Effect of endurance training on blood pressure regulation, biomarkers and the heart in subjects at a higher age.

We reported previously that two otherwise identical training programs at lower (LI) and higher intensity (HI) similarly reduced resting systolic blood pressure (BP) by approximately 4-6 mmHg. Here, we determined the effects of both programs on BP-regulating mechanisms, on biomarkers of systemic inflammation and prothrombotic state and on the heart. In this cross-over study (3 × 10 weeks), healthy participants exercised three times 1 h/week at, respectively, 33% and 66% of the heart rate (HR) reserve, in a random order, with a sedentary period in between. Measurements, performed at baseline and at the end of each period, involved blood sampling, HR variability, systolic BP variability (SBPV) and cardiac magnetic resonance imaging. Thirty-nine participants (18 men; mean age 59 years) completed the study. Responses were not different between both programs (P>0.05). Pooled data from LI and HI showed a reduction in HR (-4.3 ± 8.1%) and an increase in stroke volume (+11 ± 23.1%). No significant effect was seen on SBPV, plasma renin activity, basal nitric oxide and left ventricular mass. Our results suggest that the BP reduction observed appears to be due to a decrease in systemic vascular resistance; training intensity does not significantly affect the results on mechanisms, biomarkers and the heart.

Effect of creatine supplementation as a potential adjuvant therapy to exercise training in cardiac patients: a randomized controlled trial.

OBJECTIVE: To investigate the effect of oral creatine supplementation in conjunction with an exercise programme on physical fitness in patients with coronary artery disease or chronic heart failure. DESIGN: Single centre double-blind randomized placebo controlled trial. SETTING: Cardiac rehabilitation centre. SUBJECTS AND INTERVENTION: 70 (4 women) cardiac patients (age 57.5 (8.4) years) were randomized to a placebo (n = 37) or creatine (n = 33) treatment for three months. Combined aerobic endurance and resistance training (three sessions/ week) was performed during supplementation. MAIN MEASURES: Aerobic power was determined during graded bicycle testing, knee extensor peak isometric and isokinetic strength, endurance and recovery were assessed by an isokinetic dynamometer, and health related quality of life was evaluated with the SF-36 and MacNew Heart Disease questionnaires. In addition, blood samples were taken after an overnight fast and 24 hour urinary collection was performed. RESULTS: At baseline there were no significant differences between both groups. We observed main time effects for aerobic power, muscle performance, health related quality of life, high density lipoprotein cholesterol and triglycerides (pre vs post; P<0.05 for all). However, changes after training were similar between placebo group and creatine group (P>0.05). Further, no detrimental effect on renal or liver function was observed nor were there any reports of side effects. CONCLUSION: Oral creatine supplementation in combination with exercise training does not exert any additional effect on the improvement in physical performance, health related quality of life, lipid profile in patients with coronary artery disease or chronic heart failure than exercise training alone.

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

BACKGROUND: Many studies have focused on the prognostic power of peak oxygen uptake VO(2) 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 VO(2) during submaximal exercise in comparison with VO(2). 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 VO(2) and submaximal respiratory slopes predicted outcome before and after accounting for age, sex, and body mass index. However, whereas the prognostic power of peak VO(2) was independent of submaximal respiratory data, the prognostic significance of the slopes was lost after controlling for peak VO(2). Stepwise regression analysis even selected peak VO(2) as an independent prognostic index among the following factors: cause of heart failure, ejection fraction, pulmonary vascular resistance, natremia, and the forced expiratory volume in 1 s. CONCLUSIONS: Respiratory data during submaximal exercise are significant predictors of outcome in patients with chronic heart failure, but their prognostic power is inferior to that of peak VO(2). However, these data may be useful when maximal exercise is contraindicated or not achievable.

Response to antihypertensive therapy in older patients with sustained and nonsustained systolic hypertension. Systolic Hypertension in Europe (Syst-Eur) Trial Investigators.

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 follow-up, a lower incidence of stroke (P<0.05) and of cardiovascular complications (P=0.01) than other groups. Active treatment reduced ABP and CBP in patients with sustained hypertension but only CBP in patients with nonsustained hypertension (P<0.001). The influence of active treatment on ECG voltages (P<0.05) and on the incidence of stroke (P<0.05) and cardiovascular events (P=0.06) was more favorable than that of placebo only in patients with moderate sustained hypertension. CONCLUSIONS: Patients with sustained hypertension had higher ECG voltages and rates of cardiovascular complications than did patients with nonsustained hypertension. The favorable effects of active treatment on these outcomes were only statistically significant in patients with moderate sustained hypertension.

The pulse pressure-to-stroke index ratio predicts cardiovascular events and death in uncomplicated hypertension.

OBJECTIVES: The goal of this study was to assess the prognostic power of the pulse pressure-to-stroke index (PP-to-SVi) ratio for cardiovascular events and mortality in patients with uncomplicated hypertension. BACKGROUND: The prognostic significance of pulse pressure (PP) has been studied repeatedly, but few data are available on the PP-to-SVi ratio. METHODS: Invasive hemodynamic measurements, including brachial intra-arterial pressure and stroke index by the direct oxygen Fick method, were performed in the period 1972 to 1982 in 192 patients with uncomplicated hypertension; their outcome was ascertained in 1994. RESULTS: Age at baseline averaged 37 +/- 12 years; brachial artery pressure was 165 mm Hg +/- 30/89 +/- 17 mm Hg; PP averaged 76 mm Hg +/- 18 mm Hg, and the PP-to-SVi ratio was 1.67 mm Hg/(ml/m2) +/- 0.73 mm Hg/(ml/m2). During 3,057 patient years of follow-up, 19 patients died, and 44 experienced at least one fatal or nonfatal cardiovascular event. Cox regression analysis revealed that the PP-to-SVi ratio was a significant predictor of fatal and nonfatal cardiovascular events and of all-cause mortality after control for age and gender (p < 0.01). Its predictive power persisted after additional adjustment for mean arterial pressure and heart rate. Each 0.75-mm Hg/(ml/m2) increase in the PP-to-SVi ratio was independently associated with a 79% increase in the risk of a cardiovascular event (p = 0.01) and a 2.05-fold greater risk of all-cause mortality (p = 0.01). CONCLUSIONS: The PP-to-SVi ratio is a significant and independent predictor of cardiovascular events and mortality in selected patients with uncomplicated hypertension.

Effects of exercise, diet and their combination on blood pressure.

Epidemiological studies suggest an inverse relationship between physical activity or fitness and blood pressure. In a meta-analysis of 44 randomized controlled intervention trials, the weighted net change in conventional systolic/diastolic blood pressure in response to dynamic aerobic training averaged -3.4/-2.4 mmHg (P < 0.001). The effect on blood pressure was more pronounced in hypertensives than in normotensives. This type of training also lowered the blood pressure measured during ambulatory monitoring and during exercise. However, exercise appears to be less effective than diet in lowering blood pressure (P < 0.02), and adding exercise to diet does not seem to further reduce blood pressure.

Prognostic significance of blood pressure measured in the office, at home and during ambulatory monitoring in older patients in general practice.

The purpose of the study was to assess the prognostic significance of out-of-the-office blood pressure (BP) measurement in older patients in general practice, and to compare the results for BP measured in the office, at home and during 24-h ambulatory monitoring. All registerd patients who were 60 years or older were eligible for the study, except when bedridden, demented or admitted in a home for sick elderly people, or when they had suffered a myocardial infarction or stroke. After baseline measurements in 1990-1993, incidence of major cardiovascular events (cardiovascular death, myocardial infarction and stroke) was ascertained in 2002-2003 and related to the BPs by use of multivariate Cox regression analysis. Age of the 391 patients averaged 71+/-9 years; 40% were men. During median follow-up of 10.9 years, 86 patients (22%) suffered a cardiovascular event. The adjusted relative hazard rate, associated with a 1 s.d. increment in systolic BP was 1.13 for office BP (NS), and, respectively, 1.32, 1.33 and 1.42, for home, daytime and night time BP (P< or =0.01 for all). Results were similar for diastolic BP. The prognostic significance of all out-of-the-office BPs was independent of office BP. The prognostic value of home BP was equal to (systolic) or even better (diastolic) than that of daytime BP. Night time BP predicted cardiovascular events independent of all other BPs. Prognosis of white-coat hypertension was similar to that of true normotension, but better than in sustained hypertension. In conclusion, the prognostic value of home BP is better than that of office BP in older patients in primary care, and is at least equal to that of daytime ambulatory BP. The prognosis of patients with white-coat hypertension is similar to that of true normotensives.

Pulse pressure not mean pressure determines cardiovascular risk in older hypertensive patients.

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.

Arginine-aminopeptidase in rat cardiac fibroblastic cells participates in angiotensin peptide turnover.

OBJECTIVE: The aim of the present study was to elucidate the presence in rat cardiac fibroblastic cells of arginine-aminopeptidase and its involvement in the hydrolysis of angiotensin peptides. METHODS: Peptidase activity was measured as hydrolysis of the synthetic substrates, aryl-p-nitroanilides. Immunoblottings were performed with antibodies to aminopeptidase B and Glyceraldehyde-3-phosphate dehydrogenase. RESULTS: Arginine-aminopeptidase found in cardiac fibroblasts (Fb) was arginine and lysine specific, sensitive to various aminopeptidase (AP) inhibitors and to the inhibitor of metalloproteases, 1.10-phenatroline. Experiments with arphamenine A, a specific inhibitor of aminopeptidase B, have shown the presence of two Arginine-aminopeptidase activities: arphamenine-sensitive: chloride-stimulated Arginine-aminopeptidase, and arphamenine-insensitive: chloride-insensitive Arginine-aminopeptidase. Transforming growth factor-beta1 stimulated both Arginine-aminopeptidase activities by approximately threefold. Immunoblot with an antibody specific to rat aminopeptidase B has revealed that arphamenine-sensitive: chloride stimulated aminopeptidase is aminopeptidase B. Arginine-p-nitroanilide hydrolysis was significantly inhibited by angiotensin peptides such as angiotensin (1-10), (1-8), (1-7), (1-4), (5-8), (4-8), (3-8), and (2-8) at the concentration of 50 micromol/l which was fourfold less than the Arginine-p-nitroanilide concentration. CONCLUSIONS: Our data show that chloride-insensitive Arginine-aminopeptidase could contribute to the hydrolysis of all studied angiotensin peptides in concert with other peptidases present in fibroblasts. Some of the peptides could probably not be hydrolyzed by Arginine-aminopeptidase. Instead, they could be first hydrolyzed by another peptidase in fibroblasts and the product of this hydrolysis could be a substrate for Arginine-aminopeptidase. The data obtained suggest that Arginine-aminopeptidase could perform processing of angiotensin peptides in the myocardium and participate in processes regulated by angiotensins such as fibrosis.

Prediction of cardiac structure and function by repeated clinic and ambulatory blood pressure.

We performed imaging echocardiography, Doppler velocimetry, and repeated clinic and ambulatory blood pressure measurements in 74 hypertensive individuals to clarify why reports differ on the strength of the relationships of left ventricular characteristics with clinic blood pressure, on the superiority of ambulatory over clinic pressure, and on the importance of day-time and nighttime pressures. Clinic pressure was measured five times with an automated device and five times with the conventional technique on 2 different days. The partial correlation coefficients of left ventricular mass and wall thickness with the first automated systolic and diastolic clinic pressures amounted to .38 to .45 (P < .001), improved with increasing numbers of measurements, and reached .56 to .58 for the average of 10 automated pressure determinations. Similar trends were observed for conventional clinic pressures. Average 24-hour pressures were significantly related to mass and wall thickness (partial r = .50 to .61, P < .001) and explained 3% to 6% (systolic) and 5% to 12% (diastolic) of the variance of cardiac structure in addition to the first automated or conventional clinic pressure (P < .05). However, when 10 clinic measurements were averaged, only diastolic 24-hour pressure added information over and above clinic pressure (P < .05); the additional explained variance was larger with regard to the conventional (+4% for mass and +7% for wall thickness) rather than the automated (+3% for wall thickness only) pressures. Mass and wall thickness were more closely related to day-time than nighttime pressures and were not independently related to day-night differences in pressure, except when men and women were considered separately; the results were similar when four different definitions of day and night were applied. Finally, the weak association of left ventricular diastolic function with blood pressure did not improve on repeated clinic or ambulatory blood pressure measurements. In conclusion, increasing numbers of measurements strengthen the relationships of clinic pressure with left ventricular mass and wall thickness and, conversely, diminish the additional predictive power of 24-hour blood pressure. The importance of nighttime pressure and of the nighttime pressure fall does not seem to depend on the definition of day and night but differs in men and women.

Prognostic value of invasive hemodynamic measurements at rest and during exercise in hypertensive men.

In 1994, we ascertained the outcome of 143 hypertensive men in whom invasive hemodynamic measurements were performed at rest and during graded bicycle exercise during the period 1972-1982 to assess (1) which of the hemodynamic components of blood pressure is associated with the incidence of cardiovascular events and total mortality, and (2) whether the hemodynamic response to dynamic exercise adds prognostic precision to the data at rest. During 2186 patient years of follow-up, 38 patients suffered at least one fatal or nonfatal cardiovascular event and 17 patients died. Cox regression analysis showed that systolic pressure and systemic vascular resistance measured at rest, during submaximal exercise (50 W), and at peak effort were significant (P < .01) predictors of the age-adjusted incidence of cardiovascular events and total mortality. However, exercise blood pressure did not significantly predict the incidence of cardiovascular events over and above pressure at rest; by contrast, exercise systemic vascular resistance added prognostic precision to vascular resistance at rest (P < .01). As for total mortality, systolic pressure and systemic vascular resistance at peak exercise carried prognostic information that was independent of the results at rest (P < .05); this was not the case for measurements during submaximal exercise. We conclude that the prognostic importance of blood pressure is related to systemic vascular resistance. The prognostic precision of exercise pressure, on top of pressure at rest, is limited. Exercise systemic vascular resistance, however, provides prognostic information beyond that available from measurements at rest, particularly for the incidence of cardiovascular events.

Calcium channel blockade and cardiovascular prognosis in the European trial on isolated systolic hypertension.

In the double-blind Systolic Hypertension in Europe (Syst-Eur) Trial, active treatment was initiated with nitrendipine (10 to 40 mg/d) with the possible addition of enalapril (5 to 20 mg/d) and/or hydrochlorothiazide (12.5 to 25 mg/d) titrated or combined to reduce sitting systolic blood pressure by at least 20 mm Hg to <150 mm Hg. In the control group, matching placebos were used similarly. In view of persistent concerns about the use of calcium channel blockers as first-line antihypertensive drugs, this report explored to what extent nitrendipine, administered alone, prevented cardiovascular complications. Age at randomization averaged 70.2 years and systolic/diastolic blood pressure 173.8/85.5 mm Hg. Of 2398 actively treated patients, 1327 took only nitrendipine (average dose, 23.4 mg/d), and 1042 progressed to other treatments including nitrendipine (n=757; 35.7 mg/d), enalapril (n=783; 13.4 mg/d), and/or hydrochlorothiazide (n=294; 21.0 mg/d). Compared with the whole placebo group (n=2297), patients receiving monotherapy with nitrendipine had 25% (P=0.05) fewer cardiovascular end points, and those progressing to other active treatments showed decreases (P

The role of exercise in blood pressure control: supportive evidence.

Epidemiological studies suggest an inverse relationship between physical activity or fitness and blood pressure. In controlled intervention studies, the weighted net change in conventional blood pressure caused by dynamic aerobic training averaged -5.3 mmHg for systolic and -4.8 mmHg for diastolic blood pressure. The considerable interstudy variation in the blood pressure response can be partly explained by the more pronounced effect in hypertensive patients compared with the results in normotensive subjects. When only studies that used a random procedure and some follow-up study of the controls were included, the blood pressure-lowering effect of training was significant only in hypertensives. The same pattern is emerging for daytime blood pressure in studies that applied ambulatory pressure monitoring: night-time pressure was usually not affected by training. In conclusion, despite shortcomings in many individual studies, the overall results suggest that dynamic aerobic training may lower conventional and daytime blood pressure in adults with elevated blood pressure at baseline.

Reduction of left ventricular mass by antihypertensive treatment does not improve exercise performance in essential hypertension.

OBJECTIVE: To test the hypothesis that a reduction in left ventricular mass by long-term antihypertensive treatment, possibly associated with an improvement of diastolic function, would increase exercise performance in patients with essential hypertension. DESIGNS After a placebo run-in period, 27 patients with essential hypertension World Health Organization stages I and II were assigned randomly to 6-month double-blind treatment with either a diuretic (hydrochlorothiazide plus triamterene) or a converting enzyme inhibitor (trandolapril), to which the calcium antagonist amlodipine could be added after 3 months if required for better blood pressure control. METHOD: Investigations included clinic and ambulatory blood pressure measurements, left ventricular imaging and transmitral Doppler echocardiography and graded maximal exercise testing on the bicycle ergometer with respiratory gas analysis. RESULTS: Six-month antihypertensive therapy, which caused significant (P < 0.001) reductions in blood pressure (by 16% for clinic pressure) and in left ventricular mass (by 13%), but without convincing evidence of improved diastolic function, did not affect exercise performance or peak oxygen uptake. The influence on clinic, exercise and ambulatory blood pressures and on the peak oxygen uptake was similar in the two treatment arms but left ventricular wall thickness decreased to a greater extent in the trandolapril group (P< 0.05 at 3 months and P= 0.06 at 6 months). CONCLUSIONS: Regression of left ventricular mass caused by 6-month antihypertensive therapy does not improve exercise performance of patients with essential hypertension.

Influence of demographic, anthropometric and lifestyle characteristics on heart rate and its variability in the population.

OBJECTIVE: The purpose of this investigation was to assess the effects of age, gender, posture and their interactions, and of body mass index and lifestyle factors, on heart rate, its total variance and its variability in the frequency domain in a population-based sample of healthy subjects. METHODS: RR interval and respiration were registered in the supine and in the standing position in 302 men and 312 women, aged 25-89 years; 424 subjects were healthy and had recordings suitable for analysis. Power spectral analysis was performed by use of autoregressive modelling and by fast Fourier transform, and the low-frequency (LF) and high-frequency (HF) components were expressed in both absolute (ms2) and normalized units RESULTS: In the supine position, heart rate was higher in women than in men (P<0.001) and was not affected by age. Total variance and absolute LF and HF power markedly declined with age in each gender (P<0.001). Men had higher absolute LF power than women (P<0.001), whereas HF power was similar by gender; the age-related decline of HF power tended to be steeper in women (P = 0.06). The normalized LF and HF powers also decreased with age (P<0.01), except for the LF component in women; young men had higher LF power and lower HF power than young women, but the gender difference disappeared in the sixth decade of life. The LF: HF ratio was not influenced by age in supine men; the ratio was lower in women at young age, but increased to the level of men at greater age. Heart rate increased on standing, whereas its total variance was reduced; HF power declined, irrespective of the units, normalized LF power and the LF: HF ratio increased, whereas absolute LF power decreased (P<0.001). The postural changes of heart rate and of the frequency components did not differ by gender, but were attenuated with increasing age (P<0.05). Alcohol consumption did not influence heart rate and its variability, whereas independent effects of habitual physical activity, smoking habits and body mass index explained no more than 4% of the variance of some measures of heart rate variability. CONCLUSIONS: Age, gender and/or some lifestyle factors significantly affect heart rate and various components of its variability in the supine position and in response to standing. The results are similar for autoregressive modelling and fast Fourier transform, but may differ according to the units in which the spectral components are expressed.

Relationships of heart rate and heart rate variability with conventional and ambulatory blood pressure in the population.

BACKGROUND: Most studies on relationships between blood pressure and autonomic nervous function, assessed by power spectral analysis of heart rate variability, have used conventional or clinic blood pressure measurements in selected subjects, which may have influenced the results. OBJECTIVE: We aimed to investigate, in a population-based approach, associations of heart rate and heart rate variability, assessed in basal resting conditions and in response to standing, with conventional blood pressure measured by an investigator, and with ambulatory blood pressure monitored outside the laboratory. METHODS: RR interval and respiration were registered in 614 men and women, ages 25-89 years. After exclusion of subjects with myocardial infarction or diabetes and elimination of unsatisfactory recordings, 549 subjects remained for analyses at supine rest and 515 of these to assess the orthostatic responses. Hypertension was present in 39% of the subjects. The low-frequency (LF) and high-frequency (HF) components of heart rate variability were quantified by use of autoregressive modelling and expressed in absolute and normalized units. RESULTS: At supine rest, indices of heart rate variability were not independently related to 24 h systolic blood pressure, whereas some indices showed weak associations with diastolic 24 h pressure; the relationships were in general stronger for conventional blood pressure. For example, partial correlation coefficients of the relationships of the LF: HF ratio with systolic pressure were 0.12 (P < or = 0.01) for conventional pressure and 0.02 (NS) for 24 h pressure; these coefficients amounted to 0.20 (P < or = 0.001) and 0.11 (P < or = 0.01) for the diastolic pressures. The decrease of HF power and the increase of the LF:HF ratio on standing were significantly blunted at higher blood pressure, both when measured conventionally and by ambulatory monitoring (P < or = 0.001 for the LF: HF ratio). CONCLUSIONS: Relationships between autonomic nervous function at rest, assessed by use of power spectral analysis of heart rate variability, and conventional blood pressure, can at least partly be ascribed to the influence of the measurement conditions, whereas the orthostatic autonomic responses appear to be influenced by blood pressure per se.

Relationships between changes in left ventricular mass and in clinic and ambulatory blood pressure in response to antihypertensive therapy.

OBJECTIVE: To analyse the relationships between changes in left ventricular mass in response to 6-month antihypertensive therapy and changes in conventional and automated measurements of clinic blood pressure, average 24 h ambulatory blood pressure and daytime and night-time blood pressures. DESIGN: After a placebo run-in period, patients with essential hypertension (World Health Organization stages I-II) were treated for 6 months with one or a combination of two first-line antihypertensive drugs. METHODS: Investigations included echocardiography, conventional and automated clinic blood pressure measurements and ambulatory blood pressure monitoring. Daytime and night-time blood pressures were assessed according to two clock-time-dependent and two clock-time-independent methods, with a wide and a narrow approach for each technique. RESULTS: Fifty-four patients completed the 6-month treatment period. Left ventricular mass, adjusted for sex and body size, was correlated significantly to systolic and diastolic clinic blood pressures, both before (r = 0.57 and r = 0.48, P < 0.001) and during antihypertensive therapy (r = 0.43, P < 0.001 and r = 0.27, P < 0.05). Changes in left ventricular mass were significantly related to changes in blood pressure. The correlation coefficients amounted to 0.39 (P < 0.01) and 0.40 (P < 0.01) for the conventional and automated measurements of clinic systolic blood pressures, respectively, and to 0.45 (P < 0.001) for the average 24 h systolic blood pressure; these r values were 0.27 (NS), 0.20 (NS) and 0.43 (P < 0.01), respectively, for the diastolic blood pressure. The average 24 h blood pressure added 7.4% (P < 0.05) and 6.2% (P = 0.06) to the variance of the changes in mass explained in terms of the conventional and the automated measurements of clinic systolic blood pressures, respectively, and 11.2% (P < 0.05) and 14.5% (P < 0.01) for the diastolic blood pressures. The changes in daytime and night-time blood pressures predicted the changes in left ventricular mass significantly (P < 0.01) and to a similar extent, irrespective of the analytical method. CONCLUSIONS: The treatment-induced changes in left ventricular mass were significantly related to the changes in clinic, 24 h, daytime and night-time blood pressures; the changes in 24 h ambulatory blood pressure add to the variance of the changes in left ventricular mass explained in terms of clinic blood pressure data.

Inheritance of blood pressure and haemodynamic phenotypes measured at rest and during supine dynamic exercise.

Thirty-two pairs of monozygotic and 21 pairs of dizygotic male twins aged between 18 and 31 years were studied. Blood pressure was measured and Doppler echocardiography at the level of the aorta was performed in resting conditions and at two levels of supine submaximal bicycle exercise (at a fixed work load of 60 W and at a work load corresponding to a heart rate of 110 beats/min). In resting conditions, a genetic component in the variability of systolic and diastolic blood pressure was found; during submaximal supine exercise only a minor genetic effect was observed. At rest, genetic variance was shown for left ventricular outflow haemodynamics and for peripheral vascular resistance. However, during exercise, the transmissible effect on haemodynamics and peripheral resistance was small.

The impact of genetic and environmental influences on blood pressure variance across age-groups.

OBJECTIVE: The purpose of the present investigation was to examine the age-dependency of blood pressure heritability by use of the twin method in different age groups. DESIGN: In 272 (150 monozygous and 122 dizygous) twin pairs, aged 18 to 76 years, both conventional and ambulatory blood pressure were measured. After correction for possible confounders, model fitting was used to estimate heritability and 95% confidence limits in three age groups of similar size, i.e. 18-29, 30-39 and > or = 40 years. RESULTS: Heritability estimates were significant in each age group, ranging from 35 to 67% for the various blood pressure measurements. The estimates tended to decrease with increasing age, except for conventional diastolic blood pressure, but the intergroup differences did not reach statistical significance, despite adequate power. CONCLUSIONS: In conclusion, blood pressure heritability is significant in various age groups, but does not substantially change with advancing age. Twin analysis does not indicate that models for blood pressure regulation in various age groups should take into account the possibility of age-related changes in the expression of relevant genes, in the presence of relevant environmental agents, or in the susceptibility to the latter (gene-environment interaction).

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

OBJECTIVES: To compare the effects of a highly beta1-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.