Effects of low-dose aspirin on blood pressure and endothelial function of treated hypertensive hypercholesterolaemic subjects.

The main objective of this study was to assess whether aspirin 100 mg QD can improve blood pressure (BP) control and endothelial function in subjects with arterial hypertension (AH) and hypercholesterolaemia. In total, 21 patients of both sexes (52.1+/-11.5 years) with treated AH and hypercholesterolaemia on antihypertensive and statin therapy were included in the treatment group. In the control group, 20 matched patients of both sexes (51.3+/-12.7 years), but without statin therapy, were recruited. Treatment group subjects received aspirin (100 mg QD) for a duration of 12 weeks at randomization (Treatment phase-1), followed by single blind matching placebo for 12 weeks (Placebo phase) and then again received aspirin (100 mg QD) for an additional 12 weeks (Treatment phase-2). The control group participated in Treatment phase-1, but did not continue Placebo phase and Treatment phase-2. At randomization and at the end of each study phase, mean 24-h systolic BP (SBP) and diastolic BP (DBP) were assessed by 24-h ambulatory blood pressure monitoring (ABPM) and endothelium-dependent (flow mediated, FMD) and -independent (nitroglycerin induced, NTG) vasodilatations of brachial artery were measured using high-resolution ultrasound. In Treatment phase-1, reduction of SBP and DBP (DeltaSBP 5.7+/-2.6 mmHg, P=0.008; DeltaDBP 3.8+/-1.7 mmHg, P=0.014) and improvement of FMD (4.1+/-0.6%, P=0.019), in Placebo phase an elevation of SBP and DBP (DeltaSBP -6.2+/-2.9 mmHg, P=0.002; DeltaDBP -4.2+/-1.9 mmHg, P=0.031) and worsening of FMD (-3.8+/-0.9%, P=0.027), and in Treatment phase-2 reduction of SBP and DBP (DeltaSBP 4.9+/-2.3 mmHg, P=0.005; DeltaDBP 4.1+/-1.3 mmHg, P=0.024) and improvement of FMD (4.5+/-1.3%, P=0.009) were observed in the treatment Group but not in the control group. Addition of low-dose aspirin to antihypertensive medications and statins in hypertensive and hypercholesterolaemic subjects can reduce both SBP and DBP by improvement of endothelial function.

Twenty-four-hour blood pressure control with isradipine in mild essential hypertension.

The hypotensive effect of isradipine was assessed in 26 male patients, aged 40 to 64 years, with hypertension. After withdrawal of previous antihypertensive treatment and a four-week placebo period, patients were randomized into a double-blind active-treatment period of eight weeks to receive either placebo or 1.25 to 2.5 mg isradipine twice daily. Twenty-four-hour ambulatory blood pressure was measured by Accutracker (Suntech, Oxford, England) after the placebo period and at the end of the active-treatment period. In the isradipine group n = 13), both systolic and diastolic blood pressure and number of blood pressure spikes decreased significantly (P less than .0001), whereas there was a significant increase of these variables in the placebo control group (n = 13). The results of this study indicate that, in these subjects, blood pressure control was achieved throughout the 24-h period by monotherapy with isradipine.

The effect of fish oil on hypertension, plasma lipids and hemostasis in hypertensive, obese, dyslipidemic patients with and without diabetes mellitus.

We have recently reported that dietary fish oil supplementation (n-3) polyunsaturated fatty acid (PUFA) led to a reduction in blood pressure (BP) and serum triglycerides (TG), in addition to the normalization of the hypercoagulable state in subjects with obesity, hypertension and dyslipidemia without diabetes mellitus (OHD-DM). The aim of the present study was to explore the mechanism of this amelioration by comparing the previous results to those obtained from 19 subjects who, in addition to the conditions described above, also suffer from diabetes mellitus (OHD+DM) and proteinuria. In both the non-diabetic and diabetic groups, a similar reduction was observed in BP (from 158.7/80.8 to 146/72.9 mmHg, and from 157.6/83.2 to 141.9/75.6 mmHg, respectively, P<0.001) and TG levels (from 159.2 to 108.0 mg/dl and from 208.7 to 153.1 mg/dl, respectively, P<0.001). However, a favorable reduction in hemostasis parameters (platelet aggregation on extracellular matrix and (alpha2-antiplasmin) was only seen among the nondiabetic patients (from 12.1+/-4.9 to 4.2+/-3.2%, P<0.001). This difference may stem from a less efficient exchange between n-3 and n-6 PUFA in serum phospholipid of the OHD+DM patients. Overall, this 13-day fasting/refeeding method developed by us has proven to cause the rapid exchange of arachidonic acid for eicosapentaenoic acid. It appears to be an effective regimen for the reduction of cardiovascular risk factors (BP, TG and hemostatic variables) in OHD-DM patients and to a lesser extent in OHD+DM patients.

The different patterns of blood pressure elevation by rofecoxib and nabumetone.

Hypertension and knee osteoarthritis (OA) are frequent comorbidities. Nonsteroidal anti-inflammatory drugs (NSAIDs) are often used to relieve pain in such patients. In the last decade selective NSAIDs are used more commonly since they lead to less gastrointestinal complications. As has been shown, the treatment with NSAIDs may cause a mild rise of arterial blood pressure (BP). The influence of selective NSAIDs on BP, particularly in hypertensive patients has still to be investigated. The aim of this study was to determine arterial BP changes in patients suffering from stable arterial hypertension and knee OA and treated with rofecoxib or nabumetone. Two groups of patients with knee OA and stable arterial hypertension received either 25 mg rofecoxib once daily or namebutone 2000 mg once daily during the first week of treatment and 1000 mg for the following 3 weeks. Twenty-four hour arterial BP monitoring was performed prior to initiation of treatment and at the end of a 4-week period. The results were that no changes were found in the mean systolic and diastolic characteristics of BP in the rofecoxib treatment group during day time (delta systolic BP -0.4 mm Hg and delta diastolic BP -0.4 mm Hg), while nocturnal BP increased significantly: delta systolic BP +15.7 mm Hg and delta diastolic BP +8.5 mm Hg. The mean systolic arterial pressure in the nabumeton group raised delta systolic BP 2.9 mm Hg in the daytime and 5 mm Hg during the night-time after the treatment. The mean diastolic arterial pressure also rose delta diastolic 3.2 mm Hg and 4.9 mm Hg at day and night hours respectively. In conclusion rofecoxib treatment did not change arterial BP during day time hours, however, there was a distinct increase in night-time systolic and diastolic BP leading to a disappearance of the physiological diurnal variation. Nabumetone caused a moderate increase of day and night BP, without changes in biological diurnal variation.

Comprehensive individualised nonpharmacological treatment programme for hypertension in physician-nurse clinics: two year follow-up.

A comprehensive programme of nonpharmacological control of hypertension (balanced nutrition, satisfactory weight, enhanced physical activity, relaxation technique, smoking cessation) by primary care physician-nurse (PN) teams who were instructed and routinely advised by a paramedical professional (PP) team (psychologist, nutritionist and physical activity instructor) was developed with the aim of increasing long-term compliance. To evaluate effectiveness, 52 mild and moderate hypertensives without target organ damage were randomly allocated to six weekly meetings of individual intensive instruction by PN teams alone, or direct group instructions by PP teams (24 and 28 patients, respectively). The respective results at 11 months and 24 months follow-up compared with baseline were: (1) 56.9% and 58.8% showed minimal satisfactory reduction of weight, (2) 49% and 58.8% showed minimal satisfactory increase in physical activity, (3) the reported increase in physical activity at 11 months follow-up was validated by significantly correlated improved performance in ergometry, (4) 75% and 40% of the patients performed relaxation vs. 2% at baseline and (5) 71% and 59% needed no medication or reduced dose to control BP, and these changes were significantly (P < 0.02) correlated with weight reduction and increased physical activity. As no differences were found between the two modes of treatment, we conclude that our programme can be successfully applied by the PN primary care teams to increase adherence to nonpharmacological measures in the control of hypertension.

Partial cost-benefit analysis of two different modes of nonpharmacological control of hypertension in the community.

In the Dan and Ashkelon areas of Israel, 28 male and 24 female mild to moderate hypertensives without target organ damage aged 35-65 years were randomly assigned to treatment programmes (based on nutritional management, exercise and stress management techniques) either on an individual basis administered by physician-nurse teams (PN) or on a group basis from a team of paramedical professionals (PP) consisting of a psychologist, nutritionist and physical activity instructor. At 11 and 24 months follow-up, there were similar significant improvements in both treatment modes for such risk factors as body mass index, caloric intake and physical activity levels. There was a significant decrease in drug use from $36.28 a month at baseline to $18.94 a month at 11 month follow-up (P = 0.01) and to an estimated $20.48 at 24 months. Mean BP remained unchanged, despite the reduction in drug use, indicating a reduction in the underlying BP. The net present value (NPV) of the reduction in drug utilisation totalled $740 per person over a five year time horizon and a 7.5% discount rate. The total extra costs of treatment, training, case-note writing, travelling and follow-up booster sessions, amounted to $95 per patient for the PN mode and $234 per patient for the PP mode, yielding benefit to cost ratios of 7.79/1 and 3.16/l, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Prior antihypertensive treatment and admission blood pressure correlated with clinical outcome and early morning presentation in hypertensive ischaemic stroke patients.

Blood pressure (BP) reduction of 5-6 mm Hg reduces the relative risk of stroke by 30-40%. This effect does not appear to depend on the antihypertensive agent used to bring about the required reduction in BP. Patients with acute ischaemic stroke often exhibit an elevated BP. These patients, who previously suffered from hypertension, have significantly higher levels of BP readings on admission with increased incidence of stroke immediately after arising. The aim of this study was to compare antihypertensive agents, especially short and long acting drugs with the measurement of BP on admission, the time of the ischaemic stroke and its clinical severity. This was studied retrospectively in 109 patients (55 females and 54 males). The mean age was 69.7 +/- 10.4 years. All the patients admitted between 1 July 1996 and 30 June 1997 for ischaemic stroke as established by brain CT scan, were studied. Of the stroke subjects not treated or treated with short acting calcium blockers, 40.8% and 44.4% of them respectively appeared to have an ischaemic stroke in the early morning hours in contrast to 20% of those treated with long acting calcium blockers (P < 0.05). The last group of patients also experienced less clinical severity. These results emphasise the need for proper 24-h control of BP and by comparison to other antihypertensive agents, the long acting calcium blockers with these subjects may prevent a sudden early morning rise in BP, which is instrumental in stroke prevention.

Repeated fasting and refeeding with 20:5, n-3 eicosapentaenoic acid (EPA): a novel approach for rapid fatty acid exchange and its effect on blood pressure, plasma lipids and hemostasis.

Twenty hypertensive subjects participated in three clinical trials of 13 days each, to examine the effects of Alsepa fish oil [20:5, n-3 eicosapentaenoic acid (EPA) 180 mg, and 22:6 n-3 docosahexaenoic acid (DHA) 120 mg] on n-3 for n-6 polyunsaturated fatty acids (PUFA) exchange on serum phospholipids, blood pressure (BP), triglycerides (TG) and primary hemostasis. After 13 days, plasma phospholipids showed an increase in sigma n-3 (EPA and DHA) from 2.0 to 5.9% (P < 0.01), and a decrease in sigma n-6 (arachidonic acid and linoleic acid) from 29.8 to 22.6% (P < 0.01). A concomitantly significant reduction in systolic BP (SBP) (158.7 +/- 23.8 mm Hg to 146.5 +/- 17.0 mm Hg, P = 0.04), and diastolic BP (DBP) (80.8 +/- 8.4 mm Hg to 72.9 +/- 14.9 mm Hg, P = 0.04) as well as a significant decrease in platelet adhesion and aggregation on extra cellular matrix measured as a percentage of surface coverage (11.9 +/- 4.8% to 4.2 +/- 3.2%, P = 0.0001) was observed. In addition, a significant reduction in baseline dependent TG was observed; the higher the baseline level TG, the more pronounced the reduction (average 159.2 +/- 74.6 mg% to 108.0 +/- 46.1 mg%, P = 0.001). No change was observed in total cholesterol, high and low density lipoprotein (HDL, LDL), platelet and fibrinogen. Repeated fasting and refeeding with fish oil facilitated plasma exchange of n-3 for n-6 PUFA, improved BP, clinical metabolic parameters and lowered platelet reactivity in the vessel wall (primary hemostasis). In severe and life-threatening situations, the beneficial effects of fish oil should be considered for rapid exchange of n-3 for n-6 PUFA. In this study we describe a novel approach for rapid fatty acid exchange by fasting/refeeding with fish oil supplementation, as well as improved BP, plasma lipids and primary hemostasis. Further research is required on the therapeutic use of fish oils and the physiological mechanisms involved in fatty acid exchange.

Antihypertensive efficacy of a once a day verapamil SR/trandolapril combination.

Twenty-one patients with a sitting diastolic blood pressure between 100 and 114 mmHg after a single-blind 2-week placebo run-in period, started treatment under open conditions with the fixed combination of verapamil SR/trandolapril 180/1 mg o.d. for a period of 8 weeks. Patients whose conventionally measured diastolic blood pressure after 4 weeks' treatment was not normalised (diastolic blood pressure < 90 mmHg) received the higher dosage (verapamil SR/trandolapril 180/2 mg o.d.) for a further 4 weeks. Clinical evaluations including measurement of blood pressure were performed every 2 weeks. A 24-h ambulatory blood pressure monitoring (ABPM) was performed at weeks 0, 4 and 8 (end of the study). The mean office blood pressure decreased from 155 +/- 11/104 +/- 4 mmHg at baseline to 139 +/- 9/89 +/- 6 mmHg at week 8. In 12 patients (60%), the diastolic blood pressure was normalised after week 4. In eight patients, the dosage was increased and, of these, a further 25% were normalised at week 8. Response, defined as a reduction of diastolic blood pressure to < or approximately 90 mmHg (normalisation) or a decrease of at least 10 mmHg compared to baseline, was recorded in 18 patients (90%). The mean 24-h ABPM was reduced from 143 +/- 15/85 +/- 9 mmHg at baseline to 131 +/- 11/77 +/- 8 mmHg at week 8. The average systolic and diastolic blood pressure was reduced by a statistically significant amount (11/9 mmHg) during the day (8.00 am-10.00 pm) and 11/7 mmHg during the night (10.00 pm-8.00 am). Diurnal variation did not change. Only mild to moderate adverse events such as slight isolated elevations of SGPT, SGOT and potassium were observed. Two patients discontinued the study prematurely due to impotence which began during the placebo run-in period. No adverse events were serious or required any medical treatment. The fixed combination of verapamil SR and trandolapril appear to be a very effective and well-tolerated once-a-day antihypertensive medication.

Twenty-four hour arterial pressure and heart rate as predictors of left-ventricular hypertrophy.

Hypertrophy of the left ventricle occurs in some but not all hypertensive patients. The present study was designed to examine the office and the 24-hour arterial pressure (AP) and heart rate (HR) recordings, and the AP response to physical stress in two age- and sex-matched hypertensive groups who differed in their left-ventricular mass (LVM). In addition, we tried to determine whether AP and HR measured at rest, under stress, or with 24-hour AP monitoring correlate with LVM. Ten hypertensive subjects with left-ventricular hypertrophy (LVH) made up the study group and 10 hypertensive subjects without LVH made up the control group. Antihypertensive medication was withdrawn at least four weeks prior to evaluation. The mean office AP measured during the washout period was 157 +/- 13/100 +/- 11 mm Hg in the study group and 157 +/- 17/104 +/- 7 mm Hg in the control group. However, 24-hour AP monitoring disclosed that the study group had significantly higher AP than the control group during both day and night. The control group had a significantly faster HR in the clinic and at night. The HR response to bicycle exercise was less in the control group than in the LVH group. The maximal AP and the rise in AP during bicycle exercise did not differ between groups. The LVM index did not correlate with the office AP or with maximal AP during effort, but did correlate negatively with the office HR and with the HR prior to the exercise test.(ABSTRACT TRUNCATED AT 250 WORDS)

Urinary albumin excretion in patients with familial Mediterranean fever: a pilot study.

Amyloidosis of the kidney is the most threatening complication in familial Mediterranean fever (FMF), and colchicine has been shown to reduce its occurrence. In the preclinical stage of kidney amyloidosis, no proteinuria is observed by the standard Albustix method. However, whether these patients have normal or increased urinary albumin excretion is not known. The purpose of this study was to evaluate albumin excretion in FMF patients treated with colchicine and to compare these values to those of a normal control group. Twenty-two subjects with FMF were compared with 16 normal subjects matched with regard to age and body surface area. The two groups did not differ with regard to female/male ratio and arterial pressure. Urine samples were collected overnight while patients were recumbent and in the daytime while they were ambulant. After measuring albumin concentration (Ua) by radio-immunoassay and creatinine concentration through the standard method, the urinary albumin excretion rate (UaV) and urinary albumin creatinine ratio (Ua/c) were calculated. In the FMF group, three patients had microalbuminuria--defined as an albumin excretion rate higher than 20 micrograms/min. Two of them had this condition only in the early morning collection. These three patients were characterized by a longer duration of symptoms (18 vs. 9 years). No patient in the control group had microalbuminuria. The mean UaV in the FMF group did not differ significantly from that of the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypertension in pregnancy: hemodynamics and diurnal arterial pressure profile.

OBJECTIVE: To characterize the 24-h arterial pressure (AP) profile and the left ventricular (LV) structures and functions in women with pregnancy-associated hypertension. METHODS: Twenty nulliparous pregnant women after 20 weeks' gestation, 10 normotensive and 10 hypertensive women matched for gestational age, were hemodynamically investigated using 24-h AP monitoring and Doppler echocardiography to determine LV structures and functions, both systolic and diastolic. RESULTS: The hypertensive women had significantly higher AP determinations throughout the 24 h, with no change in diurnal variation, i.e. nocturnal decline and early morning peaks. Their LV mass was greater and it was accompanied by a slight reduction in contractility and a significant reduction in LV relaxation. The increased AP was due to peripheral vasoconstriction, while cardiac output was preserved. CONCLUSIONS: It appears that pregnancy-associated hypertension is caused mainly by arterial vasoconstriction and not by higher cardiac output. The hypertension increases the LV mass, which is associated with a fall in LV relaxation.

Impaired nitric oxide production, brachial artery reactivity and fish oil in offspring of ischaemic heart disease patients.

The offspring of coronary heart disease (CHD) patients are at particularly high risk for developing CHD. Endothelial dysfunction is present in the majority of CHD and atherosclerosis patients. Fish oil, rich in n-3 fatty acids has been shown to augment endothelium-dependent vasodilatation in human peripheral and coronary arteries. The aims of this study are to investigate presence of endothelial dysfunction determined by the brachial flow-mediated diameter, nitric oxide, plasma lipids and fibrinogen, and the effect of high doses of fish oil on these parameters. Twenty-four healthy offspring of CHD patients (study group) were supplemented with 9 g/day Alsepa fish oil (each gram containing 180 mg EPA and 120 mg DHA), for a period of two weeks. Plasma nitric oxide, urine nitric oxide, fibrinogens and flow-mediated vasodilatation (FMD) were determined prior to fish oil therapy, two weeks into therapy and four weeks after the end of therapy with fish oil. Twelve healthy subjects (control group) with no family history of heart disease were studied as controls (day one only). The offspring had a lower increase in FMD and lower nitric oxide production, compared with the control group. No other parameters varied between the two groups. The administration of fish oil did not result in any changes in the studied parameters. In healthy offspring of CHD patients, early endothelial dysfunction was documented before evidence of atherosclerosis. Ingestion of fish oil over a 13-day period did not improve endothelial dysfunction.

[Multicenter community-based trial of amlodipine in hypertension in Israel].

The safety and efficacy of Amlodipine (AML) for mild to moderate hypertension was evaluated in a "real life" setting. This open non-comparative trial included 123 men and 143 women (age 30-91 years, mean 59.4). All had sitting diastolic blood pressure (DBP) between 95 and 115 mmHg, confirmed in most by 2 baseline measurements, 2 weeks apart. Eligible patients were given AML 5 mg daily as add-on or monotherapy and were evaluated 4 weeks later. If DBP was then > 90 mmHg, the daily dose was raised to 10 mg; those with < 90 mmHg remained on 5 mg. AML was continued for 8 weeks. Other BP-lowering drugs were unchanged. Of the original 266 patients 22 (8.2%) withdrew due to adverse events (AE), and others were protocol violators, lost to follow-up or withdrew, leaving 211 available for efficacy analysis. In this major group BP was reduced from 165 +/- 15/101 +/- 4 to 139 +/- 11/83 +/- 5 after 12 weeks of AML (p < 0.05). The reduction was greater in those under 70 years, from 173 +/- 12/100 +/- 5 to 142 +/- 12/80 +/- 4 (p < 0.05). In those with BMI > 30 kg/m2, BP decreased from 165 +/- 15/101 +/- 5 to 140 +/- 12/83 +/- 5 (p < 0.05). Mean change in heart rate was -1.5 bpm (p < 0.05). Mean final AML dose was 5.5 mg/day. The most common AML-related AE requiring cessation of the drug was pedal edema in 2.6% of the 266 patients; in 3.7% it persisted during therapy. Other AE occurring in > 1% were dizziness in 1.8%, headache 1.5%, flushing 1.1% and fatigue 1.1%. We conclude that AML is an effective and well-tolerated antihypertensive suitable for most hypertensive patients.

[The "Ashkelon" hypertension detection and follow-up program].

The program described aims at enhancing awareness of high blood pressure and other risk factors for cardiovascular disease (CVD) and promoting a healthy lifestyle. The study population consisted of 11,000 workers at worksites and visitors to community centers, aged 25-65 years. The program was carried out in cooperation with primary care clinics and non-pharmacological control of high blood pressure was by a community center for prevention of CVD. In 1980, 56.0% of hypertensives were unaware of their condition, while by 1988 this was reduced to 6.1%. Body weight reduction resulted in lowering of blood pressure which enabled cessation of all antihypertensive treatment in 25%. Deep muscle relaxation enabled cessation in 47%. The savings effected in terms of antihypertensive treatment outweight the total cost of the program 3-fold.