Elsevier

Progress in Cardiovascular Diseases

Volume 57, Issue 4, January–February 2015, Pages 306-314
Progress in Cardiovascular Diseases

Physical Activity and Cardiorespiratory Fitness as Major Markers of Cardiovascular Risk: Their Independent and Interwoven Importance to Health Status

https://doi.org/10.1016/j.pcad.2014.09.011Get rights and content

Abstract

The evolution from hunting and gathering to agriculture, followed by industrialization, has had a profound effect on human physical activity (PA) patterns. Current PA patterns are undoubtedly the lowest they have been in human history, with particularly marked declines in recent generations, and future projections indicate further declines around the globe. Non-communicable health problems that afflict current societies are fundamentally attributable to the fact that PA patterns are markedly different than those for which humans were genetically adapted. The advent of modern statistics and epidemiological methods has made it possible to quantify the independent effects of cardiorespiratory fitness (CRF) and PA on health outcomes. Based on more than five decades of epidemiological studies, it is now widely accepted that higher PA patterns and levels of CRF are associated with better health outcomes. This review will discuss the evidence supporting the premise that PA and CRF are independent risk factors for cardiovascular disease (CVD) as well as the interplay between both PA and CRF and other CVD risk factors. A particular focus will be given to the interplay between CRF, metabolic risk and obesity.

Introduction

The evolution from hunting and gathering to agriculture, followed by industrialization, has had a profound effect on human physical activity (PA) patterns. Beginning with primitive civilizations, in which large amounts of energy expenditure were required to survive in the natural environment, human energy expenditure has progressively declined. Current PA patterns are undeniably the lowest they have been in human history, with particularly marked declines in recent generations and future projections indicate further declines around the globe.1., 2., 3., 4. This is attributable to trends in automation and transportation, other social and environmental changes, and increased screen time (computers, television, etc.). Non-communicable health problems that afflict current societies are undeniably attributable to the fact that PA patterns are markedly different than those for which humans were genetically adapted.1., 2., 3., 4.

Recognition of the association between PA, health, and longevity is probably as old as there are historical records. The writings of the classic Greek physicians Herodicus, Hippocrates, and Galen are replete with references to fitness; each believed that a healthy body was a prerequisite for mental well-being.5 They recommended moderate PA to promote health, but also advised that excessive exertion may have detrimental effects on health. In the early 18th century the Italian physician Bernardino Ramazzini, considered the father of occupational medicine,6 compared diseases that afflicted various occupations. He noted that professional messengers, most of whom were exceptional runners, avoided the health hazards common to more sedentary occupations such as tailors and cobblers.7 He stated, “Let tailors be advised to take physical exercise at any rate on holidays. Let them make the best use they can of some one day, and so to counteract the harm done by many days of sedentary life”. The United States (US) founding fathers were also conscious of the importance of physical fitness (PF). Benjamin Franklin advocated 15 minutes of brisk stair climbing at intervals throughout the day, along with swimming and the use of dumbbells for health purposes.8 Thomas Jefferson recognized the need for activity when he wrote, “Not less than 2 hours a day should be devoted to exercise and the weather shall be little regarded. If the body is feeble, the mind will not be strong.”9 The perspectives from these historical figures, stressing the importance of what we now refer to as PA and CRF, have all proven to be true.

The advent of modern statistics and epidemiological methods has made it possible to quantify the independent effects of CRF and PA on health outcomes. Based on more than five decades of epidemiological studies, it is now widely accepted that higher PA patterns and levels of CRF are associated with better health outcomes. The genesis of modern epidemiology in the context of PA is commonly attributed to Professor Jeremy Morris and his colleagues10 in the mid-20th century. In a series of studies, they used modern quantitative analyses, including consideration of biases due to selection and other potential confounding variables, to demonstrate that regular PA offers protection against the development of CVD. Their early work included the observation that drivers of double-decker buses in London experienced roughly twice the CVD mortality than the comparatively more physically active bus conductors.11 Further studies among British civil servants demonstrated that physically active postal service workers appeared to be protected against CVD when compared to less active clerks, telephone operators and other government workers. These studies further suggested that when CVD did develop among those in more active occupations, it developed at later ages and was less severe. These findings were confirmed and extended by others, most notably Paffenbarger and colleagues,12., 13., 14. initially among San Francisco longshoremen and later among Harvard Alumni. Dr. Paffenbarger's work more precisely identified the amounts and types of PA that were associated with longevity, along with the risks associated with being chronically inactive.

In 1956, President Eisenhower established the President's Council on Youth Fitness, a result of the growing concern for the lack of PF among American youth. The Council on Youth Fitness was specifically a response to the perception that many young men were unfit for military duty, and that poor PF was attributable to dramatic changes mechanization and thus the nature of work and recreation. A month after his inauguration in 1961, John F. Kennedy convened a national conference on PF. With the cooperation of 19 US educational and medical organizations, the president's council initiated a school curriculum with the goal of improving PF, including a minimum amount of time devoted to vigorous PA daily. For much of the mid-twentieth century, the focus of these efforts was on youth PF, but an appreciation for the health consequences of physical inactivity in adults was evolving through epidemiologic studies. In 1961, Kraus and Raab15 published the text Hypokinetic Disease, which many consider to be a landmark publication linking many chronic conditions to physical inactivity. Health problems associated with sedentary lifestyles became a focus of study by numerous medical and research communities. In the 1970s, the American College of Sports Medicine (ACSM) Guidelines for Exercise Testing and Prescription were first published, and the 8 subsequent editions of this text have provided evidence-based and widely-applied recommendations on the volume, duration, and intensity of exercise to promote health.16

During the last two decades, a wealth of epidemiologic studies has documented the health benefits of regular PA. It is now widely appreciated that higher CRF and PA patterns are beneficial for the prevention of not only CVD, but also site-specific cancers, type 2 diabetes mellitus (T2DM), improved bone health, reduced disability, and increased longevity; PA patterns provide information on risk that is independent from traditional CVD risk factors.17., 18. Expert panels convened by organizations such as the Centers for Disease Control and Prevention (CDC), the ACSM, the European Working Group on Cardiac Rehabilitation and Exercise Physiology, and the American Heart Association (AHA),16., 19., 20., 21., 22. along with the US Surgeon General's Report on Physical Activity and Health23 have synthesized and reinforced the volume of scientific evidence linking regular PA to various measures of health. Given the well-documented association between physical inactivity and adverse health outcomes worldwide, the current prevalence of physical inactivity, and the growth in the prevalence of obesity in the US and Europe in recent decades,24., 25., 26., 27. the health care provider's role is more critical than ever in terms of encouraging both patients and the public to increase PA, and to develop strategies that promote the adoption of physically active lifestyles.

Although a great deal has been learned from these epidemiologic studies on the association between PA, CRF, and health, PA remains underused as an intervention to reduce risk for CVD, all-cause mortality, and other outcomes.28., 29. Most health care providers do not appreciate the independent role of PA in prevention, nor do they recognize the fact that higher PA patterns and CRF have an important moderating influence on the traditional CVD risk factors. In the following, low levels of CRF and PA as independent risk factors for CVD are outlined, and the interplay between PA and other CVD risk factors is discussed with particular focus on metabolic risk and obesity.

Since the above-mentioned landmark work of Morris and coworkers,11 published more than 60 years ago evidence has accumulated from occupational, leisure time and PF assessment studies that support a strong, inverse, graded and independent association between PA, health and both CVD and overall mortality in apparently healthy individuals, regardless of race or gender as well as those with documented CVD. This association is independent from traditional CVD risk factors and as robust as that of the traditional CVD risk factors.17., 18. In fact, many scientists and clinicians in the field now recognize physical inactivity and low CRF as traditional risk factors themselves, which is highly justified based on the longstanding body of evidence supporting this supposition.

A number of noteworthy studies assessing CRF by standardized exercise tests have quantified risk of mortality based on peak metabolic equivalent (MET) levels achieved. These studies have permitted quantification of the dose (amount of exercise or degree of CRF) and response (mortality risk-reduction) relationship by expressing exercise capacity in the context of survival benefit per MET. The reduction in mortality risk per 1-MET increase in exercise capacity ranges between 10% and 25% in both men and women.17., 18., 28. Recent evidence suggests the mortality risk reduction may be higher than this in low fit individuals (peak MET level < 5) with CVD who participate in cardiac rehabilitation and improve their peak MET level (≈ 30% reduction per MET improvement).30 In addition, studies have established that the risk reduction is graded and that it falls precipitously beyond an age-dependent peak exercise capacity threshold of approximately 5–6 METs. A recent study more specifically defined age-specific fitness thresholds to identify mortality risk.31 For each age category, the risk was progressively higher for those with a peak MET level below the age-specific threshold and progressively lower for those with a peak MET level above it. The 5- and 10-year mortality risk estimates followed similar patterns. Importantly, these studies suggest that only modest amounts of exercise are necessary to achieve significant health benefits. In this regard, a recent study found markedly lower mortality risk in those who jog slowly as little as 5–10 minutes per day.32

Other studies have reported inverse relationships between CRF and mortality risk in the context of dyslipidemia, obesity, T2DM and hypertension (HTN) with and without additional risk factors. In HTN and T2DM, the increased risk associated with a low CRF (≤ 5 METs) and additional CVD risk factors was virtually eliminated by relatively small increases in exercise capacity (i.e., a 1 quartile increase from ≤ 5 to 5–7 METs). Together, these studies suggest that increased CRF strongly attenuates the risk of mortality imposed by a CVD risk factor or a cluster of risk factors.17

Two recent and notable studies assessed the independent and synergistic effects of CRF status and stain therapy on mortality risk in dyslipidemic33 and hypertensive34 individuals. In both studies, the risk reduction associated with a moderately higher CRF level alone was similar to that achieved by statin therapy. This was despite a less favorable lipid profile in those not treated with statins, suggesting CRF was protective via different mechanism(s). The combination of increased CRF and statin treatment was more effective in lowering risk than either condition alone. The exercise capacity necessary to achieve similar or an even greater reduction in risk than that achieved by statin therapy alone was just over 5 METs. It is also noteworthy that the mortality risk in moderate and high-fit hypertensive individuals (> 6.5 METs) not treated with statins was 24% and 52% lower, respectively, than that among individuals in the lowest CRF category treated with statins. These findings support the concept that higher CRF is at least as effective as statin therapy in lowering mortality risk. Among individuals with stage 2 HTN, moderate intensity aerobic exercise lowered blood pressure significantly after 16 and 32 weeks even with a 33% lower use of antihypertensive medication.35 The efficacy of exercise as therapy was strongly supported by a recent meta-analysis involving more than 339,000 individuals,36 in which it was reported that exercise interventions were as effective as drug therapy for secondary prevention of coronary heart disease (CHD), treatment of heart failure (HF) and prevention of T2DM.

The overwhelming evidence supporting a strong link between PA and health and the deleterious effects of inactivity led to the classification of physical inactivity as the fourth primary risk factor for CAD by the AHA more than 20 years ago.37 The importance of increased PA across all ages was also stated by the US Surgeon General's Report on PA and Health23 with the compelling message that adding moderate amounts of daily PA can substantially improve health and quality of life. Efforts to emphasize the concept that physical inactivity is a major, risk factor and the importance of increased PA for all ages has been underscored by expert panels organized by the CDC, ACSM, the European Working Group on Cardiac Rehabilitation and Exercise Physiology, and AHA.19., 20., 21., 22., 37. Moreover, numerous studies have reported fewer health problems and lower health care costs among more physically active individuals. Population-based or worksite wellness programs have consistently reported that individuals who are comparatively sedentary have higher overall health care costs, which has been attributed to factors including greater illness and hospitalization, disability, and lower productivity.28., 38.

Despite the plethora of evidence worldwide related to the independent and powerful influence of PA and CRF on human health, and despite the efforts of many health organizations to increase awareness of this evidence, physical inactivity and low CRF remain overlooked and underutilized risk factors. The pressing question is “Why is this so?” Many approaches have been attempted with various levels of success, and barriers have been identified. In general, efforts to increase PA, which would presumably increase CRF, have been fragmented. For a paradigm shift, it is essential that a unified plan be developed and implemented. Such a plan must involve healthcare providers, industry, health insurance companies, the government and the public. Healthcare providers have the greatest potential to promote PA in their patients.28 However, unwarranted fears of an acute CVD event as a result of exercise recommended by a health care provider, lack of reimbursement for patient consultation, time constraints, lack of resources for both health care providers and the public and the perceived ineffectiveness of counseling are barriers to greater investments in PA by healthcare providers. Education regarding the safety of exercise among health care providers and the public is critical. For example, although there is a small increase in the risk of a CVD event with strenuous exercise, numerous studies have shown that individuals at the highest risk for an exercise-related event are those who are habitually inactive.39 Thus, the public health message must include efforts to allay unwarranted fears related to risks associated with PA.

It is also time to seriously consider reimbursement for patient consultation and incentives implemented by the health insurance industry and employers for the public to initiate and maintain an active lifestyle. The public must also take an active role. Our health should not only be the responsibility of the physician and the drug companies, but our own. Time constrains as a reason not to exercise are largely invalidated by evidence supporting marked reductions in mortality risk by ≈ 3–10 minute sessions of moderate PA per day, and the recent evidence showing that even slow running just 5–10 minutes per day reduces risk.32 In addition, businesses should provide facilities and allocate time for employees to exercise in the workplace. Finally, the federal government must take the lead and set the example by fostering PA in government facilities.

Recent evidence from cardiac magnetic resonance imaging studies indicates that higher levels of PA are associated with more favorable cardiac structure and function.40 Higher levels of PA also attenuate the CVD mortality risk associated with obesity.41., 42., 43., 44., 45., 46., 47. Conversely, the CVD risk associated with obesity is compounded by physical inactivity. Since a sedentary lifestyle is more common among obese than normal-weight individuals,42 the association of obesity with increased CVD risk may be mediated in part by habitual physical inactivity.

To assess the full impact of physical inactivity as a CVD risk factor, it is necessary to examine interactions among PA and other lifestyle indicators. In this regard, several recent large scale studies with > 10 years of follow-up have attempted to specifically quantify the combined effects of physical inactivity and obesity on CVD risk. For example, in an investigation of over 116,000 women from the Nurse's Health Study (NHS) with 24 years of follow-up, CVD mortality was 62% higher for women who were obese and inactive compared to obese women who were active.43 Similar results were reported in a subsequent study of 24,684 women and 22,528 men from Finland aged 25 to 64 years during a mean follow-up of 18 years.44 Obese men and women who were inactive were 45% and 90% more likely, respectively, to die of CVD than their active counterparts. In another follow-up investigation from the NHS, inactive versus active obese women had a 39% higher risk for CHD events (including nonfatal myocardial infarction/MI and fatal CHD) during 20 years of follow-up.45 Data from the Women's Ischemic Syndrome Evaluation (WISE) study on 38,987 women during a mean follow-up of 11 years revealed that obese women who were inactive had a 35% higher risk for developing CHD (defined as a CVD event including nonfatal MI, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, or CHD death) compared to their active counterparts.46 Taken together, these studies provide compelling evidence that CVD risk is substantially higher (from ~ 35% to ~ 90%) for obese individuals who were physically inactive compared with their obese counterparts who were active.

Nevertheless, the interplay between physical inactivity and other lifestyle factors including obesity, as well as obesity-related metabolic disorders, is complex and not well understood. A few recent studies have attempted to unravel these intricacies by examining simultaneous measures of PA, obesity, and other risk factors. For example, the association between insulin resistance and obesity is greatly altered by PA level. In a recent study from the Multi-ethnic Study of Atherosclerosis (MESA) study, among obese men and women, those who were physically inactive had an 88% higher odds for insulin resistance compared to those who were physically active.47 In a previous MESA report, Allison et al.48 found that physical inactivity was associated with a less favorable profile of adiposity-associated markers that were independent of other relevant factors. Arsenault et al.49 quantified the combined impact of physical inactivity and abdominal obesity in 21,729 men and women from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk study during 11 years of follow-up. The influence of physical inactivity on abdominal obesity was heterogeneous with respect to sex. Abdominally obese men who were inactive were 27% more likely to develop CHD than their active counterparts. Far less of a difference was observed in abdominally obese women, among whom those who were inactive had a 10% higher CHD risk compared to their active counterparts. Overall, the compounding influence of physical inactivity on abdominal obesity appears to be far less than that observed for general obesity, indicating perhaps more co-linearity between inactivity and abdominal obesity. However, to ascertain cause and effect relationships, randomized clinical trials with PA as a long-term (i.e., > 10 years) intervention will be required.

Substantial evidence during the last two decades indicates that CRF markedly alters the relationship between adiposity and subsequent major health outcomes.50 Although clearly excess body weight and low CRF are associated with worse CVD risk factors and increased prevalence of CVD, the relative and combined importance of both remains somewhat controversial.50 Recently, Barry and colleagues51 performed a meta-analysis of ten studies and quantified the joint association of CRF and weight on mortality and demonstrated that compared to normal weight-fit individuals, unfit individuals had a two-fold higher risk of mortality regardless of body mass index (BMI). Overweight-fit and obese-fit individuals had a similar mortality risk as normal weight individuals.

Additionally, in a study of 3148 healthy adults, changes over time in both adiposity and CRF predicted development of HTN, metabolic syndrome, and hypercholesterolemia, but the impact of CRF seems somewhat better than adiposity for future risk of these disorders.52 In another study, a 1-MET increase in CRF on two maximal exercise tests separated by an average of 6.3 years was associated with reductions in all-cause and CVD mortality of 15 and 19%, respectively, among 14,345 men.53 In this large cohort, BMI changes were not associated with CVD or all-cause mortality after adjusting for changes in CRF and other confounders. Therefore, the constellation of these data suggests that CRF may be more important than adiposity regarding long-term health outcomes.

During the past decade, substantial evidence has supported an obesity paradox among many cohorts with known CVD.50., 54. Despite the adverse effects that overweight and obesity have on multiple CVD risk factors and the fact that overweight and obesity increase the prevalence of most CVDs, including HTN, CHD, and HF, among others, overweight and obese patients with these established CVDs seem to have a better prognosis than do their leaner or normal BMI counterparts with the same CVDs, which has been termed the “obesity paradox”.

The contribution of CRF to the obesity paradox has recently been reviewed in detail elsewhere.50., 54. Considerable evidence in both CHD and HF suggests that CRF markedly impacts the relationship of adiposity with subsequent prognosis.50., 54., 55., 56. In a recent study of 9563 patients with known or suspected CHD, only those in the bottom tertile of gender- and age-related CRF demonstrated a strong obesity paradox, with the leaner patients (by BMI, % body fat, as well as central obesity/waist circumference) having higher CVD and all-cause mortality than do heavier patients who are also un-fit.55 Fitter CVD patients had a favorable prognosis regardless of fatness. In a large group of 2,066 patients with HF, CRF was assessed by peak oxygen consumption (VO2); divided into un-fit with peak VO2 < 14 ml•kg 1•min 1 and fit as ≥ 14 ml•kg 1•min 1).56 Patients with low CRF had a poor prognosis, particularly the normal BMI patients, whereas the best prognosis was observed in those with BMI  30 kg/m2. On the other hand, the relatively fit patients had a good overall survival and no obesity paradox was noted.56 Therefore, CRF markedly impacts the obesity paradox.50., 55., 56. Although CRF can be impacted by genetic factors, the strongest reversible component of CRF comes from PA. Therefore, PA, which leads to higher CRF, also markedly alters the relationship between adiposity and prognosis in the general population as well as those with CVD, such as CHD and HF.

As discussed in other sections of this paper, although it is well recognized that obesity and lack of PA are both associated with increased morbidity and mortality from CVD, both risk factors are associated with each other, and this interaction is complex. Obesity is generally defined by an excess of body fat causing prejudice to health and is most commonly evaluated in clinical practice by BMI expressed as the ratio of weight in kg over height in meters squared. However, although the links between obesity and alterations in some CVD risk factors such as blood pressure, lipids, insulin resistance and T2DM have been long recognized, not every obese patient is characterized by these risk factors.57

In the late 1940s, a French physician, Jean Vague, was the first to propose the notion that the health complications of obesity were more closely related to body shape, namely to an altered body fat distribution, rather than to excess body weight/fat.58 As Vague did not have sophisticated imaging tools to validate his hypothesis, it took more than 35 years before these early clinical observations were confirmed by a series of metabolic and prospective population-based studies. In those studies, investigators used a very simple anthropometric index, the waist-to-hip circumference ratio (WHR), to crudely assess the proportion of abdominal fat, the rationale being that a preferential accumulation of abdominal fat produces a selective increase in waist circumference compared to hip girth. With the help of the WHR, a stream of reports have suggested that Vague's hypothesis was worthwhile to explore further as this index was found to be a powerful correlate of an altered cardiometabolic profile and an independent predictor of CVD outcomes and T2DM.

The introduction of imaging techniques such as computed tomography (CT) and magnetic resonance has been a revolution in the study of the link between excess fatness, body fat distribution and various health outcomes. With the availability of these noninvasive methods, it became possible to measure with great accuracy not only the amount of total body fat but to also precisely assess the accumulation of fat at any site of the body. For instance, with the use of CT, two research groups59., 60. almost simultaneously proposed that the amount of adipose tissue found in the abdominal cavity, the so-called visceral or intra-abdominal adipose tissue, was a critical correlate of the metabolic complications which had been in the past related to excess fatness per se. Indeed, these studies suggested that in the absence of excess visceral adiposity, excess body fatness alone was not associated with glucose intolerance or pro-atherogenic dyslipidemic profile (i.e., high triglycerides, apolipoprotein B, and small low-density lipoprotein-cholesterol as well as low high-density lipoprotein-cholesterol). However, for any given BMI or level of total body fat, an excess of visceral adipose tissue has been clearly associated with more severe insulin resistance leading to glucose intolerance and T2DM as well as with the pro-atherogenic dyslipidemic profile.57., 59., 61. Several recent imaging studies conducted on large populations have now confirmed the notion that excess visceral adiposity is a good imaging marker of T2DM and CVD risk in overweight and obese individuals.62., 63.

The combination of the above imaging techniques with metabolic profiling studies has allowed us to better understand why excess visceral adiposity is such a good predictor of health outcomes in overweight obese individuals. Firstly, biochemical and metabolic analyses conducted on visceral adipose tissue studied in vitro have shown that this fat has a peculiar metabolic profile with a very lively lipolysis that is resistant to the antilipolytic action of insulin.64 As a result, active tissue is drained by the portal vein; the typically insulin resistant, hyperinsulinemic, viscerally obese male patient exposes his liver to high concentrations of free fatty acids, which contributes to impaired liver metabolism with an increased secretion of triglyceride-rich lipoproteins packed with apolipoprotein B as well as with an increased hepatic glucose output, contributing to the hyperglycemic state often found in viscerally obese patients.57 Secondly, the expanded visceral adipose tissue has been shown to be loaded with macrophages which contribute to the pro-inflammatory profile of visceral obesity.65 Finally, a third explanation is that excess visceral adiposity is a marker of the relative inability of subcutaneous adipose tissue to act as a protective metabolic sink when a physically inactive individual is exposed to a surplus of calories.66 Under such a state of chronic positive energy balance, subcutaneous fat expansion through hyperplasia (more fat cells) creates an expanded metabolic reservoir protecting lean tissues against accumulation of harmful undesired lipids. However, if a given individual is unable, for whatever reason, to produce new subcutaneous fat cells, the energy then accumulates in normally lean tissue such as the liver, the heart, the kidney and the skeletal muscle, a phenomenon described as “ectopic fat deposition”.61

It would be beyond the scope of this article to review the recent literature on the topic of ectopic fat deposition and health. However, a few points must be highlighted. Firstly, all ectopic fat depots assessed in large imaging studies have been shown to be related to an altered cardiometabolic risk profile.66., 67. There is, therefore, a debate as to which of these ectopic fat depots is (are) the key actor(s). Although it is acknowledged that probably none of them are innocent bystanders, it is likely that the increased liver fat accumulation associated with visceral obesity is a key cause of the hyperglycemic, hypertriglyceridemic/apolipoprotein B and hyperinsulinemic state found in visceral obesity.61 However, the specific contribution of the ectopic fat accumulation in skeletal muscle has been suggested as an important cause of systemic insulin resistance.68 In addition, studies have suggested that the amount of fat located in the renal sinus, a tiny ectopic fat depot, could nevertheless be associated with hypertension independently from excess visceral fat.66 Accordingly, although excess epi/pericardial fat has been associated with all features of an altered cardiometabolic risk profile, it is possible that some key local aspects such as regulation of coronary blood flow and atherosclerosis or myocardial metabolism and function, to only name a couple of heart-related functions, may be related to the quantity and the quality of this local fat.66., 67. Epicardial fat has even been shown to contain brown and even beige adipocytes, which functions remain to be established.69

Thus, as the size of all the above ectopic fat depots has been related to the amount of visceral adipose tissue, a key remaining question will be to quantify the specific contribution of all these depots to the various clinical outcomes that have been related to visceral obesity.66., 67. For example, one could envision that some combinations of ectopic fat depots may be more related to specific outcomes, such as HF, whereas others could be more related to CHD or to T2DM. This question will be a very fertile area of investigation with potentially important clinical consequences. For the time being, studies suggest that excess visceral adiposity is an excellent marker of ectopic fat deposition, its specific role among the ectopic fat depots having to be defined by future and extensive cardiometabolic/imaging studies.61., 67.

Population studies have documented the relationship between the level of overall PA participation to total adiposity. Although there is clearly a selection bias, the most spectacular example of this relationship is the body composition of highly trained endurance athletes which have a very high energy expenditure and a low body fat content despite a fairly high energy intake. However, studies conducted among initially sedentary and overweight/obese individuals have generally shown more modest weight losses with PA.70 In fact, greater weight loss has been generally obtained over the short term by caloric restriction compared to exercise training. The explanation for this phenomenon is relatively simple given that a net daily energy deficit of 500 kcal per day requires almost one hour of moderate intensity exercise. Thus, one needs to exercise a lot to lose weight without caloric restriction.71

However, when we debate the respective roles of PA vs. diet in the management of overweight/obese individuals, three aspects should be addressed. First, regular exercise substantially reduces mortality/morbidity risk, even in the absence of weight loss.67 For instance, it has been shown that even in the presence of CVD risk factors such as T2DM or abdominal obesity/metabolic syndrome, individuals afflicted by these conditions but who report being very active are characterized by about a 50% reduction in their risk of CVD compared to inactive individuals.72 This finding supports the view that getting patients out of their sedentary behaviors should be a top priority in clinical practice, even before aiming at weight loss. Secondly, long-term caloric restriction, although showing efficacy over the short term, does not seem to work over years.71 Studies generally indicate that regular PA favors the maintenance of a reduced body weight and that it is the combined use of moderate caloric restriction and PA/exercise that confers the best long term prognosis. Finally and more importantly, imaging studies have shown that regular PA induces a selective mobilization of visceral adipose tissue and of other ectopic fat depots.67., 70. Furthermore, such ectopic fat mobilization could even be observed in the absence of weight loss if the patient's muscle mass is increased by the exercise program. The latter finding has led us67 and others70 to suggest that a reduction in waist circumference may represent a better outcome than weight loss when patients are removed from their sedentary behaviors and start being physically active at work and during their leisure time. Finally, as discussed in other sections of this article, regular exercise has the potential to improve CRF which is one of the key predictors of health outcomes irrespective of the patient's health status.17., 18., 22., 28., 36., 37., 38., 39. Because of the importance of CRF and of abdominal obesity (associated with excess visceral/ectopic fat), it has been proposed that reducing a patient's waistline and improving his/her CRF through regular exercise may represent more clinically relevant therapeutic targets than weight loss alone.69

Section snippets

Conclusion

The evidence supporting the value of physical activity and CRF is beyond dispute. Given the evidence supporting their value, the current healthcare model should quickly move toward integrating PA or CRF assessments into clinical practice. Given the evidence, the paradigm illustrated in Fig 1 depicts the way PA and CRF might be viewed in CVD risk assessment. No matter what an individual's health status (i.e., the traditional CVD risk factors to the left of Fig 1), higher levels of PA and CRF

Statement of Conflict of Interest

The author has no disclosure information to declare.

References (72)

  • P.A. McAuley et al.

    The obesity paradox, cardiorespiratory fitness, and coronary heart disease

    Mayo Clin Proc

    (2012)
  • C.J. Lavie et al.

    Impact of cardiorespiratory fitness on the obesity paradox in patients with heart failure

    Mayo Clin Proc

    (2013)
  • JP Despres et al.

    Regional distribution of body fat, plasma lipoproteins, and cardiovascular disease

    Arteriosclerosis

    (1990)
  • J.P. Després et al.

    Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk

    Arterioscler Thromb Vasc Biol

    (2008)
  • T.P. Fitzgibbons et al.

    Epicardial and perivascular adipose tissues and their influence on cardiovascular disease: basic mechanisms and clinical associations

    J Am Heart Assoc

    (2014)
  • S.W. Ng et al.

    Time use and physical activity: a shift away from movement across the globe

    Obes Rev

    (2012)
  • J.W. Berryman

    The tradition of “the six things non-natural”: exercise and medicine from Hippocrates through ante-bellum America

    Exerc Sport Sci Rev

    (1989)
  • G. Franco

    Bernardino Ramazzini: the father of occupational medicine

    Am J Public Health

    (2001)
  • B. Ramanazzi

    De Morbis Artificum Diatriba (translated from the Latin text of 1713, revised, with translation and notes by Wilmer Cave Wright)

    (1940)
  • B. Franklin

    The papers of Benjamin Franklin

  • N.J. Karolides et al.

    Focus on fitness: a reference handbook

    (1993)
  • V. Berridge

    Celebration Jerry Morris

    Int J Epidemiol

    (2001)
  • R.S. Paffenbarger et al.

    Work activity of longshoremen as related to death from coronary heart disease and stroke

    N Engl J Med

    (1970)
  • R.S. Paffenbarger et al.

    Work activity and coronary heart mortality

    N Engl J Med

    (1975)
    R.S. Paffenbarger et al.

    Physical activity as an index of heart attack risk in college alumni

    Am J Epidemiol

    (1978)
  • R.S. Paffenbarger et al.

    Physical activity, all-cause mortality, and longevity of college alumni

    N Engl J Med

    (1986)
  • H. Kraus et al.

    Hyokinetic disease: diseases produced by lack of exercise

    (1961)
  • American College of Sports Medicine

    Guidelines for exercise testing and prescription

    (2013)
  • P. Kokkinos et al.

    Exercise and physical activity: clinical outcomes and applications

    Circulation

    (2010)
  • E.J. Shiroma et al.

    Physical activity and cardiovascular health. Lessons learned from epidemiological studies across age, gender, and race/ethnicity

    Circulation

    (2010)
  • American College of Sports Medicine Position Stand: the recommended quantity and quality of exercise for developing and maintaining cardiorespiratory and muscular fitness, and flexibility in healthy adults

    Med Sci Sports Exerc

    (1998)
  • G.F. Fletcher et al.

    Exercise standards for testing and training: a statement for healthcare professionals from the American Heart Association

    Circulation

    (2001)
  • R.R. Pate et al.

    Physical activity and public health: a recommendation from the Centers for Disease Control and Prevention and the American College of Sports Medicine

    JAMA

    (1995)
  • P. Giannuzzi et al.

    Physical activity for primary and secondary prevention. Position paper of the working group on cardiac rehabilitation and exercise physiology of the European society of cardiology

    Eur J Cardiovasc Prev Rehabil

    (2003)
  • U.S. Public Health Service

    Office of the Surgeon General: physical activity and health: a report of the surgeon general

    (1996)
  • Centers for Disease Control and Prevention

    Facts about physical activity

  • World Health Organization

    Physical activity and health in Europe: evidence for action

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    Statement of Conflict of Interest: see page 312.

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