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Enalapril and Heart Rate Variability in Patients with Arterial Hypertension

Kamenskaya Elina; Stepanov Andrey

Central Clinical Hospital 5, Cardiology Department
Kharkov, Ukraine

Abstract
Introduction
Objectives
Material and Methods
Results
Discussion
Conclusions
References

Abstract
Introduction: Arterial hypertension (AH) is one of the risk factor of cardiovascular mortality. The treatment by ACE inhibitor enalapril maleat (EM) can decrease mortality, and this effect can be observed by method of heart rate variability (HRV).
Objectives: The aim of this study was to investigate the HRV for patients with hypertension treated by EM.
Material and Method: In this research participated 12 males and 12 females in first group 10 in age from 29 to 50 and in second 14 in age from 50 to 73 with essential AH stage II-III. 10 healthy volunteers were conceded as a control group. The patients with diabetes mellitus and symptomatic AH were excluded. The patients were treated by EM 20 mg and 125 mg of aspirin daily. HRV measurement using the standard method of 5 minute ECG duration before and after 3 weeks of treatment.
Results: After 3 weeks of treatment:cuad1i.gif (3232 bytes)

Discussion:The results of such therapy seemed to be better in elder age and in high level of BP. It was marked dependence of indexes of HRV and decreasing of level of BP.
Conclusion: Like so, therapy by EM is not only lowering the BP, but also improve the vegetative heart regulation and maybe lowering the risk of sudden cardiac death. It is possible that for further evaluation of changes it need longer time of investigation.

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Introduction:

Arterial hypertension (AH) is one of the risk factor of cardiovascular mortality. Angiotensin converting enzime (ACE) inhibitors effective in reducing mortality after myocardial infarction and probably exert an useful action on sympathovagal balance [2]. It was proven that treatment by ACE inhibitor have positive results in hypertensive patient [1]. ACE inhibitor enalapril maleat (EM) is well known antihypertensive medicine that have a different influences on body’s systems, and some effects can be observed by method of heart rate variability (HRV). HRV as the one of potential prognostic value of markers of autonomic activity has gained progressive popularity and it useful in patient with AH too [3, 4, 11]. The changes in ANS have a high relation with cardiac function and mortality [5, 6, 7, 9, 11]. Now HRV is a proven tool for examining the ANS [8].

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Objectives:

The aim of this study was to investigate the HRV for patients with hypertension treated by EM and to observe changes in HRV in different ages.

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Material and Methods:

In this research participated 12 males and 12 females in first group (I) 10 in age from 29 to 50 and in second (II) 14 in age from 50 to 73 with essential AH stage I - III. The 10 healthy volunteers were conceded as a control group. The patients with diabetes mellitus and symptomatic AH were excluded. The patients received EM 20 mg and 125 mg of aspirin daily. HRV was calculated in general agreement with the standards of measurement proposed by Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology [10]. The HRV was recorded using computer based electrocardiograph system "Cardiolab 2000" before and after 3 weeks of treatment. Noninvasive blood pressure systolic (BPs) ad diastolic (BPd) before and after 3 weeks of treatment was measured.
The HRV and BP were measured in the same time of the day after 5 minutes rest in supine position with free breathing. Patients was deprived of coffee, alcohol, smoking and medications can influencing on HRV as a minimum of 12 hour before the measurement. HRV was analyzed on 5-minute period of stable ECG recording for the frequency domain measures with the use of fast Fourier transform. We measured the total power (TP) of the R – R interval (0 – 0.5 Hz). The frequency ranges were subdivided into 0.03 – 0.15 Hz as a low frequency component (LF) and 0.15 – 0.5 Hz as a high frequency (HF) one. TP, LF, HF was expressed in absolute values (ms2). We measured also the LF/HF ratio as an index of sympathovagal balance [1]. The results are given as mean ± standard deviation (SD). A p-value <0.05 was considered significant.

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Results:

Table 1 shows the mean values and SD of HRV measurement and BP in the study groups before after 3 weeks of treatment. There were no significant changes in the control group. After treatment we observed significant decrease of BPs by 60% and 56% in I and II groups respectively, changes of BPd was similar in both groups and it was decreased approximately by 64%. TP increased in in both groups, in I group by 160% and in II group by 60%. LF increased in I grope by 123% in II grope increasing was not significant. HF increased in I grope by 153% in II grope increased by 48%. LF/HF ratio changes in I grope was not significant, but in II grope ratio decreased by 75%.

Table 1. Values of HRV and Blood Pressure before and after 3 weeks of treatment by EM
Expressed in mean ± SD.

table1.gif (4164 bytes)
I – patient under 50 age before and after (I a) 3 weeks of treatment by EM;
II – patient over 50 age before and after (II a) 3 weeks of treatment by EM;
* The values not significant

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Discussion:

As confirmed by other investigator, we found HRV to be reduced in patient with AH and balance of ANS was moved to sympathetic activity. The treatment was successful in both groups and BP decreased till normal values.
In I group increasing of total variability markedly depended of increasing in all spectral components – LF and HF. In result LH/HF ratio in I group not changed reliable. These results we can explain as predominance of sympathetic nervous system in younger persons. In II group the percentage of HF power spectral density was significant increased opposite not significant changes in LF and LF/HF decreased by 75%. The results of such therapy seemed to be better in elder age and in high level of BP. It was marked dependence of values of HRV and decreasing of level of BP. In the light of changes of ANS that more better in prognosis in treatment of AH and preventing of cardiac events monotherapy of EM possible in elderly ages, but not enough in young patient.

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Conclusions:

Like so, therapy by EM is not only lowering the BP, but also improve the vegetative heart regulation and maybe lowering the risk of sudden cardiac death. Treatment of AH by EM in patients under 50 age it will be better to combine with other medicine that have positive influence on ANS. It is possible that for further evaluation of changes it need longer time of investigation.

Acknowledgement
The authors wish to thanks the Callahan’s and Ockunzzi’s family, Cleveland, Ohio, USA for assistance.

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References

1. The six report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of high blood pressure. Archives of Internal Medicine.-1997. - Vol. 157. - ?. 2413-2446.
2. Bonaduce D, Petretta M, Morgano G et al. Effects of converting enzyme inhibition on baroreflex sensitivity in patient with myocardial infarction. J Am Coll Cardiol 20:587-93.
3. Maria Vittoria Pitzalis, Filippo Mastropasqua, et al. Assesment of cardiac vagal activity in patient with hyperthyroidism. International Journal of Cardiology 64 (1998) 145-151.
4. Simonetta Scavini, Maurizio Volterrani, Emanuela Zanelli et al. International Journal of Cardiology 67 (1998) 9-17.
5. Amara, C.E. and Wolfe, L.A. Reliability of Noninvasive Methods to Measure Cardiac Autonomic Function. Can. J. Appl. Physiol. 23(4):396-408.1998.
6. P. J. Schwartz. The autonomic nervous system and sudden death. European Heart Journal (1998) 19, (Supplement F), F72-F80.
7. Nolan, James MD; Batin, Phillip D. MD; Andrews, Richard MRCP et al. Prospective Study of Heart Rate Variability and Mortality in Chronic Heart Failure: Results of the United Kingdom Heart Failure Evaluation and Assesment of Risk Trial (UK-Heart). Circulation, Vol. 98(15). October 13, 1998. 1510-1516.
8. Singh, Jagmeet P. MD, Dphil; Larson, Martin G. ScD; O’Donnell, Christopher J. MD, MPH et al. Circulation, Vol. 99(17). May 4, 1999.2251-2254.
9. Ad. Van Boven, MD, J. Wouter Jukema, MD, Jaap Haaksma, BSc. Depressed heart rate variability is associated with events in patients with stable coronary artery disease and preservsd left ventricular function. American heart Journal Vol. 135, Number 4, 571-575.
10. Task Force of the European Sosiety of Cardiology and the North American Sosiety of Pacing and Electrophysiology. Heart Rate Variability. Standards of Measurements, physiological interpretation, and clinical use. Circulation. - 1996. -V. 93.1043-1065.
11. Franco Rabbia, Gianpiero Martini et al. Assessment of Heart Rate Variability after Calcium Antagonist and Beta-Blocker Therapy in Patients with Essential Hypertension. Clin Drug Invest 17(2):111-118, 1999.

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Questions, contributions and commentaries to the Authors: send an e-mail message (up to 15 lines, without attachments) to hbp-pcvc@pcvc.sminter.com.ar , written either in English, Spanish, or Portuguese.

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