Michael Joyner & Jill Barnes
Department of Anesthesiology, Mayo Clinic, USA

https://doi.org/10.36866/pn.90.18

Physical inactivity now rivals smoking as the leading cause of ‘preventable’ deaths in the developed world (Lee et al. 2012). Additionally, physical inactivity-related mortality is rising rapidly in the developing world. These observations have led to questions about whether physical inactivity should be viewed as a separate medical diagnosis or even a medical condition (Chakravarthy, Joyner & Booth 2002; Joyner 2012). Taking it a step further, it might also be possible to ‘split’ a physical inactivity diagnosis into two parts: primary deconditioning which is just too little physical activity and too much sitting around; or secondary deconditioning as result of inactivity caused by some other medical condition – for example, enforced bed rest during certain complications of pregnancy, bed rest associated with infectious disease, or reduced activity due to orthopedic injuries.

Activity and inactivity versus fitness

Before going further in this discussion it is important to distinguish between physical activity or inactivity and physical fitness. Many studies looking at the relationships between activity or inactivity use questionnaires or tracking devices like pedometers to get some idea about the total amount of activity people get per day. This activity is then estimated to be light, moderate or vigorous. Analysis of this data can then be framed in the context of activity or inactivity with some estimate of exercise intensity (Troiano et al. 2008). For many years the discussion was mostly about activity as an experimental intervention and the inactive state was considered the ‘normal control condition’ or frame of reference. In recent years this has changed, primarily as a result of the thinking of Frank Booth and colleagues who have pointed out that humans were designed to be active and that our cultural and genetic heritage as hunter-gatherers and traditional agriculturalists included high volumes of a wide range of physical activity (Chakravarthy & Booth, 2004). Thus came the idea that the active state is the physiologic norm and the inactive state should be seen as the intervention or deviation from normal (Booth, Laye & Roberts, 2011). This idea has exploded in the popular press and it is interesting to note that, for a number of rodent models that have what might be broadly described as metabolic diseases, the disease phenotype of interest is prevented or attenuated when the caged animals are given access to voluntary running wheels (Brown et al., 2012; Engber, 2011; Park et al., 2012; Rector et al., 2011). So the question is: have we been studying the condition of primary physical inactivity instead of the disease of interest?

Some studies have also looked at death and disease rates versus varying levels of cardiorespiratory fitness typically determined by a graded exercise test on a treadmill providing an objective measurement of fitness. In general, people who are highly active will have greater cardiorespiratory fitness than less active individuals, but high cardiorespiratory fitness can theoretically be achieved by relatively limited periods of vigorous intensity exercise, in the absence of large volumes of physical activity. The point is that physical activity and fitness, while usually related, are not synonymous.

Activity, inactivity, heart disease and death

Exercise is perhaps best known as being protective against cardiovascular disease. Data from numerous population-based studies suggests individuals that have some combination of either high daily physical activity or greater levels of cardiorespiratory fitness (as noted above, they are not exactly the same thing) have much lower all-cause mortality (Barlow et al., 2012; Berry et al., 2012; Moore, 2012). People in the highest categories of physical activity and fitness typically have cardiovascular mortality rates that are about 50% of that seen in the general public as a whole. From a public health perspective, many of the benefits of exercise begin to accrue as people move from the least active categories to the moderate levels of physical activity. Figure 1 shows the relationships between physical activity levels, rates of mortality and years of life gained. For many years this reduced mortality was seen as primarily due to the fact that exercise had powerful effects on traditional cardiovascular risk factors. For example, exercise lowers blood pressure, improves blood lipids, and has powerful anti-diabetic effects. However, when the effects of exercise on traditional risk factors for cardiovascular disease are looked at in total, only about 60% of the risk reduction is accounted for (Mora et al., 2007). This means that 40% of the protective effects of exercise might be described as ‘physiological dark matter’ (Joyner & Green, 2009).

Hints about ‘physiological dark matter’

There are a few obvious candidates for the as-yet unexplained protective effects of exercise. First, high levels of physical activity and/or structured exercise training have profound effects on the autonomic nervous system and these might be generically described as ‘pro-vagal’ and would tend to protect individuals from arrhythmias (Billman, 2009). Exercise also has preconditioning-like effects on the cardiac muscle which would be protective against myocardial infarction and other cardiac problems (Powers, Quindry & Kavazis, 2007). Exercise training and physical activity also improve endothelial function, which is both anti-atherogenic and anti-thrombogenic, both of which would be protective against cardiovascular disease (Green, 2009). Individuals who participate in prolonged intense exercise have larger coronary arteries and structural remodeling associated with the exercise might also in fact be protective (Nguyen et al. 2011). Finally, exercising muscle also secretes a number of myokines that have potent anti-inflammatory and anti-diabetic effects (Pedersen & Febbraio 2012). From a physiological perspective these adaptations, generally associated with increasing cardiorespiratory fitness, would all be protective against heart disease.

Physical activity as an independent risk factor for cardiovascular disease

Is physical inactivity (or lack of cardiorespiratory fitness) a risk factor? One way to look at this is to consider data showing the relationship between all-cause mortality and/or traditional risk factors and physical activity or cardiorespiratory fitness. In a classic study from the mid-1990s, Blair and colleagues demonstrated that individuals with high levels of traditional risk factors who also had high cardiorespiratory fitness scores had only minimal increases in risk as a result of these additional factors (Blair et al. 1996). By contrast, the risk factors showed what might be described as their full expression only in the least fit individuals. Additionally, risk was increased in the least fit people with relatively low traditional risk factor scores and more recent data has confirmed this idea (Barlow et al. 2012). These types of data and subsequent analysis suggests that physical inactivity and the associated lack of cardiorespiratory fitness are in fact independent risk factors for cardiovascular disease and all-cause mortality. Some might argue this is semantic hair-splitting, but if you accept that fact that primary inactivity is a risk factor for hypertension diabetes, and may extend to cancer and dementia, then isn’t it a medical condition deserving of an independent diagnosis?

Adverse responses to exercise training?

One interesting idea about the protective effects of exercise that seem to be independent of traditional risk factors, is the observation from large training studies that at least some individuals might be described as adverse responders to exercise training (Bouchard et al. 2012). This means that their blood pressure rises in response to training, their lipids get worse, or perhaps their blood glucose increases. Typically, adverse responses are seen for only one risk factor and do not cluster in the same person. That having been said, are these individuals in fact adverse responders to exercise? Are the protective effects of exercise that seem to be independent of traditional risk factors also somehow also ‘not responding’ to exercise training? Are there other lifestyle-related behaviors that may explain the seemingly counterintuitive response to exercise? These are important questions about what might be described as ‘surrogate markers’ for effective exercise interventions designed to improve both individual health and public health in general. In other words, do we tell people who do not have improvements in their traditional risk factors, or in fact have
‘adverse’ changes in their traditional risk factors, that they shouldn’t exercise? Are we in fact denying them the benefits of the significant but less well understood positive effects of exercise?

New ideas about sedentary behavior

High levels of physical activity or cardiorespiratory fitness are protective in terms of all-cause mortality, especially cardiovascular mortality. However, it also appears that bouts of intensive exercise followed by sedentary behavior the rest of the day can be problematic. Additionally, recent evidence clearly demonstrates that going from ‘normal’ levels of activity to very low levels of physical activity has extremely negative consequences on metabolic regulation in humans (glucose homeostasis) in a matter of a week or so (Olsen et al. 2008). All of this would seem to suggest that a combination of relatively intense leisure time physical activity (sufficient to increase cardiorespiratory fitness) and low-grade physical activity throughout the day are probably an optimal pattern to maximize the health benefits of exercise and physical activity.

Exercise and healthcare costs

The data on physical activity and mortality are convincing. How do the data on physical activity relate to healthcare use or healthcare costs? The literature on this topic is much less robust than the literature on mortality. It also suffers from the problem that it is generally cross-sectional in nature and questions about ‘nature versus nurture’ often arise. For example, perhaps only the most robust and healthy individuals began to exercise in the first place and this confounds the interpretation of cause and effect. One excellent study from the United States on more than 40,000 older individuals on the Federal Medicare Program demonstrated that the most active individuals had yearly healthcare costs that were about 20% lower, and that was also true for the most active obese patients in the study (Wang et al. 2005).

Do exercise interventions work?

Exercise interventions clearly improve fitness and risk factors in the vast majority of people who undertake them. However, one of the ideas behind inactivity as a medical diagnosis is that while interventions work, they are hard to implement and people do not stick with them. Additionally, it is unclear how well public education campaigns are working. The number of people meeting physical activity guidelines for health is also incredibly low (Troiano et al. 2008). So, could this be improved if inactivity or deconditioning becomes a medical diagnosis complete with an exercise prescription? It is relatively straight forward for a middle-aged person with hypertension, diabetes, or high cholesterol to visit their physician and be given a prescription for drugs that can conveniently be obtained at the local pharmacy. There exists cultural, commercial and governmental infrastructure to support this approach to disease management. What if it were that easy for a physician to send someone to the gym or tell them to go for a walk? Would it work? The data to date are not convincing one way or the other, but probably deserving of serious study (Pavey et al. 2011).

Lessons from smoking

Smoking rates have declined in many countries and at least some of this has been due to active intervention and advice by physicians. However, other public health strategies such as making cigarettes less available to young people and higher taxes have probably done more to reduce smoking rates than people being urged to quit, or being enrolled in smoking cessation programs (CDC 2007). The smoking experience suggests that a combination of approaches will be needed to promote physical activity out in the real world. These approaches will likely include a combination of public health initiatives (education), government initiatives (public places promoting physical activity), and medical initiatives (low-cost access to supervised exercise intervention programs, insurance deductions for participation). However, another important aspect to the declining smoking rates may be the societal shift on acceptability. It is often viewed as distasteful, for example, to smoke in most public indoor spaces. In terms of physical inactivity, we have not reached the tipping point for social preference.

The role of society

If large-scale public health initiatives demonstrate varying results, what roles do individuals play in initiating such change? In particular, what role do social networks have in promoting healthy behaviors? Recently, Li et al. (2012) discussed the use of social media as an intervention tool to prevent childhood obesity. In addition, others have used statistical approaches to document how behaviors, such as weight gain or alcohol use, spread throughout a social network (Christakis & Fowler, 2012). These innovative techniques may reveal much about initiating positive health behaviors and using social media to promote the idea that an active lifestyle is the healthy norm.

Conclusion

Physical inactivity is a major cause of disease and the effects of exercise on morbidity and mortality are at least partially independent of so-called traditional risk factors. These observations justify the position that physical inactivity (and deconditioning) should be viewed as an independent medical diagnosis amenable to prevention via public health measures and treatment via the medical community.

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