Biomedical subjects

A Amery

Publications and source records attributed to A Amery.

At least 19 recordsLinked to original sources

PubMed1996

Power spectral analysis of RR interval and blood pressure short-term variability at rest and during dynamic exercise: comparison between cyclists and controls.

To determine the adaptations of the autonomic nervous system in the control of heart rate and blood pressure induced by endurance training, 10 competitive cyclists aged 27 +/- 7 years and 10 age-, weight- and height-matched sedentary controls were subjected to Power Spectral Analysis of the RR interval and of blood pressure at supine rest and during submaximal cycloergometric exercise test in the supine position at 20% and 40% of maximal workload. At rest, the high-frequency (HF) power of the RR interval was higher in cyclists (p < 0.05) compared to controls, whereas the power spectrum of both systolic and diastolic blood pressure did not differ between cyclists and controls. During exercise the variance, the low-frequency (LF) and the HF power of the RR interval decreased significantly (p < 0.005) and similarly in cyclists and controls. The LF/HF ratio of the RR interval increased (p < 0.001) and the alfa index of baroreflex sensitivity decreased (p < 0.05) without differences between cyclists and controls. The variance of both systolic and diastolic blood pressure increased (p < 0.001 and p < 0.005, respectively) as well as the HF power of systolic blood pressure (p < 0.001) similarly in cyclists and in controls. In conclusion, the data of the present study suggest that competitive cycling causes an enhanced vagal drive to the sinus node, whereas the neural control of blood pressure is not affected. During exercise a vagal withdrawal and a sympathetic activation in the neural control of heart rate, together with a reduction of baroreflex sensitivity are operative. These changes are similar in cyclists and controls.

Adaptation, Physiological↗

PubMed1995

Prognostic value of training-induced change in peak exercise capacity in patients with myocardial infarcts and patients with coronary bypass surgery.

An inverse association between mortality and exercise capacity has been demonstrated previously in patients with coronary artery disease. Physical training generally increases exercise capacity. Only 1 study investigated the prognostic value of exercise capacity after training, but only in a limited number of patients. No data are available on the relation between mortality and the change in exercise performance with training. Peak oxygen uptake (VO2) was measured before and after a 3-month, predominantly dynamic training period in 417 patients with coronary artery disease. Apart from peak VO2, several patient characteristics, risk factors for cardiovascular disease, and exercise data were considered in a Cox proportional-hazards model. Peak VO2 had increased by 33% after the training period. During the total follow-up of 2,583 patient-years, 37 patients died. The cause of death was cardiovascular in 21. The prognostic value of peak VO2 was higher after training than before training, even after adjustment for age and other significant covariates. Cardiovascular mortality decreased more with greater increases in peak VO2 after training. The relative hazard rate of 0.98 indicates that a 1% greater increase in peak VO2 after training would be associated with a decrease in cardiovascular mortality of 2%. No differences in prognostic value and in training effects were observed between patients with myocardial infarcts and patients after coronary bypass grafting. Peak VO2, evaluated after a physical training program, and its change in response to training are independent predictors for cardiovascular mortality in patients with coronary artery disease.

Adult↗

PubMed1995

Relation of left ventricular mass and filling to exercise blood pressure and rest blood pressure.

Ninety-two young men with normal blood pressure (BP) or borderline elevated BP underwent echocardiography and maximal exercise testing to study whether left ventricular (LV) mass and the mitral inflow velocity pattern are more closely related to BP measured during dynamic exercise than to pressure measured at rest. LV mass was significantly related (p < 0.05) to systolic BP measured at rest and at various workloads; however, the variance of LV mass that could be explained by exercise pressures, in addition to preexercise pressure, age, body size, resting heart rate, and peak oxygen uptake, was not significant. The ratio of the late to early mitral inflow velocity was significantly related to systolic BP at rest but not to the pressures during exercise, and there was no independent contribution of exercise BP to its variance. Thus, systolic BP at various levels of dynamic exercise does not contribute independently to the interindividual variance of LV mass and mitral inflow pattern in young men with normal or borderline elevated BP.

Adolescent↗

PubMed1995

The ambulatory blood pressure in normotensive and hypertensive subjects: results from an international database.

OBJECTIVE: To delineate more precisely an operational threshold for making clinical decisions based on ambulatory blood pressure (ABP) measurement by studying the ABP in subjects who were diagnosed as either normotensive or hypertensive by conventional blood pressure (CBP) measurement. SUBJECTS: Twenty-four research groups recruited 7069 subjects. Of these, 4577 were normotensive (systolic CBP < or = 140 mmHg and diastolic CBP < or = 90 mmHg) and 1773 were hypertensive (systolic CBP > or = 160 mmHg and/or diastolic CBP > or = 90 mmHg). Of the latter, 1324 had systolic and 1310 had diastolic hypertension. RESULTS: Ninety-five percent of the normotensive subjects had a 24-h ABP below (systolic and diastolic, respectively) 133 and 82 mmHg. Of the patients with systolic hypertension, 24% had a 24-h systolic ABP of < 133 mmHg. Similarly, 30% of those with diastolic hypertension had a 24-h diastolic ABP of < 82 mmHg. The probability that hypertensive patients had a 24-h ABP below these thresholds was higher in women than in men, increased with age and was 2- to 4-fold greater if the CBP of the patient had been measured at only one visit and if fewer than 3 CBP measurements had been averaged to establish the diagnosis of hypertension. By contrast, for each 10-mmHg increment in systolic CBP, this probability decreased by 54% for the 24-h systolic ABP and by 25% for the 24-h diastolic ABP, and for each 5 mmHg increment in diastolic CBP it increased by 6 and 9%, respectively. CONCLUSION: The ABP distributions of the normotensive subjects included in the present international database were not materially different from those in previous reports in the literature. One-fifth to more than one-third of the hypertensive patients had an ABP which was below the 95th centile of the ABP in normotensive subjects, but this proportion decreased if the hypertensive patients had shown a higher CBP upon repeated measurement. The prognostic implications of elevated CBP in the presence of normal ABP remain to be determined.

Adolescent↗

PubMed1995

Once-daily antihypertensive treatment with calcium antagonists: utopia or reality?

Although a large number of antihypertensive drugs have been approved for once- or twice-daily dosing, no standardized set of evidence is required to demonstrate that the blood pressure reduction is sustained for 24 h. The recent literature on calcium antagonists was therefore searched for the arguments usually put forward to objectify a long duration of action. Most studies relied on ambulatory blood pressure monitoring. However, several published reports were difficult to interpret for a variety of reasons, such as: (1) a non-blinded non-randomized study design; (2) a statistical analysis, which was discordant with the study design; (3) analyses confined to the 24 h, day-time and night-time pressure means; (4) the absence of a baseline adjustment and/or formal statistical testing; (5) the "post hoc" subdivision of patients into responders and non-responders; and (6) the absence of a well-specified time-frame linking drug intake to the observed antihypertensive effects. According to the authors' interpretation, amlodipine, diltiazem SR (modified release), felodipine SR, isradipine SR, nifedipine SR, nitrendipine and verapamil SR have all been confirmed to reduce both the conventional and the 24 h blood pressure. Some studies went beyond the 24 h blood pressure means and also presented separate results for the day-time (or awake) and night-time (or sleeping) periods, or investigated the blood pressure reduction at the end of the dosing interval, or compared the diurnal blood pressure profiles on different treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure Monitoring, Ambulatory↗

PubMed1995

Multiple standardized clinic blood pressures may predict left ventricular mass as well as ambulatory monitoring. A metaanalysis of comparative studies.

It is generally recognized that the relation between left ventricular mass (index) and blood pressure measured in the clinic is weak. Several investigators have studied whether ambulatory blood pressure outside the hospital environment can explain more of the variance of left ventricular mass than does clinic pressure. In a metaanalysis of such comparative studies, the weighted correlation coefficient averaged 0.35 (95% confidence limits: 0.30 to 0.40) for systolic clinic pressure and was significantly (P < .001) higher for the 24-h pressure (r = 0.50; range 0.45 to 0.54). In several studies, however, the methodology and conditions of the clinic pressure measurements were poorly described or standardized, whereas multiple meticulously obtained measurements were present in other reports. The ambulatory pressure monitoring was usually performed with great care and reported in detail. In some studies in which clinic blood pressure consisted of multiple readings in well-standardized conditions in the resting subject, clinic pressure seemed to predict left ventricular mass as well as ambulatory monitoring. We suggest that the strength of the relationship of left ventricular mass with ambulatory pressure may not differ from that with clinic pressure when an adequate number of blood pressures are measured in well-standardized conditions in the clinic.

Adult↗

PubMed1995

Double-blind comparison of antihypertensive treatment with ramipril and piretanide, given alone or in combination.

In a double-blind, randomized, multicenter trial, we compared the efficacy and safety of the fixed combination of 5 mg ramipril and 6 mg piretanide and the respective component monotherapies in hypertensive patients [supine diastolic blood pressure (DBP) 100-114 mm Hg]. After a single-blind run-in period on placebo, 611 patients were randomized to ramipril (n = 209), piretanide (n = 201), or the combination therapy (n = 201). At randomization, the three groups had the same characteristics (51% men, age 55 +/- 10 years, BP 165 +/- 18/104 +/- 6 mm Hg). At 4 weeks, BP decreased more with combined therapy than with monotherapy. As compared with piretanide monotherapy, the gain in the antihypertensive effect in the supine position averaged 2.1 mm Hg [90% confidence interval (CI) -0.8-5.0 mm Hg; p = 0.07] systolic BP (SBP) and 1.9 mm Hg (CI 0.3-3.5 mm Hg, p = 0.02) DBP and, as compared with ramipril monotherapy, these differences were 4.2 mm Hg (CI 1.3-7.0 mm Hg, p = 0.008) and 2.0 mm Hg (CI 0.5-3.6 mm Hg, p = 0.009). The incidence of adverse events (AE) and the changes in biochemical measurements were similar in the three treatment groups with the exception of spontaneously reported polyuria and serum uric acid concentration. Polyuria was reported more frequently (p < 0.001) with piretanide therapy (n = 23) and combined therapy (n = 19) than with ramipril therapy (n = 1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

A consensus view on the technique of ambulatory blood pressure monitoring. The Fourth International Consensus Conference on 24-Hour Ambulatory Blood Pressure Monitoring.

This review, based on the Fourth International Consensus Conference on Ambulatory Blood Pressure Monitoring (Leuven, Belgium, 1994), deals with the technical aspects of ambulatory blood pressure monitoring. Ambulatory blood pressure monitoring by noninvasive intermittent techniques is widely used despite artifacts due to cuff size, movement, body position, short-term blood pressure variability, and interference with sleep. The performance of the currently available monitors under truly ambulatory conditions and during exercise remains a matter of debate, as are the procedures required to validate portable monitors under these circumstances. There is general agreement that whenever a monitor is to be used in special populations, such as older subjects or pregnant women, or in special conditions, such as exercise, a specific demonstration of its accuracy in these defined subgroups or conditions is warranted. Whether the auscultatory or oscillometric method is preferred remains controversial because each technique has specific advantages and disadvantages and because both can provide accurate results. Most experts in the field strongly believe that manufacturers should disclose the algorithms of their devices and that they should specify all changes made to the hardware and software of a previously validated monitor. Finally, the development of the volume-clamp method, which makes continuous noninvasive registration of blood pressure at the finger possible in both stationary and ambulatory conditions, opens new perspectives in research, in particular in relation to short-term blood pressure variability.

Adult↗

PubMed1995

Lack of association between HLA class II polymorphisms and essential hypertension in a Belgian population.

The aim of the present study was to investigate whether the HLA class II polymorphisms contributes to the susceptibility to essential hypertension in the Belgian population. For this purpose we studied 120 hypertensive patients and 168 normotensive controls by means of a PCR-SSO assay. No significant difference in allele and genotype frequencies of the DRB and DPB1 loci could be found between the two groups. We concluded that essential hypertension as a multifactorial and heterogeneous disease cannot be associated with one of the HLA class II DRB and DPB1 alleles in Belgian patients.

Adult↗

PubMed1995

Low-level lead exposure and blood pressure.

The possible association between low-level lead exposure and blood pressure (BP) remains debated. The purpose of this review was: (1) to determine whether the available studies in humans support a positive association, in particular at lower exposure levels (blood lead concentration < 1 mumol/l), and (2) to explore whether animal studies and the proposed pathophysiological mechanisms are supportive of a positive and causal association between lead exposure and hypertension. A meta-analysis of 23 studies included 33,141 subjects recruited from the general population in 13 surveys and from occupational groups in 10 studies. In all but four studies the results had been adjusted for age, and most studies also considered additional confounders. The association between BP and blood lead was similar in both sexes. In all 23 studies combined, a two-fold increase in blood lead concentration was associated with a 1 mm Hg rise in the systolic pressure (CI 0.4-1.6 mm Hg; P = 0.002) and with a 0.6 mm Hg increase in the diastolic pressure (CI 0.2-1.0 mm Hg; P = 0.02). Of 21 animal studies, one was carried out in dogs, one in pigeons and the remainder in various rat strains. In 15 studies, in which the lead dose in drinking water or food exceeded 1 p.p.m. the association between BP and exposure was found to be positive in seven, inconsistent in three, absent in four and negative in one. Of the six studies at lower exposure levels (< or = 1 p.p.m.), five found a pressor effect attributable to lead. Whether the lead doses in the animal studies are equivalent to the human exposure levels and to what extent one can extrapolate from genetically heterogeneous animals to humans, remains doubtful. If a causal relation between lead exposure and hypertension exists, the proposed mechanisms may include interference of lead with ion transport across cell membranes, interactions with calcium homeostasis and calcium-mediated processes, direct vasomotor actions and the potentiation of sympathetic stimulation. Interference of lead with the balance between the renin-angiotensin-aldosterone and the kallikrein-kinin systems and impairment of renal function are unlikely to be implicated. On balance, the published evidence suggests that there can only be a weak positive association between BP and lead exposure. The latter relation, which is barely visible at the horizon of epidemiological observation, may not be causal in nature and is unlikely to entail any public health implication in terms of hypertension-related complications.

Animals↗

PubMed1994

Renal function and historical environmental cadmium pollution from zinc smelters.

We investigated whether there was an association between renal function and cadmium pollution in areas with different exposures. Cadmium was measured in the soil and in vegetables in 10 districts, 6 of which were close to zinc smelters; and renal function and the concentrations of metals in blood and urine were measured in 703 randomly selected residents. 6 polluted areas, compared with 4 others showed higher cadmium concentrations in the soil (4.86 vs 0.81 ppm) and in locally grown vegetables, such as celery (2.43 vs 0.68 ppm) and beans (0.42 vs 0.15 ppm). Residents in polluted areas had higher urinary cadmium (10.5 vs 7.9 nmol/24 hours) and copper (0.16 vs 0.14 mumol/24 hours); higher serum creatinine (100 vs 97 mumol/L) urinary excretions of beta 2-microglobulin (109 vs 95 micrograms/24 hours), retinol-binding-protein (136 vs 118 micrograms/24 hours), and N-acetyl-beta-glucosaminidase (1.78 vs 1.38 U/24 hours). Serum zinc (12.2 vs 12.6 mumol/L) and creatinine clearance (87 vs 92 mL/min) were reduced in the 6 polluted areas. In all 10 districts, cadmium in the soil was positively correlated with cadmium in celery (r = 0.77), in beans (r = 0.67), and in residents' urine (r = 0.76). The creatinine clearance was inversely correlated with cadmium in soil (r = -0.78), in celery (r = -0.90), and in beans (r = -0.70). Past emissions from zinc smelters gave rise to contamination of the environment with cadmium, which gets into the food chain and has the potential to cause renal dysfunction and alterations in zinc and copper homeostasis.

Adult↗

PubMed1994

Role of cyclic GMP in atrial-natriuretic-peptide stimulation of erythrocyte Na+/H+ exchange.

Human atrial natriuretic peptide (ANP) fragments ANP-(127-150) or ANP-III and ANP-(127-149) or ANP-II activate Na+/H+ exchange in human erythrocytes at concentrations as low as 1 pM. Both ANP-(127-147) or ANP-I and ANP-(129-150) or des-Ser5, Ser6-ANP-III have no effect on erythrocyte Na+/H+ exchange. ANP-III also produces a time-dependent increase of intraerythrocyte guanosine 3',5'-phosphate (cGMP) concentration. M&B 22,948, a specific inhibitor of cGMP phosphodiesterase, increases Na+/H+ exchange and the intracellular concentration of cGMP. Both 8-bromoguanosine 3',5'-phosphate (8-Br-cGMP) and dibutyryl-cGMP mimic the effect of ANP-III on erythrocyte Na+/H+ exchange. Our data suggest that human erythrocytes possess guanylate-cyclase activity stimulated by ANP-III and that activation of Na+/H+ exchange by this peptide is mediated by cGMP. Human erythrocytes display a high degree of sensitivity to ANP-III or ANP-II and a specificity for ANP-fragment structures just as cells with established ANP-specific receptors.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed1994

Effects of celiprolol vs. nifedipine on serum lipoproteins in patients with mild to moderate hypertension.

During a double-blind, randomized study in hypertensive patients, changes in plasma lipid and lipoprotein levels during treatment with celiprolol were compared with those occurring during nifedipine treatment. Fifty-three patients (28 men and 25 women) with mild-to-moderate hypertension, aged 20-64 years, were studied. After a 1-month placebo run-in period, patients were randomly assigned to receive either nifedipine (40 mg daily) or celiprolol (200 mg daily), each time using a double-dummy technique. After 6 weeks, dosages of each drug could be doubled. After 6 weeks, there were no differences in plasma lipids between the two treatment groups. However, the changes after 12 weeks of treatment were different (p < 0.05) between the groups, leading to lower levels of plasma esterified cholesterol, low-density lipoprotein (LDL) cholesterol, and apoprotein AI, AII, and B in the celiprolol group. Plasma lecithin cholesterol acyltransferase activity (LCAT) was not modified. The present study showed that celiprolol was at least equivalent to nifedipine in terms of secondary effects on plasma lipids and lipoprotein.

Adult↗

PubMed1994

Pravastatin has no direct effect on transmembrane cationic transport systems in human erythrocytes and platelets.

In vitro incubation of human erythrocytes and platelets with the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor pravastatin in the concentration range 1 nM to 10 microM did not affect the activity of the Na(+)-K(+)-pump, Na(+)-K(+)-cotransport or Na(+)-Li(+)-countertransport, or the ground membrane leak for Na+ and K+. The data indicate that pravastatin has no direct effect on transmembrane cationic transport systems in red blood cells or platelets.

Antiporters↗

PubMed1994

Prognostic significance of peak exercise capacity in patients with coronary artery disease.

OBJECTIVES: The aim of this study was to investigate the prognostic significance of peak oxygen uptake in patients with coronary artery disease who had an exercise test that could be sustained to exhaustion without limiting symptoms. BACKGROUND: Many studies have reported an inverse association between the level of exercise reached during a stress test and mortality or cardiovascular morbidity. These studies have used submaximal or symptom-limited exercise testing in patients with a recent myocardial infarction. METHODS: Peak oxygen uptake was measured in male patients > or = 4 weeks after myocardial infarction (312 patients) or coronary artery surgery (215 patients) by use of a graded uninterrupted exercise test performed to exhaustion. Apart from peak oxygen uptake, several risk factors for cardiovascular disease, patient and exercise characteristics and drug treatment were considered in the Cox proportional hazards model. RESULTS: During the total follow-up period of 3,213 patient-years, 53 patients died. Of these 53 patients, 33 died of cardiovascular causes. All-cause and cardiovascular mortality decreased with increasing peak oxygen uptake, even after adjustment for significant covariates. The relative hazard rates of 0.43 and 0.29 indicate that a hypothetic increase in peak oxygen uptake by 1 liter/min could be associated with decreases in all-cause and cardiovascular mortality of 57% and 71%, respectively. CONCLUSIONS: Exercise capacity is an independent predictor for subsequent all-cause and cardiovascular mortality in patients able to perform an exercise test until exhaustion.

Coronary Artery Bypass↗

PubMed1994

Effect of age on the hemodynamic response to posture in nonelderly hypertensive patients.

The objective of this study was to assess the effects of age on the hemodynamic response to a change in posture in essential hypertension. Invasive hemodynamic measurements were performed in the supine and sitting position in 110 men, aged 16 to 64 years, in whom cardiovascular complications were virtually excluded. The change of systolic and diastolic intraarterial pressure, from 153/83 mm Hg after 30 min of supine rest to 156 (P < .05)/92 (P < .001) mm Hg after sitting for 10 min, was not significantly (P > .10) related to age. Heart rate (+9 beats/min) and systemic vascular resistance (+4.6 mm Hg/L/min) increased (P < .001) on sitting; cardiac output (-1.7 L/min), stroke volume (-31 mL), and pulmonary capillary wedge pressure (-2.1 mm Hg) fell (P < .001). Whereas the postural changes of heart rate (P < .01), cardiac output (P < .001), stroke volume (P < .001), and wedge pressure (P = .06) were less pronounced in older than in younger patients, the increase of systemic vascular resistance was not related to age (P > .10). The slopes of the postural changes of heart rate and of systemic vascular resistance differed significantly (P = .01). The results were not confounded by the level of blood pressure or weight. In conclusion, the smaller postural falls of cardiac output, stroke volume, and wedge pressure in older patients suggest less thoracic blood volume displacement to the lower parts of the body, possibly resulting from a lesser peripheral venous distensibility. The increase of heart rate in response to the upright posture is less pronounced at older age, whereas the reflex control of the peripheral vasculature is preserved and blood pressure maintained.

Adolescent↗

PubMed1994

Life style as a determinant of blood pressure in the general population.

This study investigated which life style factors were correlated with the level and the variability of systolic (SBP) and diastolic (DBP) pressure in a random population sample. Ten blood pressure readings were obtained at home in 405 men and 379 women (20 to 84 years). Each person's average pressure level was computed together with the standard deviation as index of variability. Sodium, potassium, and alcohol intake, smoking habits, social class, psychoemotional stress, and the calories spent at work and in sports were assessed from a questionnaire and from determinations on serum and on a 24-h urine sample. A P10 to P90 (10th and 90th percentile) increase of alcohol intake, as reflected by serum gamma-glutamyltransferase, was associated with a 3.2 +/- 0.9 mm Hg higher DBP in men and with a 3.1 +/- 1.6 mm Hg higher SBP and a 1.5 +/- 0.8 mm Hg higher DBP in women. A P10 to P90 increase in the calories spent in sports was accompanied by a decrease in pressure, averaging 1.5 +/- 0.8 mm Hg for DBP in men and 2.4 +/- 1.2 mm Hg and 1.8 +/- 0.8 mm Hg for SBP and DBP in women. A 2.2 +/- 0.7 mm Hg higher DBP was observed in women living in a working class area. After adjustment for age, the variability of DBP was inversely correlated with self-rated physical activity in men, whereas women living in a working class area showed a decreased SBP variability. In conclusion, in an affluent Western population, alcohol intake, participation in sports, and living in a working class area were identified as the life style factors of importance for the blood pressure level. By contrast, blood pressure variability, as measured in the present study, was only to a minor extent influenced by life style.

Adult↗

PubMed1994

Ambulatory blood pressure and blood pressure measured at home: progress report on a population study.

To determine reference values for ambulatory blood pressure, a population sample of 718 subjects (20 through 88 years old) was investigated. Ambulatory blood pressure was recorded over 24 h, taking measurements at 20-min intervals from 8 a.m. to 10 p.m. and at 45-min intervals from 10 p.m. to 8 a.m. Trained nurses also measured the conventional pressure at each participant's home. The ambulatory blood pressure in the 718 subjects averaged 119/71 mm Hg over 24 h, 125/76 mm Hg during the day (10 a.m.-8 p.m.), and 108/62 mm Hg at night (0 a.m.-6 a.m.). Compared with the daytime pressure, blood pressure at home was on average the same in all 718 subjects but was 3/1 mm Hg lower in 530 normotensive subjects. The 95th percentiles of the 24-h pressures were 134/85 mm Hg in 182 men below age 50, 145/87 mm Hg in 164 men aged > or = 50 years, 127/80 mm Hg in 198 women below age 50, and 141/81 mm Hg in 174 women aged > or = 50 years. In the normotensive subjects of these four strata, these percentiles were 132/82 mm Hg (n = 149), 128/80 mm Hg (n = 103), 125/79 mm Hg (n = 180), and 131/79 mm Hg (n = 98). In comparison with earlier results in a smaller sample (n = 318) from which treated patients were excluded, this analysis demonstrated consistent results in the determination of a reference frame for ambulatory monitoring. Nevertheless, the prognostic significance of such reference values needs to be established in longitudinal studies and clinical trials.

Adult↗