Baroreflex sensitivity in children and adolescents: physiology, hypertension, obesity, diabetes mellitus.

The increased prevalence of obesity in children and its complications have led to a greater interest in studying baroreflex sensitivity (BRS) in children. This review of BRS in children and adolescents includes subtopics on: 1. Resting values of BRS and their reproducibility, 2. Genetics of BRS, 3. The role of a primarily low BRS and obesity in the development of hypertension, and 4. Association of diabetes mellitus, BRS, and obesity. The conclusions specific to this age follow from this review: 1. The mean heart rate (HR) influences the measurement of BRS. Since the mean HR decreases during adolescence, HR should be taken into account. 2. A genetic dependency of BRS was found. 3. Low BRS values may precede pathological blood-pressure elevation in children with white-coat hypertension. We hypothesize that low BRS plays an active role in the emergence of hypertension in youth. A contribution of obesity to the development of hypertension was also found. We hypothesize that both factors, a primarily low BRS and obesity, are partially independent risk factors for hypertension in youths. 4. In diabetics, a low BRS compared to healthy children can be associated with insulin resistance. A reversibility of the BRS values could be possible after weight loss.

Development of causal interactions between systolic blood pressure and inter-beat intervals in adolescents.

Systolic blood pressure (SBP) changes control the cardiac inter-beat intervals (IBI) duration via baroreflex. Conversely, SBP is influenced by IBI via non-baroreflex mechanisms. Both causal pathways (feedback - baroreflex and feedforward - non-baroreflex) form a closed loop of the SBP - IBI interaction. The aim of this study was to assess the age-related changes in the IBI - SBP interaction. We have non-invasively recorded resting beat-to-beat SBP and IBI in 335 healthy subjects of different age, ranging from 11 to 23 years. Using a linear autoregressive bivariate model we obtained gain (Gain(SBP,IBI), used traditionally as baroreflex sensitivity) and coherence (Coh(SBP,IBI)) of the SBP-IBI interaction and causal gain and coherence in baroreflex (Gain(SBP->IBI), Coh(SBP->IBI) and coherence in non-baroreflex (Coh(IBI->SBP)) directions separately. A non-linear approach was used for causal coupling indices evaluation (C(SBP->IBI), C(IBI->SBP)) quantifying the amount of information transferred between signals. We performed a correlation to age analysis of all measures. Coh(IBI->SBP) and C(IBI->SBP) were higher than Coh(SBP->IBI) and C(SBP->IBI), respectively. Gain(SBP,IBI) increased and Coh(SBP->IBI) decreased with age. The coupling indices did not correlate with age. We conclude that the feedforward influence dominated at rest. The increase of Gain(SBP,IBI) with age was not found in the closed loop model. A decrease of Coh(SBP->IBI) could be related to a change in the cardiovascular control system complexity during maturation.

The vibration plethysmographic method of arterial compliance analysis in dependence on transmural pressure.

The aim of this study was to obtain a detailed analysis of the relationship between the finger arterial compliance C [ml/mm Hg] and the arterial transmural pressure P(t) [mm Hg]. We constructed a dynamic plethysmograph enabling us to set up a constant pressure P(css) [mm Hg] and a superimposed fast pressure vibration in the finger cuff (equipped with a source of infra-red light and a photoelectric sensor for the measurement of arterial volume). P(css) could be set on the required time interval in steps ranging between 30 and 170 mm Hg, and on sinusoidal pressure oscillation with an amplitude P(ca) (2 mm Hg) and a frequency f (20, 25, 30, 35, 40 Hz). At the same time continuous blood pressure BP was measured on the adjacent finger (Portapres). We described the volume dependence of a unitary arterial length on the time-varying transmural pressure acting on the arterial wall (externally P(css)+P(ca).sin(2pif), internally BP) by a second-order differential equation for volume. This equation was linearized within a small range of selected BP. In the next step, a Fourier transform was applied to obtain the frequency characteristic in analytic form of a complex linear combination of frequency functions. While series of oscillations [P(ca), f] were applied for each P(css), the corresponding response of the plethysmogram was measured. Amplitude spectra were obtained to estimate coefficients of the frequency characteristic by regression analysis. We determined the absolute value: elastance E, and its inverse value: compliance (C=1/E). Then, C=C(P(t)) was acquired by applying sequences of oscillations for different P(css) (and thus P(t)) by the above-described procedure. This methodology will be used for the study of finger arterial compliance in different physiological and pathological conditions.

[Baroreflex sensitivity: diagnostic importance, methods of determination and a model of baroreflex blood-pressure regulation]. / Citlivost baroreflexu: diagnostický význam, metody stanovení a model baroreflexní regulace krevního tlaku.

Baroreflex regulation of blood pressure primarily moderates its fluctuations and also affects mean blood pressure. Heart rate baroreflex sensitivity is described as changes of the inter-beat interval induced by a change of blood pressure of 1 mmHg (BRS). BRS is decreased in many cardiovascular diseases (hypertension, diabetes mellitus, obesity, cardiac failure, etc.). Decreased BRS in disposed individuals, especially after myocardial infarction, increases the risk of sudden cardiac death. Therefore, early diagnosis of BRS decrease gains in importance. This article describes different methods of determination of baroreflex sensitivity. The methods are based on evaluation of the spontaneous fluctuation of heart rate and blood pressure (spectral, sequential or nonlinear methods), or of primary changes of blood pressure induced by a vasoactive substance or a physiological manoeuvre and corresponding changes of cardiac intervals (Valsalva manoeuvre, phenylephrine administration). Each method has its advantages and disadvantages resulting from a different difficulty of calculation or from inclusion of different deviations in the results, which are not directly linked with baroreflex. Baroreflex regulating total peripheral resistance is less described. A mathematical model of baroreflex blood pressure regulation by fluctuation of heart rate and peripheral resistance is presented in this paper.

Diagnostic significance of a mild decrease of baroreflex sensitivity with respect to heart rate in type 1 diabetes mellitus.

Decreased baroreflex sensitivity is an early sign of autonomic dysfunction in patients with type-1 diabetes mellitus. We evaluated the repeatability of a mild baroreflex sensitivity decrease in diabetics with respect to their heart rate. Finger blood pressure was continuously recorded in 14 young diabetics without clinical signs of autonomic dysfunction and in 14 age-matched controls for 42 min. The recordings were divided into 3-min segments, and the mean inter-beat interval (IBI), baroreflex sensitivity in ms/mm Hg (BRS) and mHz/mm Hg (BRSf) were determined in each segment. These values fluctuated in each subject within 42 min and therefore coefficients of repeatability were calculated for all subjects. Diabetics compared with controls had a decreased mean BRS (p=0.05), a tendency to a shortened IBI (p=0.08), and a decreased BRSf (p=0.17). IBI correlated with BRS in diabetics (p=0.03); this correlation was at p=0.12 in the controls. BRSf was IBI independent (controls: p=0.81, diabetics: p=0.29). We conclude that BRS is partially dependent on mean IBI. Thus, BRS reflects not only an impairment of the quick baroreflex responses of IBI to blood pressure changes, but also a change of the tonic sympathetic and parasympathetic heart rate control. This is of significance during mild changes of BRS. Therefore, an examination of the BRSf index is highly recommended, because this examination improves the diagnostic value of the measurement, particularly in cases of early signs of autonomic dysfunction.

Spectral peak frequency in low-frequency band in cross spectra of blood pressure and heart rate fluctuations in young type 1 diabetic patients.

In this study we tested whether joint evaluation of the frequency (f(cs)) at which maxima of power in the cross-spectra between the variability in systolic blood pressure and inter-beat intervals in the range of 0.06-0.12 Hz occur together with the quantification of baroreflex sensitivity (BRS) may improve early detection of autonomic dysfunction in type 1 diabetes mellitus (T1DM). We measured 14 T1DM patients (age 20.3-24.2 years, DM duration 10.4-14.2 years, without any signs of autonomic neuropathy) and 14 age-matched controls (Co). Finger arterial blood pressure was continuously recorded by Finapres for one hour. BRS and f(cs) were determined by the spectral method. Receiver-operating curves (ROC) were calculated for f(cs), BRS, and a combination of both factors determined as F(z)=1/(1+exp(-z)), z=3.09-0.013*BRS-0.027*f(cs). T1DM had significantly lower f(cs) than Co (T1DM: 88.8+/-6.7 vs. Co: 93.7+/-3.8 mHz; p<0.05), and a tendency towards lower BRS compared to Co (T1DM: 10.3+/-4.4 vs. Co: 14.6+/-7.1 ms/mm Hg; p=0.06). The ROC for Fz showed the highest sensitivity and specificity (71.4 % and 71.4 %) in comparison with BRS (64.3 % and 71.4 %) or f(cs) (64.3 % and 64.3 %). The presented method of evaluation of BRS and f(cs) forming an integrated factor Fz could provide further improvement in the risk stratification of diabetic patients.

Association of eNOS gene polymorphisms T-786C and G894T with blood pressure variability in man.

The aim of this study was to evaluate the association of single nucleotide polymorphisms (SNPs) T-786C and G894T in the gene encoding eNOS with blood pressure variability (BPV) in man. Blood pressure was recorded beat-to-beat at rest three times in periods of one week (5 min, Finapres, breathing at 0.33 Hz) in 152 subjects (19-24 years). Systolic (SBPV(0.1r)/SBPV(0.1a)) and diastolic (DBPV(0.1r)/DBPV(0.1a)) blood pressure variabilities in relative (r.u.) and absolute (mm Hg(2)/Hz) units were determined by the spectral method as spectral power at the frequency of 0.1 Hz. Genotypes of both polymorphisms were detected using polymerase chain reaction and restriction analysis using enzymes Msp I and Ban II. Significant differences were observed in BPV among genotypes of T-786C SNP (p<0.05; Kruskal-Wallis), and among haplotypes of both SNPs (p<0.05; Kruskal-Wallis) as well. In T-786C SNP, carriers of less frequent allele (CC homozygotes and TC heterozygotes) showed significantly greater SBPV(0.1r) and SBPV(0.1a) compared to TT homozygotes (Mann-Whitney; p<0.05). The G894T variant showed no significant differences, but, both SNPs were in linkage disequilibrium (D'=0.37; p<0.01). Carriers of haplotype CT/CT (CC homozygotes of -786C/T and TT homozygotes of G894T) displayed significantly greater SBPV(0.1r), SBPV(0.1a) and DBPV(0.1a) compared to carriers of other haplotype combinations (Kruskal-Wallis; p=0.015, p=0.048, and p=0.026, respectively). In conclusion, the haplotype formed by less frequent alleles of both eNOS variants was associated with increased systolic and diastolic BPV in this study.

Comparison of baroreflex sensitivity determined by cross-spectral analysis at respiratory and 0.1 Hz frequencies in man.

Non-invasive methods of determination of baroreflex sensitivity (BRS, ms/mmHg) are based on beat-to-beat systolic blood pressure and inter-beat interval recording. Sequential methods and spectral methods at spontaneous breathing include transient superposition of breathing and 0.1 Hz rhythms. Previously, a cross-spectral method of analysis was used, at constant breathing rate using a metronome set at 0.33 Hz, enabling separate determination of BRS at 0.1 Hz (BRS(0.1Hz)) and respiratory rhythms (BRS(0.33Hz)). The aim of the present study was to evaluate the role of breathing in the spectral method of BRS determination with respect to age and hypertension. Such information would be important in evaluation of BRS at pathological conditions associated with extremely low BRS levels. Blood pressure was recorded by Finapres (5 minutes, controlled breathing at 0.33 Hz) in 118 healthy young subjects (YS: mean age 21.0+/-1.3 years), 26 hypertensive patients (HT: mean age 48.6+/-10.3 years) with 26 age-matched controls (CHT: mean age 46.3+/-8.6 years). A comparison of BRS(0.1Hz) and BRS(0.33Hz) was made. Statistically significant correlations were found between BRS(0.1Hz) and BRS(0.33Hz) in all groups: YS: r=0.52, p<0.01, HT: r=0.47, p<0.05, and CHT: r=0.70, p<0.01. The regression equations indicated the existence of a breathing-dependent component unrelated to BRS (YS: BRS(0.33Hz)=2.63+1.14*BRS(0.1Hz); HT: BRS(0.33Hz)=3.19+0.91*BRS(0.1Hz); and CHT: BRS(0.33Hz)=1.88+ +1.01*BRS(0.1Hz); differences between the slopes and the slope of identity line were insignificant). The ratios of BRS(0.1Hz) to BRS(0.33Hz) were significantly lower than 1 (p<0.01) in all groups (YS: 0.876+/-0.419, HT: 0.628+/-0.278, and CHT: 0.782+/-0.260). Thus, BRS evaluated at the breathing rate overestimates the real baroreflex sensitivity. This is more pronounced at low values of BRS, which is more important in patients with pathologic low BRS. For diagnostic purposes we recommend the evaluation of BRS at the frequency of 0.1 Hz using metronome-controlled breathing at a frequency that is substantially higher than 0.1 Hz and is not a multiple of 0.1 Hz to eliminate respiratory baroreflex-non-related influence and resonance effect on heart rate fluctuations.

Reproducibility of blood pressure and inter-beat interval variability in man.

Increased blood pressure variability (BPV) and decreased inter-beat interval (heart rate, respectively) variability (IBIV, HRV respectively) are associated with cardiovascular disorders. The aim of this study was to evaluate the reproducibility of BPV and IBIV (HRV) in young healthy individuals. Blood pressure and inter-beat intervals (instantaneous values of heart rate, respectively) were recorded beat-to-beat at rest (5 min, Finapres, breathing at 0.33 Hz) in 152 subjects (19-24 years) 3 times in periods of one week. Systolic (SBPV(0.1r)/SBPV(0.1a)) and diastolic (DBPV(0.1r)/DBPV(0.1a)) blood pressure variability in relative (r.u.) and absolute (mmHg(2)/Hz) units and inter-beat interval (IBIV(0.1r)/IBIV(0.1a)), or heart rate (HRV(0.1r)/HRV(0.1a)) variability in relative (r.u.) and absolute (ms(2)/Hz, resp. mHz(2)) units were determined by the spectral method as spectral power at the frequency of 0.1 Hz and 0.33 Hz (SBPV(0.33r)/SBPV(0.33a), DBPV(0.33r)/DBPV(0.33a), IBIV(0.33r)/IBIV(0.33a), HRV(0.33r)/HRV(0.33a)). All indices of BPV and IBIV (resp. HRV) revealed a lower intraindividual than interindividual variability (ANOVA; p<0.001). The mean values of all indices in each subject significantly correlated with distribution of individual values in the same subject (Pearson's correlation coefficient; p<0.001). Blood pressure and inter-beat interval (heart rate) variability is an individual characteristic feature.

Radiofrequency ablation in treatment of atrial fibrillation.

Beside heart failure and metabolic syndrome, atrial fibrillation is termed the cardiovascular epidemic of the twenty-first century. Its increased morbidity and mortality is alarming. The present, most effective therapy of atrial fibrillation is catheter ablation. Successful ablation of atrial fibrillation prevents the occurrence and progression of electrical, structural and mechanic myocardium remodelling, improves function of the left ventricle, and prevents the risk of thrombembolism. Onset of sinus rhythm activates the reversal remodelling leading to wall reconstruction and atrium reduction. The paper reviews the technique and presents own experience with catheter ablation.

Logit and fuzzy models in data analysis: estimation of risk in cardiac patients.

The aim of this study was a comparison of risk stratification for death in patients after myocardial infarction (MI) and of risk stratification for malignant arrhythmias in patients with implantable cardioverter-defibrillator (ICD). The individual risk factors and more complex approaches were used, which take into account that a borderline between a risky and non-risky value of each predictor is not clear-cut (fuzzification of a critical value) and that individual risk factors have different weight (area under receiver operating curve - AUC or Sommers' D - Dxy). The risk factors were baroreflex sensitivity, ejection fraction and the number of ventricular premature complexes/hour on Holter monitoring. Those factors were evaluated separately and they were involved into logit model and fuzzy models (Fuzzy, Fuzzy-AUC, and Fuzzy-Dxy). Two groups of patients were examined: a) 308 patients 7-21 days after MI (23 patients died within period of 24 month); b) 53 patients with left ventricular dysfunction examined before implantation of ICD (7 patients with malignant arrhythmia and electric discharge within 11 month after implantation). Our results obtained in MI patients demonstrated that the application of logit and fuzzy models was superior over the risk stratification based on algorithm where the decision making is dependent on one parameter. In patients with implanted defibrillator only logit method yielded statistically significant result, but its reliability was doubtful because all other tests were statistically insignificant. We recommend evaluating the data not only by tests based on logit model but also by tests based on fuzzy models.

Anthracycline therapy and 24-hour blood-pressure profile in long-term survivors of childhood cancer.

In our previous studies, a decreased blood pressure was reported in children treated by anthracycline (AC). The aim of this study was to assess the long-term effects of AC anticancer therapy in 45 subjects aged 13-22 years by repeated 24-hour Holter monitoring of blood pressure. Sixty four aged-matched subjects served as controls. The differences between mean values of systolic (SBP) and diastolic blood pressure (DBP) in each hour of both groups were evaluated by Mann-Whitney test. Also the parameters of the least-squares fit of the sinusoidal curve in each subject were estimated (M - mesor, midline-estimating, a mean value of sinusoidal curve corresponds to 24-hours mean pressure; A - amplitude, double amplitude corresponds to night-day difference; Acr - acrophase is a time of maximal value of a sinusoidal curve). SBP and DBP was significantly lower only during night hours in anthracycline patients 19-22 years old. Also M was lower in this age subgroup of patients comparing to age matched controls (SBP: 112+/-6 mm Hg versus 117+/-7 mm Hg, p<0.05; DBP: 67+/-3 mm Hg versus 69+/-6 mm Hg, p<0.05), A was not different, Acr in patients was shifted one hour earlier (SBP: 2.4 p.m. versus 3.6 p.m., p<0.05; DBP: 2.1 p.m. versus 3.3 p.m., p<0.01). This corresponds to the shift of the morning blood-pressure increase seen on 24-hours blood pressure profiles. M correlated with age in controls (SBP: r=0.374, p<0.01; regression coefficient b=1.34 mm Hg/1 year; DBP: r=0.365, p<0.01; b=0.95 mm Hg/1 year), but not in patients (SBP: r=0.182, DBP: r=0.064). A and Acr were age-independent in all subjects. It is concluded that blood pressure in 19-22 years old AC patients is lower during night hours, the age-dependent increase of blood pressure seen in healthy controls between 13 and 22 years of age does not occur in patients. This finding is consistent with the long-lasting impairment of the sympathetic nervous system caused by anthracyclines.

[The progress of autonomic parameters in patients after myocardial infarction with ST elevation]. / Vývoj autonomních parametru u pacientu po infarktu myokardu s ST elevacemi.

The patients after myocardial infarction with ST elevation (STEMI) are endangered by the development inception of autonomic dysfunction, decreased baroreflex sensitivity, decreased heart rate variability, and increased blood pressure variability as a result of increased sympathetic activity and/or decreased parasympathetic activity. Thanks to direct angioplasty and optimal pharmacotherapy of coronary artery disease and heart failure, we didn't found any significant changes of these parameters within a one-year follow-up, and mortality due to cardiac etiology was very low in this group. Autonomic dysfunction and negative left ventricular remodeling is related only to a small group of patients after STEMI, whose risk stratification will be difficult.

Association of A1166C polymorphism in AT(1) receptor gene with baroreflex sensitivity.

The aim of this study was to evaluate the association of A1166C polymorphism in angiotensin II type 1 receptor (AT(1)R) gene with baroreflex sensitivity (BRS in ms/mm Hg; BRSf in mHz/mm Hg) in man. BRS and BRSf were determined by a spectral method in 135 subjects (19-26 years) at a frequency of 0.1 Hz. Genotypes were detected by means of polymerase chain reaction and restriction analysis using enzyme DdeI. We compared BRS and BRSf among genotypes of this polymorphism. The frequency of genotypes of AT(1)R A1166C polymorphism was: 45.9 % (AA, n=62), 45.9 % (AC, n=62), 8.2 % (CC, n=11). Differences in BRS (p<0.05) and BRSf (p<0.01) among genotypes of this single nucleotide polymorphism were found (Kruskal-Wallis: BRS - AA: 7.9+/-3.3, AC: 8.6+/-3.6, CC: 5.9+/-2.3 ms/mm Hg; BRSf - AA: 12.0+/-4.0, AC: 12.0+/-5.0, CC: 8.0+/-3.0 mHz/mm Hg). Compared to carriers of other genotypes (AA+AC) the homozygotes with the less frequent allele (CC) showed significantly lower BRSf (Mann-Whitney: BRSf - AA+AC: 12.0+/-4.0, CC: 8.0+/-3.0 mHz/mm Hg; p<0.01) and borderline lower BRS (BRS - AA+AC: 8.2+/-3.5, CC: 5.9+/-2.5 ms/mm Hg; p=0.07). We found a significant association of A1166C polymorphism in AT(1) receptor gene with baroreflex sensitivity. Homozygosity for the less frequent allele was associated with decreased baroreflex sensitivity.

Baroreflex sensitivity and essential hypertension in adolescents.

It has been known for many years that baroreflex sensitivity is lowered in hypertensive patients. There are several known factors implicating this association, e.g. high blood pressure leads to remodeling of the carotid arterial wall, to its stiffness and to a diminished activation of baroreceptors; leptin released from a fatty tissue activates the sympathetic nervous system etc. On the other hand, low baroreflex sensitivity (BRS, usually quantified in ms/mmHg) can be inborn. Studies on primary hypertension in children and adolescents have brought new information about the role of baroreflex in the development of an early stage of primary hypertension. BRS lower than 3.9 ms/mmHg was found in 5 % of healthy subjects. This value approaches the critical value for the risk of sudden cardiac death in patients after myocardial infarction and corresponds to the value present in hypertensive patients. A decreased BRS and BRSf (baroreflex sensitivity expressed in mHz/mmHg, index independent of the mean cardiac interval), was found not only in children with hypertension, but also in those with white-coat hypertension. This is in accordance with a single interpretation. The decrease of BRS/BRSf precedes a pathological blood pressure increase. The contribution of obesity and BRS/BRSf to the development of hypertension in adolescents was also compared. Both factors reach a sensitivity and a specificity between 60 % and 65 %, but there is no correlation between the values of the body mass index and BRS either in the group of hypertensive patients or in healthy controls. If a receiver operating curve (sensitivity versus specificity) is plotted for both values together using logistic regression analysis, a sensitivity higher than 70 % and a specificity over 80 % are reached. This means that low baroreflex sensitivity is an independent risk factor for the development of primary hypertension. Studies demonstrate that adolescents with increased blood pressure and with BRS under 7 ms/mmHg should be given care and intensively motivated to change their lifestyle including a change in diet and increase in physical activity.

Overweight and decreased baroreflex sensitivity as independent risk factors for hypertension in children, adolescents, and young adults.

We studied the relationship between blood pressure (BP), body mass index (BMI, kg/m(2)) and baroreflex sensitivity (BRS, ms/mmHg) in adolescents. We examined 34 subjects aged 16.2+/-2.4 years who had repeatedly high causal BP (H) and 52 controls (C) aged 16.4+/-2.2 years. Forty-four C and 22 H were of normal weight (BMI between 19-23.9), and 8 C and 12 H were overweight (BMI between 24-30). Systolic BP was recorded beat-to-beat for 5 min (Finapres, controlled breathing 0.33 Hz). BRS was determined by the cross-spectral method. The predicting power of BMI and BRS for hypertension was evaluated by sensitivity, specificity, and receiver operating curve (ROC - plot of sensitivity versus specificity). H compared with C had lower BRS (p<0.01) and higher BMI (p<0.05). Multiple logistic regression analysis (p<0.001) revealed that a decreased BRS (p<0.05) and an increased BMI (p<0.01) were independently associated with an increased risk of hypertension. No correlation between BMI and BRS was found either in H or in C. Following optimal critical values by ROC, the sensitivity, specificity and area under ROC were determined for: BMI - 22.2 kg/m(2), 61.8 %, 69.2 %, 66.0 %; BRS - 7.1 ms/mmHg, 67.7 %, 69.2 %, 70.0 %; BMI and BRS - 0.439 a.u., 73.5 %, 82.7 %, and 77.3 %. Decreased BRS and overweight were found to be independent risk factors for hypertension.

Arterial blood pressure and baroreflex sensitivity 1-18 years after completing anthracycline therapy.

UNLABELLED: The analysis of short-term blood pressure regulation in children, adolescents and young adults 1 to 18 years after the treatment with anthracyclines known to have cardiotoxic side effects for oncological diseases was the aim of the present study. Thirty-one subjects treated with anthracyclines (PA) and 11 subjects treated with different antitumour drugs (P0) were investigated twice (the interval between two investigations 1-9 years). Three hundred and thirty-nine healthy subjects served as controls (C). Systolic (SBP), diastolic blood pressures (DBP) in the finger arteries and inter-beat interval (IBI) were recorded beat-to-beat (FINAPRES, Ohmeda, metronome controlled breathing, 5 minute recording); the values were corrected by auscultatory blood pressure measurements. Baroreflex sensitivity (BRS, ms/mmHg) was determined by a spectral method. As the investigated subjects were of different ages, the measured values were standardised on the age of 16 years by linear regression, and only standardised values (IBI16, SBP16, DBP16 and BRS16) were further analysed. No differences were found between PA, P0 and C in BRS16 and IBI16. SBP16 and DBP16 were significantly lower in PA (102.1+/-8.3/59.7+/-7.1 versus C: 114.1+/-12.4/69.0+/-9.5 mmHg; p<0.001/p<0.001; mean from two investigations). SBP16 but not DBP16 was also lower in P0 (102.7+/-12.6/64.5+/-9.7 mmHg; p<0.01/no significant) than in C. The correlation coefficient between SBP16 and period after treatment in PA was -0.11 (no significant) and -0.06 in DBP16 (no significant). Thus, there is not seen a trend to normalisation. CONCLUSION: The anthracycline antitumour therapy in children decreases blood pressure and within 18 years after the treatment there is not observed a trend toward normal values. BRS was not influenced by the anthracycline therapy.

Baroreflex sensitivity in children, adolescents, and young adults with essential and white-coat hypertension.

UNLABELLED: Hypertension, which is a common cardiovascular disease in adults, could originate in childhood. The aim of the study was to show differences in baroreflex sensitivity and short-term blood-pressure variability between healthy and hypertensive children, adolescents and young adults, and those with white-coat effect with respect to obesity. We examined 54 subjects (11-21 years) who had repeatedly high causal blood pressure. Basing on 24-hour blood pressure monitoring, the subjects were divided into groups: 24 subjects with hypertension (Hy) and 30 subjects with white-coat effect (WhC). Hy and WhC subjects were compared with age-matched healthy controls in a ratio of 1 : 2 for both groups: 48 controls for hypertensive subjects (CoHy) and 60 for subjects with white-coat effect (CoWhC). Totally, 162 subjects were studied. Systolic blood pressure (SBP) and inter-beat intervals (IBI) were recorded in all subjects for 5 min (Finapres, metronome controlled breathing at a frequency of 0.33 Hz). The power spectra of SBP and IBI were calculated. Indices of baroreflex sensitivity (BRS [ms/mmHg] and BRSf [mHz/mmHg]) were determined by the cross-spectral method. The SBP variability was determined as SBP spectral power in the range of 10-second rhythm (SBP (0.1Hz)). The body mass index (BMI) was significantly higher in both Hy and WhC compared with their controls (Hy vs. CoHy; WhC vs. CoWhC: 24.6 +/- 6.0 kg/m (2) vs. 20.4 +/- 2.8 kg/m (2), p < 0.001; 23.2 +/- 5.9 kg/m (2) vs. 20.3 +/- 2.6 kg/m (2), p < 0.05). BRS was significantly decreased in both groups (Hy vs. CoHy; WhC vs. CoWhC: 6.0 +/- 2.7 ms/mmHg vs. 9.5 +/- 3.9 ms/mmHg, p < 0.001; 7.2 +/- 3.1 ms/mmHg vs. 10.9 +/- 6.2 ms/mmHg, p < 0.01), and BRSf as well (Hy vs. CoHy; WhC vs. CoWhC: 10.8 +/- 4.6 mHz/mmHg vs. 16.2 +/- 6.1 mHz/mmHg, p < 0.001; 13.0 +/- 4.9 mHz/mmHg vs. 18.3 +/- 8.7 mHz/mmHg, p < 0.01). The decrease of baroreflex sensitivity was linked with the increase in the variability of SBP (0.1Hz), which was significant in hypertensives only (Hy vs. CoHy; WhC vs. CoWhC: 142 +/- 96 mmHg (2)/Hz vs. 94 +/- 83 mmHg (2)/Hz, p < 0.01; 121 +/- 131 mmHg (2)/Hz vs. 107 +/- 98 mmHg (2)/Hz). CONCLUSION: The mild increase of BMI was associated with white-coat effect and a BRS and BRSf decrease. The greater increase of BMI was associated with hypertension and a deeper BRS and BRSf decrease. This greater decrease of BRS and BRSf in hypertensives was linked with the increased SBP-variability.

Baroreflex sensitivity as an individual characteristic feature.

The reproducibility of baroreflex sensitivity (BRS in ms/mmHg; BRSf in mHz/mmHg) determined with respect to the coherence between the variability in systolic blood pressure (SBP) and inter-beat intervals (IBI) or heart rate (HR) was tested. SBP and IBI were recorded beat-to-beat for 5 min (Finapres, breathing at 0.33 Hz) in 116 subjects (aged 19-24 years) sitting at rest three times in periods of one week. BRS and BRSf was determined by a cross-spectral method in a frequency range of 0.067-0.133 Hz. Eight indices were evaluated: BRS(0.1 Hz) /BRSf(0.1 Hz) - the value at a frequency of 0.1 Hz; BRS(COHmax)/BRSf(COHmax) - the value at maximum coherence; BRS(Wcoh)/BRSf - weighted value with respect to coherence values in the whole frequency range; BRS(WPcoh)/BRS(WPcoh) - weighted value with respect to coherence for frequencies with coherence above 0.5. All indices revealed a lower intraindividual than interindividual variability (p<0.001). The individual mean values of BRS or BRSf correlated (p<0.001) with standard deviation of their individual values for all indices. Baroreflex sensitivity is an individual characteristic feature with the highest reproducibility at its low values in spite of its resting variation. Reproducibility is not influenced by modification of the spectral method used.

Age-dependent relationship between the carotid intima-media thickness, baroreflex sensitivity, and the inter-beat interval in normotensive and hypertensive subjects.

The interrelationship between baroreflex sensitivity expressed in ms/mm Hg (BRS) or in Hz/mm Hg (BRSf), carotid wall thickness (IMT), and age was investigated in hypertensive and normotensive subjects with respect to the mean inter-beat interval (IBI) and blood pressure (BP). BP monitoring was performed in 25 treated hypertensives (Hy; 47.4+/-9.2 years of age) and 23 normotensives (Norm; 44.5+/-8.1 years). IMT was measured by ultrasonography. BRS and BRSf were determined by the spectral method (five-minute non-invasive beat-to-beat recording of BP and IBI, Finapres, controlled breathing at a frequency of 0.33 Hz). Significant differences between Hy and Norm were detected in IMT (Hy: 0.624+/-0.183, Norm: 0.522+/-0.070 mm; p<0.01), BRS (Hy: 3.5+/-1.6, Norm: 5.7+/-2.3 ms/mm Hg; p<0.01), BRSf (Hy: 0.005+/-0.002, Norm: 0.009+/-0.004 Hz/mm Hg; p<0.01), systolic BP (Hy: 131+/-21, Norm: 116+/-17 mm Hg; p<0.01) and diastolic BP (Hy: 77+/-16, Norm: 64+/-12 mm Hg; p<0.01). A significant correlation was found between age and IMT (Norm: 0.523, p<0.05; Hy+Norm: 0.419, p<0.01), age and BRS (Norm: -0.596, p< 0.01; Hy+Norm: -0.496, p<0.01), age and BRSf (Norm: -0.555, p<0.01; Hy: -0.540, p <0.01; Hy+Norm: -0.627, p<0.01), age and IBI (Hy: 0.478, p<0.05), age and diastolic BP (Hy: -0.454, p<0.05), BRS and IMT (Hy+Norm: -0.327, p<0.05) and BRSf and IMT (Hy+Norm: -0.358, p<0.05). Hypertensive patients have increased IMT and decreased BRS and BRSf. The positive correlation between age and IMT and the negative correlation between age and BRS and BRSf are in agreement with the hypothesis that the age-dependent decrease of baroreflex sensitivity corresponds to the age-related structural changes of the carotid wall. Using two indices of baroreflex sensitivity, BRS and BRSf, we could show that baroreflex sensitivity in hypertensives is lower not only due to thickening of the carotid wall, but also due to aging.