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Medicine & Science in Sports & Exercise:
CLINICAL SCIENCES: Clinically Relevant

Genetic Correlation of Exercise with Heart Rate and Respiratory Sinus Arrhythmia


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DE GEUS, E. J. C., D. I. BOOMSMA, and H. SNIEDER. Genetic Correlation of Exercise with Heart Rate and Respiratory Sinus Arrhythmia. Med. Sci. Sports Exerc., Vol. 35, No. 8, pp. 1287–1295, 2003.

Purpose: A twin design was used to test whether the association between exercise behavior and heart rate and the association between exercise behavior and respiratory sinus arrhythmia (RSA) derive from a common genetic factor.

Methods: Data were available from 157 adolescent (aged 13–22) and 208 middle-aged twin pairs (aged 35–62), divided into five sex by zygosity groups (male and female monozygotic twin pairs, and dizygotic twin pairs of same or opposite sex). Exercise behavior was assessed as the average weekly METs spent on sports activities or other vigorous activities in leisure time (sportMETS) in the last 3 months. RSA and heart period (HP) were assessed in the time domain from the combined ECG and respiration signals.

Results: Heritability estimates were 16% and 29% for RSA, 64% and 68% for HP, and 79% and 41% for sportMETS in young and middle-aged twins, respectively. A significant association was found between RSA and sportMETS (0.17) in the adolescent twins that derived entirely from a common genetic factor. No association was found between sportMETS and RSA in the older twins. A significant association was found between HP and sportMETS in both adolescent (0.35) and middle-aged (0.18) twins. A large contribution of common genetic factors to these associations was found amounting to 84% and 88% in the young and middle-aged twins, respectively.

Conclusions: Although the results of this study do not preclude causal effects of exercise on RSA and heart rate, they show that the association between exercise and these cardiovascular risk factors largely derives from a common genetic factor.

Prospective studies have repeatedly suggested that regular vigorous exercise in leisure time (e.g., sports, jogging, aerobics) is associated with a reduced risk for myocardial infarction and sudden death. An exercise-induced increase in cardiac vagal nerve activity is one of the mechanisms put forward to explain this reduced risk in exercisers (2,22). Individual differences in vagal contribution to resting heart rate can be assessed as the increase in heart rate after parasympathetic blockade or the increase in heart rate from complete sympathetic blockade to complete dual sympathetic and parasympathetic blockade. Using this pharmacological blockade approach, the contribution of vagal nerve activity to resting heart rate was found to be higher in well-trained than in untrained persons in some (24,27), but not in other, studies (13,15). Most blockade studies point to a lower intrinsic heart rate as the most consistent source of resting bradycardia in exercisers (13,15,27), and this is supported by findings in animals.

As a noninvasive alternative to pharmacological blockade, vagal contribution to resting heart rate in exercisers is increasingly quantified by measures of heart rate variability. Total heart rate variability, measured as the variance or standard deviation of the heart period (HP), provides a first crude index of vagal effects but includes the substantial contribution of sympathetic activity to variability in the low frequency ranges. In contrast, respiratory sinus arrhythmia (RSA), the heart rate variability in the respiratory frequency band, is not affected by manipulations of sympathetic activity and responds in a dose-response way to muscarinergic blockers or vagal cooling (30).

Cross-sectional studies have fairly consistently suggested higher RSA in exercisers than in nonexercisers (11,12), although not all studies support this and some even report the opposite finding of lower RSA in exercisers (23). Likewise, cross-sectional studies of the association between aerobic fitness and RSA show highly significant positive correlations with the more-fit subjects having higher RSA (2,11), although exceptions have been found (6,7). All these cross-sectional studies comparing high-fit exercisers with low-fit nonexercisers suffer from the shortcoming that “correlation does not imply causation.” This can be resolved by the experimental manipulation of exercise behavior in longitudinal training studies.

A number of such studies have supported an effect of exercise on RSA (8,17), but most failed to find a training-induced increase in RSA (4,6,7,18). We, for example, used a training-detraining paradigm in 62 young adults (6) to test the effects of aerobic fitness training and subsequent de-training on time and frequency domain measures of RSA. Although heart rate followed our (de)training manipulations closely, we found no systematic training-induced increase in RSA even after 8 months of intensive training. The clear discrepancy in the results of cross-sectional and longitudinal studies could be due to the relatively short duration of the training programs—the autonomic nervous system effects of exercising may take years to develop. Alternatively, the cross-sectional association between exercise behavior and RSA may largely derive from an unobserved underlying third factor. This may be an environmental factor like low socioeconomic status (SES). Low SES is associated with reduced exercise behavior, but it is also a source of chronic stress that, in turn, may reduce RSA. The underlying third factor may also be genetic. A favorable endowment that includes high aerobic fitness and high RSA may lead a person to more often seek out the exercise behavior he or she excels in.

This favorable genetic make-up may further include a low resting heart rate. After maximal oxygen consumption, resting heart rate is one of the parameters that fairly consistently discriminates endurance exercisers from nonexercisers. In training studies, heart rate often is seen to decrease (6,7,15,17,18,24) although strong individual differences in the size of the training effect are found (21). Importantly, heart rate rapidly increases to the initial levels during de-training manipulations (6). This strongly suggests that exercise has a causal effect on heart rate. Such a causal effect does not rule out the possibility that part of the association derives from a common underlying factor influencing both heart rate and exercise behavior.

The aim of this paper is to test the hypotheses that a) the association between exercise behavior and RSA and b) the association between exercise behavior and heart rate derive from a common genetic factor. Previous studies using a (multigenerational) family or twin design have already shown that genetic factors play a pivotal role in determining individual differences in leisure time physical activity (1,16,25). Likewise, significant genetic influences are apparent for RSA (3,5,26,28) and heart rate (20,29). No study, however, has addressed the question whether the genes influencing exercise behavior, RSA, and heart rate could be partly overlapping.

Data was available from 730 individuals in two large twin cohorts participating in the cardiovascular research program of The Netherlands Twin Registry (3,28). In these two twin cohorts, resting ECG was measured under highly comparable and standardized resting conditions, and both cohorts filled out an identical questionnaire on the average time spent per week on sports activities or other vigorous activities in leisure time. HP and RSA were assessed in the time domain from the combined ECG and respiration signals. In a twin design, structural equation modeling can be used to estimate the genetic and environmental covariance between multiple traits measured in the same subject. This covariance, together with estimates of the genetic (heritability) and environmental contribution to the variance of the traits, can be used to estimate the contribution of genetic and environmental factors to the observed associations between multiple traits, in this case RSA, HP, and exercise behavior.

©2003The American College of Sports Medicine


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