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Showing papers by "Robert Fagard published in 1978"


Journal ArticleDOI
TL;DR: In this paper, 119 elderly, hypertensive patients were followed-up for 1 year and 48 for 2 years in a double-blind, randomised, controlled trial in which they received either placebo or 25-50 mg hydrochlorothiazide and 50-100 mg of triamterene daily.

184 citations


Journal Article
TL;DR: Hypotensive treatment is indicated in elderly hypertensive patients with hypertensive retinopathy grade III or IV, congestive heart failure or cerebral haemorrhage, in elderly patients with a markedly elevated diastolic blood pressure and a trial of hypotensive therapy should be offered in milder forms of hypertension when it is accompanied by certain specific symptoms such as angina, headache and dyspnoe.
Abstract: With advancing age blood pressure rises in most populations with the exception of some isolated tribes. In western countries 30 to 40% of the people above the age of 60 years have casual blood pressure levels greater than or equal to 160/95 mm Hg. Advancing age per se produces a number of physiological changes related to blood pressure, such as a decrease in cardiac output, an increase in peripheral vascular resistance and a decrease in plasma renin-angiotensin-aldosterone levels. The mechanism causing the elevation in pressure with age are unknown though increased rigidity of the great vessels contributes to the rise in systolic pressure. There is a decline in the sensitivity of the baroreceptor reflex, but the contribution of this to the elevation of pressure has not be elucidated. Elderly patients with uncomplicated essential hypertension have a low cardiac output and high peripheral vascular resistance. The rise in blood pressure is associated with an increased cardiovascular morbidity and mortality even in the elderly hypertensives. The available data on the efficacy of hypotensive treatment in the elderly is scanty. There are no data proving that hypotensive therapy prolongs life. Controlled studies on the prevention of organ damage especially cerebrovascular accidents are inconclusive, showing either a significant decrease or no effect. Isolated reports illustrate, however, that drastic blood pressure reduction can provoke serious side effects, thus decreasing the quality of life. Hypotensive treatment is indicated in elderly hypertensive patients with hypertensive retinopathy grade III or IV, congestive heart failure or cerebral haemorrhage, in elderly patients with a markedly elevated diastolic blood pressure (greater than or equal to 120 mm Hg) and a trial of hypotensive therapy should be offered in milder forms of hypertension when it is accompanied by certain specific symptoms such as angina, headache and dyspnoe. The management of elderly hypertensive patients is more difficult than in the young. General measures are often not well accepted. The dose adjustment of the hypotensive agent is more critical and volume depletion or orthostatic hypotension are more likely to occur.

144 citations


Journal ArticleDOI
27 May 1978-BMJ
TL;DR: A single-dose of 300 mg of metoprolol can therefore be recommended if the only aim is to reduce blood pressure but not if a steady degree of beta-blockade is needed.
Abstract: In a double-blind, crossover trial 16 hypertensive patients were treated, in random order, with placebo, metoprolol 300 mg in a single daily dose, or metoprolol 300 mg/day in three doses. Both therapeutic regimens produced detectable plasma metoprolol concentrations and appreciable beta-blockade, estimated from exercise tachycardia, throughout the day. Fluctuations throughout the day in plasma drug concentrations and degree of beta-blockade were insignificant on the thrice-daily regimen, but they varied considerably on the single-dose regimen. Both therapeutic regimens also significantly lowered blood pressure throughout the day. Although the thrice-daily regimen again tended to produce a stronger and less fluctuating hypotensive action, the differences in hypotensive effect between the two regimens were not statistically significant. A single-dose of 300 mg of metoprolol can therefore be recommended if the only aim is to reduce blood pressure but not if a steady degree of beta-blockade is needed.

55 citations


Journal ArticleDOI
TL;DR: Plasma aldosterone concentration in normal subjects was significantly and negatively related to age and to the 24-h urinary sodium excretion, and this direct radioimmunoassay using an antibody of high specificity is described, which is simpler and less time-consuming.

52 citations


Journal Article
TL;DR: A favourable influence on prognosis by active treatment can be expected on the basis of the blood pressure reduction and in the absence of major electrolytes disturbances, but this benefit must be proven by observed statistical differences in terminating events between the groups.
Abstract: Three hundred forty nine hypertensive patients above the age of 60 have entered the double-blind multicentre trial of the European Working Party on High blood pressure in the Elderly (EWPHE). After stratification and randomisation half were treated with one or two capsules containing 25 mg hydrochlorothiazide and 50 mg triamterene and if blood pressure control was insufficient methyldopa was added up to 2 g daily; the other half received matching placebo. No significant differences between the groups were present prior to randomisation. A significant blood pressure difference of 25/10 mm Hg was obtained between the groups and maintained during two years of follow-up. No major disturbances in serum potassium or serum sodium were noted with the present drug combination. However, during the initial phase an increase in serum creatinine and serum uric acid was noted in the actively treated group, which was maintained for two years. Also glucose tolerance was impaired after 2 years in the actively treated group. A favourable influence on prognosis by active treatment can be expected on the basis of the blood pressure reduction and in the absence of major electrolytes disturbances. But this benefit must be proven by observed statistical differences in terminating events between the groups. Therefore the patients are being followed for a longer period of time and more patients are admitted into the trial.

51 citations


Journal ArticleDOI
TL;DR: A reliable, direct radioimmunoassay of plasma angiotensin II (PAII) is described, and the combination of EDTA and o-phenanthroline has been found to be a very efficient ang Elliotensinase inhibitor in plasma and is of equal potency as EDta and diisopropylfluorophosphate in inhibiting the angiotENSinase and converting enzyme activity.

46 citations


Journal ArticleDOI
TL;DR: A favourable influence on prognosis by active treatment can be expected on the basis of the blood pressure reduction and in the absence of major electrolytes disturbances, however, the balance between this decreased risk and the increased risk produced by the rise in blood glucose and the other treatment effects remains to be determined.
Abstract: 1. A total of 450 hypertensive patients above the age of 60 years have entered the double-blind multicentre trial of the European Working Party on High blood pressure in Elderly (EWPHE). After stratification and randomization half were treated with one capsule daily containing 25 mg of hydrochlorothiazide and 50 mg of triamterene and half were given placebo. In those receiving active treatment, if blood pressure control was not adequate they were given a second capsule and if necessary up to 2 g of methyldopa/day. 2. No significant differences between the groups were present before randomization. A significant blood pressure difference of 25/10 mmHg was obtained between the groups and maintained during 4 years of follow-up. No major disturbances in serum potassium or serum sodium were noted with the present drug combination. 3. During the initial phase an increase in serum creatinine and serum uric acid was noted in the actively treated group, which was maintained during the later years. This increase in serum creatinine in the actively treated group was related ( P = 0·003 and r = −0·247) to the decrease in sitting systolic blood pressure. Changes in serum uric acid were ( r = 0·3 and P = 0·003) correlated with the changes in serum creatinine both in the placebo and in the actively treated group, but independent of the change in creatinine; the serum uric acid was on average 1 mg higher in the actively treated than in the placebo group. 4. Fasting blood glucose did not change significantly in the placebo-treated group but in the active treatment group the rise was statistically significant. 5. A favourable influence on prognosis by active treatment can be expected on the basis of the blood pressure reduction and in the absence of major electrolytes disturbances. However, the balance between this decreased risk and the increased risk produced by the rise in blood glucose and the other treatment effects remains to be determined. Therefore the trial continues and more patients are being admitted.

41 citations


Journal ArticleDOI
TL;DR: No systematic difference was shown between (a-v)CO2 content difference determined on whole blood and end-tidal gas, which justified the exclusion of a correction factor for blood to alveolar gas PCO2 gradients and in the calculation of cardiac output by the direct Fick method for CO2 and by CO2 rebreathing.
Abstract: 1. To study the validity of a CO 2 -rebreathing method at rest and during graded exercise, cardiac output was measured simultaneously on 59 occasions in 16 subjects with normal pulmonary function with the CO 2 -rebreathing method and the direct Fick method for oxygen. The correlation coefficient between the results of both methods was significantly higher during exercise than at rest. 2. No systematic difference was shown between (a-v)CO 2 content difference determined on whole blood and end-tidal gas, which justified the exclusion of a correction factor for blood to alveolar gas P co 2 gradients. 3. In the calculation of cardiac output by the direct Fick method for CO 2 and by CO 2 rebreathing, a standard CO 2 dissociation curve was preferred to a synthetic CO 2 dissociation curve, constructed by allowance for changes in haemoglobin concentration, pH and oxygen saturation. The latter curve tended to increase values for cardiac output and induced a large dispersion around the line of identity, when compared with simultaneous cardiac output estimates by the direct Fick method for oxygen.

38 citations


Journal Article
TL;DR: The normal range found for angiotensin I in venous blood of apparently normal, male subjects was 25 to 143 pg/ml, and a significant correlation between PA-I and PRA was found in normal subjects, while no differences were observed in hypertensive patients.

21 citations


Journal ArticleDOI
TL;DR: Angiotensin II may have a role in the maintenance of P- in the supine sodium-deplete normal subjects, and stimulation of the renin angiotENSin system during physical exercise contributes to a minor extent to the increase in P- during exercise in these conditions.
Abstract: Mean intra-arterial pressure (P-), heart rate (HR), cardiac index (CI), total peripheral resistance index (TPRI), and plasma renin activity (PRA), norepinephrine (PNE), and epinephrine (PE) were estimated in five normal male subjects placed on a low-sodium diet for the previous 7 days. Subjects were studied during rest in recumbency and during intravenous infusion of either glucose or saralasin in a) recumbent position, b) sitting position on the bicycle ergometer, and c) during submaximal graded exercise. At rest recumbent saralasin induced pressure changes that were closely related to logPRA. During exercise the increase in P- was significantly lower during saralasin as compared to glucose from 110 W on, related to a greater reduction in TPRI. The increase of PRA during exercise was about three times greater with saralasin as compared to glucose, but the rises in PNE and PE were similar in both series of tests. Angiotensin II may thus have a role in the maintenance of P- in the supine sodium-deplete normal subjects, and stimulation of the renin angiotensin system during physical exercise contributes to a minor extent to the increase in P- in these conditions.

19 citations


Journal ArticleDOI
TL;DR: Log PRA and log PRC3.3 were significantly and similarly related to sodium intake, age, and plasma aldosterone concentration in normal subjects and during beta adrenergic blockade, and at maximal exercise, PRA increased significantly by 168% while the PRC 3.3 increase of 24% was not significant.
Abstract: Plasma renin activity (PRA) and concentration, measured after acid treatment of the plasma (PRC3.3), were determined on the same plasma samples in different conditions. Log PRA and log PRC3.3 were significantly (P less than 0.001) and similarly related to sodium intake, age, and plasma aldosterone concentration in normal subjects. The correlation coefficient between log PRA and log PRC3.3 was 0.49 in 80 sodium-replete and sodium-deplete normal subjects, and it was 0.84 in 84 hypertensive patients untreated or under treatment with thiazides. On the contrary, during beta adrenergic blockade, PRA decreased significantly (P less than 0.001) by 62% while the changes in PRC3.3 were not significant. At maximal exercise, PRA increased significantly by 168% while the PRC3.3 increase of 24% was not significant. In hypertensive patients with unilateral renal artery stenosis the ipsilateral renal vein/artery ratio was higher for PRA (2.46) than for PRC3.3 (1.56), whereas both ratios on the controlateral side were similar and close to one (1.14 and 1.06). The conditions in which PRA and PRC3.3 determinations are concordant or discordant are discussed.

Journal ArticleDOI
TL;DR: AIIA did not affect RBF, GFR, FF, nor diuresis in sodium replete dogs suggesting that endogenous AII has no tonic influence on renal function in these conditions.
Abstract: In order to elucidate the effects of angiotensin II on renal function, angiotensin II (AII; 1 ng/kg per min) and the AII antagonist 1-sar-8-ala-angiotensin II (AIIA; 200 ng/kg per min) were infused into the renal artery of anesthetized dogs (pentobarbital), on either a high (8 mmol/kg per day for seven days) or a low sodium intake (0.5 mmol/kg). In sodium replete dogs AII produced renal vasoconstriction with decreased RBF (−28%;P<0.001), but with less decrease of GFR (−14%;P<0.001), leading to an increase of FF (+19%;P<0.01),andantidiuresis(−39%;P<0.001); the antinatriuresis (−58%;P<0.001) exceeded the antidiuresis (P<0.001). ΔRBF (−10%;P<0.001) was less pronounced (P<0.001) during AII in sodium deplete dogs, GFR remained unchanged, but FF increased to the same extent (+16%;P<0.05); diuresis and urinary electrolyte excretion were however not affected. AIIA did not affect RBF, GFR, FF, nor diuresis in sodium replete dogs suggesting that endogenous AII has no tonic influence on renal function in these conditions. In sodium deplete animals AIIA produced an 11% (P<0.001) increase of RBF, without changes of GFR; FF decreased by 12% (P<0.01), but diuresis, natriuresis and kaliuresis were not affected.

Journal ArticleDOI
TL;DR: The angiotensin II antagonist, 1‐Sar‐8‐Ala‐angiotens in II (saralasin), was infused intravenously at a rate of 10 μg/kg per min in thirty‐three hypertensive patients, on a normal sodium diet and/or during sodium depletion by low Sodium diet and chlorthalidone.
Abstract: SUMMARY 1.The angiotensin II antagonist, 1-Sar-8-Ala-angiotensin II (saralasin), was infused intravenously at a rate of 10 μg/kg per min in thirty-three hypertensive patients, on a normal sodium diet (130 mmol per day) and/or during sodium depletion by low sodium diet (20 mmol per day) and chlorthalidone. 2. In both series, saralasin induced a transient rise in intra-arterial pressure (P < 0.01), accompanied by a slight decrease in heart rate (P < 0.01). The elevation of systolic arterial pressure reached its maximum after 4 min and was more pronounced in sodium-replete patients. Plasma noradrenaline was significantly elevated by 29.7% (P<0.01), but the rise in pressure was not related to concomitant changes in plasma noradrenaline. 3. After the initial pressor effect, arterial pressure, heart rate, cardiac output and total peripheral resistance remained unchanged in the sodium-replete patients, while in the sodium-depleted conditions mean arterial pressure and peripheral resistance were reduced, by 17.8% and 18.6% (P< 0.001) respectively, within 60min. Reflex increases in heart rate (+3.8%) and cardiac output (+ 11.1%) occurred after 10 min (P<0.05), but were not sustained thereafter. 4. Pulmonary vascular resistance was not affected by saralasin. In sodium-depleted patients, pulmonary capillary wedge pressure decreased by 1.2mmHg (P<0.01), with parallel changes of pulmonary artery pressure (P< 0.01).

Journal ArticleDOI
TL;DR: The drug produced significant decreases of plasma renin activity and of plasma aldosterone concentration and the drug reduced mean pulmonary artery and capillary wedge pressures only in the sitting position.
Abstract: 1. Labetalol was administered to 18 hypertensive patients for an average duration of 2·44 weeks, with an average final daily dose of 1·65 g. 2. Labetalol decreased resting heart rate by 16% and maximal exercise heart rate by 21%; the phenylephrine-induced rise of systolic brachial artery pressure was reduced by 36%. 3. During labetalol brachial artery pressure was lowered by 29/15 mmHg in the recumbent position, by 41/23 mmHg at rest sitting, and by 53/23 mmHg at maximal exercise; total peripheral resistance was not significantly affected at rest recumbent, but was reduced at sitting and at exercise; cardiac output decreased in all conditions. 4. Labetalol reduced mean pulmonary artery and capillary wedge pressures only in the sitting position. Pulmonary vascular resistance remained unchanged. 5. The drug produced significant decreases of plasma renin activity and of plasma aldosterone concentration.

Book ChapterDOI
TL;DR: 1-Sar-8-ala-angiotensin II did not change intra-arterial pressure in 25 sodium replete hypertensive patients, whilst the pressure changes were closely related to the plasma renin level during sodium depletion, indicating that arterial pressure is not dependent on angiotens in II in Sodium replete patients and in sodium deplete subjects with low PRC.
Abstract: 1-Sar-8-ala-angiotensin II did not change intra-arterial pressure in 25 sodium replete hypertensive patients, whilst the pressure changes were closely related to the plasma renin level during sodium depletion (r = -0.87; n = 32). The study indicates that arterial pressure is not dependent on angiotensin II in sodium replete patients and in sodium deplete subjects with low PRC, while it is angiotensin dependent during sodium depletion in the others. Plasma renin is unaffected in sodium replete subjects, but increases during saralasin in sodium deplete conditions. Saralasin stimulates aldosterone secretion only in sodium replete patients.