DYNAMICS OF HEART RATE AND BLOOD PRESSURE IN HYPERTENSIVE PATIENTS
Received for publication: 10th of February, 2013
Revised: 15th of April, 2013
SUMMARY: (Hide the summary)
Hipertensiunea arterială reprezintă o condiție clinică importantă care la nivel mondial afectează populația adultă și contribuie în mod semnificativ la creșterea morbidității și mortalității prin accident vascular cerebral , insuficiență cardiacă , boală coronariană și insuficiență renală. Deși patogeneza hipertensiunii arteriale este neclară, disautonomia sistemului nervos autonom a fost implicată în etiopatogenia sa . Variabilitatea frecvenței cardiace ( VFC ), s-a dezvoltat ca o metodă complexă însă des utilizată și implementată în majoritatea echipamentelor de monitorizare Holter ECG , cu scopul de a evalua imbalanța tonusului autonom și implicațiile clinice, respectiv de a stabili riscul de moarte subită. Scopul studiului a fost de a demonstra complexitatea modulării frecvenței cardiace în hipertensiunea arterială și de a analiza comportamentul intervalelor RR prin prisma dinamicii frecvenței cardiace la pacienții hipertensivi. Pacienți hipertensivi incluși în acest studiu au fost monitorizați 24 ore folosind un sistem combinat de monitorizare ECG și a tensiunii arteriale. Semnalele ECG și determinările tensiunii arteriale au fost înregistrate și analizate. Cel mai important aspect al acestui studiu este faptul că și în prezența stadiilor incipiente ale hipertensiunii arteriale, mecanismele de reglare a tonusului autonom sunt detectabile prin metode neinvazive și sunt implicate atât în evoluția cât și în prognosticul acestor pacienți.
Hypertension, heart rate variability, nonlinear analysis, circadian rhythm
Hypertension represents an important condition that affects the adult population worldwide; it contributes significantly to morbidity and mortality from stroke, heart failure, coronary heart disease and renal failure (1). There are a lot of studies and data that suggest that the autonomic nervous system plays an important role in blood pressure regulation and in the development of hypertension (3). Early identification of individuals prone to hypertension, may allow for early interference such as: lifestyle modifications, regular exercise and weight loss, targeted at reducing the risk factors for hypertension, and reducing sympathetic nervous system activation (2).
Abnormalities of autonomic nervous system function (ANS) exist in patients with hypertension and have been considered as one of the important factors in developing of essential hypertension. Lower HRV was associated with greater risk for developing hypertension (4).
The sympatho-vagal balance is altered in the resting conditions of numerous pathophysiological processes. It is the case of essential arterial hypertension (Guzzetti et al. 1988), even in the presence of arterial pressure values still in the high normal range (Lucini et al. 2002).The ability of decreased heart rate variability to predict incident hypertension has not been well studied, and there are no studies of whether hypertension leads to changes in heart rate variability (5).
Although the pathogenesis of most hypertension is unclear, imbalance of the autonomic nervous system has been implicated in its development. Heart rate variability (HRV) has emerged as a practical, noninvasive tool to quantitatively investigate cardiac autonomic imbalance in hypertension. Studies have reported decreased HRV among hypertensive patients and that the relation between blood pressure and HRV is present across a wide range of pathologies (1, 5).
The aim of our study was to highlight the complex heart rate modulation in hypertension and to analyze the behavior of RR intervals dynamics compared to normotensives subjects.
The study was performed at the Cardiology Clinic of the Emergency County Hospital Timis, University of Medicine and Pharmacy "V. Babes "Timisoara, starting from a former study performed by one of the authors at the Riga Eastern Clinical University Hospital, Latvia. The study group ( n: 47, men: 23, women: 24, mean age: 54.2 yrs) has included hypertensive patients with stage II and III of essential hypertension. A control group of twenty normotensive subjects (men: 11, women: 9, mean age: 46.7 yrs) was selected to compare the clinical data and autonomic tone parameters. ECG signal analysis and blood pressure measurements have been done using a EC-3H/ABP Combined Holter System, Labtech Ltd. The system performs simultaneously recording of the ECG signal and measurements of the blood pressure.
Twenty four hours of combined ECG and blood pressure monitoring has been performed and more than 90 % of the signals and measurements are eligible for the study. Artefacts and noise was manually removed from the signals.
All ECG analysed signals are in sinus rhythm and analysis of heart rate variability was performed in time domain, mean RR intervals (ms.), standard deviation of all RR intervals ms) and frequency domain, very low frequency (VLF, 0.01-0.04 Hz), low frequency (LF, 0.05 -0.15 Hz) and high frequency (HF, 0.15-0.50 Hz), LF/HF ratio. Kubios v. 2.1, Finland (http://kubios.uku.fi/) was used for the measurement of the nonlinear parameters of the RR series. Approximate Sample entropy, detrended fluctuation analysis, and Poincare plots, have been used for the study of the behavior of the heart rate dynamics in both groups.
During blood pressure monitoring we have checked also the circadian changes in blood pressure. Trends of heart rate (b/min) and blood pressure (mmHg) have been recorded for both groups (fig. 1).
Left ventricular ejection fraction (LVEF, %) has been measured echocardiographic by an independent member of the team.
For more accurate results we have selected a subgroup of 18 hypertensive patients (men: 8, women: 10, mean age: 60.5 yrs), characterized by ischemic and or arrhythmic events in the clinical history. Heart failure and altered left ventricular ejection fraction are the main clinical features of these patients.
For the statistical analysis we have used Graph Pad Prism. All numeric variables were expressed as mean and the statistical analysis was performed using Student's t-test and correlation analysis by Pearson method. A p value < 0.05 was considered statistically significant.
Table 1. Main clinical characteristics of the study and the control group
Table 2. Main clinical differences in the hypertensive group. Blood pressure is in a similar range independently from gender.
RESULTS AND DISCUSSIONS
In the hypertensive group the gender distribution is almost equal, suggesting a higher incidence of essential hypertension in the women population and probably that the men are much earlier hypertensive than women. In the study group, women had mean age: 57 yrs. compared to men mean age: 50.4 yrs. (p< 0.005).
Differences have been noticed also in relation to the mean heart rate. Women are more tachycardic than the men hypertensive population (mean heart rate: 87 b/min vs. 80 b/min), but the differences are not statistically significant. Considering only the gender aspects, in the hypertensive group, the left ventricular ejection fraction (LVEF %) seems to be preserved, LVEF: 60 %, mean LVEF in the men population: 58 % compared to the women mean value: 61 %. In the hypertensive group, those with events have a lower left ventricular ejection compared with the events free hypertensive population (LVEF: 48 % vs. 68 %, p< 0.005). All the clinical data are resumed in table 1.
The gender differences in the hypertensive patients group are highlighted in the table 2.
Analyzing the hypertensive group, we noticed differences between the dynamics of heart rate and systolic blood pressure as a measure of the circadian rhythm. The difference between day/night heart rate and blood pressure is considered a useful parameter of the influence of the circadian rhythm (table 3).
During the study we have not observed significant differences between the absolute values of the systolic blood pressure inside the hypertensive group. Despite this fact some parameters like the difference between day and night mean heart rate can suggest important modulations of the tone autonomic tone in hypertension.
More of this, HR (b/min) and SBP (mmHg), the later as expression of the day-night differences in systolic blood pressure, seems to correlate (figure 2).
The recordings obtained from the EC-3H/ABP Combined Holter System, Labtech Ltd, are resumed in figure 1.
Table 3. The influence of arrhythmic events and heart failure in the hypertensive group.
Figure 1. The complexity of the heart rate and blood pressure relationship.
The correlation between DHR (b/min) and DSBP (mmHg) like in figure 2, opens the opportunity to analyze the influence of the autonomic tone in the modulation of heart rate and blood pressure in the hypertensive population.
The role of the autonomic tone in essential hypertension is assessed using linear and nonlinear parameters. Heart rate variability and nonlinear dynamic parameters like entropy and detrended fractal analysis was applied to the ECG signals obtained from hypertensive patients. As aspect essential hypertension is characterized by alteration of the autonomic tone, and probably those alterations are responsible for the arrhythmic events in relation with the worsening of the performance of the left ventricle. Hypertensive patients are characterized by a higher sympathetic activity responsible for the poor outcome of these patients. All analyzed parameters are altered in the hypertensive patients group. The degree of this disautonomia is related to the degree of the impairment of the left ventricle and the presence of co morbidities (table 4).
Paradoxically the autonomic imbalance seems not to be very evident in hypertensive patients. This was the reason to select a subgroup of patients, considered by the authors of the study, to be vulnerable hypertensive patients.
From this perspective we have identified hypertensive patients that could be subjects exposed for ventricular arrhythmic events (table 5). Also discrete differences in the autonomic tone parameters can occur between men and women population.
Even in a limited and selected group of patients it is difficult to identify vulnerable hypertensive patients. It seems adequate to perform nonlinear analysis at hypertensive patients during heart rate variability. Not all parameters will have spectacular changes but approximate entropy (ApEn) and detrended fluctuation analysis parameter (DFA ?1) confirm the capacity to identify risk patients even in apparently stable patients, like in essential hypertension (6, 7). An important aspect regarding the value of these parameters is related to the coexistence of co morbidities.
Figure 2. The correlation ( r: -0.24) between D HR (b/min) and DSBP (mmHg) reflects the influence of the baroreceptors in the modulation of blood pressure and the relationship with the autonomic tone. D HR (b/min), on the horizontal axis and DSBP (mmHg) on the vertical axis.
Table 4. Linear and nonlinear heart rhythm parameters changes in hypertensive patients.
Table 5. The severity of the autonomic imbalance in the high risk hypertensive patient's subgroup.
CONCLUSIONS AND LIMITATIONS
The aim of the study was to offer significant data about the complex mechanisms involved in essential hypertension. The most important aspect of this study is that even in the presence of early stages of essential hypertension, the autonomic tone mechanisms involved in the outcome and prognosis of those patients are detectable by noninvasive methods.
Beside the now consecrated well known heart rate variability parameters, it seems that new parameters like DHR (b/min) and SBP (mmHg) can offer data related to the involvement of the circadian rhythm in hypertension. The study has two major limitations, one is related to the relatively small number of patients included in the study, and the other is that all the patients in the study have been under complete medical treatment.
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