 +/- 4.6%; P < 0.005) than white subjects. In conclusion, hypertensive children and adolescents have a similar diurnal BP pattern as their normotensive counterparts, except that the entire BP profile is shifted upward with a greater absolute fall in SBP at night. Race also appears to influence the diurnal BP profile of normotensive and hypertensive children and adolescents.     

Race specific altitude effects on blood pressure

Altitude affects blood pressure (BP) depending on duration and absolute altitude of exposure. Until now changes in BP during exposure to altitude were studied only in Caucasians. It is not known whether BP is affected differently in black and white people in response to altitude. During a 6-day climb on Kilimanjaro, BP was measured in five white and four black people. All participants (mean +/- s.d.: age 31 +/- 8 years, body mass index 22 +/- 2 kg/m2, BP 125 +/- 11/84 +/- 9 mm Hg) had previous similar experience of high-altitude mountaineering. In the base camp (3040 m) systolic BP (SBP) was similar in both groups (131 +/- 9 vs 119 +/- 8 mm Hg). During ascent until 4600 m SBP increased in all whites (6.5 +/- 2.2 mm Hg) and decreased in all blacks (-7.3 +/- 4.6 mm Hg; P = 0.02, blacks vs whites). During descent SBP returned to initial values in whites, whereas it decreased further in blacks. Diastolic BP (DBP) and heart rate remained constant in all participants. During ascent body weight increased in all whites (1.0 +/- 0.8 kg) and decreased in all blacks (-1.9 +/- 1.4 kg; P = 0.02, blacks vs whites) whereas it returned approximately to initial levels during descent: +0.8 +/- 0.4 kg in blacks and -1.0 +/- 1.3 kg in whites (P = 0.03, blacks vs whites). In this study changes in SBP and body weight during exposure to high altitudes varied between whites and blacks. Fluid balance, acclimatisation, physical fitness or genetics could explain these findings.     

Code Stroke: rapid transport, triage and treatment using rt-PA therapy. The NINDS rt-PA Stroke Study Group

In view of the concern regarding the potential risks and benefits of sodium restriction, the effect on biochemical and orthostatic responses from a moderate reduction in sodium intake in elderly persons that is sufficient to lower systolic blood pressure (SBP) was examined. Seventeen hypertensive subjects aged 65-79 years entered a double-blind randomized placebo controlled cross-over trial of a low sodium diet plus placebo tablets vs a low sodium diet plus sodium tablets (80 mmols/day) each for 5 weeks. At the end of high and low sodium periods, two 24-h urine collections and venous blood samples were undertaken and supine and standing BPs were recorded. On the low compared to the high sodium phase (urinary sodium excretion 95 +/- 36 vs 174 +/- 40 mmols/24-h, respectively), clinic supine SBP fell by 8 mm Hg (95% CI: 1-15 mm Hg, P< 0.05) and diastolic BP (DBP) by 1 mm Hg (CI: -3 to 5 mm Hg); there was no change in total LDL- and HDL-cholesterol and triglyceride levels, serum calcium, phosphate, parathyroid hormone, glucose, creatinine clearance or urinary albumin excretion rate. Serum urate was significantly higher during the low compared to high sodium intake (304 +/- 56 vs 277 +/- 44 micromols/l). Orthostatic BP responses during the high and low sodium intakes were unchanged. In summary, after 5 weeks of moderate sodium restriction no adverse effects other than an increase in serum urate was seen in elderly hypertensive persons.     

The use of ambulatory pressure monitoring for evaluating antihypertensive treatment in clinical practice

OBJECTIVE: To describe the clinical experience of our Centre in the assessment of antihypertensive therapy with 24-hour ambulatory blood pressure monitoring (ABPM). DESIGN AND PATIENTS: We retrospectively studied all the 241 out-patients on antihypertensive therapy submitted to ABPM (SpaceLabs 90207, USA) between March 1992 and March 1993 for clinical purposes. We evaluated: 1) the clinical indications for the test; 2) the modifications of drug treatment suggested by the ABPM results; 3) the referring physicians' acceptance of these suggestions; 4) the changes of office BP measured before and 3-6 months after ABPM. RESULTS: 1) The indications for ABPM were: resistant or poorly controlled hypertension (n = 170-71%); suspected "white coat effect" (n = 51-21%); assessment of symptoms (n = 20-8%). 2) The analysis of ABPM suggested to modify drug treatment in 51% of the patients; a "white-coat effect" was found in 18% of the patients. 3) The ABPM suggestions about treatment were accepted by the referring physicians in 89% of the patients. 4) Office BP decreased from 163 +/- 18/99 +/- 9 mm Hg (before ABPM) to 151 +/- 13/91 +/- 7 (3-6 months after ABPM), (p < 0.001). CONCLUSIONS: The use of ABPM in our Centre, which is based on specific clinical indications, provided indications to modify the drug treatment in a high percentage of patients.     

Stress-management training for essential hypertension: a controlled study

Forty three patients with essential hypertension participated in a study on the effectiveness of stress-management training for essential hypertension. After 6-9 clinic and 48 self-measured readings of systolic and diastolic blood pressures (SBP and DBP), 22 patients were treated with a program based on education, relaxation, and problem-solving training; and another 21 patients were assigned to a waiting list control group. At post-treatment, mean reductions of clinic BP (17/13 mm Hg vs. 6.9/4.7 mm Hg for SBP/DBP), percentages of subjects who achieved at least a 5 mm Hg reduction (86/86% vs. 48/48% for SBP/DBP) and percentages of subjects who in addition achieved a normotensive level (59/68% vs. 29/14% for SBP/DBP) were significantly higher in the treated group than in the control group. Concerning self-measured BP, the effectiveness of the stress-management training was not so considerable (mean reductions of 3.6/2.4 mm Hg and percentages of subjects who achieved a 5 mm Hg reduction of 52/38% for SBP/DBP), but it was significant and maintained in a 4-month follow-up assessment (mean reductions of 4/2 mm Hg and percentages of subjects who achieved a 5 mm Hg reduction of 48/33% for SBP/DBP). It is suggested that stress-management training can be beneficial for treatment of essential hypertension.     

Postexercise decrease in arterial blood pressure, total peripheral resistance and in circulatory responses to brief hyperoxia in subjects with mild essential hypertension

The objective of our study was: (1) to compare the influence of moderate exercise on circulatory after-response in mildly hypertensive (n = 8) and normotensive male subjects (n = 9); (2) to examine the circulatory response to 3-min hyperoxic inactivation of arterial chemoreceptors at rest and during postexercise period in both groups. Hypertensive men (HTS) with a systolic blood pressure (SBP) 148 +/- 5 mm Hg, diastolic blood pressure (DBP) 92.4 +/- 4 mm Hg; and normotensive men (NTS), with a SBP 126 +/- 3 mm Hg, DBP 75.6 +/- 1.3 mm Hg, were submitted to 20-min of moderate exercise on a cycloergometer (up to the level of 55% of each subject's resting heart rate reserve). Finger arterial BP was recorded continuously with Finapres, impedance reography was used for recording stroke volume, cardiac output and arm blood flow. In HTS a significant decrease in SBP by 14.5 +/- 3.4 mm Hg, DBP by 8.9 +/- 1.9 mm Hg, total peripheral resistance (TPR) by 0.45 +/- 0.05 TPR u. (33.7 +/- 2.7%), and in arm vascular resistance (AVR) by 11.0 +/- 2.7 PRU u. (35.6 +/- 7%), was observed over a 60-min postexercise period. NTS exhibited insignificant changes in SBP, DBP, AVR except a significant decrease in TPR limited only to 20-min postexercise period. Hyperoxia decreased SBP, DBP and TPR in HTS. This effect was significantly attenuated during the postexercise period. Long-lasting antihypertensive effect of a single dynamic exercise in HTS suggests that moderate exercise may be applied as an effective physiological procedure to reduce elevated arterial BP in mild hypertension. We suggest also that the attenuation of the sympathoexcitatory arterial chemoreceptor reflex may contribute to a postexercise decrease in arterial BP and in TPR in mildly hypertensive subjects.     

Indomethacin does not attenuate the hypotensive effect of trandolapril

This is a randomised, double-blind, placebo-controlled, four-way crossover study to determine if indomethacin attenuates the hypotensive effect of trandolapril. Twenty-three hypertensive patients (diastolic blood pressure (DBP) 95-115) requiring NSAID were recruited. Seventeen completed the study. Three week treatment periods: trandolapril 2 mg od and indomethacin 25 mg tds, trandolapril 2 mg and placebo, indomethacin and placebo, placebo and placebo. Clinic and ambulatory BP after 3 weeks of each treatment. Study had 85% power to detect a 5 mm Hg difference in BP (s.d. 7 mm Hg). End of treatment clinic BPs were: 152.9/98 mm Hg (95% CI 147.2, 158.6/95.8, 101.4) with placebo and placebo; 150.4/94.9 mm Hg (95% CI 144.7, 156.1/92.1, 97.7) with trandolapril and indomethacin; 148.2/96.5 mm Hg (95% CI 142.5, 153.9/93.7, 99.3) with trandolapril and placebo; and 156.6/97.4 mm Hg (95% CI 150.9, 162.3/94.6, 100.2) with indomethacin and placebo. There were no significant interactions between trandolapril and indomethacin for clinic systolic BP (SBP) (P = 0.79) or clinic DBP (P = 0.87). When trandolapril treatments (placebo or with indomethacin) were compared to treatments without trandolapril (placebo or indomethacin), trandolapril lowered clinic SBP by 5.4 mm Hg (P = 0.047) and DBP by 2.3 mm Hg (P = 0.08). Mean ambulatory BP was: 140.6/88.2 mm Hg (trandolapril and placebo); 142.8/89.7 mm Hg (trandolapril and indomethacin); 149.6/95.0 mm Hg, (indomethacin and placebo); 147.7/94.0 mm Hg (placebo and placebo). Compared with placebo, trandolapril and placebo lowered BP by 6.5/7.5 mm Hg (P < 0.001, SBP; P < 0.001, DBP). Compared with indomethacin, trandolapril and indomethacin lowered BP by 5.0/5.5 mm Hg (P = 0.001, SBP; P < 0.001, DBP). In the present study trandolapril 2 mg lowered clinic SBP and ambulatory BP, but indomethacin did not attenuate this. Indomethacin had no significant effect on either clinic or ambulatory BP. The antihypertensive effects of trandolapril in this study were modest. Patient selection factors may have contributed to the observed responses, but it seems unlikely from these data that a clinically important drug interaction has occurred.     

Conserved themes but novel activities in recombinases and topoisomerases

OBJECTIVE: Hypertension is thought to play an important role in the pathogenesis of acromegalic cardiomyopathy. So far, hypertension has been defined by clinical measurement, with considerable variations reported concerning its prevalence in acromegalics. DESIGN: To determine the mean blood pressure (BP) values and the prevalence of hypertension in patients with active acromegaly according to non-invasive 24-hour ambulatory BP monitoring (ABPM) and to compare the data obtained with those provided by clinical measurement. PATIENTS: Forty patients with active acromegaly (22 women, 18 men, mean age 48.6 +/- 12.5 years) were included. Patients were in wash-out for antihypertensive treatment and none had been using any medical treatment for acromegaly for at least 3 months before the study. All were studied as outpatients. MEASUREMENTS: Clinical BP values were calculated as the mean of BP values obtained by standard sphygmomanometric measurement in three separate occasions. Mean 24-hour, daytime and night-time BP values were obtained by ABPM. RESULTS: The mean 24-hour BP values were lower than clinical BP values, the difference being significant for both systolic BP (SBP: 131.1 +/- 21.5 versus 136.1 +/- 16.3 mmHg, P < 0.02) and for diastolic BP (DBP: 74.6 +/- 10.6 versus 88.8 +/- 9.1 mmHg, P < 0.0001). ABPM values recorded during the daytime were 137.8 +/- 20.9 mmHg for SBP and 78.6 +/- 11.5 mmHg for DBP, the latter being significantly lower than the corresponding clinical BP values (P < 0.0001). About 60% of the patients considered hypertensive by clinical measurement were found to be normotensive by ABPM, thereby decreasing the prevalence of hypertension in this series from 42.5% to 17.5% according to ABPM (P < 0.02). In contrast, all patients defined as normotensive by clinical measurement were also normotensive by ABPM. CONCLUSIONS: Ambulatory blood-pressure monitoring indicated a lower prevalence of hypertension in acromegalic patients then usually reported, suggesting that the role of hypertension in the pathogenesis of acromegalic cardiomyopathy is commonly overestimated. We propose that ambulatory blood-pressure monitoring should be routinely proposed in acromegalics with high or borderline clinical blood pressure values although it is not useful in patients defined normotensive according to repeated clinical measurement.     

Multiple injuries in peacetime and wartime estimate of severity of injury by the Injury Severity Score and Polytraumaschlüssel

The aim of this study was to evaluate the efficacy and tolerability of valsartan, a new angiotensin II receptor antagonist, versus atenolol in the treatment of severe primary hypertension. A total of 103 adult out-patients were randomised to receive either valsartan 160 mg or atenolol 100 mg once daily for 6 weeks. If necessary, additional blood pressure (BP) control could be provided as add-on therapy. Both valsartan and atenolol decreased mean sitting diastolic BP (DBP) and mean sitting systolic BP (SBP): least squares mean change from baseline in DBP; valsartan, -20.0 mm Hg; atenolol, -20.4 mm Hg: in SBP; valsartan, -30.0 mm Hg; atenolol, -25.5 mm Hg. There was no statistically significant difference between the treatment groups. Add-on hydrochlorothiazide (HCTZ) 25 mg was required by 97.2% of patients receiving atenolol and 83.6% of patients receiving valsartan; additional verapamil SR 240 mg was also required by 58.3% of patients receiving atenolol and 64.2% receiving valsartan. Valsartan was well tolerated, with a comparable incidence of treatment-related adverse experiences in both groups. In conclusion valsartan 160 mg is as well tolerated and effective as atenolol 100 mg in lowering BP in severely hypertensive patients.     

A study of losartan, alone or with hydrochlorothiazide vs nifedipine GITS in elderly patients with diastolic hypertension

We conducted a randomised, double-blind, parallel design study comparing the efficacy and tolerability of the angiotensin II receptor antagonist, losartan, alone or with low-dose hydrochlorothiazide (HCTZ) to the dihydropyridine calcium channel blocker, nifedipine GITS (gastro-intestinal therapeutic system), in elderly patients (> or =65 years old) with a diastolic blood pressure (DBP) between 95 and 115 mm Hg. After a placebo wash out period, 140 patients were randomly assigned to receive either losartan 50 mg or nifedipine GITS 30 mg. Patients were evaluated at 4-week intervals during a 12-week treatment period. Patients receiving losartan had HCTZ 12.5 mg added and increased to 25 mg to reduce DBP <90 mm Hg. Patients receiving nifedipine GITS had their dose increased to 60 mg and 90 mg to reduce DBP <90 mm Hg. Efficacy, tolerability and quality of life were assessed during the 12 weeks on each regimen. Patients treated with the losartan regimen (n = 73) had reductions in trough sitting DBP of -10, -13, and -13 mm Hg after 4, 8, and 12 weeks of therapy, respectively. Patients receiving the nifedipine GITS regimen (n = 67) had DBP reductions of -14, -15, and -15 mm Hg, respectively. There were no significant differences in the DBP response between the treatment groups except at week 4 (P < 0.05). Similar reductions in systolic BP (SBP) between the two treatment groups were observed at all time points. The percentages of patients in the two treatment groups reaching goal DBP (<90 mm Hg or DBP > or =90 mm Hg with a reduction from a baseline of > or =10 mm Hg) were comparable (81% on the losartan regimen and 90% on the nifedipine GITS regimen). There were significantly more adverse events reported in patients receiving nifedipine GITS when compared to the losartan regimen (54% vs 36%, P < 0.05). A patient-reported symptom inventory also showed that swollen ankles was bothersome in significantly more patients treated with the nifedipine GITS regimen when compared to the losartan regimen (24% vs 5%, P = 0.001). Thus, in elderly patients with diastolic hypertension, a regimen of losartan alone or with HCTZ has similar efficacy to a regimen of nifedipine GITS with greater tolerability and less symptom bother due to swollen ankles.     

ACE inhibition but not angiotensin II antagonism reduces plasma fibrinogen and insulin resistance in overweight hypertensive patients

The aim of this study was to compare the effects of the angiotensin-converting enzyme (ACE) inhibitor perindopril and the angiotensin II antagonist losartan on insulin sensitivity and plasma fibrinogen in overweight hypertensive patients. Twenty-eight overweight mild to moderate [diastolic blood pressure (DBP) >90 and <110 mm Hg] hypertensives aged 43-64 years, after a 4-week placebo period, were randomized to perindopril, 4 mg o.d., or losartan, 50 mg o.d., for 6 weeks. Then, after a new placebo period, patients were crossed to the alternative regimen for further 6 weeks. At the end of the placebo and of the treatment periods, blood pressure was measured, plasma fibrinogen was evaluated, and insulin sensitivity was assessed by the euglycemic, hyperinsulinemic clamp technique. Glucose infusion rate (GIR) during the last 30 min of clamp and total glucose requirement (TGR) were evaluated. Both perindopril and losartan reduced SBP (by a mean of 20.2 mm Hg, p < 0.001 vs. placebo; and 15.8 mm Hg, p = 0.002 vs. placebo, respectively) and DBP (by a mean of 15.2 mm Hg, p = 0.001 vs. placebo, and 11.8 mm Hg, p = 0.01 vs. placebo respectively), with no difference between the two treatments. GIR was significantly increased by perindopril (+2.91 mg/min/kg, p = 0.042 vs. placebo), but not by losartan (+0.28 mg/min/kg, NS). TGR was not modified by losartan but was increased by perindopril (+9.3 g, p = 0.042 vs. placebo). Plasma fibrinogen levels were reduced by perindopril (-53.4 mg/dl, p = 0.022 vs. placebo) but not by losartan (-16.8 mg/dl, NS). The perindopril-induced decrease in fibrinogen was correlated with the increase in GIR (r = 0.39; p < 0.01). These findings suggest that fibrinogen decrease produced by the ACE inhibitor is related to its action on insulin sensitivity, which seems to be dependent not on angiotensin II blockade but rather on other mechanisms.     

Ambulatory systolic blood pressure patterns in elderly hypertensives

In a recent study we found that patients with isolated systolic hypertension (ISH) had two patterns of systolic blood pressure (SBP) elevations by ambulatory BP monitoring (ABPM), sustained (S) and intermittent (I), the prognostic significance of which seems to be different. In the present study we tried to determine whether such patterns of SBP elevations may be detected among other hypertensives as well. Twenty-eight elderly patients (mean age 65.5+/-5.1 years), nine with ISH, 10 with systolodiastolic hypertension (SDH), and nine with white coat hypertension (WCH), underwent ABPM. Average clinic BP in the ISH group was 184/83 mm Hg, in the SDH group 172/101 mm Hg, and in the WCH group 166/91 mm Hg, where as the ABPM averages were 169/80, 167/95 and 132/73 mm Hg, respectively, and differences held true for both daytime and night-time. Five ISH and four SDH patients had S patterns on ABPM, while the other four ISH and six SDH patients exhibited I patterns; none of the nine WCH subjects had either S or I patterns. ECG revealed left ventricular hypertropy (LVH) and/or ischaemic changes in eight patients with S patterns (ISH and SDH groups combined), as opposed to two patients with I patterns and only one patient of the WCH group. This seems to further suggest that an S pattern of SBP elevation on ABPM may have worse prognostic implications than either an I pattern or no SBP elevation.     

Comparison of amlodipine and quinapril on ambulatory blood pressure and platelet function in hypertension

The effect of calcium channel blocker (CCB), amlodipine (5-10 mg/day) and angiotensin-converting enzyme (ACE) inhibitor, quinapril (10-40 mg/day) on ambulatory blood pressure (ABP), rheological and platelet function in hypertension were compared in this randomised double-blind placebo-controlled cross-over study. This study was preceded by 4 weeks placebo run-in period and the total duration of the study was 28 weeks. Casual and 24 h ABP, plasma renin activity (PRA) and plasma aldosterone (PA) concentration as well as metabolic and platelet function were determined before and at the end of each drug therapy. A total of 27 patients completed this study. Casual BP was significantly reduced after amlodipine or quinapril treatment, but there was no change in heart rate. Regarding the 24 h ABP, amlodipine produced a fall from 145 +/- 8/94 +/- 7 to 130 +/- 13/85 +/- 10 mm Hg (P < 0.001 for both SBP and DBP). Quinapril also caused a reduction from 144 +/- 10/94 +/- 7 to 134 +/- 12/88 +/- 8 mm Hg (P < 0.001 for both SBP and DBP). Neither amlodipine nor quinapril produce any significant change in heart rate. The level of 6-keto-prostaglandin Fl alpha (6-Keto-PGFl alpha) was increased from 36.8 +/- 4.4 to 45.1 +/- 2.5 pg/ml (P < 0.05) and no significant change of thromboxane B2(TXB2) was noted after amlodipine treatment. PRA was increased from 1.24 +/- 0.31 to 1.62 +/- 0.41 ng/ml/h (P < 0.05) after quinapril treatment. Other biochemical parameters were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Severe manifestations in carrier females in X linked retinitis pigmentosa

The aim of this study was to assess the effect of menopause on circadian profile of blood pressure (BP) and heart rate (HR) in the normotensive pre- and postmenopausal women. Systolic BP (SBP), diagnostic BP (DBP) and HR were monitored every 30 min for 48 hrs using noninvasive ambulatory BP monitoring in 24 premenopausal and 40 postmenopausal women. Mean 48-hours, daytime (awake), and nighttime (sleeping) SBP, DBP and HR values were analyzed by reviewing the patients' diaries, and the nocturnal reduction rate (NRR) of SBP, DBP and HR were calculated according to the following formula. NRR (%9 = [(daytime mean-nighttime mean)/daytime mean] x 100. The study subjects were then divided into two groups according to the presence (dipper) or absence (nondipper) of a significant reduction in nocturnal BP (> 10%). Mean SBP, DBP and HR measured over 48 hours were similar between the premenopausal and the postmenopausal group. The NRR of DBP and HR in the postmenopausal group were significantly smaller than those in the premenopausal group (17.1 +/- 6.0% vs. 13.5 +/- 7.0%, 241.1 +/- 6.0% vs. 19.8 +/- 9.0%: p < 0.05). There tended to be higher prevalence of nondipper in the postmenopausal (37%) than in the premenopausal group (29%).     

Resection of the metatarsal head for diabetic foot ulcers

Dobutamine-induced hypotension has been disregarded as a marker of more severe functional abnormalities in patients with suspected coronary artery disease. However, its functional significance in patients with myocardial infarction has not been studied. The aim of this study was to define the predictors of systolic blood pressure (SBP) response to dobutamine in patients with previous myocardial infarction. Dobutamine stress (up to 40 microg/kg per minute) echocardiography was performed in 326 patients with prior myocardial infarction referred for evaluation of myocardial ischemia. A 16-segment, four-grade score model was used to assess left ventricular function. Wall motion score index was derived by summation of wall motion score divided by 16. SBP and heart rate increased from rest to peak dobutamine stress (127 +/- 22 vs 134 +/- 27 mm Hg and 72 +/- 14 vs 122 +/- 24 bpm, p < 0.00001 in both). An increase of SBP > or = 30 mm Hg occurred in 50 patients (15%). By multivariate analysis, independent predictors of failure of SBP increase were higher peak wall motion score index (p < 0.001), higher resting SBP (p < 0.01), and medication with calcium channel blockers (p < 0.05). SBP drop > or = 20 mm Hg occurred in 54 patients (17%). Independent predictors of SBP drop were higher resting wall motion score index (p < 0.001), higher resting SBP (p < 0.0001), and older age (p < 0.05). In patients with myocardial infarction, left ventricular function and baseline systolic blood pressure are powerful predictors of SBP response to dobutamine stress testing.     

Role of nitrates in pharmacologic modulation of reflected waves and their significance in the treatment of arterial hypertension in the elderly

OBJECTIVE: To analyse the efficacy of a sustained release form of isosorbide mononitrate in the treatment of isolated systolic hypertension in the elderly. PATIENTS: 24 patients suffering from essential hypertension and with an average age of 68.5 +/- 1.1 years were studied: 20 male and four female patients, all with isolated systolic hypertension (systolic blood pressure (SBP) > 160 mmHg and diastolic blood pressure (DBP) < 90 mmHg). None of the patients had received pharmacological treatment for their hypertension. None were receiving other medication or displayed concomitant pathologies. METHODS: Assessment of all the patients was made with the measurement of their occasional blood pressure, ambulatory measurement of blood pressure and the measurement of pulse wave velocity in two arterial zones (carotid-femural) by mecanography before and after thirty days of monotherapy with a single 50 mg dose of a sustained release form of isosorbide mononitrate. Four patients were withdrawn from tests due to signs of intolerance to the drug. RESULTS: A fall in occasional blood pressure was recorded, with statistical significance in relation to SBP only: SBP-192 +/- 15.5-->164 +/- 10.2 mm Hg (p < 0.001); DBP-85 +/- 4.2-->83 +/- 5.4 mm Hg. Ambulatory blood pressure readings also showed a significant drop in average SBP readings over the 24 hours: SAP 152.6 +/- 13.6-->140.5 +/- 15.4 mm Hg (p < 0.03); DBP 77.2 +/- 8.7-->72.3 +/- 5.47 mm Hg. No significant changes in pulse wave velocity were recorded for the zones studied: carotid-femural -20.8 +/- 6.0-->21.7 +/- 5.1 m/sec; femural-foot -4.5 +/ -1.4-->4.4 +/- 2.6 m/sec; a marked alteration in the morphology of arterial pulse in the aortic zone was observed, however, with a clear levelling off and reduction of the systolic peak. CONCLUSION: Treatment with nitrates may be a new and effective alternative for the treatment of the age group in question. It acts specifically on the pathophysiological mechanisms of isolated systolic arterial hypertension in the elderly. Changes in reflected wave velocity (retrogrades) seem to cause the significant reduction in SBP, observed in this group of patients.     

Mortality of aerospace workers exposed to trichloroethylene

We assessed the differential effects of a chronotherapeutic agent (controlled-onset extended release [COER] verapamil), administered at bedtime versus a conventional, homeostatic therapy (nifedipine gastrointestinal therapeutic system [GITS]) taken in the morning, on early morning and 24-hour blood pressure (BP), heart rate (HR), and the HR x systolic BP product. The study was a multicenter (n = 51), randomized, double-blind prospective clinical trial with a 10-week treatment period. Dose titration was performed by study investigators based on systolic and diastolic BP values at the doctor's office. Ambulatory BP monitoring was performed at placebo baseline, after 4 weeks of stable double-blind therapy, and at end of the study. Twenty-four-hour BP profiles were studied in 557 hypertensive patients. Changes in BP, HR, slope of the rate of rise of BP and HR, and the HR-systolic BP product during the 4 hours from 1 hour before to 3 hours after awakening were evaluated. The study was powered to show equivalence between the 2 regimens, predefined as a difference between treatment groups in mean change from baseline in early morning BP of +/- 5 mm Hg systolic and +/- 3 mm Hg diastolic. Changes in the early morning BP fell within the definition of equivalence for the 2 treatment strategies (-12.0/-8.2 mm Hg for COER-verapamil and -13.9/-7.3 mm Hg for nifedipine GITS). Changes in both the early morning HR and rate-pressure product were significantly greater following COER-verapamil therapy versus nifedipine GITS (HR, -3.8 beats/minute vs +2.6 beats/minute, p < 0.001 and HR-systolic BP product, -1,437 beats/min x mm Hg vs -703 beats/min x mm Hg, respectively, p < 0.001). Changes in ambulatory BP demonstrated clinically similar reductions for the awake period, but nifedipine GITS lowered systolic BP to a greater extent than COER-verapamil during sleep (-11.0 vs -5.8 mm Hg, p < 0.001). COER-verapamil and nifedipine GITS had equivalent effects (+/- 5/3 mm Hg) on early morning BP. In addition, both extended-release calcium antagonists effectively lowered 24-hour BP. However, COER-verapamil had greater effects than nifedipine GITS on early morning hemodynamics (HR, HR-systolic BP product, rate of rise of BP and HR) and lesser effects during sleep due to its intrinsic pharmacologic properties and chronotherapeutic delivery system.