An evidence based study of autonomic dysfunction in children

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* Corresponding author. Chiranjeevi kumar EndukuruDepartment of Physiology, Narayana Medical College, Nellore, AP, India

AN EVIDENCE BASED STUDY OF AUTONOMIC DYSFUNCTION IN CHILDRENWITH A FAMILY HISTORY OF HYPERTENSION

*Chiranjeevi kumar Endukuru, Maruthy K.N. and Sharan B.SinghDepartment of Physiology, Narayana Medical College, Nellore, AP, IndiaARTICLE INFO ABSTRACT

Article History:

Received10th, February, 2015Received in revised form24th,February, 2015 Accepted16th, March,2015 Published online 28th,March,2015

Aim: The aim of the present study was to perform the set of standard autonomic functiontests in children with a family history of hypertension and compare the results withchildren of normotensive parents.Background: Hypertension is considered one of the highest causes of morbidityworldwide and it becomes one of the leading causes of death due to cardiovascular andrenal failure. Hypertension can be especially hard to manage when combined with otherdisorders, such as diabetes or obesity. Most of the children with a family history ofhypertension forms the risk factor for being hypertensive in future life.Results: The study included 60 young and healthy children. Out of them, 30 children wereselected based on their family history of hypertension while the remaining were thechildren of normotensive parents. Thesubjects were selected based on exclusion-inclusioncriteria. All the children underwent for a set of autonomic function tests which are non-invasive, simple and comfortable. Results showed that children with a family history ofhypertension have abnormal values on autonomicfunction testing, when compared withchildren of normotensive parents. The results were obtained using ANOVA and student‘t’–test, to study the significance of autonomic parameters.Conclusion: This study stated that the children with family history of hypertensionexperienced mild to moderate autonomic fluctuations in early age which may make themmore susceptible to hypertension in their future life

Key words:

Hypertension, Autonomic functiontests, Sympathetic activity,Normotension

Copyright © 2015 Chiranjeevi kumar Endukuru et al., This is an open-access article distributed under the terms of the CreativeCommons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided theoriginal work is properly cited.INTRODUCTION

The autonomic nervous system is a part of the peripheralnervous system and plays a central role in maintainingcardiovascular homeostasis. It does this by regulating thestroke volume, heart rate, peripheral resistance and waterretention. Autonomic function testing is designed todetermine the mechanisms involved in the regulation ofblood pressure and heart rate and some otherfunctions. During these tests, heart rate is measured usingan electrocardiogram and blood pressure using a cuff

around your arm. The autonomic nervous system and itssympathetic arm play important roles in the regulation ofblood pressure. Many cardiovascular disease have beenshown to be characterized by a marked increase insympathetic drive to the heart and peripheral vascularresistance which forms the main reason for essentialhypertension and other cardiovascular disorders like heartfailure, circulatory failure etc. This study focuses on thesympathetic nervous system and its pathophysiological rolein the development of hypertension and forms an importanttarget for the therapeutic intervention.

RESEARCH ARTICLE

INTERNATIONAL JOURNAL OF CURRENT MEDICAL AND PHARMACEUTICAL RESEARCH(2015)35–39

Hypertension is the chronic elevation of blood pressure andan important human health problem. The main cause of thedisease remains unknown till now in most of the cases.One of the important causes of primary hypertension isgenetic susceptibility. Parental history of hypertensionhave been regarded as important risk factors ofcardiovascular disorders.Family members share geneticfactors, activities, habits and attitude that can determine thehealth and their risk for disease. When members of afamily pass traits from one generation to another throughgenes, that process is called heredity. Genetic factors likelyto play some role in hypertension, cardiovascular diseasesand other related conditions. However, it is also seems thatpeople with a family history of high blood pressure sharecommon environments and other potential factors thatincrease their risk. The risk for high blood pressure canincrease even more when heredity combines withUnhealthy diet, alcohol consumption and smoking. Variousstudies suggested that the risk of becoming hypertensivefor an individual with a family history of hypertension hasbeen estimated to be up to four times higher than averagethroughout the world.

It was also reported by some studies that the excess activityof the sympathetic nervous system increases blood pressureand contributes to hypertension. In our studies it was foundthat children with a family history of hypertension showedhyperactivity of sympathetic nervous system. It has beenfound that children with a family history of hypertensionpresented some abnormal features like weight gain, raisedblood pressure and increased Blood pressure response tosympathetic function tests like cold pressor and isometrichand grip tests. The present study aims that thedetermination of presence of autonomic dysfunction isusually based on a variety of autonomic function tests.From the current study, we attempted to conduct bothsympathetic and parasympathetic function tests in childrenwith family history of hypertension and children ofnormotensive parents by measuring the blood pressureresponse to standing, blood pressure response to isometrichandgrip, deep breathing test, valsalva ratio and coldpressor test and signifying that an assessment of cardiacautonomic functions may be of prognostic value in suchindividuals.

METHODS

This study was undertaken by me on behalf of Departmentof Physiology, Narayana Medical College. The approval ofMedical ethics committee of Narayana Medical College,Nellore was taken for this “An Evidence based Study ofAutonomic dysfunction in Children with a family historyof Hypertension”. Subjects were physiotherapy, labtechnology, medical and dental students selected fromNarayana medical college aged between 18 – 25 years,who volunteered to take part in the study. The procedurewas explained and written consent was obtained from the

subjects. All the subjects underwent a detailed clinicalexamination before being included in the study as per thestudy protocol. The subject selection was based on thepredetermined exclusion-inclusion criteria.

Sixty healthy volunteers aged between 18–25 years wereparticipated in the present study. The participants weredistributed into two groups. Study group includes childrenwith family history of hypertension and control groupincludes children of normotensive parents. All participantscompleted a questionnaire regarding family history ofhypertension. The family history was taken by having eachparticipant select “yes,” “no,” or “uncertain” in a table ofquestions onthe presence of hypertension in thegrandfather,grandmother, father, mother, siblings, andchildren. Positivefamily history of hypertension wasdefined ashaving at least one member in the groupincluding the father, mother and siblings withhypertension.

INCLUSION AND EXCLUSION CRITERIA

Normotensive children including males and females aged18-25 years with normal body mass index (BMI: 19-25Kg/m2) were included in the present work.All the subjects were thoroughly examined clinically torule out any illness which might impact the autonomicactivity.

No history of Cardiovascular and Respiratory systemdisordersNo history of SmokingNo history of Diabetes mellitusNo history of any acute infectious diseasesNo history of any chronic diseasesNo history of metabolic disorder

Subjects with acute illness, on hypertensive medication andhaving known metabolic disorder were excluded.

Cardiovascular Autonomic function tests were carried outin the morning in the department between 10 AM to 12 Pmafter 2 hours of light breakfast, after intimate testingprocedures with the subjects.

The Autonomic function tests which were performed toassess the cardiovascular sympathetic functional status:

Cold Pressor test (cold pressure test)

Subject was instructed regarding the test. Blood pressurewas recorded under basal conditions. Cold water was takenin a container. Subject was asked to submerge one of hisupper limbs in cold water for 60 seconds. Blood pressurewas recorded at the end of 60 seconds of submersion of thelimb. Submersion of the limb in ice cold water increasessystolic blood pressure by about 10-20 mm of Hg anddiastolic blood pressure by about 10 mm of Hg.


Hand Grip Test

In the hand grip test, there is a rise in heart rate and bloodpressure. The blood pressure rise is due to increasedsympathetic activity and heart rate rise is due to decreasedparasympathetic activity. Subject was made to lie down insemi recumbent position. ECG electrodes were connectedfor lead II recording of ECG and sphygmomanometer forblood pressure measurement. Basal heart rate and bloodpressure were recorded. Subject was asked to maintain apressure of 30% of the maximum activity in the hand gripdynamometer for about 5 minutes. Heart rate and change inSBP, DBP were recorded.

Blood pressure response to standing

Patient is again allowed to assume a supine position, and arecording of blood pressure is done in the supine position.Patient is then asked to stand up and blood pressure isrecorded at 0 and 1 minute intervals. The Autonomicfunction tests which were performed to assess thecardiovascular parasympathetic functional status:

Deep breathing test

This test is used to assess the parasympathetic activity.Subject was instructed to maintain deep breathing at a rateof six breaths per minute and was made to lie downcomfortably in supine position with head elevated to 300.ECG electrodes were connected for recording Lead IIECG. While subject was breathing deeply at a rate of 6breaths per minute (allowing 5 seconds each for inspirationand expiration) maximum and minimum heart rates wererecorded with each respiratory cycle. Expiration toinspiration ratio was determined by using the formula.

Valsalva Manoeuver

The valsalva ratio is a measure of parasympathetic andsympathetic functions. Subject was made to lie down in asemi recumbent or sitting position. Nostrils were closedmanually. Mouth piece was put into the mouth of thesubject and the Mercury manometer was connected to themouth piece. ECG machine was switched on forcontinuous recording. Subject was asked to exhaleforcefully into the mercury manometer and asked tomaintain the expiratory pressure at 40 mm of Hg for 10 –15 seconds. ECG changes were recorded throughout theprocedure, 30 seconds before and after the procedure.Valsalva ratio were calculated by using the formula.

Heart rate response to standing

On changing the posture from supine to standing heart rateincreases immediately by 10-20 beats per minute. Thisresponse is detected by recording ECG in supine andstanding postures. Subject was made to lie down in supineposture. ECG electrodes were connected from the subjectto the cardiowin system. Subject was asked to relaxcompletely for a minimum period of 10 minutes. Basal

heart rate was recorded by using cardiowin system. Subjectwas asked to stand up immediately and change in heart rateis noted from the monitoring screen of cardiowin. Heartrate response to standing was determined by using theformula heart rate in standing position – heart rate insupine position.

RESULTSThe collected data was expressed as Mean ±SD. Theseresults were analyzed by ANOVA with SPSS version 17.0using an unpaired‘t’ test. The results of the above testswere compared between Study group and control group

Table 1: Shows that there were no significant findingsbetween anthropological variables like age and BMI.

Table 2: Shows that the physiological findings like basalheart rate, SBP and DBP values were found to be higher insubjects of study group as compared with control group butthis difference was statistically insignificant (p>0.05).

Table 3: Shows that all the parasympathetic autonomicfunction tests like heart rate response to standing i.e. 30:15ratio, heart rate response to deep breathing i.e. E: I andvalsalva ratios in the children of study group were almostsimilar to control group. These results were statistically notsignificant (p>0.05). It indicates that the parasympatheticreactivity tests are similar in both the groups.

Table 4: shows that all the sympathetic autonomic functiontests like Blood pressure response to standing, Cold pressortest and Hand grip test shows marginally higher values instudy group as compared with the control group. Thesefindings were statistically significant (p< 0.001 and p<0.05). It indicates that hyperactivity of sympatheticnervous system in children of study group.

Table 1 Anthropometric variables

VariablesControl group

(n = 30)Study group

(n = 30) P value

Age (yrs.) 18.96 ± 1.76 20.00 ± 1.68 0.91Height (cm) 164.60 ± 8.26 166.68 ± 6.93 0.07Weight (Kg) 57.16 ± 9.73 57.96 ± 9.11 0.74BMI (Kg/m2 21.54 ± 2.61 21.96 ± 2.2 0.55

Table 2 Physiological Considerations

VariablesControl group

(n = 30)Study group

(n = 30) P value

Basal Heart rate BPM 84.28 ± 4.95 86.11 ± 5.11 0.05Resting SBP (mm of Hg) 115.64 ± 4.92 119.52 ± 6.30 0.06Resting DBP (mm of Hg) 76.64 ± 5.02 81.40 ± 4.69 0.23Resting-RR (breath/min) 13.01 ± 3.26 14.68 ± 4.61 0.74

Table 3 Statistical analysis of Parasympatheticfunction tests in Study group and control group

Variables Control group(n = 30)

Study group(n = 30) P value

Heart rate response tostanding 30:15 Ratio

1.15 ± 0.05 1.17 ± 0.04 0.12

Valsalva ratio 1.25 ± 0.02 1.26 ± 0.04 0.26Heart rate response to

deep breathing E: I Ratio1.25 ± 0.02 1.23 ± 0.05 0.07


Figure 1 Parasympathetic Function tests

Figure 2 Sympathetic Function tests

DISCUSSION

In the present study, we demonstrated that youngchildren with a family history of hypertension haveincreased risk of developing hypertension. Further, theblood pressure (BP) response to hyperactive sympatheticstimuli in young children can predict the futuredevelopment of hypertension. Inour study it was clearthat children with family history of hypertensionexpressed statistically significant exaggeratedcardiovascular and sympathetic reactivity whencompared to children of normotensive parents. In ourstudy it was seen that young normotensives with apositive family history of hypertension had higher bloodpressure and also increased resting heart rate than youngnormotensives with a negative family history ofhypertension. This increased blood pressure and heartrate observed in this study in the children ofhypertensive parents indicated the importance of geneticinfluence on hypertension in children.The results of the present study indicated that all the

parasympathetic autonomic function tests like heart rateresponse to standing i.e. 30:15 ratio, heart rate response todeep breathing i.e. E: I and valsalva ratios in the childrenwith a family history of hypertension were almost similarto control group. These results were statistically notsignificant (p>0.05). It indicates that the parasympatheticreactivity tests are similar in both the groups. These testsprimarily provide an index to cardiac vagal functions.Itwas also indicated that sympathetic autonomic functiontests cold pressor test, isometric handgrip test, bloodpressure response to standing have both prognostic anddiagnostic importance to determine sympathetic reactivity.There was significant increase of blood pressure responseto cold pressor test and isometric hand grip test in the testgroup which points towards sympathetic hyperactivity inchildren with a family history of hypertension. Bloodpressure responds to standing values also slightly higher intest group when compared to control and these values alsostatistically significant.

The mechanisms of increased sympathetic nervous systemactivity in hypertension involve alterationsin baroreflex and chemoreflex pathways at both peripheraland central levels. Persons with a family history ofhypertension manifest augmented vasoconstrictor andsympathetic responses to laboratory stressors, such as coldpressor test and isometric handgrip test that may predisposethem to hypertension. Exposure to stress increasessympathetic nervous system activity and this recurrentstress produces vasoconstriction leading to progressiveincreases in peripheral resistance and blood pressure. Thisstudy support the concept of inherited vascular reactivity asan indicator of sympathetic hyperactivity which forms thebasis for the development of hypertension in the childrenwith a family history of hypertension in their future life.

CONCLUSION

This study concluded that hyperactivity of sympatheticnervous system in children with a family history ofhypertension increases the risk of hypertension in theirfuture. The parasympathetic nervous systems remainsunchanged in both test and control groups. Initiallychildren of study group may be normotensive but there ischance of development of hypertension in later life.Regular supervision of autonomic activity may prove to bea useful tool in predicting the future hypertension. Childrenbelonging to hypertensive families should therefore, betargeted for primary prevention regular blood pressuremonitoring along with dietary and lifestyle modification. Itis also important to screen these children to identifymarkers to assist in prediction of development of essentialhypertension in adulthood.

List of abbreviations

ECG – ElectrocardiogramSBP – Systolic blood pressureDBP – Diastolic blood pressure

Table 4 Statistical analysis of Sympathetic functiontests in Study group and control group

Variables Control group(n = 30)

Study group(n = 30)

P value

Isometric Handgrip SBP 14.85 ± 1.20 19.55 ± 0.86 <0.01**Isometric Handgrip DBP 19.36 ± 2.05 26.72 ± 2.93 <0.001**Cold Pressor Test SBP 8.2 ± 1.4 14.29 ± 1.6 <0.05Cold Pressor Test DBP 12.24 ± 1.56 18.24 ± 1.56 <0.001**

Bp Response to standingSBP change

4.64 ± 1.38 6.60 ± 1.41 <0.001**

Bp Response to standingDBP change

2.20±0.43 5.43±0.66 <0.001**


CPT – Cold pressor testIGH – Isometric handgrip test

Competing interests

The Authors declare that they have no competing interests.

Authors Contributions

Dr. K.N. Maruthy have made substantial contributions toconcept and study design. He has also done final approvalof the work to be published. Dr. Sharan b.Singh wasinvolved in acquisition of data, analysis and interpretationof data. Mr. Chiranjeevi Kumar Endukuru have done spellcheck, proof read, sequence alignment and statisticalanalysis. Each author should have participated sufficientlyin the work to take public responsibility for appropriateportions of the content. All authors read and approved thefinal manuscript. All contributors who do not meet thecriteria for authorship should be listed in anacknowledgements section.

Authors' information

Chiranjeevi Kumar Endukuru received the B.Sc. degreein Medical lab technology and M.Sc. degree in Medicalphysiology from Narayana Medical College, Nellore,Andhra Pradesh, India in 2009 and 2012, respectively.Currently working as a Tutor/Demonstrator in theDepartment of physiology, AIIMS Bhopal.

Acknowledgment

The authors are thankful to Dr. K.N.Maruthy and Dr.Sharan B.Singh for his kind support and Concept. Weare also thankful to subjects and all the technical stafffor their contribution in the completion of the project.

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How to cite this article:Chiranjeevi kumar Endukuru et al., An Evidence Based Study Of Autonomic Dysfunction In Children With AFamily History Of Hypertension. International Journal of Current Medical and Pharmaceutical Research, 1, (2),35-39.www.journalcmpr.com/

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An evidence based study of autonomic dysfunction in children