Showing papers by "Robert Fagard published in 2000"

Pulse Pressure Not Mean Pressure Determines Cardiovascular Risk in Older Hypertensive Patients

Abstract: Background: Current guidelines for the management of hypertension rest almost completely on the measurement of systolic and diastolic blood pressure. However, the arterial blood pressure wave is more correctly described as consisting of a pulsatile (pulse pressure) and a steady (mean pressure) component. Objective: To explore the independent roles of pulse pressure and mean pressure as determinants of cardiovascular prognosis in older hypertensive patients. Methods: This meta-analysis, based on individual patient data, pooled the results of the European Working Party on High Blood Pressure in the Elderly trial (n = 840), the Systolic Hypertension in Europe Trial (n = 4695), and the Systolic Hypertension in China Trial (n = 2394). The relative hazard rates associated with pulse pressure and mean pressure were calculated using Cox regression analysis, with stratification for the 3 trials and with adjustments for sex, age, previous cardiovascular complications, smoking, and treatment group. Results: A 10-mm Hg wider pulse pressure increased the risk of major cardiovascular complications; after controlling for mean pressure and the other covariates, the increase in risk ranged from approximately 13% for all coronary end points (P = .02) to nearly 20% for cardiovascular mortality (P = .001). In a similar analysis, mean pressure predicted the incidence of cardiovascular complications but only after removal of pulse pressure as an explanatory variable from the model. Furthermore, the probability of a major cardiovascular end point increased with higher systolic blood pressure; at any given level of systolic blood pressure, it also increased with lower diastolic blood pressure, suggesting that the wider pulse pressure was driving the risk of major complications. Conclusions: In older hypertensive patients, pulse pressure not mean pressure is the major determinant of cardiovascular risk. The implications of these findings for the management of hypertensive patients should be further investigated in randomized controlled outcome trials in which the pulsatile component of blood pressure is differently affected by antihypertensive drug treatment. Arch Intern Med. 2000;160:1085-1089

Response to Antihypertensive Therapy in Older Patients With Sustained and Nonsustained Systolic Hypertension

Abstract: Background—The goal of the present study was to assess the effect of antihypertensive therapy on clinic (CBP) and ambulatory (ABP) blood pressures, on ECG voltages, and on the incidence of stroke and cardiovascular events in older patients with sustained and nonsustained systolic hypertension. Methods and Results—Patients who were ≥60 years old, with systolic CBP of 160 to 219 mm Hg and diastolic CBP of <95 mm Hg, were randomized into the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) Trial. Treatment consisted of nitrendipine, with the possible addition of enalapril, hydrochlorothiazide, or both. Patients enrolled in the Ambulatory Blood Pressure Monitoring Side Project were classified according to daytime systolic ABP into 1 of 3 subgroups: nonsustained hypertension (<140 mm Hg), mild sustained hypertension (140 to 159 mm Hg), and moderate sustained hypertension (≥160 mm Hg). At baseline, patients with nonsustained hypertension had smaller ECG voltages (P<0.001) and, during f...

Peak oxygen uptake better predicts outcome than submaximal respiratory data in heart transplant candidates.

Abstract: Background—Many studies have focused on the prognostic power of peak oxygen uptake (Vo2) in patients with chronic heart failure, but maximal exercise testing is not without risk. The purpose of the present study was, therefore, to assess the prognostic significance of the steepness of changes in ventilation and carbon dioxide output (Vco2) during submaximal exercise in comparison with Vo2. Methods and Results—The study population consisted of 284 adult heart transplant candidates who performed a graded maximal bicycle ergometer test with respiratory gas analysis. Using the respiratory data up to a gas exchange ratio of 1.0, 3 submaximal slopes were calculated in each patient. During follow-up (median, 1.33 years), 57 patients died and 149 had ≥1 cardiovascular event. When using Cox proportional hazards analysis, both peak Vo2 and submaximal respiratory slopes predicted outcome before and after accounting for age, sex, and body mass index. However, whereas the prognostic power of peak Vo2 was independ...

Antihypertensive treatment modulates the association between the D/I ACE gene polymorphism and left ventricular hypertrophy: a meta-analysis

Abstract: Antihypertensive treatment modulates the association between the D/I ACE gene polymorphism and left ventricular hypertrophy: a meta-analysis

Modern approaches to blood pressure measurement

Abstract: BACKGROUND—Blood pressure (BP) is usually measured by conventional sphygmomanometry. Although apparently simple, this procedure is fraught with many potential sources of error. This review focuses on two alternative techniques of BP measurement: ambulatory monitoring and self measurement. REVIEW—BP values obtained by ambulatory monitoring or self measurement are characterised by high reproducibility, are not subject to digit preference or observer bias, and minimise the transient rise of the blood pressure in response to the surroundings of the clinic or the presence of the observer, the so called white coat effect. For ambulatory monitoring, the upper limits of systolic/diastolic normotension in adults include 130/80 mm Hg for the 24 hour BP and 135/85 and 120/70 mm Hg for the daytime BP and night time BP, respectively. For the the self measured BP these thresholds include 135/85 mm Hg. Automated BP measurement is most useful to identify patients with white coat hypertension. Whether or not white coat hypertension predisposes to sustained hypertension remains debated. However, outcome is better correlated with the ambulatory BP than with the conventional BP. In patients with white coat hypertension, antihypertensive drugs lower the BP in the clinic, but not the ambulatory BP, and also do not improve prognosis. Ambulatory BP monitoring is also better than conventional BP measurement in assessing the effects of treatment. Ambulatory BP monitoring is necessary to diagnose nocturnal hypertension and is especially indicated in patients with borderline hypertension, elderly patients, pregnant women, patients with treatment resistant hypertension, and also in patients with symptoms suggestive of hypotension. CONCLUSIONS—The newer techniques of BP measurement are now well established in clinical research, for diagnosis in clinical practice, and will increasingly make their appearance in occupational and environmental medicine. Keywords: ambulatory blood pressure; self measurement; white coat hypertension

Induction of cardiac fibrosis by angiotensin II.

Abstract: The possible contributions of the angiotensin receptor subtypes 1 (AT1) and 2 (AT2) to angiotensin II-induced changes in collagen secretion and production were studied using the specific angiotensin receptor AT1 and AT2 antagonists telmisartan and P-186. The role of the renin-angiotensin system and its interaction with transforming growth factor-beta 1 (TGF-beta 1) in collagen deposition in cardiac fibroblasts in relation to the development of myocardial fibrosis is also discussed. Cardiac fibroblasts (from normal male adult rats) from passage 2 were cultured to confluency and incubated in the presence of angiotensin II (ANG II) in a concentration range of 10(-10)-10(-6) M in serum-free Dulbecco's MEM medium for 24 h. Collagen production and secretion were assayed by [3H]-proline incorporation and noncollagen production and secretion were also analyzed. ANG II dose-dependently increased collagen secretion and production in rat adult cardiac fibroblasts in culture. Noncollagen secretion and production were also concentration-dependently increased by ANG II. Addition of 100 nmol/l ANG II increased (p < 0.01) collagen secretion and production by 75 +/- 6 (SEM) and 113 +/- 23%, respectively, and noncollagen secretion and production by 65 +/- 6 and 57 +/- 16%, respectively. Pretreatment of cardiac fibroblasts with telmisartan completely blocked the ANG II-induced increase in collagen secretion (p < 0.001) and production (p < 0.05) and in noncollagen secretion (p < 0.01) and production (p < 0.01). P-186 had no effect on the ANG II-induced increase in collagen secretion and production. Addition of telmisartan and P-186 did not affect collagen secretion and production in basal cardiac fibroblasts. TGF-beta 1 also concentration- and time-dependently increased the secretion and production of collagen in cardiac fibroblasts. Our data demonstrate that the effects of ANG II on collagen secretion and production in adult rat cardiac fibroblasts in culture are AT1-receptor mediated since they were abolished by the specific AT1-receptor antagonist telmisartan but not by the specific AT2-receptor antagonist P-186. The ability of ANG II to induce collagen synthesis in cardiac fibroblasts may be mediated by increased TGF-beta 1 production.

Transforming growth factor-β1 induces angiotensin-converting enzyme synthesis in rat cardiac fibroblasts during their differentiation to myofibroblasts

Abstract: Objectives Appearance of angiotensin-converting enzyme (ACE) in fibrotic tissue can be the result of the action either of one particular growth factor or of cross-talk between multiple factors. Transforming growth factor-β1 (TGF-β1) is an effective inducor of the differentiation of cultured fibroblasts to myofibroblasts, which are heterogeneous cells with different phenotypes. The present study investigated whether TGF-β1 is able to induce, in vitro, the differentiation of cultured fibroblasts to myofibroblasts with a phenotype containing ACE. Design Adult rat cardiac ventricular fibroblasts were obtained from hearts perfused with collagenase. Cells from second passage were always used. Rat cardiac ventricular fibroblasts were incubated with TGF-β1 (10 ng/ml) for seven days. Cell characterisation was performed using light microscopy and indirect immunostaining. Presence of vimentin, desmin, factor VIII, α -smooth muscle actin, and ACE was checked with both immunostaining and Western blotting. ACE activity was measured fluorometrically with hippuryl-histidyl-leucine as substrate. Synthesis of DNA was measured as 3 H-thymidine incorporation.

The systolic hypertension in Europe trial

Abstract: The Systolic Hypertension in Europe (Syst-Eur) study investigated whether antihypertensive treatment could decrease the risk of cardiovascular complications in elderly patients with isolated systolic hypertension. Patients < 60 years old were randomly assigned to treatment with the dihydropyridine calcium antagonist nitrendipine (n=2398), with the addition of enalapril and hydrochlorothiazide if needed, or to matching placebo (n=2297). In the intent to treat analysis, the between group difference in blood pressure was 10.1/4.5 mm Hg (p<0.001). Active treatment decreased the total incidence of stroke (the primary end point) by 42% (p=0.003), all cardiac end points by 26% (p=0.03), and all cardiovascular end points combined by 31% (p<0.001). Cardiovascular mortality was somewhat lower with active treatment (-27%, p=0.07); all cause mortality was not significantly different (-14%; p=0.22). For total (p=0.009) and cardiovascular (p=0.09) mortality, the benefit of antihypertensive treatment weakened with advancing age, and for total mortality it decreased with lower systolic blood pressure at entry (p=0.05). The benefits of active treatment were not independently related to gender or to the presence of cardiovascular complications at entry. Antihypertensive treatment was significantly more effective in patients with diabetes. In the 2418 patients randomized in the dementia substudy, active treatment also prevented dementia (50%; p=0.05). The per-protocol analysis largely confirmed the intent to treat results. It is concluded that stepwise antihypertensive drug treatment, starting with nitrendipine, improves the prognosis in elderly patients with isolated systolic hypertension.

Effect of bisoprolol and atenolol on endurance exercise capacity in healthy men.

Abstract: Objectives To compare the effects of a highly beta(1)-selective adrenoceptor antagonist bisoprolol with those of atenolol and placebo on endurance exercise capacity in young, healthy male volunteers. Design Twelve subjects randomly received oral placebo, atenolol (100 mg/day) or bisoprolol (10 mg/day) for 3 weeks, following a double-blind cross-over design. Methods At the end of each period, the subjects performed an endurance exercise test on the bicycle ergometer at 70% of maximal aerobic power. Cardiac output was measured by means of an automated CO2-rebreathing method. Venous blood was sampled before, during and after exercise. Results Exercise duration was not significantly different between the two drugs tested. Total exercise duration was significantly reduced by bisoprolol (-19.4 +/- 6.7%, P < 0.01) (mean +/- SEM) and by atenolol (-29.8 +/- 6.6%, P < 0.001), compared with placebo. Atenolol and bisoprolol were equally effective in lowering resting plasma renin activity, heart rate and systolic blood pressure. Resting and exercise stroke volume were significantly increased by both drugs, so that cardiac output was not significantly affected. Both drugs induced significant decreases in plasma-free fatty acid concentrations during recovery and blunted the exercise-induced increase. There were no significant relationships between the reduction of exercise duration and the haemodynamic changes or the degree of impairment of the exercise-induced increase in free fatty acid release resulting from beta-blockade. Conclusions It is concluded that both drugs affect endurance exercise capacity in young, normotensive men, with a tendency to a smaller reduction during bisoprolol treatment. Haemodynamic variables are unlikely to be involved in the reduction of endurance exercise capacity. The role of the reduced availability of plasma free fatty acids remains unclear. J Hypertens 2000, 18:35-43 (C) Lippincott Williams & Wilkins.

Efficacy of diuretics and beta-blockers in diabetic hypertensive patients. Results from a meta-analysis

Abstract: OBJECTIVE- To review the effectiveness of diuretic or β-blocker-based treatment of hypertension in diabetic patients. RESEARCH DESIGN AND METHODS- A meta-analysis on individual patient data was performed on four trials of the treatment of hypertension in which diabetic patients were included and treated with first-line diuretics or β-blockers. The main outcomes were the relative risk of death, fatal or nonfatal stroke, fatal or nonfatal coronary events, and major cardiovascular events. RESULTS- There were 92 diabetic patients who received first-line β-blockers and 1.008 who received diuretics. In the control groups, diabetic patients had nearly twice the risk of any outcome when compared with nondiabetic patients. The same blood pressure reduction was achieved under treatment in the diabetic and nondiahetic patients, except for systolic pressure, which decreased more in the nondiabetic patients at 1 year. In the 15,843 nondiabetic patients, the risk of all four outcomes was reduced significantly in the treated group In the 2,254 diabetic patients, the risk reduction was significant only for fatal and nonfatal stroke (36%, P = 0.011) and major cardiovascular events (20%, P = 0.032), but not for death (5%, P = 0.65) and fatal or nonfatal coronary events (15%, P = 0.23). However, no heterogeneity was detected between diabetic patients and nondiabetic patients for any outcome. The numbers of outcomes avoided for 1,000 patients treated for 5 years were higher in diabetic patients (e.g. 38 major cardiovascular events) than with nondiahetic patients (e.g., 28 major cardiovascular events). CONCLUSIONS- These results show that hypertensive diabetic patients benefit from first-line treatment with diuretics. No conclusion can be drawn for β-blockers, owing to the small sample size.

Exercise performance and training in cardiac patients with atrial fibrillation

Abstract: PURPOSE Exercise training in cardiac patients with chronic atrial fibrillation (AF) has received little attention in the literature. Therefore, this study compared exercise performance and the effect of an exercise training program over a period of 3 months in patients with and without AF. METHODS Data in patients with AF (n = 19) were compared with a control group of patients in sinus rhythm (n = 44), drawn from a database of 2,116 patients. Patients performed a maximal exercise test on the bicycle until exhaustion before and after an ambulatory exercise training program where exercise training was offered 3 times a week for 3 months. RESULTS Before training, peak oxygen uptake (VO2) was significantly lower in patients with AF compared with the control group (1271 +/- 368 versus 1496 +/- 414 mL/min, P < 0.05). Exercise training significantly increased peak VO2 in both groups (+31%, P < 0.001 in AF and +25%, P < 0.001 in the control group). The gain in peak VO2 did not significantly differ between both groups. A significant decrease in resting heart rate was achieved in both groups after exercise training. AF was also a significant and independent determinant of peak VO2 in the total database, but not of the change in peak VO2. CONCLUSIONS Exercise training significantly improves exercise performance in cardiac patients with AF. AF affects exercise performance but does not impair the beneficial effects of training. Patients with chronic AF should therefore not be dissuaded from participating in exercise training after a cardiac event.

Comparison of cardiac output measured by two automated methods of CO2 rebreathing

Abstract: VANHEES, L., J. DEFOOR, D. SCHEPERS, S. BRUSSELLE, T. REYBROUCK, and R. FAGARD. Comparison of cardiac output measured by two automated methods of CO2 rebreathing. Med. Sci. Sports Exerc., Vol. 32, No. 5, pp. 1028–1034, 2000.PurposeThe aim of the present study was to investigate the reproducibility o

Efficacy of diuretics and beta-blockers in diabetic hypertensive patients. Results from a meta-analysis. The INDANA Steering Committee

Abstract: Objective To review the effectiveness of diuretic or beta-blocker-based treatment of hypertension in diabetic patients. Research design and methods A meta-analysis on individual patient data was performed on four trials of the treatment of hypertension in which diabetic patients were included and treated with first-line diuretics or beta-blockers. The main outcomes were the relative risk of death, fatal or nonfatal stroke, fatal or nonfatal coronary events, and major cardiovascular events. Results There were 92 diabetic patients who received first-line beta-blockers and 1,008 who received diuretics. In the control groups, diabetic patients had nearly twice the risk of any outcome when compared with nondiabetic patients. The same blood pressure reduction was achieved under treatment in the diabetic and nondiabetic patients, except for systolic pressure, which decreased more in the nondiabetic patients at 1 year. In the 15,843 nondiabetic patients, the risk of all four outcomes was reduced significantly in the treated group. In the 2,254 diabetic patients, the risk reduction was significant only for fatal and nonfatal stroke (36%, P = 0.011) and major cardiovascular events (20%, P = 0.032), but not for death (5%, P = 0.65) and fatal or nonfatal coronary events (15%, P = 0.23). However, no heterogeneity was detected between diabetic patients and nondiabetic patients for any outcome. The numbers of outcomes avoided for 1,000 patients treated for 5 years were higher in diabetic patients (e.g., 38 major cardiovascular events) than with nondiabetic patients (e.g., 28 major cardiovascular events). Conclusions These results show that hypertensive diabetic patients benefit from first-line treatment with diuretics. No conclusion can be drawn for beta-blockers, owing to the small sample size.

Dihydropyridine calcium-channel blockers for the treatment of hypertensive diabetic patients.

Abstract: Diabetes mellitus and hypertension are commonly associated conditions. The prevalence of hypertension in type 2 diabetes is higher than in the general population. At the age of 45 around 40% of patients with type 2 diabetes are hypertensive, the proportion rising to 60% by the age of 75. Hypertension potentiates the already high risk of cardiovascular complications associated with diabetes mellitus. In 1997, the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure recommended the use of angiotensin-converting enzyme inhibitors, alpha-blockers, calcium-channel blockers or low-dose diuretics to initiate antihypertensive drug treatment in hypertensive diabetic patients. In patients with diabetic nephropathy, angiotensin-converting enzyme inhibitors were proposed as the first-line treatment. At variance with these guidelines, two studies published in 1998 raised major concerns about the use of dihydropyridines in diabetic patients. Subsequent papers published in 1998 and 1999, based on larger numbers of patients, demonstrated that longacting calcium-channel blockers are not only safe to use in diabetic patients, but that they may even confer particular benefit to this important subgroup of the hypertensive population. These recent studies are shortly reviewed (Table 1) and put into perspective.

Twenty-four hour blood pressure after exercise in patients with coronary artery disease.

Abstract: The objective was to assess the influence of a cardiac rehabilitation training session on blood pressure measured shortly after exercise and during the subsequent 24 h in patients with stable coronary artery disease. Blood pressure was measured conventionally and by use of 24-h ambulatory blood pressure monitoring in seven men, mean age 53+/-8 (s.d.) years, after participation in a cardiac rehabilitation session and, in randomised order, on a non-exercise control day. Conventional blood pressure averaged 112+/-7/77+/-5 mm Hg in the sitting position on the control day and was not different at the same time of the day shortly after the patients had participated in a cardiac rehabilitation training session. Standing systolic pressure was lower by 7.8+/-4.3 mm Hg (P < 0.005) after exercise compared to the control situation, but this was not associated with orthostatic symptoms. However, ambulatory monitoring showed no differences in blood pressure with the non-exercise day during the subsequent 24-h period. In conclusion, standing but not sitting blood pressure was slightly lower shortly after a cardiac rehabilitation session, but the postexercise orthostatic hypotension was not sustained during normal activities of daily living.