Chapter 14: Preventing Chronic Disease: Physical Activity and Healthy Eating

By studying this chapter, you should be able to do the following:

1. Contrast infectious with degenerative diseases as causes of death.

2. Identify the three major categories of risk factors and examples of specific risk factors in each.

3. Describe the difference between primary and secondary risk factors for coronary heart disease (CHD).

4. Characterize physical inactivity as a coronary heart disease risk factor comparable to smoking, hypertension, and high serum cholesterol.

5. Describe the process of atherosclerosis related to coronary heart disease.

6. Describe the role of low-grade chronic inflammation in the development of chronic diseases.

7. Describe the metabolic syndrome and possible causes.

8. Describe the role of diet and physical activity from an anti-inflammatory standpoint.

• Risk Factors for Chronic Diseases 331

  • Inherited/Biological 331

  • Environmental 331

  • Behavioral 331

• Risk Factors for Coronary Heart Disease 333

  • Physical Inactivity as a Risk Factor 333

  • Physical Activity and Health 334

• Inflammation and Coronary Heart Disease 336

  • Obesity, Inflammation, and Chronic Disease 336

  • Healthy Eating and Physical Activity to Combat Inflammation 338

• The Metabolic Syndrome 339

atherosclerosis

degenerative diseases

infectious diseases

low-grade chronic inflammation

primary risk factor

secondary risk factor

web of causation

In this section of the textbook, the Physiology of Health and Fitness, we focus on the importance of two major variables, physical activity (Chaps. 15, 16, and 17) and healthy eating (Chap. 18), as crucial ingredients to a healthy lifestyle. There is absolutely no question that physical inactivity is a major risk factor for numerous chronic diseases including heart disease, type 2 diabetes, and cancer (65). In like manner, choosing healthy foods to obtain essential nutrients, while matching caloric intake with caloric expenditure, goes a long way in dealing with our obesity epidemic and its dire consequences. In this chapter, we begin with a discussion of risk factors for chronic diseases that examines the environmental, genetic, and behavioral links to health and disease. These risk factors direct public health interventions to reduce the overall risk to the population (e.g., stop-smoking campaigns). Although risk factors describe the causes of disease from a macro level, they don’t address the underlying physiological causes of these chronic diseases. We will try to do that by exploring the proposition that it is a low-level systemic inflammation (see Chap. 6) that is causing many of these chronic diseases. Finally, we will bring the discussion back to physical activity and healthy eating as ways of dealing with chronic disease.

Over the past 100 years, attention has shifted from infectious diseases (e.g., tuberculosis and pneumonia) as the major causes of death to chronic degenerative diseases, such as cancer and cardiovascular diseases. The leading causes of death describe the specific diseases linked to that outcome. In 2013, the top five leading causes of death were diseases of the heart, malignant neoplasms (cancer), chronic lower respiratory diseases, accidents (unintentional injuries), and cerebrovascular diseases (stroke) (71). The onset of most of the leading causes of death can be delayed or prevented by addressing the risk factors for these diseases. Epidemiologists are the scientists who play a major role in exploring the distribution of diseases in the population and the factors that have an impact on those diseases. Figure 14.1 shows that risk factors associated with chronic diseases can be divided into three categories (68).

Inherited/Biological

These factors include the following:

• Age—Older individuals have more chronic diseases than younger individuals.

• Gender—Men develop cardiovascular disease at an earlier age than women, but women experience more strokes than men (4).

• Race—African Americans develop about 30% more heart disease than non-Hispanic whites (67).

• Susceptibility to disease—Several diseases have a genetic component that increases the potential for having a disease.

Environmental

Environmental factors that affect health and disease include the following:

• Physical factors (e.g., climate, water, altitude, pollution)

• Socioeconomic factors (e.g., income, housing, education, workplace characteristics)

• Family (e.g., parental values, divorce, and extended family and friends)

Behavioral

The actual causes of death describe which behaviors (e.g., smoking) are linked to death (see the right side of Fig. 14.1). That smoking is at the top of the list should be no surprise given its connection to both lung cancer and cardiovascular diseases. In fact, it is the number one actual cause of deaths, accounting for 18% of all deaths. The existence of smoking-cessation programs and laws that restrict areas in which one can smoke speak to the seriousness with which our society takes that risk to our health. The number two actual cause of death is poor diet and physical inactivity (15.2%), with alcohol consumption being number three (3.5%) (39, 40). The emphasis on healthy eating at work and in schools, the creation of new parks and bike trails to enhance opportunities to be physically active, and “don’t drink and drive” campaigns are examples of some systematic attempts to help alter these behaviors.

In contrast to infectious disease, in which a single pathogen may be the cause of a disease, establishing the cause of a disease is much more difficult when dealing with chronic, degenerative diseases such as cardiovascular disease. The reason is that genetic, environmental, and behavioral factors interact in a complex manner to cause the disease. The difficulty of establishing “cause” for these complex diseases is best described by an epidemiologic model called the web of causation (37, 62).

In an oversimplification, Figure 14.2 shows links among three major classes of risk factors: genetic (e.g., gender, race), environmental (e.g., access to inexpensive high-fat foods; access to convenient places to walk, cycle, and play), and behavioral (e.g., diet, smoking, inadequate physical activity, too much physical inactivity [TV, video, computer]) (62, 63). They act alone and interact with each other to cause atherosclerosis, a condition in which a fatty plaque builds up in (not on) the inner wall of an artery. Many of the risk factors interact to cause overweight, obesity, and type 2 diabetes—problems that are connected to cardiovascular disease. Trying to tease out the effect that one factor has on another and on the final disease process is a difficult task that makes work in epidemiology interesting and challenging. The factors in the web of causation are positively associated with the development of cardiovascular diseases but are not sufficient in and of themselves to cause them. These are called risk factors, and they play a major role in developing prevention programs aimed at reducing disease and premature death associated with degenerative diseases. To expand on this risk factor concept, we will focus on coronary heart disease.

Coronary heart disease (CHD) is associated with a gradual narrowing of the arteries serving the heart due to a thickening of the inner lining of the artery. This process, called atherosclerosis, is the leading contributor to heart attack and stroke deaths (20). It is now widely accepted that some people are at a greater risk of developing CHD than others.

Historically, risk factors for CHD were divided into primary, or major, and secondary, or contributing. Primary meant that a factor in and of itself increased the risk of CHD, and secondary meant that a certain factor increased the risk of CHD only if one of the primary factors was already present, or that its significance had not been precisely determined (15). Lists of risk factors have evolved over time as more epidemiological evidence has accumulated, showing the association between various behaviors (e.g., physical inactivity) or characteristics (e.g., obesity) and CHD. Consequently, a practical approach used to classify risk factors is to list those that can be changed and those that can’t, no matter whether they are primary or secondary.

Currently, the American College of Sports Medicine (ACSM) lists eight risk factors (2):

• Age

• Family history

• Cigarette smoking

• Sedentary lifestyle

• Obesity

• Hypertension

• Dyslipidemia

• Prediabetes

Some of these risk factors, like age and family history, cannot be changed, but most can. An analysis of modifiable risk factors highlighted the impact that intervention programs have had on specific risk factors such as smoking and hypertension (19); however, interventions, in general, have not resulted in much of a reduction in the risk of CHD (22). This has been taken as a call to action to develop better behavior-change interventions to achieve better results.

You may have noticed that a high-fat diet was not listed in the above list of risk factors. In part, that is due to the fact that the impact of a high-fat diet is represented in the dyslipidemia and obesity risk factors. That said, there is clear evidence that high dietary salt and transfat intake and low omega-3-fatty acid intake are implicated as risk factors in chronic disease (19). In fact, dietary factors have an impact on a wide variety of the risk factors: obesity, hypertension, dyslipidemia, and prediabetes. Characteristics of a healthy diet will be addressed in Chap. 18. Finally, and important from the standpoint of this text, there exists a substantial body of evidence that physical inactivity is a major cause of many chronic diseases, including different cancers and various cardiovascular and metabolic diseases (11, 12, 65). We will see more on this in the next section and in Chaps. 16 and 17. To estimate your or your parent’s ten-year risk of having a heart attack, go to http://cvdrisk.nhlbi.nih.gov.

Physical Inactivity as a Risk Factor

After looking at the web of causation for cardiovascular disease in Figure 14.2, one can understand how difficult it is to determine whether an observed association between a risk factor and a disease is a causal one or is due simply to chance. To facilitate the process of determining cause, epidemiologists apply the following guidelines (6):

• Temporal association—Does the cause precede the effect?

• Plausibility—Is the association consistent with other knowledge?

• Consistency—Have similar results been shown in other studies?

• Strength—What is the strength of the association (relative risk) between the cause and the effect? Relative risk is sometimes expressed as the ratio of the risk of disease among those exposed to the factor to the risk of those unexposed. The greater the ratio, the stronger the association.

• Dose-response relationship—Is increased exposure to the possible cause associated with increased effect?

• Reversibility—Does the removal of the possible cause lead to a reduction of the disease risk?

• Study design—Is the evidence based on strong study design?

• Judging the evidence—How many lines of evidence lead to the conclusion?

The concern about whether a risk factor is causally related to cardiovascular disease has special significance for physical activity. For many years, physical inactivity was believed to be only weakly associated with heart disease and was not given much attention as a public health concern. However, in the late 1980s and early 1990s, that view changed rather dramatically. In 1987, Powell et al. (54) did a systematic review of the literature dealing with the role of physical activity in the primary prevention of coronary heart disease, applying the just-listed guidelines to establish causation. They found that the majority of studies indicated that the level of physical inactivity predated the onset of CHD, thus meeting the temporal requirement. They also found a dose-response relationship in that as physical activity increased, the risk of CHD decreased, and the association was stronger in the better studies. The latter results met the consistency and study design criteria for causality. The review found the association to be plausible given the role of physical activity in improving glucose tolerance, increasing fibrinolysis (breaking of clots), and reducing blood pressure. The investigators calculated the relative risk of CHD due to inactivity to be about 1.9, meaning that sedentary people had about twice the chance of experiencing CHD that physically active people had. The relative risk was similar to smoking (2.5), high serum cholesterol (2.4), and high blood pressure (2.1). When the authors controlled for smoking, blood pressure, cholesterol, age, and sex (all of which are associated with CHD), the association of physical activity and CHD remained, indicating that physical activity was an independent risk factor for CHD (54). In 1992, the American Heart Association added physical inactivity to its list of primary or major risk factors for cardiovascular disease (3).

To estimate the real impact a risk factor may have on a population, epidemiologists try to balance the relative risk with the number of people in the population that have the risk factor. This balancing act is summed up in the calculation of the population-attributable risk for each risk factor (16). Figure 14.3 describes the relative risk for selected risk factors and the percentage of the population affected. Given the large number of people who are inactive, changes in physical activity habits have a great potential to reduce CHD and other chronic diseases (11, 65).

Physical Activity and Health

Regular participation in physical activity has a positive impact on our health. In 2001, a special symposium examined whether a dose-response relationship existed between physical activity and a variety of health outcomes (31). At the end of that decade, another systematic review of the literature (66) was conducted on this same topic prior to the publication of the first set of national physical activity guidelines: 2008 U.S. Physical Activity Guidelines (65). This review supported the vast majority of the findings in the earlier report. Regular participation in physical activity was associated with:

• Lower rates of all-cause mortality, total cardiovascular disease (CVD), and coronary heart disease incidence and mortality

• Increased weight loss and reduced amount of weight regain after weight loss

• A lower incidence of obesity, type 2 diabetes, and metabolic syndrome

• A lower risk of colon and breast cancer

• An improvement in the ability of older adults to do activities of daily living

• Reduced risk of falls in older adults at risk of falling

• A reduction in depression and cognitive decline in adults and older adults

• Favorable changes in cardiovascular risk factors, including blood pressure and blood lipid profile

In general, the review found that:

• The volume of physical activity done was the most important variable tied to health outcomes.

• The risk of many chronic diseases was reduced about 20% to 40% by regular participation in physical activity, with the greatest gains made by those moving from doing no activity to doing some activity (55).

• Some physical activity is better than none and there is no lower threshold for benefits. Individuals are encouraged to be active even if they cannot meet the minimum intensity or duration recommendations (55, 65).

• A dose-response relationship existed for most health outcomes, meaning that “more is better.” See Figure 14.4 as an example for the health outcome “death from all causes.”

  Figure 14.4

  Dose-response of physical activity related to all-cause mortality.

  U.S. Department of Health and Human Services, Physical Activity Guidelines Advisory Committee Report 2008, Figure G1.3, p.G1-19. www.health.gov/paguidelines/committeereport.aspx.

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That last finding, “more is better,” had to be balanced by the increased risk of adverse outcomes when too much was done or when the exercise was a major change from what was currently being done. See more on this in Chap. 16. For information on two individuals who have had a major impact on our understanding of physical activity and heart disease, see A Look Back—Important People in Science.

We have just seen that a wide variety of risk factors are linked to heart disease. But how are these risk factors connected physiologically to the actual appearance of the disease? In atherosclerosis, the narrowing of the coronary artery can result in a reduction in blood flow that may ultimately lead to a heart attack. The decrease in the diameter of the lumen is due to a buildup of lipid and fibrous materials (plaque) in the inner lining of the artery, called the intima (see Fig. 14.5). In many ways, atherosclerosis has been viewed as a plumbing issue, and procedures to flatten the plaque back to the arterial wall (angioplasty) or change out the pipe (coronary artery bypass graft) have been used to correct the problem (see Chap. 17 for more on those procedures). However, most of the heart attacks and many strokes occur, not from a gradual occlusion of an artery, but from a sudden rupture of the plaque that triggers a blood clot and blocks blood flow. Let’s look at this in more detail (35, 36).

It has become clear that atherosclerosis is caused by the process of inflammation initiated in the inner lining of the artery (35, 36). Inflammation is a response of a tissue to injury that involves the recruitment of white blood cells (leukocytes) to the site of the injury (see Chap. 6). Normally, the endothelial cells (endothelium) that line the inner surface of the artery do not support the binding of leukocytes; however, when the endothelium is activated by risk factors such as smoking, high blood pressure, a high-fat diet, or obesity, the endothelium generates adhesion molecules on its surface that can bind readily to leukocytes (especially monocytes and T cells) in the blood (see Fig. 14.5) (34, 35, 36)

• Once bound to the adhesion molecules, the endothelial cells secrete chemokines that attract the monocytes to enter the intima, where they mature into macrophages (see Fig. 14.5A).

• The macrophages develop scavenger receptors on their surface that help them ingest large amounts of modified LDL cholesterol.

• The macrophages become loaded with fatty droplets and develop into foam cells (see right side of Fig. 14.5A). These foam cells and the T cells make up the “fatty streak,” the earliest form of atherosclerotic plaque.

• As the process continues, the macrophages multiply due to growth factors they produce, and the size of the plaque increases.

• As this is developing, some of the smooth muscle cells in the middle layer (media) of the artery move to the top layer of the intima (near the lumen) where they multiply and, with connective tissue, form a fibrous matrix cap over the fatty core of the plaque (see Fig. 14.5B).

At some point, the foam cells release inflammatory signals that lead to the digestion and weakening of the fibrous matrix cap. If the cap ruptures, the chemicals from the foam cell interact with factors in the blood to form a clot (thrombus) that might be large enough to completely block an artery (see Fig. 14.5C). It is this process that causes most heart attacks (35, 36).

Obesity, Inflammation, and Chronic Disease

It is now recognized that a low-grade chronic inflammation is linked to a wide variety of chronic diseases, including hypertension, heart disease and stroke, some cancers, respiratory conditions, type 2 diabetes, and the metabolic syndrome (to be discussed in more detail in the next section) (38, 60). The chronic low-grade inflammation is characterized by a two- to threefold increase in inflammatory cytokines (e.g., tumor necrosis factor alpha [TNF-α], interleukin-6 [IL-6], and C-reactive protein [CRP]).

Of interest to the readers of this text is the impact of obesity on inflammation and chronic disease. Currently in the United States, 35.7% of adults are obese (46). Obesity is linked to a variety of chronic diseases, including CHD, hypertension, and type 2 diabetes, to name a few. The physiological connection between having too much adipose tissue and the inflammation related to chronic disease includes the hormones and inflammatory cytokines released by adipose tissue (27, 69).

Under normal conditions, adipocytes synthesize and store lipids and release anti-inflammatory hormones (e.g., adiponectin—see A Closer Look 5.2). However, the adipocytes have the capacity to secrete a variety of inflammatory cytokines (e.g., IL-6). When the adipocytes, especially those in the visceral area, increase in size, as seen in obesity, they secrete more IL-6 and less adiponectin (27). In addition, macrophages infiltrate the enlarged visceral adipose tissue, promote a local inflammation, and secrete TNF-α, a potent inflammatory cytokine (69). Increased amounts of free fatty acids (FFA), IL-6, and TNF-a (and reduced amounts of adiponectin) are released from the visceral adipose tissue into the liver and then the general circulation. In combination, they interfere with the action of insulin (causing insulin resistance), which is linked to type 2 diabetes, cardiovascular disease, and the metabolic syndrome (21, 27, 60, 69).

C-reactive protein (CRP) is released from the liver in response to these inflammatory factors, and the concentration of CRP in the blood is used as a marker of inflammation (35, 36). Although CRP may (69) or may not (35) be directly involved in the atherosclerotic process, it is clear that CRP is a risk factor for heart disease and a useful predictor of disease risk in those with other risk factors (14). Investigators have used it and other inflammatory markers to evaluate the impact of different strategies on the low-grade inflammation associated with chronic diseases. Both pharmacological (i.e., drugs) and nonpharmacological (i.e., diet and exercise) interventions have been used to try to reduce this systemic inflammation.

Healthy Eating and Physical Activity to Combat Inflammation

In terms of healthy eating, Esposito et al. have shown that eating a Mediterranean-style diet (high in fruits, vegetables, legumes, whole grains, and olive oil) for two years resulted in a dramatic reduction in CRP and IL-6, with no changes observed in the control group (23). Further, such results were observed even without weight loss (58). This dietary-induced reduction in inflammatory markers is believed to be linked to suppression of pathways that stimulates the transcription of genes involved in the inflammation process (28). We will see more on healthy eating plans in Chap. 18.

As mentioned earlier, there is an abundance of research showing that regular participation in physical activity reduces the risk of many chronic diseases. Related to systemic inflammation, there is a growing body of evidence from prospective longitudinal studies that higher levels of physical activity and/or cardiorespiratory fitness are associated with lower levels of inflammation (8, 9, 33). Intervention studies confirm these findings, but the reduction in inflammation may be due more to weight loss than exercise itself, except in those populations (e. g., patients in cardiac rehabilitation, obese individuals) that have higher baseline levels of inflammation (7, 8, 9, 18, 29, 33, 45, 51, 59, 73). Figure 14.6 shows potential mechanisms through which exercise training might reduce chronic inflammation in obesity (73):

• Acute exercise stimulates IL-6 release from skeletal muscle, which suppresses proinflammatory cytokines.

• Exercise training may increase angiogenesis (creation of new blood vessels) in adipose tissue to result in an increase in blood flow and a reduction in hypoxia and associated chronic inflammation in adipose tissue.

• Exercise also reduces adhesion molecule production in endothelial cells and lowers vascular wall inflammation.

• Exercise training may reduce the expression of toll-like receptors (that recognize molecules tied to pathogens) and the number of proinflammatory monocytes.

It is clear that anti-inflammatory activity is not the only mechanism responsible for the health benefits of exercise (13, 24, 38, 53). Exercise affects a wide variety of risk factors (e.g., blood pressure, abdominal fat, HDL-C), and the evidence is overwhelming that exercise training is very important in reducing the risk of many chronic diseases (11). Given all this, it is clear that to reduce the risks of chronic diseases, we should use a combination of dietary change to the Mediterranean style, a reduction in body weight to an appropriate level, and an increase in physical activity and/or cardiorespiratory fitness to achieve that goal, since each has an independent effect (see Chaps. 16, 17, and 18 for more on each of these).

We end this chapter with a discussion of the metabolic syndrome as a way of pulling together all of what we have seen and emphasizing, again, the importance of healthy eating and physical activity in the prevention and treatment of chronic diseases. Epidemiologists are not the only scientists interested in examining potential relationships between variables in order to have a greater understanding of what causes chronic diseases. Physiologists study how tissues and organs function to maintain homeostasis and try to uncover the source of a problem when homeostasis is not maintained. A good example of a failure to maintain homeostasis is hypertension, a problem that affects more than 28% of adult Americans (72). Interestingly, investigators have found that hypertension does not generally occur in isolation. It is not uncommon for hypertensive individuals to also have multiple metabolic abnormalities, such as

• Obesity—especially abdominal obesity

• Insulin resistance—a condition in which tissues do not take up glucose easily when stimulated with insulin; muscle is the primary site of insulin resistance

• Dyslipidemia—abnormal levels of triglycerides and other lipids

The fact that these abnormalities often occur as a group suggests a common underlying cause that might give us a better understanding of the disease processes associated with hypertension. The coexistence of insulin resistance, dyslipidemia, and hypertension has been called Syndrome X (57); those who add obesity to the model call it the Deadly Quartet (30). However, metabolic syndrome is currently the preferred term. To establish the prevalence of metabolic syndrome in the population, scientists first established an operational definition of the syndrome—a person has to have three or more of the following to be considered as having the syndrome (44):

• Abdominal obesity: waist circumference >102 cm in men and >88 cm in women

• Hypertriglyceridemia: ≥150 mg/dl

• Low high-density lipoprotein (HDL) cholesterol: <40 mg/dl in men and <50 mg/dl in women

• High blood pressure: ≥130/85 mm Hg

• High fasting blood glucose: ≥100 mg/dl

The overall prevalence of metabolic syndrome in the United States from 2003 to 2012 was 33%, with a greater prevalence for women (35.6%) than men (30.3%) (1).

What causes the metabolic syndrome? Two theories have been advanced, and they are not mutually exclusive. One theory is that the cause of metabolic syndrome is a low-grade chronic inflammation, similar to what we have just seen for atherosclerosis. Figure 14.7 shows the complex interrelationships of the various metabolic disorders that these authors call the cardiovascular metabolic syndrome because of its obvious connection to cardiovascular disease (56, 70). The double arrows in the figure indicate that each of the disorders can affect the others. The sheer complexity of this web of causation makes it difficult to identify a single cause of metabolic syndrome. Two potential interpretations include the following:

• The increased levels of inflammatory cytokines (e.g., TNF-α, IL-6, CRP) cause the insulin resistance that leads to obesity and type 2 diabetes (56).

• The central obesity leads to an increase in inflammatory cytokines and FFA that, in turn, cause the insulin resistance (41).

Obviously, there are other interpretations, and the inflammation theory is not alone in suggesting cause. The other theory is that an elevated level of oxidative stress causes metabolic syndrome. Oxidative stress exists when free radicals (highly reactive molecules that are missing an electron) accumulate because they are being produced faster than our antioxidant systems can neutralize them, or because the level of antioxidants is inadequate, or both. These highly reactive free radicals react with and can damage lipids, enzymes, and DNA. This can lead, in turn, to altered cellular function and to an inflammation response to deal with the cell damage. A growing body of evidence links oxidative stress to hypertension, insulin resistance, cardiovascular disease, type 2 diabetes, and metabolic syndrome (26, 61). We are sure to hear more about these theories in the years ahead. What can we do about these chronic diseases?

Figure 14.8 provides some clear suggestions that make it a nice wrap-up of what we have just seen and points the way for what is ahead (32). There is a large body of evidence showing that endurance exercise training favorably affects a majority of the risk factors making up metabolic syndrome (25), with less support for resistance training (5, 17). You will read more about exercise programming in Chaps. 16 and 17. In addition, the importance of diet in achieving a healthy body composition will be explained in detail in Chap. 18. Not surprisingly, diet and exercise are the principal nonpharmacological interventions used to prevent and treat a variety of chronic diseases. See Suggested Readings for the most current guidelines for both diet and physical activity.

1. What are the leading causes of death? How about the top three actual causes of death?

2. List the major categories of risk factors and give examples of some in each category.

3. In the web of causation for atherosclerosis, are the various risk factors directly linked to the disease? How do the risk factors interact?

4. Physical inactivity was long considered only a secondary risk factor. What “proof” did investigators have to offer to convince the scientific community otherwise?

5. List the steps (beginning with activation of epithelial cells on the intima) leading to the rupture of plaque that can result in a clot that can cause a heart attack.

6. Discuss the role that enlarged adipose tissue cells (seen in obesity) play in the inflammation response related to numerous chronic diseases.

7. What is metabolic syndrome and what are its potential underlying causes?

8. What two behaviors should be the focus of attention to minimize the systemic inflammation that is linked to chronic disease?