Showing papers by "Robert Fagard published in 1988"

Salt intake and blood pressure in the general population: a controlled intervention trial in two towns

Abstract: A controlled trial was conducted in two Belgian towns to investigate the feasibility and effects of a reduction in salt consumption at the community level. The low-sodium intervention in one town was mainly directed at women and implemented through mass media techniques, while the control town was merely observed. Cross-sectional random sampling at baseline and 5 years later was employed, the participation rate being similar (67%) in the two towns. During the study a total of 2211 subjects were examined. In adult women (greater than or equal to 20 years) in the intervention town the 24-h urinary excretion of sodium (UVNa) decreased by 25 mmol/24 h (P less than 0.001) and this reduction differed (P = 0.01) from the concurrent trend in UVNa in the control town (+8 mmol/24 h). However, both systolic (SBP, -7.5 versus -7.9 mmHg) and diastolic (DBP, -2.3 versus -3.0 mmHg) pressures declined to a similar extent in the women from the two towns. In adult men in the intervention town, decreases were observed in UVNa (-12 mmol/24 h) and in SBP (-5.6 mmHg) and DBP (-2.4 mmHg), but these trends were not significantly different from the concurrent changes in the control town (-14 mmol/24 h, -4.9 and +0.2 mmHg, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

The relationship between body weight and blood pressure.

Abstract: In adults of Western societies the positive relationship between blood pressure and body weight has often been demonstrated, both cross-sectionally and longitudinally. This correlation is even stronger in children and early adulthood. In most studies in children, the association between age and blood pressure disappears after controlling for weight. Association must be differentiated from causation. It has however been shown in several intervention studies that treatment of obesity by weight loss decreases blood pressure substantially both in hypertensive and normotensive subjects. Although combining results from several intervention trials is difficult this is the only practical way to get an overall estimate of the hypotensive response to be expected from weight reduction. In the randomised controlled intervention studies, conducted in obese hypertensive patients and reviewed in the present meta-analysis, a decrease in body weight by 1 kg resulted in a reduction of systolic and diastolic pressure by 1.2 and 1.0 mmHg, respectively. Blood pressure generally decreased before normal weight was achieved and remained reduced as long as there was no marked regain in body weight. Although a decrease in salt intake during dieting may contribute to the blood pressure lowering effect of weight reduction, also other mechanisms, such as a reduction in plasma renin activity and a decrease in sympathetic tone may also be involved.

Primary Prevention With Metoprolol in Patients With Hypertension

Abstract: To the Editor.— We read with interest the recent article by Wikstrand and coworkers. 1 These investigators employed the Gehan-Wilcoxon nonparametric test for survival analysis and found in male hypertensive patients with diastolic blood pressures ranging from 100 through 129 mm Hg that total ( P =.028) and cardiovascular ( P =.012) mortality were reduced by metoprolol therapy compared with treatment with a thiazide diuretic. The 95% confidence interval for the reduction in total mortality at median follow-up (4.16 years) ranged from - 68% to -17%. However, the 95% confidence limits for the differences between the two treatment groups in cardiovascular mortality at median followup and in both total and cardiovascular mortality at the end of the study were not published. Using methods that were described previously 2 and the results published in Table 3 of the Metoprolol Atherosclerosis Prevention in Hypertensives Study, 1 we calculated these 95% confidence intervals. We confirmed that

Effects of physical endurance training on the plasma renin-angiotensin-aldosterone system in normal man.

Abstract: The effect of physical endurance training on the plasma renin-angiotensin-aldosterone system was studied in 27 normal sedentary volunteers aged between 20 and 55 years, using a randomized two-period cross-over study design. After 4 months of training (2.5 h/week), peak oxygen uptake and physical working capacity at a heart rate of 130 beats/min were increased by 16% (P less than 0.01) and 29% (P less than 0.001) respectively, whereas resting heart rate was decreased by 15% (P less than 0.001). The plasma noradrenaline concentration and haematocrit were both decreased (P less than 0.01) after training. For the total group of subjects, the small decreases in plasma renin activity (PRA) and in the plasma concentrations of angiotensin-I, angiotensin-II and aldosterone were not statistically significant. However, the change in PRA during the training period was negatively correlated with the increase in physical working capacity (r = -0.49, P less than 0.01), suggesting that PRA decreased only in those subjects with the greatest increase in exercise capacity. Also, the change in plasma aldosterone during training was negatively related to the rise in physical working capacity (r = -0.57, P less than 0.01). Furthermore, the changes in plasma angiotensin-I (r = 0.75), angiotensin-II (r = 0.49) and aldosterone (r = 0.43) during the training period correlated positively with the change in PRA. It is concluded that physical endurance training, leading to a substantial gain of physical working capacity, suppresses the plasma renin-angiotensin-aldosterone system in normal man.

Erythrocyte, plasma and urinary magnesium in men before and after a marathon

Abstract: Erythrocyte, plasma and urinary magnesium (Mg2+) concentration was measured in 23 runners before and after a marathon race. Blood samples were drawn from an antecubital vein the morning before the race (baseline), at 3 p.m. (2 h before the start), upon finishing and 12 h later. Compared with the baseline values, the intra-erythrocyte and plasma Mg2+ were decreased (p<0.05 or less) immediately after the marathon, from 2.13±0.16 to 2.02±0.18 mmol · l−1 cells and from 0.88±0.06 to 0.81±0.07 mmol · l−1 respectively. The Mg2+ concentration returned to pre-race values 12 h after completion of the marathon. The urinary Mg2+ excretion rate decreased (p<0.001) from 29±13 to 5±3 μmol · min−1 during the marathon and increased (p<0.05) 12 h after the race to 38±18 μmol · min−1. It is concluded that the reduction in plasma Mg2+ ion concentration during the marathon cannot be attributed to erythrocyte uptake, urinary excretion or loss in sweat. It is suggested that Mg2+ may be released from erythrocytes into the extracellular fluids during sustained exercise and taken up from these fluids by the adipose cells.

Mortality in various intervention trials in elderly hypertensive patients: a review.

Abstract: Results on total and cause-specific mortality from various randomized intervention trials on antihypertensive drug treatment in elderly hypertensives are reviewed, compared and pooled. Mortality from all causes tended to decrease in all trials, but this decrease was not statistically significant in any of the trials separately, nor when all results were pooled. When the results of all the trials were combined, there was a significant overall decrease in cardiovascular mortality of 28%. This decrease in cardiovascular mortality was mainly related to a significant reduction in cerebrovascular mortality of 41%. Mortality from coronary heart disease also tended to decrease by 28%, but statistical significance was not reached.

Indicators of cell breakdown in plasma of men during and after a marathon race

Abstract: Plasma indicators of muscle cell leakage and of hemolysis were studied in 23 runners before and after a marathon race. Blood samples were drawn from an antecubital vein the morning before the race (baseline), at 3 p.m., i.e., 2 h before the start, on arrival, 12 and 36 h, and 7 days later. Compared with the baseline values, the plasma creatinine phosphokinase MM and MB subfractions, aldolase and glutamicoxaloacetic transaminase activity were increased immediately after the race, rose further 12 h after the marathon, and remained elevated the race, rose further 12 h after the marathon, and remained elevated 36 h and 7 days later. The plasma lactate dehydrogenase activity and myoglobin concentration were increased on arrival and returned to the pre-race activity 7 days after the marathon. Compared with the pre-race values, the plasma haptoglobin concentration was decreased immediately and 12 h after the marathon. Our data show that indicators of muscle cell leakage and of hemolysis in plasma, withdrawn after a marathon race, remained elevated for up to 7 days after the race.

Maximal aerobic power in essential hypertension.

Abstract: Fifty untreated male patients aged 32 +/- 10 (s.d.) years, referred for hypertension, in whom organ damage was limited to WHO stages I and II, without underlying disease, performed a graded, uninterrupted exercise on a bicycle ergometer up to exhaustion. Mean brachial intra-arterial pressure at rest ranged from 74 to 152 mmHg. Maximal voluntary oxygen uptake was independently and negatively related to resting blood pressure (P less than 0.05), age (P = 0.05), and positively to body weight (P less than 0.05). Pulmonary wedge pressure and the components of the Fick equation--heart rate, stroke volume and arteriovenous oxygen difference--were measured in order to study the mechanisms involved. Stroke volume at peak exercise was inversely (P less than 0.05), and pulmonary wedge pressure positively (P less than 0.01), related to mean brachial artery pressure at rest. Peak heart rate was not significantly related to the severity of hypertension, but was inversely related to age (P less than 0.01). Stroke volume and pulmonary wedge pressure at the end of exercise were both similar in older and younger patients. Arteriovenous oxygen difference at peak exercise was not related either to blood pressure or to age. In conclusion, both high blood pressure and age reduce maximal voluntary oxygen uptake independently of each other by separate mechanisms; the former by an impairment of cardiac function, the latter by the limitation of peak heart rate.

Changes in erythrocyte sodium and plasma lipids associated with physical training.

Abstract: The intracellular concentrations and transmembrane fluxes of Na+ and K+ in erythrocytes, and plasma lipids were investigated in 30 middle-aged volunteers, before and after physical training. During the first 4 months of the study, half of the subjects (group A) were subjected to a training programme (3 h/week), while the others (group B) served as controls. At the end of the control period the group B subjects also underwent a period of training. At the end of the training, in both experimental groups, the intra-erythrocyte Na+ concentration was decreased (P less than 0.001); the magnitude of this decrease was related to the increase achieved in physical working capacity (r = -0.44; P less than 0.05). After training the activity of the erythrocyte Na+-Li+ counter-transport system was decreased (P less than 0.001) in both groups, whereas Na+,K+ cotransport activity was increased (P less than 0.001). The training intervention did not affect erythrocyte ouabain-sensitive 86Rb uptake, or the calculated rate constant for ouabain-sensitive Na+ efflux. Furthermore, the plasma concentrations of high density lipoproteins (HDL)2- and HDL3-cholesterol (P less than 0.001) markedly increased in both groups during the training period. However, these changes were not significantly correlated with the observed training-induced changes in erythrocyte transmembrane cationic fluxes. It is concluded that physical training decreases intra-erythrocyte Na+ concentration. No significant associations between training-induced changes in plasma lipids and erythrocyte sodium balance could be demonstrated.

The pulmonary circulation in essential systemic hypertension

Abstract: Seventy-one men, ages 16 to 59 years, were referred for systemic hypertension, which was without detectable cause and with limited organ damage (World Health Organization stages I to II). They performed a graded exercise test on the bicycle ergometer in the sitting position. Mean brachial intraarterial pressure, mean pulmonary artery and wedge pressures and cardiac output (Fick method) were measured. At rest mean brachial artery pressure ranged from 72 to 168 mm Hg. Mean pulmonary wedge pressure was significantly (p

Intracellular sodium and the response to nitrendipine or atenolol in African blacks.

Abstract: The relationship between the hypotensive effect of nitrendipine (N), 20 mg/day (n = 17), or atenolol (A), 100 mg/day (n = 17), and the erythrocyte sodium [( Na]i) and potassium [( K]i) concentrations was investigated in hypertensive African blacks during a randomized double-blind study. After 6 weeks, both treatments significantly reduced supine and standing blood pressures; however, the magnitude of the decrease in supine systolic (-22.0 +/- 2.0 vs -12.1 +/- 3.4 mm Hg) and diastolic (-14.1 +/- 1.3 vs -7.6 +/- 2.1 mm Hg) pressures and in standing diastolic pressure (-16.0 +/- 1.7 vs -9.2 +/- 2.0 mm Hg) was more pronounced (p less than 0.05) in the N-treated than in the A-treated group. Pulse rate, plasma aldosterone, and plasma renin activity were lower (p less than 0.05) in the A-treated patients. Neither treatment had significant influence on [Na]i, [K]i, or ouabain-sensitive sodium efflux. The N-induced changes in supine systolic and diastolic pressure correlated (p less than 0.05) with age (r = -0.65 and r = -0.58, respectively) and pretreatment plasma renin activity (r = 0.71). Multiple regression analysis demonstrated a negative association between pretrial [Na]i and the change in systolic pressure during N treatment that was independent of age, pretreatment blood pressure, and change in pulse rate. Age and the change in supine pulse rate were also independently correlated with the change in diastolic pressure during N treatment. The results show a greater antihypertensive efficacy of N than A in the patients entered in this study and suggest that a higher intracellular sodium concentration could predict a better hypotensive response to N.

Left ventricular structure and function, assessed by imaging and Doppler echocardiography, in athletes engaged in throwing events.

Abstract: Ten male athletes engaged in throwing events and ten control subjects, matched for age, height, and weight, were investigated with echocardiography and Doppler velocimetry to assess cardiac structure and systolic and diastolic left ventricular function at rest. Left ventricular (LV) internal diameter, wall thickness, LV mass, and systolic LV function were not different between athletes and nonathletes. The possibility that strength training could alter LV diastolic function was further investigated. Both early diastolic function, estimated from the velocity of LV relaxation and the LV inflow pattern, and late diastolic function, assessed by Doppler velocimetry, were similar in throwers and controls. The unchanged ratio of the peak velocities of LV filing during atrial contraction and early filling suggests that LV distensibility is unaltered in these athletes. In conclusion, the amount and type of training performed by these throwers was not associated with changes in LV structure and function.

Erythrocyte 2,3-diphosphoglycerate concentration before and after a marathon in men.

Abstract: Erythrocyte 2,3-diphosphoglycerate (2,3-DPG) concentration was studied in 23 runners before and after a marathon race. Blood samples were drawn from an antecubital vein the morning before the race (baseline), at 3 p.m. 2 h before the start, on finishing, and 12 and 36 h later. Compared to the baseline values, erythrocyte 2,3-DPG concentration was increased (p<0.001) immediately after the marathon from 4.62±0.14 to 5.56±0.13 μmol·ml−1 RBC and remained elevated 12 h later (5.45±0.14 μmol·ml−1 RBC): it returned to prerace values 36 h after completion of the marathon.

Effect of calcium channel blockade and beta-adrenoceptor blockade on short graded and single-level endurance exercises in normal men.

Abstract: The effect of verapamil (240 mg) on exercise capacity was studied during a short graded and a single-level endurance exercise test in 12 normal volunteers; it was compared to the effects of atenolol (100 mg × day−1). Intake of verapamil, atenolol and placebo, administered according to a randomized, double-blind cross-over design, was started 3 days before the exercise tests. Compared to placebo, verapamil did not affect peak oxygen uptake in the graded test or exercise duration in the endurance test. Heart rate, systolic blood pressure, rating of perceived exertion and respiratory data at submaximal and peak exercise were unaffected in either test. On the other hand atenolol reduced maximal oxygen uptake by 5% (p<0.001) and endurance exercise duration by 17% (p<0.05). Besides marked decreases in heart rate and systolic blood pressure during the two types of exercise, atenolol also reduced oxygen uptake at submaximal exercise levels and it increased the rating of perceived exertion (p<0.05), the latter only during the endurance exerice test.

Effects of training on erythrocyte 2,3-diphosphoglycerate in normal men.

Abstract: The erythrocyte 2,3-diphosphoglycerate concentration (2,3-DPG) and the activity of red cell hexokinase, pyruvate kinase, glucose-6 phosphate dehydrogenase and gluthatione reductase were studied in 27 normal volunteers before and after 2 and 4 months of physical endurance training. The 4 months of training increased maximal oxygen uptake and physical working capacity (PWC130) by 16% (p<0.001) and 29% (p<0.001) respectively. Resting heart rate was decreased (p<0.001) by 11 beats·min−1. With 2 months of training the erythrocyte 2,3-DPG concentration increased by 9% (p<0.001); with 4 months training the increase was only 4% (p<0.05). The training-induced increase in red cell 2,3-DPG was not accompanied by enhanced activity of erythrocyte hexokinase, pyruvate kinase, glucose-6 phosphate dehydrogenase or glutathione reductase. It is concluded that the rise in red cell 2,3-DPG induced by physical endurance training is not due to activation of red cell glycolytic enzymes or the enzymes involved in the pentose-phosphate cycle

Effects of opioid antagonism on the haemodynamic and hormonal responses to exercise.

Abstract: 1. Physical effort involves, along with an increase in the plasma concentration of beta-endorphin, profound adaptations of the circulation and the endocrine system. The effects of opioid antagonism on the responses of blood pressure, heart rate and several hormones to exercise were therefore studied in 10 normal men. They exercised in the supine position up to 33% and 66% of their maximal exercise capacity and received in a randomized double-blind cross-over protocol, either saline or naloxone (10 mg intravenously, followed by a continuous infusion of 10 mg/h). 2. Intra-arterial pressure and heart rate were continuously monitored, but were not affected by naloxone. 3. At rest, opioid antagonism produced a rise in plasma renin activity and in plasma adrenocorticotropin, cortisol and aldosterone, but only the stimulation of the two adrenocortical hormones differed significantly from the control experiments; at rest naloxone also prevented the fall in plasma adrenaline, which occurred with saline infusion. Furthermore, the exercise-induced rises in plasma angiotensin II, aldosterone, cortisol, noradrenaline and adrenaline were higher on naloxone than on saline, while a similar tendency was also present for the increases with exercise in plasma renin activity and plasma adrenocorticotropin. Neither at rest nor during exercise did opioid antagonism alter plasma lactate and glucose and serum insulin and growth hormone. 4. In conclusion, (1) endogenous opioids are not involved in the responses of blood pressure and heart rate to supine exercise; (2) at rest and during exercise, the endogenous opioids inhibit the secretion of adrenocorticotropin, aldosterone, cortisol, noradrenaline and adrenaline; (3) they also inhibit the plasma renin-angiotensin II system indirectly via the catecholamines.

Antihypertensive drug treatment in elderly hypertensive subjects: evidence of protection.

Abstract: The different intervention trials in elderly hypertensive subjects are compatible with the hypothesis that antihypertensive drug treatment decreases cardiovascular mortality, mainly by a reduction of cerebrovascular mortality. Antihypertensive drug treatment in elderly hypertensive subjects also leads to a decrease in fatal and nonfatal cardiovascular and cerebrovascular events. It has not yet been proven whether antihypertensive drug treatment should be recommended for symptomless patients with isolated systolic hypertension and for patients with uncomplicated hypertension above the age of 80 years.

Obesity and hypertension.

Abstract: In adults of Western societies the positive relationship between blood pressure and body weight has often been demonstrated, both cross-sectionally and longitudinally. This correlation is even stronger in children and early adulthood. In most studies in children, the association between age and blood pressure disappears after controlling for weight. Association must be differentiated from causation. It has however been shown in several intervention studies that treatment of obesity by weight loss decreases blood pressure substantially both in hypertensive and normotensive subjects. Although combining results from several intervention trials is difficult this is the only practical way to get an overall estimate of the hypotensive response to be expected from weight reduction. In the studies presently reviewed, a decrease in weight by 1 kg resulted in a reduction in blood pressure by 3.4/1.3 mm Hg in hypertensive patients and in normotensive subjects the corresponding reductions averaged 1.4 mm Hg and 0.6 mm Hg for systolic and diastolic pressure, respectively.

The effect of ageing on the plasma renin-angiotensin-aldosterone system in elderly hypertensive patients.

Abstract: Plasma renin activity, renin concentration and aldosterone concentration were measured in 78 untreated hypertensive patients aged 60-83 years. In a cross-sectional analysis, plasma renin activity, renin concentration and aldosterone concentration showed no relationship with age. Half of these patients were subsequently followed on placebo over a 3-year period during which the plasma constituents of the renin-angiotensin-aldosterone system remained stable. From these cross-sectional and longitudinal observations we conclude that beyond the age of 60 ageing has no detectable effect on plasma renin and aldosterone levels in these elderly hypertensive patients.

Long-term double-blind comparison of doxazosin and atenolol in patients with mild to moderate hypertension.

Abstract: The antihypertensive effect and safety of doxazosin once-daily was compared with that of atenolol once-daily in 40 patients with mild to moderate hypertension. During the first 4 weeks all patients received placebo therapy. During the subsequent 10 weeks patients were randomized to doxazosin or atenolol treatment. Treatment was initiated with 1 mg doxazosin or 50 mg atenolol once-daily. The dose could be doubled biweekly until a final dose of 16 mg doxazosin or 100 mg atenolol was reached. The average final dose of doxazosin was 6.4 +/- 0.8 mg (SEM) and that of atenolol 66.7 +/- 5.7 mg. During the 10 weeks of active treatment, the systolic and diastolic blood pressure tended to be lower (p less than 0.05) in patients on atenolol, this difference was however not significant for the standing blood pressure. Recumbent and standing heart rate were lower (p less than 0.01) during atenolol. Multiple regression analysis showed that in the doxazosin group the recumbent systolic blood pressure after 10 weeks of treatment was significantly (p less than 0.05) and independently related to age, recumbent systolic blood pressure at randomization, and the changes in recumbent heart rate. In neither group severe adverse reactions were observed. However, two patients on doxazosin dropped out of the study: one because of blurred vision and persistent high blood pressure, and one because of fatigue and palpitations. No patient dropped out of the atenolol group during the study.

Double-blind comparison of ketanserin and propranolol in hypertensive patients.

Abstract: In this double-blind study in general practice, 444 patients were randomized to ketanserin (K, 40 mg b.i.d.) and 229 patients were randomized to propranolol (P, 80 mg b.i.d.). After 3 months, more patients on K (15%) than on P (9%) had been withdrawn (p less than 0.02). Although at 3 months the falls in systolic blood pressure (SBP) and diastolic blood pressure (DBP) were similar in both groups, the reduction in SBP was slower on K, and up to 2 months SBP was higher on K than on P (p less than 0.04 or less). At randomization and after 3 months, average weights were similar in both groups. However, during the first month of the study, patients on K gained weight, and this change in weight differed (p less than 0.02) from the unchanged weight on P. On K, BP lowering was greater when weight gain was less. Multiple regression analysis showed that after adjusting for BP at randomization and subsequent weight changes, DBP at 1 month on K was lower with advancing age, whereas SBP and DBP at 1 and 3 months on P were higher with age. Severe adverse effects were absent. However, dry mouth, edema, fatigue, and dizziness occurred more frequently with K (p less than 0.04 or less).

Erythrocyte and leucocyte sodium and potassium transport systems during long-term diuretic administration in men.

Abstract: The effect of xipamide on the intracellular concentration and transmembrane fluxes of Na+ and K+ was studied in 12 normal male subjects, using a double-blind cross-over design. After a run-in period on placebo for 1 week, the subjects were treated with either placebo (n = 6) or xipamide 20 mg once a day (n = 6) for 16 weeks and were then switched to the alternative medication for another 16 weeks. The intra-erythrocyte and intra-leucocyte Na+ concentration was increased by 11 and 7%, respectively, during xipamide administration, while the intracellular K+ concentration was decreased by 3 and 4%, respectively. No significant effect of xipamide could however be demonstrated on the ouabain-sensitive, bumetanide-sensitive or ouabain-bumetanide-resistant 86Rb uptake and on the maximal 3H-ouabain binding in erythrocytes and leucocytes. The red cell Na+-Li+ countertransport was also not changed in the xipamide-treated subjects. Our data suggest that the increased intracellular Na+ concentration and the decreased K+ concentration in red and white blood cells of xipamide-treated subjects cannot be attributed to changes in the activity of the Na+ pump, the Na+-K+ cotransport or Na+-Li+ countertransport system or to changes in the number of active Na+ pump units.

In vitro effect of xipamide on sodium-potassium transport systems in human erythrocytes.

Abstract: The in vitro effects of xipamide in a concentration range of 10(-8) to 10(-2) M were investigated on various Na+ and K+ transport systems in human red blood cells. Xipamide inhibited the anion carrier or DIDS-sensitive LiCO3- -influx starting from a concentration of 10(-5) M. However, a decrease in the Na+, K+-pump and the Na+, K+-cotransport activity and a rise in the passive permeability of the cell membrane was only observed starting from a concentration of 10(-4) M xipamide.