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Prehypertension is defined as borderline blood pressure levels that do not fall in the range defined as hypertension. Since the definition of hypertension has changed over the years, the definition of prehypertension has changed too. The term “prehypertension” was used in 2003, by the Joint National Committee on Hypertension. However, already in the 1920s and 1930s, insurance companies used the term prehypertension for slightly elevated blood pressure levels which were well within the normal range but were clearly associated with increased morbidity and mortality. These data, accumulated by insurance companies, were used for risk calculation in order to price insurance policies.

ACT-280778 is an oral, non-dihydropyridine, dual L-/T-type calcium channel blocker. This phase 2a, double-blind, randomized, placebo- and active-controlled study investigated the efficacy and safety of 10 mg ACT-280778. Patients with mild-to-moderate essential hypertension received once-daily placebo (n=53), ACT-280778 10 mg (n=52) or amlodipine 10 mg (n=54) for 4 weeks. The primary end point was the change from baseline to week 4 in placebo-adjusted mean trough sitting diastolic blood pressure (SiDBP) with ACT-280778. Tolerability was assessed by recording treatment-emergent adverse events (TEAEs). Baseline clinical characteristics were similar across groups. No significant difference was observed at week 4 in mean trough SiDBP between placebo (-9.9 (95% confidence limit (CL) -12.7, -7.0) mm Hg) and ACT-280778 (-9.5 (-12.4, -6.5) mm Hg; P=0.86); amlodipine reduced mean trough SiDBP by -16.8 (-19.0, -14.5) mm Hg, confirming assay validity. Change in mean PR interval at week 4 (pre-dose) differed between placebo (-1.0 (95% CL -4.4, 2.3) ms) and ACT-280778 (6.5 (3.5, 9.6) ms); amlodipine did not increase PR interval (1.1 (-1.6, 3.9) ms).Treatment-emergent adverse events (TEAE) frequency was 32.1% (placebo), 32.7% (ACT-280778) and 33.3% (amlodipine). The most common TEAEs were headache, peripheral edema, hypertension and second-degree atrioventricular block. ACT-280778 (10 mg) did not lower blood pressure in mild-to-moderate hypertension.

Nous avons emis ľhypothese que ľincidence ďhypotension pendant ľarthroplastie totale du genou (ATG) serait plus faible avec ľanesthesie rachidienne et peridurale combinee (RPC) qu’avec ľanesthesie peridurale seule. Lors ďune etude prospective, 80 patients ďetat physique ASA I–II, de 40 a 80 ans, subissant une ATG reglee, ont ete repartis aleatoirement pour recevoir une anesthesie RPC (groupe RPC, n = 40) ou peridurale seule (groupe peridural,n = 40). Les mesures hemodynamiques comprenaient la tension arterielle moyenne (TAM) oscillometrique, la frequence cardiaque (FC) et ľindex cardiaque (IC) determine par la bio-impedance thoracique; la resistance vasculaire generale (RVG) a ete calculee. Notre principal parametre etait le nombre ďepisodes ďhypotension definie par une TAM < 70 mmHg). Selon une analyse univariee, il n’y avait aucune difference intergroupe quant a la TAM, la FC, ľIC ou la RVG perioperatoires. Ľincidence ďhypotension etait similaire dans les deux groupes (deux dans chaque groupe), aussi ľincidence de bradycardie (12 avec ľanesthesie RPC et 7 avec la peridurale; P = 0,2). Les autres mesures hemodynamiques ne presentaient pas de difference intergroupe, y compris ĽIC et la RVG calculee. Un supplement ďanalgesie avec du fentanyl a ete plus souvent requis dans le groupe peridural (20 vs 6 patients — P = 0,03). Ľanesthesie rachidienne et peridurale combinee et ľanesthesie peridurale seule, utilisees pendant ľATG, sont associees a la meme incidence ďhypotension et a des reactions hemodynamiques similaires au plan statistique et clinique.

Background This study investigates the effect of amlodipine on arterial compliance (AC), and the effect of atorvastatin on AC when given in combination with amlodipine. Methods Twenty-one consecutive hypertensive hyperlipidemic patients were included in this study. Patients were followed every month for 6 months (3 months of amlodipine therapy and 3 months of amlodipine and atorvastatin combination). Results During the 3 months of amlodipine monotherapy, large and small AC were improved by 26% and 38%, respectively, and the systemic vascular resistance was reduced by 10%. The addition of atorvastatin during the next 3 months improved small AC by an additional 42% and decreased the systemic vascular resistance by another 5%, but large AC and blood pressure did not change. Conclusions Amlodipine improves large and small AC, and the beneficial effect of atorvastatin on small AC is additive to the effect achieved by amlodipine.

Objective The aim of this study was to determine whether reduction of hyperinsulinemia with rosiglitazone will improve vascular elasticity in patients with non-insulin dependent diabetes mellitus. Methods In an open label study 52 patients with non-insulin dependent diabetes mellitus and at least one additional cardiovascular risk factor, were treated for 6 months with 4 mg of rosiglitazone, and uptitrated to 8 mg after 3 months of treatment, if needed. At the beginning of the study and at its end, blood was drawn for insulin, C- peptide, and 24-h urine collected for microalbuminuria/proteinuria. Glucose, chemistry, lipid profile, and hemoglobin A1C were determined at 0, 3, and 6 months. Vascular compliance was measured in monthly intervals. Results Treatment increased significantly small artery elasticity from 1.45 to 2.43 mL/mm Hg × 100. Large artery elasticity tended to increase toward the end of the study ( P = not significant). Systolic blood pressure decreased from 144 to 124 mm Hg and diastolic blood pressure decreased from 80 to 68 mm Hg, despite mild weight gain. Heart rate tended to decrease from 76.3 to 74.7 beats/min ( P = not significant). Systemic vascular resistance decreased from 1789.8 to 1329.4 dyne sec/cm 5 . Plasma insulin, in patients not treated with insulin, decreased from 42.45 ± 24.90 to 27.86 ± 14.86 IU/mL ( P = .0001). Conclusions Treatment with rosiglitazone reduced hyperinsulinemia and improved small artery elasticity with a tendency to improve large artery elasticity, in hypertensive and in normotensive patients. Because rosiglitazone improves insulin receptor sensitivity (IRS), it is logical to assume that the reduction in hyperinsulinemia reflects improvement in IRS. Our data support the hypothesis that hyperinsulinemia and IRS participate in the mechanisms of tissue injury and their improvement induces improvement in arterial elasticity.

We hypothesise that routinely applied short sessions of slow and regular breathing can lower blood pressure (BP). Using a new technology BIM (Breathe with Interactive Music), hypertensive patients were guided towards slow and regular breathing. The present study evaluates the efficacy of the BIM in lowering BP. We studied 33 patients (23M/10F), aged 25-75 years, with uncontrolled BP. Patients were randomised into either active treatment with the BIM (n = 18) or a control treatment with a Walkman (n = 15). Treatment at home included either musically-guided breathing exercises with the BIM or listening to quiet music played by a Walkman for 10 min daily for 8 weeks. BP and heart rate were measured both at the clinic and at home with an Omron IC BP monitor. Clinic BP levels were measured at baseline, and after 4 and 8 weeks of treatment. Home BP measurements were taken daily, morning and evening, throughout the study. The two groups were matched by initial BP, age, gender, body mass index and medication status. The BP change at the clinic was -7.5/-4.0 mm Hg in the active treatment group, vs -2.9/-1.5 mm Hg in the control group (P = 0.001 for systolic BP). Analysis of home-measured data showed an average BP change of -5.0/-2.7 mm Hg in the active treatment group and -1.2/+0.9 mm Hg in the control group. Ten out of 18 (56%) were defined as responders in the active treatment group but only two out of 14 (14%) in the control group (P = 0.02). Thus, breathing exercise guided by the BIM device for 10 min daily is an effective non-pharmacological modality to reduce BP.

Decreased arterial compliance (AC) is considered an early marker of vascular wall damage. Hypertension gradually decreases arterial compliance. We studied whether treatment with the angiotensin type 1 (AT(1)) antagonist valsartan will affect AC in patients with essential hypertension (EH).Twenty-two patients with EH, 6 men and 16 women, mean age 58.7 +/- 4.1 years, without overt target organ damage were included. Antihypertensive medications were withdrawn for 3 weeks, Valsartan was given at 80- and 160-mg doses. The AC, blood pressure (BP), blood, and urine were measured monthly. Large (C1) and small (C2) AC were derived from radial artery waveforms, obtained using a calibrated tonometer (model CR-2000, HDI Inc., Eagan, MN).After 3 months, systolic BP decreased from 172 +/- 17 to 142 +/- 13 mm Hg (P.0001) and diastolic BP from 95 +/- 9 to 82 +/- 8 mm Hg (P.0001). The decrease in BP was significant within 1 month and improved further on. The C1 increased by 22%, from 8.0 +/- 3.1 to 9.7 +/- 2.3 mL/mm Hg x 10 (P.01). The C2 increased by 35%, from 2.9 +/- 1.3 to 3.9 +/- 1.9 mL/mm Hg x 100 (P.01). Both C1 and C2 reached statistical significance only after 3 months. Systemic vascular resistance (SVR) decreased by 15% from 2,140 +/- 376 to 1,817 +/- 262 dynes/sec/cm(-5) (P.0001).Treatment with valsartan in patients with EH improves small and large AC. The improvement in AC was significant only after 3 months of treatment, whereas systolic BP, diastolic BP, and SVR decreased earlier. The AT(1) receptor blockade with valsartan seems to be an effective means of not only lowering BP but of reversal of vascular wall damage, which predisposes to cardiovascular events.

The efficacy, safety and side-effects of treatment with losartan (Ocsaar) was studied for the first time in Israel in a large group of patients with mild to moderate hypertension in several community clinics. The 421 patients (51% men) aged 30-86 years (mean 58.6) received 50 mg of losartan daily, increased when necessary to 100 mg, and/or a second antihypertensive drug was given. After 4 weeks blood pressure was normalized in 344 and after 12 weeks in 363. Side-effects were minimal and treatment was effective in all age groups.

In a multicenter study in community clinics, 413 patients with mild to moderate essential hypertension were treated with cilazapril (Vasocase), 2.5 mg daily. Patients had either been untreated or had developed side-effects from previous antihypertensive treatment. When response was inadequate the dose was either increased to 5 mg or another antihypertensive medication was added, or both. Treatment significantly reduced systolic and diastolic blood pressures. Pulse rate decreased significantly from the second month of treatment onwards. At the end of the 3rd month of treatment blood pressure was normalized or had decreased by more than 10 mmHg in 91.9% of patients. Physicians' evaluations revealed improvement in 62%; patients' self-evaluations suggested improvement in 61%. Efficacy was equal in all age groups and in both obese and nonobese patients. Antihypertensive response was superior in those with normal renal function. Side-effects were rare and similar to those reported in the literature.

To evaluate the antihypertensive efficacy, tolerability, safety, and dose-response characteristics of the novel calcium antagonist, mibefradil, in combination with a diuretic regimen.A multinational, double-blind, randomised, placebo-controlled, parallel-design trial.Three hundred and seven patients whose mild-to-moderate essential hypertension remained uncontrolled after 4 weeks of treatment with hydrochlorothiazide (HCTZ) 25 mg/day and placebo were randomised to receive combined treatment with HCTZ and once-daily doses of 12.5, 25, 50, or 100 mg of mibefradil or placebo. After 8 weeks of combined treatment, HCTZ was withdrawn and the mibefradil groups continued on their respective doses for an additional 6 weeks.After 8 weeks, the addition of once-daily doses of mibefradil to the initial HCTZ regimen resulted in clinically relevant, dose-related reductions in sitting diastolic blood pressure (SDBP) and sitting systolic blood pressure (SSBP) at trough, which were significantly greater in the 50 and 100 mg dose groups compared to the placebo group (Por = 0.003). Placebo-corrected treatment effects on SDBP and SSBP at the end of the combined treatment period relative to baseline were, respectively, -4.1 and -8.0 mm Hg in the 50 mg mibefradil group and -9.5 and -8.0 mm Hg in the 100 mg mibefradil group. Therapeutic response rates to combination mibefradil and HCTZ therapy were high and dose related, reaching 82% for SDBP in the 100 mg group.The addition of once-daily doses of 50 or 100 mg of mibefradil to patients whose hypertension is not controlled by HCTZ alone is well tolerated and effective in improving BP control.

Hypertension is often associated with impaired glucose tolerance and high insulin levels, factors that contribute to insulin resistance. The present study evaluates the effect of acarbose, a hypoglycemic drug that inhibits carbohydrate digestion in sucrose-induced hypertension in rats. The effects of diets fed to 3 groups of rats for a 16-week period were studied: sucrose + NaCl (1% wet volume [w/v]) with acarbose (0.04% wet weight [w/w]), sucrose + NaCl (1% w/v) without acarbose, and a third diet of complex carbohydrates. There was no statistical difference in the body weight between rats fed with or without acarbose. Fasting glucose levels were significantly lowered when treated with acarbose. Postprandial blood glucose and insulin levels were attenuated in rats fed sucrose + acarbose. Systolic blood pressure increased significantly (p0.001) in rats fed sucrose + NaCl for 3 months, whereas systolic blood pressure of acarbose-fed rats remained at the initial level. Blood pressure changes in the complex carbohydrate-fed group were lower than in rats fed sucrose. The urinary volume, Na+, and K+ of rats fed acarbose tended to increase compared to the acarbose-free diet (p0.05). We conclude that high insulin levels, impaired glucose tolerance and Na+ retention may contribute to the development of sucrose-induced hypertension. Acarbose prevents sucrose-induced increases in plasma glucose and insulin levels. Increases in urinary Na + may contribute indirectly to this effect with resultant normal systolic blood pressures.

The hemodynamic effects of oral nisoldiopine in 12 hypertensive patients aged 35-55 years were determined using the impedance cardiography method. Hemodynamic measurements were performed at hourly intervals before and following ingestion of the medication. Nisoldipine significantly decreased systolic and diastolic blood pressure, with a slight increase in heart rate. Stroke volume did not change significantly following the medication. Total peripheral resistance decreased gradually reaching its lowest values 2 h after ingestion of nisoldipine. We conclude that nisoldipine is a potent oral antihypertensive agent that induces peripheral vasodilatation without decrease in cardiac output.

The efficacy of cilazapril monotherapy was evaluated in 2 multicentre double-blind dose-response trials. After 4 weeks of a single-blind placebo run-in period, patients with uncomplicated mild to moderate essential hypertension and a sitting diastolic blood pressure of 100 to 115 mm Hg, 24 hours after the last placebo dose (trough), were randomised to take either placebo or cilazapril 2.5 mg or 5 mg for 4 weeks (study 1, 86 patients) or 8 weeks (study 2, 78 patients). Sitting diastolic blood pressure was checked every 2 weeks at trough in both studies and at peak in study 2. The reductions in sitting diastolic blood pressure from baseline at trough, and the difference from placebo, were clinically and statistically significant for both cilazapril groups in the 2 studies. The reduction in blood pressure in both active treatment groups was similar, but the response rate with cilazapril 5 mg was greater than that with 2.5 mg. More than 50% of the peak effect was still present at trough for both cilazapril groups. It is concluded that both dosages of cilazapril are effective and reduce blood pressure compared with placebo over a 24-hour period.

Cilazapril (CLZ) is a new, long-acting nonsulfhydril converting enzyme inhibitor (ACE-I). Its effect on peak and trough sitting diastolic blood pressure (SDBP) was studied in a total of 85 patients with uncomplicated, essential hypertension at three centers. After 4 weeks of a single-blind placebo (PLA) run-in period, patients whose SDBP was between 100 and 115 mm Hg, were randomized into active treatment with either PLA (n = 27), CLZ 2.5 mg (n = 29), or CLZ 5 mg (n = 29) once daily in a double-blind fashion for another 8 weeks. At the end of the PLA run-in and after 4 and 8 weeks active therapy, an hourly blood pressure (BP) profile during 1-10 and 21-24 h postdose was performed. The drop in SDBP at the end of the active treatment period at peak and trough was statistically and clinically significant for both CLZ doses in comparison with the PLA group. The peak/trough ratio after subtraction of the PLA effect was 62% for CLZ 2.5 mg and 59% for CLZ 5 mg. These results indicate that the dose regimen of CLZ 2.5-5 mg once daily is adequate and effective for 24 h.

We tested the validity of thoracic impedance cardiography for measuring cardiac output in man by comparing absolute values obtained using the non-invasive impedance method with values obtained using the invasive thermodilution method. We also compared per cent changes in cardiac output using impedance cardiography and thermodilution in response to environmental manipulations including cardiac pacing and intravenous administration of ergonovine, dipyridamole, or isoproterenol. Among 19 patients, absolute values for cardiac output, using the impedance and the thermodilution techniques, agreed well (r = 0.85, P less than 0.001). The per cent change in cardiac output by impedance cardiography was positively correlated with the per cent change by thermodilution for the several manipulations (overall r = 0.87, P less than 0.001). Impedance cardiography does appear, in general, to measure cardiac output and stroke volume validly in man, even in situations where heart rate and stroke volume change in opposite directions.