Feasibility of adjuvant chemotherapy for breast cancer patients

The prevalence and natural history of severe proteinuria in mild to moderate hypertension are not completely defined. We screened 1635 men with a history of hypertension and randomized 1292 with untreated diastolic blood pressure (DBP) 95-109 mmHg to single-drug treatment with either hydrochlorothiazide, atenolol, captopril, clonidine, diltiazem-SR, prazosin, or placebo in a double-blind prospective trial. Twenty-seven of 1635 patients (1.7%) satisfying clinical criteria for primary hypertension were found to have developed proteinuria > 1000 mg/24 hours and were removed from the study. Follow-up data were obtained on 19 of these 27 patients. One patient was found to have focal segmental sclerosis and progressed to end-stage renal disease. Three other patients developed severe (serum creatinine > 3.5 mg/dl) chronic renal failure (one with diabetic nephropathy), one progressed from serum creatinine 1.4 to 2.2 mg/dl, but 14 of the 19 remained with stable serum creatinine < 2.0 mg/dl on follow-up for 6-9 years. Data were available for 1076 of 1155 (93%) treated study patients at end titration, 522/600 (87%) at one year and 322/444 (73%) at two years. There were significant associations for proteinuria with obesity and higher systolic blood pressure. There was a trend toward significant difference in mean 24-hour protein excretion rates at baseline between black (127 mg) and white (139 mg) patients (p = 0.07). There were no statistically significant changes in urinary protein excretion/24 hours between or within the different treatment groups (including placebo). Eighteen patients were removed from the study during the active treatment phase for proteinuria > 1000 mg/24 hours: hydrochlorothiazide 4, placebo 3, diltiazem 3, prazosin 3, atenolol 2, clonidine 2, and captopril 1. We conclude: (1) the prevalence of severe (> 1 g/24 hours) proteinuria in the hypertensive population is significant but does not necessarily imply a poor prognosis; (2) mean 24-hour urinary protein excretion rates did not vary in response to the different classes of antihypertensive drugs; and (3) there was no drug-specific increase in proteinuria detected in this study.     

Double-blind, parallel, comparative multicentre study of a new combination of diltiazem and hydrochlorothiazide with individual components in patients with mild or moderate hypertension

OBJECTIVE: To compare the antihypertensive efficacy and tolerability of a new combination preparation of diltiazem (150 mg) and hydrochlorothiazide (12.5 mg) with the individual constituents in patients with mild/moderate hypertension. DESIGN: Multi-centre, double-blind, randomised parallel group study. PATIENTS: Seventy-one patients with essential hypertension were recruited to the study. TREATMENT: Following completion of the placebo run-in period 63 patients fulfilled the prerandomisation criteria and entered the 10 week treatment period. Patients were randomised to receive either the combination preparation (D 150 mg/H 12.5 mg), diltiazem (150 mg) or hydrochlorthiazide (12.5 mg). The dosage was increased in three patients who had not attained target blood pressure (BP) control after 6 weeks. OUTCOME MEASURES: Response to treatment assessed by change from baseline in clinic and 24 h ambulatory BP. RESULTS: The proportion of patients achieving target BP (a reduction in resting supine diastolic blood pressure (DBP) to below 90 mm Hg or a reduction of 10 mm Hg from baseline) was 80% in the combination group, 55% in the diltiazem group, and 38% in the hydrochlorothiazide group. The respective figures for reduction in supine DBP from baseline were 13.5 mm Hg, 11.2 mm Hg and 5.9 mm Hg. A similar treatment order appeared throughout each of the efficacy variables. BP control throughout the 24 h dosing interval was demonstrated by ambulatory BP monitoring. Each treatment was well tolerated. CONCLUSION: This study provides clear evidence of the efficacy of combination therapy with diltiazem and hydrochlorothiazide in the management of patients with hypertension.     

Optimal blood pressure control in treated hypertensive patients. Report from the Department of Health Hypertension Care Computing Project (DHCCP)

BACKGROUND: We wished to determine the range of treated systolic (SBP) and diastolic blood pressure (DBP) associated with the best survival in hypertensive patients. METHODS AND RESULTS: We conducted a cohort study of patients enrolled in the DoH Hypertension Care Computer Project. Five specialist hypertension clinics (95% of patients) and general practitioners (5%) followed 6214 patients (3070 men and 3144 women) with an average age of 52 years for a mean of 107 months. Total, cardiovascular, ischemic heart disease, (IHD) and stroke mortality were the outcome measures. Age-adjusted relative hazard rates were calculated giving the effect on mortality of systolic or diastolic pressure being higher by 1 mm Hg. In men the optimal level of SBP for all four measures of mortality was the lowest pressure range observed, 92 to 133 mm Hg (median 127). For women the treated SBP range of 96 to 148 mm Hg (median 137) was associated with a low total mortality and also with low to moderate rates for IHD and stroke mortality. Relative hazard rates (P < .001) for IHD mortality were 1.010 for men and 1.013 for women and for stroke mortality were 1.018 and 1.021, respectively. The results were similar in men under and over the age of 60. SBP and DBP tended to be more important in younger than older women. For treated DBP in men, a pressure of 55 to 94 mm Hg (median 87) was associated with a low total mortality. The lowest stroke mortality in men was observed for a DBP range of 55 to 83 mm Hg (median 80) but with a tendency for an increase in IHD mortality. For women DBP < 95 mm Hg (range 55 to 94, median 87) also was associated with a low total mortality. IHD mortality in women was not closely related to treated DBP, relative hazard rate = 1.003, [95% confidence index (CI); 0.990,1.017] but the relative hazard rate for men was 1.011, (95% CI; 1.000, 1.022). The relative hazard rates for treated DBP and stroke were high at 1.035 and 1.028 for men and women, respectively (P < .001). IHD mortality increased in the one third of patients with the greatest fall in DBP on treatment, provided they were not initially in the one-third group with highest untreated DBP. CONCLUSIONS: The best overall survival was associated with a treated SBP of < 134 mm Hg in men and < 149 mm Hg in women and a treated DBP of < 95 mm Hg.     

Effects of sodium restriction on blood pressure, renin, aldosterone, catecholamines, cholesterols, and triglyceride: a meta-analysis

CONTEXT: One of the controversies in preventive medicine is whether a general reduction in sodium intake can decrease the blood pressure of a population and thereby reduce the number of strokes and myocardial infarctions. In recent years the debate has been extended by studies indicating that reduced sodium intake has adverse effects. OBJECTIVE: To estimate the effects of reduced sodium intake on systolic and diastolic blood pressure (SBP and DBP), body weight, and plasma or serum levels of renin, aldosterone, catecholamines, cholesterols, and triglyceride, and to evaluate the stability of the blood pressure effect in relation to additional trials. DATA SOURCES: MEDLINE search from 1966 through December 1997 and reference lists of relevant articles. STUDY SELECTION: Studies randomizing persons to high-sodium and low-sodium diets were included if they evaluated at least one of the effect parameters. DATA EXTRACTION: Two authors independently recorded data. DATA SYNTHESIS: In 58 trials of hypertensive persons, the effect of reduced sodium intake as measured by urinary sodium excretion (mean, 118 mmol/24 h) on SBP was 3.9 mm Hg (95% confidence interval [CI], 3.0-4.8 mm Hg) (P<.001) and on DBP was 1.9 mm Hg (95% CI, 1.3-2.5 mm Hg) (P<.001). In 56 trials of normotensive persons, the effect of reduced sodium intake (mean, 160 mmol/24 h) on SBP was 1.2 mm Hg (95% CI, 0.6-1.8 mm Hg) (P<.001) and on DBP was 0.26 mm Hg (95% CI, -0.3-0.9 mm Hg) (P=.12). The cumulative analysis showed that this effect size has been stable since 1985. In plasma, the renin level increased 3.6-fold (P<.001), and the aldosterone level increased 3.2-fold (P<.001); the increases were proportional to the degree of sodium reduction for both renin (r=0.66; P<.001) and aldosterone (r=0.64; P<.001). Body weight decreased significantly, and noradrenaline, cholesterol, and low-density lipoprotein cholesterol levels increased. There was no effect on adrenaline, triglyceride, and high-density lipoprotein cholesterol. CONCLUSION: These results do not support a general recommendation to reduce sodium intake. Reduced sodium intake may be used as a supplementary treatment in hypertension. Further long-term studies of the effects of high reduction of sodium intake on blood pressure and metabolic variables may clarify the disagreements as to the role of reduced sodium intake, but ideally trials with hard end points such as morbidity and survival should end the controversy.     

The treatment of severe hypertension with trandolapril, verapamil, and hydrochlorothiazide. Trandolapril/Verapamil Multicenter Study Group

A multiple drug regimen consisting of trandolapril, verapamil and hydrochlorothiazide (HCTZ) were sequentially added in an open-label evaluation of patients with severe hypertension. Ninety patients (58 white and 32 black patients) were titrated on one or more drugs and followed for a 19-week maintenance period. Statistically significant (P = 0.001) mean (+/-s.d.) decreases in supine diastolic blood pressure (DBP) were 9.0 (+/-9.3) mm Hg for trandolapril, 13.9 (+/-11.0) mm Hg for the trandolapril + verapamil (TV) combination, and 19.0 (+/-12.3) mm Hg when hydrochlorothiazide was added to the combination. The decrease in BP observed on TV combination therapy plus HCTZ was significantly (P = 0.001) greater than the decrease observed for the TV combination, which was significantly (P = 0.001) greater than the decrease observed for trandolapril monotherapy. Clinical responder rates were 44.8%, 56% and 77.7% for trandolapril monotherapy, trandolapril + verapamil combination therapy and triple therapy, respectively. Black and white patients had similar response rates, but black patients appeared to benefit more from the addition of HCTZ; 20% of black patients achieved a post-treatment supine DBP <90 mm Hg compared to 12.8% of white patients. This study demonstrates that the addition of verapamil to trandolapril has an additive effect on BP that is maintained throughout the day.     

Centralized i.v. team provides inpatient and home-care treatment

AIM: The study of the effects of the inhibitor of angiotensin converting enzyme ramipril (tritace) on the 24-h profile of blood pressure (BP) in patients with mild and moderate arterial hypertension. MATERIALS AND METHODS: Ramipril was given to 21 males aged 45-68 years with essential hypertension stage II (WHO criteria) with stable elevated diastolic blood pressure (95-114 mm Hg) in a single dose 2.5-10 mg/day. Captopril controls received 100 mg twice a day. BP was monitored using "SpaceLabs Medical" unit (model 90207, USA). RESULTS: Compared to placebo, ramipril lowered systolic and diastolic blood pressure both for the 24-h period and in the day time; captopril lowered only diastolic BP in the day time. Side effects of long-term application of ramipril occurred 2 times less frequently than in application of captopril. CONCLUSION: Long-term treatment with ramipril in the above regimen provides more effective control of BP than captopril in the above doses in patients with mild and moderate hypertension.     

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.     

Prevalence, knowledge, treatment and control of arterial hypertension in Oporto, Portugal

The aim of this study was to assess the prevalence, awareness, treatment and control of hypertension among subjects above the age of 39 years living in the urban area of Oporto, Portugal. One hundred and seventy seven individuals from the community were selected by random digit dialing. Each subject was asked about his/her personal history of hypertension, antihypertensive treatment and had his/her blood pressure measured. The prevalence of hypertension was 57.1%, defined by systolic blood pressure (SBP) > or = 140 mm Hg and/or diastolic blood pressure (DBP) > or = 90 mm Hg and/or administration of current the antihypertensive medication. If the values defining hypertension were SBP > or = 160 mm Hg, and DBP > or = 95 mm Hg the prevalence would be 37.9%. The overall prevalence of hypertension was higher in females, but a slightly higher non significant value was found in males in the fifth and sixth decades. Among hypertensives, 62.7% were aware of their condition, 56.7% were treated, 84.2% of hypertensives treated were controlled (SBP < 160 mm Hg and DBP < 95 mm Hg) and 44.7% were very well controlled (SBP < 140 mm Hg and DBP < 90 mm Hg). The question "Are you hypertensive?" had a sensitivity of 62.7%, a specificity of 83.6% and an accuracy of 75.7%. In the preliminary results of this study of an urban population with a high prevalence of hypertension, the awareness of hypertension is similar to that described in the United States of America twenty years ago, the percentage of hypertensives treated is similar to the American percentage fifteen years ago and the percentage of hypertensives treated and controlled is close to the current American percentage.     

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.     

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.     

Comparative antihypertensive effectiveness of once-daily mibefradil and diltiazem CD. Mibefradil Hypertension Study Group

This multicenter, double-masked, randomized, forced-titration, parallel-group trial was designed to determine whether we could confirm the results of a previous trial that demonstrated a significantly greater antihypertensive effect for mibefradil compared with diltiazem CD. Two hundred thirty-nine patients with uncomplicated mild-to-moderate essential hypertension and a baseline sitting diastolic blood pressure (SDBP) between 95 and 114 mm Hg were randomized to receive once-daily treatment with mibefradil 50 mg (n = 119) or diltiazem CD 180 mg (n = 120). After 4 weeks of treatment, all patients underwent forced titration to mibefradil 100 mg or diltiazem CD 360 mg for an additional 8 weeks. After 12 weeks of active treatment, the mean reduction from baseline in trough SDBP was significantly greater with mibefradil than with diltiazem CD (-14.3 +/- 6.6 mm Hg vs -11.7 +/- 7.4 mm Hg, respectively). In addition, significantly more patients receiving mibefradil had a decrease in SDBP > or = 10 mm Hg or a decrease to < or = 90 mm Hg by week 12 than did patients receiving diltiazem CD (82% vs 72%, respectively). The tolerability of mibefradil and diltiazem CD were comparable, with similar percentages of patients in both groups reporting at least one adverse event (21% vs 22%, respectively) that was considered to be at least remotely related to the study drug. The results of this study confirm those of the previous trial. Once-daily treatment with mibefradil 100 mg is significantly more effective than diltiazem CD 360 mg in lowering both diastolic and systolic blood pressure. Both drugs are well tolerated.     

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.     

Management of severe childhood hypertension with minoxidil: a controlled clinical study

The therapeutic efficacy of four antihypertensive regimens (minoxidil, propranolol, and hydrochlorothiazide; propranolol and hydrochlorothiazide; methyldopa and hydroch-orothiazide; and hydrochlorothiazide alone) was evaluated in one child with systolic hypertension and in eight children with systolic and diastolic hypertension. The mean blood pressure of 148/98+/-8/4 mm Hg observed during the hydrochlorothiazide control period fell to 142/88+/-8/4 mm Hg following methyldopa and hydrochlorothiazide, 141/85+/-6/2 mm Hg following propranolol and hydrochlorothiazide, and 128/74+/-4/2 mm Hg following minoxidil, propranolol, and hydrochlorothiazide. The only side effect directly associated with administration of minoxidil was hypertrichosis. The effectiveness of minoxidil in the present study suggests that this drug offers an important adjunct to current antihypertensive therapy in children.     

Fenoldopam mesylate versus sodium nitroprusside in the acute management of severe systemic hypertension

Thirty-three patients with severe systemic hypertension defined as a diastolic blood pressure (DBP) > or = 120 mm Hg were randomized in a single-blind fashion to be treated with either intravenous fenoldopam mesylate (FNP) or sodium nitroprusside (NTP). Fenoldopam mesylate and NTP infusion rates began at 0.1 microgram/kg/minute and 0.5 microgram/kg/minute, respectively and were titrated to achieve a goal DBP of between 95 and 110 mm Hg; or a reduction of at least 40 mm Hg if the baseline DBP was > 150 mm Hg. Fenoldopam mesylate (n = 15) reduced blood pressure from 217/145 +/- 6/5 to 187/112 +/- 6/3 mm Hg (P < .001) at an average infusion rate of 0.5 +/- 0.1 microgram/kg/minute. The average time to achieve goal DBP with FNP was 1.5 +/- 1.4 hours. Nitroprusside (n = 18) reduced blood pressure from 210/136 +/- 5/2 to 172/103 +/- 6/2 mm Hg (P < .001) at an average infusion rate of 1.2 +/- .24 micrograms/kg/minute. Nitroprusside response time averaged 2 +/- 2.5 hours. There was no significant difference between the magnitude of effect seen with either FNP or NTP; nor was there any difference observed in the adverse effect rates of the two agents. Fenoldopam mesylate and NTP demonstrate similar overall efficacy in the treatment of severe systemic hypertension.     

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.     

Prognostic factors in restoration of pulmonary flow after submassive pulmonary embolism: a multiple regression analysis

There is now increasing evidence that high pulse pressure, which is an indicator of large artery stiffness, is an independent risk factor for cardiovascular mortality, especially coronary mortality, in different populations. We have recently shown in a large French population that in male subjects aged 40 to 69 years, increased pulse pressure was a strong predictor of cardiovascular mortality, especially coronary mortality. In the present report, we analyzed the effect of pulse pressure in men and women of the same cohort after classifying them as normotensive (systolic blood pressure [SBP] <140 mm Hg and DBP <90 mm Hg) or hypertensive (SBP >/=160 mm Hg or DBP >/=95 mm Hg). After adjustment for age, mean blood pressure, and other risk factors, the relative risk (95% confidence limits) for cardiovascular mortality for an increase of 10 mm Hg of pulse pressure was 1.20 (1.01 to 1.44) in normotensives and 1.09 (1.03 to 1.14) in hypertensives. Cardiovascular and coronary death rates were similar in the group of normotensive men with a pulse pressure >50 mm Hg and in the group of hypertensive men with a pulse pressure <45 mm Hg. No association between cardiovascular mortality and pulse pressure was observed in either normotensive or hypertensive women (0.85 [0.60 to 1.21] and 1.0 [0. 91 to 1.11], respectively). Low mortality rates could explain this observation in normotensive but not in hypertensive women, in whom cardiovascular mortality rates were relatively high. Because a high pulse pressure in men is an independent predictor of cardiovascular mortality in both hypertensives and in those considered as having normal blood pressure, this parameter could aid in evaluating cardiovascular risk.     

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.     

Comparison of the efficacy and safety of once-daily versus twice-daily formulations of diltiazem in the treatment of systemic hypertension. The Canadian Multicenter Diltiazem-CD Hypertension Trial Group

The efficacy and safety of optimally titrated once-daily (CD) and twice-daily (SR) diltiazem were compared in 111 patients with mild to moderate systemic hypertension [seated diastolic blood pressure (DBP) > or = 95 mmHg and < or = 114 mmHg] in a multicenter, randomized, double-blind, placebo run-in, parallel-group trial. Following a 4 week washout and placebo-controlled run-in period, patients were randomized to receive diltiazem CD 180 mg and matching placebo (n = 54), or diltiazem SR 90 mg bid (n = 57). Total daily doses were titrated from 180 mg to 360 mg to achieve a goal of seated DBP < 90 mmHg during a 6 week titration period. The patients continued to receive their optimal dose for a 6 week follow-up period. Ninety-six (96) patients (diltiazem CD: 47, diltiazem SR: 49) completed the study protocol, with 60% of the diltiazem CD and 55% of the diltiazem SR patients achieving the goal of seated DBP of < 90 mmHg (p = 0.685). Although significant decreases occurred in seated and standing measurements of diastolic and systolic BP and heart rate with treatment in both groups, there were no significant differences between treatment groups. Both medications were well tolerated, with a similar frequency of adverse effects [diltiazem CD: 24/54 (37%) patients; diltiazem SR: 24/57 (42.1%) patients] with the most frequently reported adverse effects being headache and edema.     

Optimization of antihypertensive therapy with a novel, extended-release formulation of diltiazem: results of a practice-based clinical study

Although the effectiveness of diltiazem for the treatment of patients with hypertension has been well demonstrated in numerous placebo-controlled and comparative clinical trials, most physicians have had some concern about its efficacy and have used it predominantly in patients with mild hypertension. Few large-scale studies have evaluated the efficacy and safety of higher dosages of diltiazem for the treatment of patients with hypertension, and few have evaluated the use of diltiazem in patients with more severe hypertension. Tiazac (Forest Pharmaceuticals, Inc., St. Louis, Missouri), a new, extended-release formulation of diltiazem, provides 24-hour blood pressure control with a single daily dose of up to 360 mg. The Study of Titration and Response to Tiazac (START) is an ongoing practice-based, open-label, multicenter study designed to evaluate the efficacy and safety profiles of Tiazac at greater-than-traditional doses in hypertensive patients and to assess the ability of Tiazac to decrease the rate-pressure product, a surrogate marker for cardiac workload. Patients were eligible for study entry whether their hypertension was newly diagnosed or previously treated with a different formulation of diltiazem or any other antihypertensive agent. Normotensive (sitting diastolic blood pressure [SDBP] < 90 mm Hg) subjects and those with mild (SDBP 90 to 99 mm Hg), moderate (SDBP 100 to 109 mm Hg), severe (SDBP 110 to 119 mm Hg), and very severe (SDBP > or = 120 mm Hg) hypertension were assessed at baseline (visit 1), visit 2 (10 to 14 days after visit 1), and visit 3 (25 to 28 days after visit 1). A total of 3082 patients were enrolled, and data from 2802 assessable patients (i.e., those who completed visits 1, 2, and 3) were analyzed. No subjects were lost to follow-up as a result of adverse effects. All subjects received a starting dose of Tiazac 180 mg or 240 mg once daily, and doses were titrated upward to 360 mg once daily as clinically indicated. Blood pressure reduction matched the severity of hypertension in all patients. Subjects who were switched from another diltiazem formulation demonstrated further decreases in SDBP. Antihypertensive monotherapy with Tiazac was well tolerated. This interim START report demonstrates that a daily dose of up to 360 mg of diltiazem is optimal in terms of both control of hypertension and patient compliance. It also provides the practice-based physician with useful clinical information on dose titration and response to a new formulation of an approved drug and supports the efficacy and safety profiles of diltiazem documented in previous well-controlled clinical trials.     

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)