European Journal of Cardiovascular Medicine

Aging in humans is associated with a dramatic increase in the prevalence of a number of cardiovascular diseases.  Cardiovascular diseases are responsible for ~50% of all deaths in the industrialized nations.  Aging is associated with an increased dependency on sympathetic control of cardiac responses and reduced vagal responsiveness. Cardiac electrophysiological studies have demonstrated a progressive decline in sino-atrial conduction and sinus node recovery time with age. Studies have revealed an increase in empty Schwann cell bands or reduced number of fibers in the vagus nerve among old subjects [1]. There is evidence for impaired baroreflex functions with aging. Increase in circulating levels of norepinephrine and thereby sympathetic over activity might account for reduced vagal efferent drive in advancing age [2].Sympathetic nervous system activation, impaired cardiac and peripheral adrenergic function, and reduced baroreflex circulatory control are fundamental features of a number of cardiovascular disorders including coronary artery disease, congestive heart failure, essential hypertension, and type 2 diabetes.  As such, these ANS changes may play an important mechanistic role in the etiology of age-associated cardiovascular disease and the resulting morbidity and mortality.

Reports of studies on age related changes in cardiovascular autonomic functions of human body are very few in the North –East India. Therefore, it is important to evaluate the Cardiovascular Sympathetic functions in apparently healthy subjects of various age groups of Guwahati, the capital of Assam.

AIMS AND OBJECTIVES:

• Assess the Cardiovascular Sympathetic function in 150 adult, healthy males of different age groups of Guwahati city by a battery of three standard bedside autonomic function tests.

• Compare the findings in subjects of different age groups and assess the effect of age on the CardiacSympathetic Functions.

STUDY DESIGN

The cross – sectional study was carried out in one hundred and fifty healthy male subjects of Guwahati city.Eachsubjecttakingpartwasexplainedabouttheproceduretobeadaptedinthe research. All thesubjectsafter a thorough understanding of the procedurestobe adopted signed an informed consent form provided to them.

INCLUSION CRITERIA

The subjects selected were between the ages 20 years to 70 years. The subjects who were non-obese and without any sign sofcardio vascular, respiratory, endocrinological, neurological, hematological & inflammatory diseases wereselectedforthestudy.

EXCLUSIONCRITERIA

The subjects with any of the following findings were excluded from the study:

1) Evidenceofhypertension

2) Clinical signs of cardiac failure or ECG changes suggestive of arrhythmia, ischemia.

3) Subjects having diabetes mellitus, respiratory diseases, giddiness son standing, syncopal spells and visual disturbances.

4)Subjectsreceivingdrugsthatareknowntointerferewithcardiacfunctionor respiratory functions such as betablockers, sympathomimetic drugs, vasodilators and diuretics.

5) Associated disease or conditions known to affect autonomic function like GuillenBarre syndrome, Poliomyelitis, Diphtheria, Tuberculosis, Syphilis, Amyloidosis, Chronic renal failure.

6)Any disease condition affecting the autonomic nervous system.

SAMPLE SIZE:

The study was carried out in one hundred and fifty healthy male subjects of Guwahati city. The entire sample was         divided int of ive   groups as follows.  Each group had a total of 30 subjects

METHODOF COLLECTION OF DATA

The subjects were instructed to come on emptys tomach with over night abstinence from coffee and teaor any form of exercise. All the tests were conducted between 8: 00  am to11:00 amin cool and calm atmosphere at room temperature varying from270 to300 Celsius. The subjects were asked to relax in supine position for 30 minutes in the examination room. All the subjects were subjected to recording of their physical anthropometry, various physiological parameters and autonomic function parameters.

All the subjects were subjected to a battery of three standard cardiovascular autonomic function tests asre commended by American Diabetic Association and performed asper methods described by Sir Roger Bannister [3].

In our study it was seen that there is a very highly significant (p=0.000) gradual increase in the fall of Systolic Blood Pressure in response to standing from Group I to Group V (Table 1). The values were significantly higher in Group IV and Group V compared to Group I, Group II, and Group III. Also, there was no statistically significant difference between the values of Group IV and Group V.However, in Group V subjects the value showed borderline abnormality (according to Ewing and Clarke).

Ourresults are in accordance with the earlier works of Michael A. Pfeifer et al[5], Gautschy B et al[6],  Vita G et al[7], LowPA et al[8] , Gerritsen J et al [9],  who observed that the systolic bloodpressureresponsetostanding decreased with age in apparently healthy subjects.

The very highly significant gradual decrease in blood pressure response to standing can probably be attributed to the fact that there is attenuation in the baroreflex-mediated peripheral vasoconstriction and tachycardia with increasing age.

In our study it is also observed that there is a very highly significant (p=0.000) gradual decrease in the mean Diastolic Blood Pressureresponse to sustained handgrip from Group I to Group V (Table 1). However even though therise in DBP is lower in GroupIV and Group V as compared to that of Group I, Group II and Group III; itisstillin the normal range (according toEwing and Clarke grading).

The findings of our study are in accordance to Kaijser& Sachs [10] who observed a decreased blood pressure response to sustained hand grip test in older subjects, above 60 years. They attributed this toreduced capacity of older subjects to release nor-epinephrine up onexercise provocation.

Inourstudy,correlation(byPearsoncorrelation)ofdifferentsympathetic nervefunctionparameterswithagewasanalyzed and seenthat the Systolic Blood Pressure response to standing positively correlated with age and the Diastolic Blood Pressure responsetosustained handgripnegatively correlated with age and all these relationships were statistically significant. OurresultsareinaccordancewithChuTS&co-workers [11]whoobservedthatage   correlated positively with a fall in systolic blood pressure.

The results of present study therefore suggest impairment of sympathetic nerve functions in apparently healthy elderly subjects. There is an age-related decrease in chronotropic response to sympathetic stimulation which can be attributed to multiple molecular and biochemical changes in beta receptor–coupling and postsynaptic signaling. Thus, age-associated alterations in beta-adrenergic response may be caused by desensitization of the adenylate cyclase system in response to chronic increase of plasmacatecholamine levels (PRIMER ON THE AUTONOMIC NERVOUS SYSTEM, 2^nd edition, pg 192).

Moreover, aging is also associated with increased vascular stiffness and peripheral resistance. Vasoconstriction responses are preserved, and endothelium-dependent vasodilatation is progressively impaired with aging. In addition, aging is also associated with a progressive decline in plasma renin, angiotensin II, and aldosterone levels, and increase in atrial natriuretic peptide; all of which promote salt wasting by the kidney.

The study evaluated and compared the status of the cardiovascular sympathetic functions in 150 healthy male subjects in the age group of 20yrs –70 yrs of Guwahati city and alsoassessed the effect of age on the same.

The standard bedside non- invasive Sympathetic Function tests were performed in each subject. The results showed a significant reduction in autonomic function with increasing age of the subjects. There is also a gradual increase in the number of subjects with borderline or abnormal autonomic function score in the older age groups.

ETHICS APPROVAL AND CONSENT TO PARTICIPATE

The study was approved by Institutional Ethics Committee of Gauhati Medical College and Hospital, Guwahati, Assam (dtd: 19 November 2011). Regn number: MC/190/2011/Rt.11/16. Informed consent was taken from the study participants

DATA AVAILABILITY

The data can be accessed in the department of Physiology, Gauhati Medical College, Guwahati. It can also be made available on request by emailing the same to the Principal Investigator on the email id: rpohamrcleh@gmail.com

CONFLICTS OF INTEREST

The author(s) declare(s) that there is no conflict of interest regarding the publication of this paper.

FUNDING STATEMENT

The study was self-funded by the principal workers.

AUTHORS' CONTRIBUTIONS

RR collected, analyzed and interpreted the subject data. DN was a majorcontributor in writing the manuscript. All authors read and approved the final manuscript.

1. V.Huikuri, M.J. Koistinen, S. Yli-Mayry et al.,“Impaired Low-Frequency Oscillations of Heart Rate in Patients With Prior Acute Myocardial Infarction and Life-Threatening Arrhythmias.” American journal of cardiology, vol.76, no.1, pp. 56-60, 1995.
2. D J Ewing, B F Clarke “Diagnosis and management of diabetic autonomic neuropathy” British Medical Journal, Volume 285
3. Bannister, R. & Mathias CJ 1988, "Testing Autonomic Reflexes," In Autonomic Failure: A Textbook of Clinical Disorders of the Autonomic Nervous System, 2nd ed. R. Bannister & Mathias CJ, eds., London: Oxford University Press, 52-63
4. Walter M. Kirkendall, Alan C. Burton, Frederick H. Epsteinand Edward D. Freis “Recommendations for Human Blood Pressure Determination by Sphygmomanometers”1 1967; 36:980–988
5. M A Pfeifer, C R Weinberg, D Cook, J D Best, A Reenan, J B Halter “Differential changes of autonomic nervous system function with age in man”Am J Med 1983 Aug;75(2):249-58
6. B Gautschy, P Weidmann, M P Gnädinger “Autonomic function tests as related to age and gender in normal man” KlinWochenschr, 1986 Jun 2;64(11):499-505.
7. G Vita, P Princi, R Calabro, A Toscano, L Manna, C Messina “Cardiovascular reflex tests. Assessment of age-adjusted normal range” J Neurol Sci. 1986 Oct; 75(3):263-74.
8. Low PA, Opfer-Gehrking TL, Proper CJ, Zimmerman I. “The effect of aging on cardiac autonomic and postganglionic sudomotor function.” Muscle Nerve (1990) 13:152–7
9. J Gerritsen, B. J. TenVoorde, J. M. Dekker, R. Kingma, P. J. Kostense, M. Bouter, R. M. Heethaar “Measures of cardiovascular autonomic nervous function: agreement, reproducibility, and reference values in middle age and elderly subjects” Diabetologia (2003) 46:330–338.
10. Kaijser L, Sachs C. Autonomic cardiovascular reflexes in old age.Clin Physiol1985;5: 347–357.
11. Chu TS, Tsai TJ, Lai JS, Chen WY. Evaluation of cardiovascular autonomic function tests in normal subjects. Journal of the Formosan Medical Association. 1989 Apr;88(4):404-6.