Review
The relationship of autonomic imbalance, heart rate variability and cardiovascular disease risk factors

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Abstract

Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. The understanding of the risk factors for CVD may yield important insights into the prevention, etiology, course, and treatment of this major public health concern. Autonomic imbalance, characterized by a hyperactive sympathetic system and a hypoactive parasympathetic system, is associated with various pathological conditions. Over time, excessive energy demands on the system can lead to premature aging and diseases. Therefore, autonomic imbalance may be a final common pathway to increased morbidity and mortality from a host of conditions and diseases, including cardiovascular disease. Heart rate variability (HRV) may be used to assess autonomic imbalances, diseases and mortality. Parasympathetic activity and HRV have been associated with a wide range of conditions including CVD. Here we review the evidence linking HRV to established and emerging modifiable and non-modifiable CVD risk factors such as hypertension, obesity, family history and work stress. Substantial evidence exists to support the notion that decreased HRV precedes the development of a number of risk factors and that lowering risk profiles is associated with increased HRV. We close with a suggestion that a model of autonomic imbalance may provide a unifying framework within which to investigate the impact of risk factors, including psychosocial factors and work stress, on cardiovascular disease.

Introduction

Recent research has strongly suggested that negative affective states, dispositions and work stress are associated with diseases and ill health [1], [2], [3], [4], [5], [6], [7]. Work stress, in particular, has been associated with substantial economic consequences, including increased absenteeism, increased worker turnover, decreased worker job satisfaction and associated decreases in worker productivity [8], [9]. Stress at work is also a major public health risk associated with cardiovascular morbidity [10], [11]. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in both men and women. This is particularly true in developed countries [12], [13]. A wide range of risk factors for CVD have been identified but as yet a unified model that can account for this diversity of risk factors has not been put forward.

A recent report from the Whitehall Study [11] has shown that work stress is associated with decreased heart rate variability (HRV). Decreased HRV is an independent risk factor for morbidity and mortality. The important role that the vagus nerve plays in health and disease has been known for some time [14]. However, only relatively recently have researchers and clinicians started to investigate how this knowledge can be incorporated into a greater understanding of the etiology, manifestations, course, outcomes, and treatment of disease.

In this illustrative review we show that autonomic imbalance, in which vagal inhibitory influences are deficient, is associated with increased morbidity and all-cause mortality. We also review evidence linking vagal function to established and emerging risk factors including work stress, for CVD and mortality. Importantly, we discuss evidence that factors that increase HRV are associated with decreased risk and an improved health profile. Thus, the model of autonomic imbalance may provide a unified approach to the understanding of the role of HRV in the risk for cardiovascular disease and all-cause mortality.

Section snippets

Autonomic imbalance and disease

There is growing evidence for the role of the autonomic nervous system (ANS) in a wide range of diseases. The ANS is generally conceived to have two major branches—the sympathetic system, associated with energy mobilization, and the parasympathetic system, associated with vegetative and restorative functions. Normally, the activity of these branches is in dynamic balance. However, the activity of the two branches can be rapidly modulated in response to changing environmental demands.

Heart rate variability and mortality

In one of the first studies to investigate the relationship between indices of HRV and mortality, Kleiger et al. [21] showed in almost 900 post-myocardial infarction (MI) patients that HRV was a significant independent predictor of mortality in this high risk group. Numerous studies have since supported the notion that decreased vagal activity, as indexed by HRV, predicts mortality in high risk as well as low risk populations. In an elderly sub-sample of the Framingham Heart Study (FHS),

Heart rate variability and the etiology and progression of cardiovascular disease risk

The evidence for an association between reduced HRV and mortality appears to be quite strong. Most of these studies examined the association after controlling for other known risk factors such as diabetes and hypertension. However, there is also evidence to suggest that reduced HRV leads to such risk factors. Thus, those studies that control for those known risk factors for which there exists evidence that reduced HRV might lead to those risk factors may, in fact, be underestimating the role of

Emerging risk factors: psychosocial factors including work stress

Psychosocial factors such as stressful life events, general stress, hostility, depression, and anxiety are also emerging as risk factors for CVD [10], [63], [64], [65], [66], [67], [68], [69], [70], [71]. Decreased HRV has been associated with several psychosocial conditions and states [1], [2], [66], [67], [72], [73], [74], [75]. Another emerging psychosocial factor associated with CVD and HRV is work stress.

In terms of work stress, several studies have found significant associations with

Heart rate variability and the prevention of cardiovascular disease

There are several pathways via which the deleterious effects of modifiable factors such as work stress can be prevented or minimized. All of these pathways involve efforts to increase HRV. As noted above, smoking cessation, physical exercise, and weight loss are all associated with increased HRV. Dietary changes including the consumption of fruits and vegetables, moderate alcohol consumption, and intake of omega-3 fatty acids and vitamin D through fish or nut consumption are also effective

Summary

In this paper we have tried to provide an overview of some of the evidence for the role of HRV in cardiovascular disease risk and mortality. Although not exhaustive, this review shows that there is a large body of data to suggest that decreased vagal function is an independent risk factor for all-cause mortality. In addition, we examine evidence that decreased vagal function is a common factor in all of the major risk factors for CVD, both modifiable and non-modifiable. Furthermore, we showed

Acknowledgements

We would like to thank Tammy N. Sadle for her assistance with the tables. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [90].

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