Intraventricular administration of gabapentin in the rat increases flurothyl seizure threshold.

INTRODUCTION: We investigated efficacy of prolonged intraventricular gabapentin (GBP) infusion in the rat flurothyl epilepsy model. METHODS: Sprague-Dawley rats, under anesthesia, were implanted with bilateral Alzet model 2001 osmotic pumps. The pumps infused GBP 80 microg/microL (3.8 mg/day) or isotonic saline control at 1.0 microL/h into each ventricle for 5 days. After 5 days of GBP infusion, seizures were induced by flurothyl dripped onto filter paper. Time to first myoclonic jerk, first partial seizure and first tonic-clonic seizure was recorded by an observer unaware of the treatment group. Determination of seizures was behavioral. RESULTS: Data were obtained from 54 rats. First tonic-clonic seizure was at 295.8+/-58.8s (n=28) for control rats, versus 338.0+/-89.9 s (n=26) for rats with GBP in the pump (p=0.049). First myoclonic jerk occurred at 158.7+/-20.8 versus 164.6+/-33.5 s (p=0.44, n.s.). Regression of time to seizure versus weight was not significant. No animal had measurable serum levels (<1 microg/ml) of GBP. The distribution of GBP in brain was not studied, but qualitative observations of methylene blue dye installed in the pumps showed dye in periventricular white matter and also over cortex, especially ipsilaterally. DISCUSSION: GBP instilled into the lateral ventricles by pump for 5 days delays onset of generalized tonic-clonic seizures produced by flurothyl in the rat. Time to first myoclonic or partial seizure was not influenced. Effects were not due to systemic absorption of GBP. This study provides a proof-in-principle for intraventricular therapy with AEDs.

Long-term prognostic impact of repeated measurements over 1 year of pulse pressure and systolic blood pressure in the elderly.

Systolic blood pressure (SBP) and pulse pressure (PP) have been identified in western industrialized countries as major predictors of cardiovascular events in the elderly on the basis of measurements taken at a single visit. Considering the wide variability of blood pressure (BP) in older people, this study set out to assess the prognostic significance of measurements of SBP and PP taken over several months according to a monitoring scheme mimicking routine care. A total of 444 Italian general practitioners enrolled a cohort of 3858 unselected elderly outpatients and followed them up for 10 years. BP was recorded at recruitment, 1 week later and at quarterly visits during the first year. The average BP of these six visits was used to define the patient's BP status. During the 10-year follow-up, 1561 participants died, 709 from cardiovascular diseases. Proportional hazard regression analysis, adjusted for all main prognostic factors including antihypertensive treatment, showed that for each 10-mmHg increment in SBP and PP there were, respectively, 5 and 9% increases in risk for total mortality (TM) and 9 and 13% increases in risk for cardiovascular mortality (CVM) (all P < 0.01). However, including both SBP and PP in the model, only PP showed an independent, significant relationship with TM and CVM. In conclusion, prognostic information based on repeated measurements of PP is stronger than that given by SBP and consequently should be recommended in the definition of cardiovascular risk in the elderly.

The long-term prognostic significance of repeated blood pressure measurements in the elderly: SPAA (Studio sulla Pressione Arteriosa nell'Anziano) 10-year follow-up.

BACKGROUND: In young and middle-aged people, both systolic (SBP) and diastolic (DBP) blood pressure have a continuous, strong, and independent relationship with subsequent cardiovascular morbidity and mortality. These relationships are not well documented in older people and, until now, studies in the elderly do not provide homogeneous results on the importance of DBP compared with SBP as a cardiovascular risk factor. OBJECTIVE: To determine whether SBP and DBP are independent indicators of mortality risk in the elderly. DESIGN: An observational prospective cohort study to analyze the long-term prognostic significance of repeated SBP and DBP measurements in the elderly. PATIENTS AND METHODS: A total of 3858 outpatients 65 years or older (mean age [SD], 72.9 [4.9] years, 43.5% men) were selected randomly by 444 Italian National Health Service general practitioners in 1983. The population was followed up for 10 years. Crude and adjusted incidence rates of total and cardiovascular mortality were analyzed for classes of SBP and DBP based on the values recorded at the 2 initial visits 1 week apart and those measured during the first 12 months of follow-up. RESULTS: During the 10-year follow-up, 74 patients (1.9%) were lost to follow-up and 1561 (41.3%) died, 709 (45.4% of all deaths) from cardiovascular causes. A positive continuous, graded, strong, and independent association was observed with both total (P<.001) and cardiovascular (P<.001) mortality for SBP but not for DBP. The pattern was similar in both sexes, in persons younger and older than 75 years, regardless of preexisting cardiovascular diseases, and whether they had been receiving antihypertensive treatment at baseline. There was no J-shaped mortality curve in the subjects with the lowest SBP and DBP. CONCLUSIONS: These findings suggest that SBP, but not DBP, is a strong, positive, continuous, independent indicator of mortality risk in the elderly and should be stressed much more than DBP in the diagnosis and treatment of hypertension in this age group.

Assessment of ventricular function in arterial hypertension with radionuclide ventriculography.

Diastolic function of the left ventricle was assessed in 29 untreated patients with mild to moderate hypertension and in 21 normotensive control subjects using gated radionuclide ventriculography. In hypertensive patients, the time to peak filling rate was significantly longer (p less than 0.01) than that in control subjects, and first-third filling fraction and peak filling rate were significantly reduced (p less than 0.001). The ejection fraction and peak ejection rate were also significantly reduced in hypertensive patients (p less than 0.001). No relation was observed between diastolic functional impairment and age, cardiac hypertrophy, or severity of hypertension. Thus, early impairment of ventricular filling is present in hypertension, even in young patients without evidence of cardiac hypertrophy.

Long-term efficacy of screening for hypertension in a community.

Screening for hypertension in the community leads to the identification of hypertensive people not previously detected, and those detected but inadequately treated or not treated at all. The aim of the present study was to assess the long-term efficacy of screening for blood pressure control in a general population. During 1981, 2139 parents of high school students were invited to our institute for a blood pressure measurement; 1533 persons (71.7%) attended the screening; 239 of them (15.6%) were found to be hypertensive (diastolic blood pressure greater than or equal to 95 mmHg or already receiving antihypertensive treatment). Among the hypertensives, 42.3% did not know that they had high blood pressure, and only 7.5% had their blood pressure controlled by treatment. After being informed about the importance of lowering their blood pressure levels, all hypertensives were invited again to the institute for a further evaluation. Two hundred and two persons (84.5%) attended the re-examination. Of these, 154 (76.2%) were still hypertensive. Of the 202, 151 (74.7%) had contacted their physicians. The most common advice was to make further measurements of blood pressure over a period of time, followed by laboratory tests. The proportion of treated hypertensives rose from the initial 33.1% to 53.9%, but in about half the patients normalization of blood pressure was not achieved. Physicians tended to treat only people with moderate to severe hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of long-term treatment with prazosin on left ventricular diastolic function in mild to moderate hypertension.

It is not well established if blood pressure control is associated with an improvement in diastolic function, whose impairment represents an early marker of cardiac involvement in systemic hypertension. The purpose of this study was to evaluate whether a prolonged treatment with an alpha 1-blocking agent can lead to a reversal of the abnormalities of left ventricular filling. Eleven never-treated patients with mild to moderate essential hypertension were examined before and after at least six months of treatment with prazosin. Cardiac function and left ventricular mass were measured by means of radionuclide ventriculography and echocardiography. Average blood pressure values significantly decreased during the treatment period: from 163.54 +/- 17.80 mm Hg to 146.81 +/- 13.14 mm Hg for systolic blood pressure and from 106.09 +/- 6.96 mm Hg to 92.90 +/- 8.93 mm Hg for diastolic blood pressure. All the indices of left ventricular mass showed a trend toward reduction, but the differences with respect to the baseline values did not reach statistical significance. Average value of ejection fraction was normal before treatment and did not change significantly after treatment. All indices of diastolic function were significantly lower than normal controls' values at the beginning of the study and tended to worsen at the end of the study. Our findings suggest that diastolic function is not consistently affected by the therapy with alpha 1-adrenoreceptor antagonists despite good blood pressure control.

Albuminuria and transferrinuria in essential hypertension. Effects of antihypertensive therapy.

The objectives of this study were to evaluate the effects of an ACE inhibitor (fosinopril) and a calcium antagonist (amlodipine) on the urinary albumin and transferrin excretion and their relationship to the blood pressure in essential hypertension. Twenty-four never-treated patients (mean age, 46.4 +/- 8.9 years) with a diastolic blood pressure between 90 and 114 mm Hg and normal renal function, randomly received amlodipine or fosinopril and, if the diastolic blood pressure was not normalized, doxazosin was added to the therapy. Twenty-four-hour ambulatory blood pressure monitoring and 24-h urine collection for albumin and transferrin measurements were performed before and after 3 and 6 months of therapy. Diastolic blood pressure was normalized in 23 patients (96%). Before treatment, microalbuminuria was present in 50% of patients. In the amlodipine and fosinopril group, antihypertensive therapy significantly decreased blood pressure and, only in the fosinopril group, albuminuria. Transferrinuria did not change significantly in both groups. Fosinopril lowered albuminuria in all patients, whereas amlodipine only in half of patients. Albuminuria, but not transferrinuria, was significantly correlated to the ambulatory blood pressure. This correlation was more pronounced for systolic than for diastolic pressure. In essential hypertensive patients with normal renal function, a high prevalence of microalbuminuria can be observed. Albuminuria appears to correlate with ambulatory blood pressure, particularly with systolic pressure. Intrarenal hemodynamic changes seem to play a more important role than systemic blood pressure decrease in the reduction of albuminuria. Transferrinuria does not seem a useful marker to follow-up nondiabetic hypertensive patients with early signs of glomerular dysfunction.

Effects of vitamin E on clinic and ambulatory blood pressure in treated hypertensive patients. Collaborative Group of the Primary Prevention Project (PPP)--Hypertension study.

A randomized controlled open trial studied the effect of vitamin E supplementation (300 mg/day) on clinic and 24-h ambulatory blood pressure (BP) in 142 treated hypertensive patients. After 12 weeks, clinic BP decreased whether or not patients were randomized to vitamin E. Ambulatory BP showed no change in systolic BP and a small decrease in diastolic BP (-1.6 mm Hg, 95% confidence intervals from -2.8 to -0.4 mm Hg), approaching statistical significance in comparison to the control group (P = .06). Vitamin E supplementation thus seems to have no clinically relevant effect on BP in hypertensive patients already under controlled treatment.

Effects of low-dose aspirin on clinic and ambulatory blood pressure in treated hypertensive patients. Collaborative Group of the Primary Prevention Project (PPP)--Hypertension study.

Nonsteroidal antiinflammatory drugs may affect blood pressure (BP) control in hypertensive patients receiving drug treatment, but data on the effects of low-dose aspirin are scanty. This study assessed the effects of chronic treatment with low doses of aspirin (100 mg/day) on clinic and ambulatory systolic (SBP) and diastolic (DBP) BP in hypertensives on chronic, stable antihypertensive therapy. The study was conducted in the framework of the Primary Prevention Project (PPP), a randomized, controlled factorial trial on the preventive effect of aspirin or vitamin E in people with one or more cardiovascular risk factors. Fifteen Italian hypertension units studied 142 hypertensive patients (76 men, 66 women; mean age 59 +/- 5.9 years) treated with different antihypertensive drugs: 71 patients were randomized to aspirin and 71 served as controls. All patients underwent a clinic BP evaluation with an automatic sphygmomanometer and a 24-h ambulatory BP monitoring, at baseline and after 3 months of aspirin treatment. At the end of the study the changes in clinic SBP and DBP were not statistically different in treated and untreated subjects. Ambulatory SBP and DBP after 3 months of aspirin treatment were similar to baseline: deltaSBP -0.5 mmHg (95% confidence intervals [CI] from -1.9 to +2.9 mm Hg) and deltaDBP -1.1 mm Hg (95% CI from -2.5 to +0.3 mm Hg). The pattern was similar in the control group. No interaction was found between aspirin and the most used antihypertensive drug classes (angiotensin converting enzyme inhibitors and calcium antagonists). Despite the relatively small sample size our results seem to exclude any significant influence of low-dose aspirin on BP control in hypertensives under treatment.

Feasibility of a long-term low-sodium diet in mild hypertension.

The present study set out to assess the feasibility of long-term moderate dietary sodium restriction in patients with mild hypertension in general practice. After screening and a run-in phase of 6-8 weeks, a total of 77 previously undiagnosed mildly hypertensive patients were identified. Half of them were randomized to receive a few simple dietary instructions from their general practitioners in order to reduce salt usage; the others were randomized to receive no advice. The patients were followed up for 12 months with quarterly visits. A total of 56 patients (72.7%) completed the study, 26 on a low-sodium diet (LD) and 30 on their usual diet (UD). At each visit in the diet phase, patients provided 24h urine, which was analysed for volume and sodium concentration in order to assess their sodium intake. Blood pressure, heart the rate and body weight were recorded. The mean urinary sodium excretion for all diet phase visits overlapped in the two groups (177.0 +/- 32.9 vs. 169.3 +/- 49.4 mEq/24h respectively in the LD and UD groups). Nevertheless the mean systolic and diastolic blood pressures for all diet phase visits were significantly lower in the LD than in UD group (144.2 +/- 11.1/91.6 +/- 6.4 and 148.0 +/- 13.7/95.6 +/- 4.7 mmHg respectively, P less than 0.01). Our data suggest that it is not feasible at present to reduce sodium intake in mild hypertensives with simple and inexpensive dietary instructions, the only ones suitable for widespread application in general practice.

Antihypertensive treatment of the elderly in general practice.

In order to assess the antihypertensive care received by the elderly, where clear therapeutic guidelines are lacking, a population of 3,858 aged over 64 years was studied. Data were derived from a large Italian 'Study on Blood Pressure in the Elderly', carried out in general practice. Over 90% of the 2,059 known hypertensive patients were receiving drug treatment, with no age or sex-related differences. A single drug was prescribed to 50.2% of treated patients; only 5.5% were receiving three or more drugs. Diuretics and older sympatholytic agents were by far the most frequently prescribed categories, with four drugs (hydrochlorothiazide, amiloride, methyldopa and chlorthalidone) accounting for over 50% of all prescriptions. Low-dosage treatment schedules were frequently used, often associated with less-often-than-daily drug administration. Our study shows that physicians' attitudes to the treatment of arterial hypertension in the elderly are fairly uniform, with treatment of all subjects but with low drug dosages.

Left ventricular diastolic function in normotensive adolescents with different genetic risk of hypertension.

Abnormalities of the diastolic function of the left ventricle are the first sign of cardiac involvement in arterial hypertension. We have studied the diastolic function in a group of normotensive adolescents with confirmed family history of hypertension. M-mode echocardiography was performed in 86 normotensive males aged 14-19 years: 41 sons of at least one hypertensive parent (SHT) and 45 sons of normotensive parents (SNT). Cross-sectional area of the left ventricle and left ventricular (LV) mass index were significantly greater in the SHT than in the SNT group (10.05 +/- 1.84 vs. 8.9 +/- 1.56 cm/m2, p less than 0.01 and 129.3 +/- 296.3 vs. 109.23 +/- 25.7 g/m2, p less than 0.002, respectively). No significant difference between the two groups was observed in the indices of left ventricular diastolic function, except for mitral valve opening rate (463.51 +/- 90.45 in SHT vs. 416.71 +/- 78.84 mm/s in SNT; p less than 0.02). From the analysis of the subgroup of adolescents having left ventricular mass greater than the upper normal value, we observed that they showed mean time of rapid filling significantly longer than SNT: this could represent an early marker of the pathological character of such hypertrophy. Our results suggest that the higher LV mass observed in the SHT is not associated with chamber and myocardial stiffness abnormalities.

Arm position as a source of error in blood pressure measurement.

The present study was designed to assess the value of correct positioning of a patient's arm when measuring blood pressure (BP). A total of 181 subjects were examined, 141 hypertensives on treatment, 25 untreated hypertensives, 15 normotensives. All the subjects underwent three BP measurements after a 5-min resting period in supine position. Then two BP readings were recorded in standing position with the arm either positioned by the patient's side or supported passively at patient's heart level. Average systolic BP (SBP) in standing position were 144.6 +/- 20.2 mmHg with the arm at the side and 136.4 +/- 21.1 mmHg with the arm at the heart level (p less than 0.001); average diastolic pressures were 99.0 +/- 12.0 mmHg and 90.2 +/- 12.3 mmHg (p less than 0.001), respectively. A fall in SBP greater than or equal to 20 mmHg from the supine to the upright position was detected in 18.2% of cases when measurement was performed at heart level; such a reduction was inapparent in two-thirds of cases when the arm was placed at the patient's body side. Incorrect positioning of a patient's arm during BP measurements in standing position leads to overestimation of BP values and masks the presence of postural hypotension.

Awareness, treatment, and control of hypertension in the elderly in a general practice experience. Study Group on Hypertension in the Elderly.

In 3858 ambulatory elderly people (age greater than or equal to 65 years) prevalence of hypertension was 67.8%. The hypertensive status was unknown to both the doctor and the patient in 21.4% of cases. More than 90% of known hypertensives were treated, but hypertension could be considered as controlled in less than 30% of them.

Effects of a screening program for hypertension in a community.

The effect of a population screening for hypertension was assessed through a subsequent survey performed 1 year later. All the hypertensives identified at the first visit (239 subjects, 15.6% of the whole screened population) were invited for a re-examination: the adhesion rate was 84.5%. After the screening, a high proportion of subjects (74.7%) had contacted their physicians because of their blood pressure. The most common advice physicians gave was to have further measurements of blood pressure (72.8%). Laboratory tests were prescribed in 62 patients (41.1%), but a complete assessment of a target organ damage was carried out in few cases (1.9%). Only 19.5% of patients started a course of treatment during the year following the screening and no more than one-third of those with moderate to severe hypertension. Out of the 176 subjects showing other cardiovascular risk factors at the screening, only 12 reported they had modified their habits 1 year later. Our results suggest that a screening for hypertension, when performed without any liaison with other medical facilities, seems to have a poor impact on physicians' and patients' attitudes towards hypertension.

Prevalence of symptoms generally attributed to hypertension or its treatment: study on blood pressure in elderly outpatients (SPAA).

A number of symptoms that appear to be associated with high blood pressure (headache, dizziness, epistaxis, tinnitus, weakness, drowsiness), and are usually regarded as secondary to hypertension or to antihypertensive drug therapy, were studied in 3858 elderly patients, 67.8% of whom were hypertensive. Of the hypertensive patients, 71.2% were under treatment. Headaches and dizziness were significantly more prevalent in the hypertensive than in the normotensive subjects (32.5 versus 27.4% and 41.5 versus 35.3%, respectively; P less than 0.05) and in treated compared with untreated hypertensives (33.3 versus 29.4% and 43.3 versus 37.1%; P less than 0.05). These differences disappeared after statistical correction for 'awareness of hypertension'. In multiple logistic analysis, female sex, age and awareness of hypertension were significantly associated with a higher prevalence of symptoms, whereas hypertension and antihypertensive treatment were not. We conclude that the presence of these symptoms does not constitute a reliable criterion for starting antihypertensive treatment or judging its efficacy.

[Isolated systolic hypertension in the elderly]. / L'ipertensione sistolica isolata nell'anziano.

Isolated systolic hypertension (ISH) is a very common condition in the elderly, even more than diastolic hypertension. Several studies indicate that ISH is a considerable cardiovascular risk factor in the elderly but the benefit of antihypertensive treatment has not been proved. Data in the literature on prevalence, pathophysiology, prognostic meaning and treatment of ISH are critically reviewed.

How informed general practitioners manage mild hypertension: a survey of readers of drug bulletins in 7 countries. International Society of Drug Bulletins (ISDB).

OBJECTIVE: To determine whether general practitioners (GP) who are readers of independent drug bulletins can be used as an international epidemiological observatory of the criteria adopted by "well informed" doctors in various countries in the management of mild hypertension. DESIGN: Questionnaire study of GPs' diagnostic criteria for mild hypertension, routine investigation and management of patients with this diagnosis. PARTICIPANTS: 206 GPs readers of independent drug bulletins in 7 countries, comprising 95 known systematic readers of a local bulletin and 111 randomly selected regular subscribers. MAIN OUTCOME MEASURES: Response rate to the questionnaire. Diagnostic criteria, routine investigations, and treatment used for patients with mild hypertension. RESULTS: The study required two months for planning and implementation. Four countries out of eleven had a response rate < or = 50% and were excluded; the frequency of responses from other countries was 69%. The average diastolic blood pressure (DBP) considered diagnostic of mild hypertension range from 94 mm Hg (lower threshold) to 106 (upper threshold). A minority (17%) of GPs routinely request the minimum recommended laboratory tests to assess patients. GPs routinely advise non-drug measures before starting a drug. Most would not start drug treatment in patients without other risk factors and a DBP below 100 mmHg. The top first choice drugs were diuretics and beta-adrenoceptor blockers. Half of the doctors were able to quote some published guide to the management of mild hypertension, and 18% cited a relevant trial. Attitudes in diagnosing and treating mild hypertension differed widely between GPs and countries. CONCLUSIONS: GP readers of drug bulletins can be used quickly and inexpensively to assess the extent to which recommended diagnostic and therapeutic practices are accepted by "well informed" doctors. The results suggest that attitudes in managing mild hypertension vary widely among GPs and countries and differ remarkably from the recommendations of published guidelines.