Figure 5.1: Multivariable-adjusted with body mass index hazard ratios. (HRs) and 95% confidence intervals for leisure time ...
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5 Physical activity and health Dr Ian Lahart, Professor George Metsios and Chris Kite Abstract: Epidemiologic evidence supports the inverse, dose-response relationship between both physical activity and cardiorespiratory fitness and the risk of premature all-cause and disease-related mortality, in addition to the chances of developing of chronic diseases, such as cardiovascular disease (CVD), type 2 diabetes, and cancers of the breast and colon. However, there is a dearth of randomised controlled trials (RCTs) studying the effects of exercise on early mortality. The RAMIT trial failed to find a significant effect of exercise-based cardiac rehabilitation on early mortality after two years, whereas the Look Ahead lifestyle intervention (exercise plus caloric restriction) did not result in a reduction in CVD mortality rates at 9.6 years in overweight or obese patients with type 2 diabetes. However, a pooled analysis of 63 RCTs suggests that exercise-based cardiac rehabilitation reduces risk of CVD mortality and hospitalisation, and health-related quality of life, but not total mortality, risk of myocardial infarction, or revascularisation. Furthermore, current evidence demonstrates that exercise can be an effective adjunct intervention to improve and manage symptoms of major non-communicable diseases. In particular, exercise may have beneficial effects on high blood pressure, insulin sensitivity, visceral fat, long-term smoking cessation, mental health, arthritis, osteoporosis, and risk of falling.
Keywords: Physical activity, exercise, chronic disease, epidemiology, randomised controlled trials Key points
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Epidemiologic evidence supports the inverse, dose -response relationship between both PA and CRF and the risk of premature all-cause and disease-related mortality, and development of non-communicable diseases, such as cardiovascular disease (CVD), type 2 diabetes, and breast and colon cancer.
Epidemiologic studies need to be interpreted in light of their limitations and the extent that biases, such as selection bias, misclassification bias, and confounding, may have influenced the observed associations.
There is evidence for the beneficial effects of exercise on premature mortality in CVD, but not type 2 diabetes, but studies investigated the effects of exercise on mortality in other non-communicable diseases are lacking.
There is a dearth of relevant RCTs on the effects of exercise on disease outcomes for the most prevalent non-communicable diseases, however, exercise may have beneficial effects on mental health, arthritis, osteoporosis, and risk of falling,
Evidence suggests that exercise may be beneficial in reducing high blood pressure, improving insulin sensitivity, promoting visceral fat loss, and facilitating long-term smoking cessation.
Although RCTs are valuable tools to investigate causal relationships, they can never be completely objective. The accuracy, applicability, and general isability of exercise RCT results must be interpreted in light of the risks of bias, validity and reliability of measures, magnitude and precision of estimates, and trial sample size.
Introduction
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In this chapter we aim to present an up-to-date synthesis of the best available evidence for the therapeutic role of physical activity (PA) and exercise for
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communicable diseases (NCDs) and health. Firstly, we examine the epidemiologic evidence for an association between PA and cardiorespiratory fitness (CRF) and premature mortality, and the prevention and management of NCDs. To help readers interpret this type of evidence, we will also explore the limitations of epidemiology and the risk of biases inherent in this type of research. Next, we review randomised controlled trials (RCTs) of the effects of exercise interventions on early death and the prevention and management of some of the most prevalent NCDs for which sufficient data exist (e.g., cardiovascular disease, type 2 diabetes, breast and colorectal cancers, and chronic respiratory diseases). Finally, as in the case with the epidemiologic evidence, RCTs are not without their limitations, and we , therefore, provide an overview of the risk of biases these studies are prone to.
Epidemiological evidence for physical activity In PA epidemiology, the reduction in risk of developing a particular outcome (e.g., disease incidence) following exposure to PA is typically expressed in terms of relative risk (RR) reduction. We will present RR reductions in this chapter as percentages, and all included RR reductions referred to were statistically significant (i.e. the 95% confidence intervals of the RR reduction do not pass the line of no effect), unless specifically identified as nonsignificant. The modern history of PA and disease research arguably began wi th the seminal work of Jerry Morris and colleagues in the 1950s. Morris and colleagues (1953) observed
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lower incidences of coronary artery disease (CAD), later onset of CAD, and lower CAD related mortality in double-decker bus conductors (who climbed on average 500–750 steps/day) compared with sedentary bus drivers. Similar findings were also observed by Morris and his team when comparing postmen who cycled or walked to deliver mail with less active co-workers (e.g., postal supervisors) and sedentary counte rparts (e.g., telephonists). Subsequent work of Morris and colleagues (1973; 1966; 1956) noted that 1) CAD incidence was higher in bus drivers compared with conductors independent of physique and blood pressure, 2) CAD was lower in the most active compared with the least active in three separate social classes (skilled, semi -skilled, and unskilled workers), and 3) civil servants who performed more vigorous leisure-time PA experienced lower rates of fatal CAD events. There is further information in regard to the work of Morris and co-workers in Chapter 3. Two other often cited classical studies were conducted by Ralph Paffenbarger (see also Chapter 3) and colleagues on San Francisco longshoremen (known as dock workers in the UK) (Paffenbarger et al., 1970) and college alumni (Paffenbarger, Wing & Hyde, 1978), respectively. In a 16-year follow-up of 3,263 men (aged 35–64 years), Paffenbarger and coworkers (1970) observed that the most active group of longshoremen had fewer CAD deaths than their less active co-workers, regardless of smoking patterns, weight for height, and blood pressure. Similarly, in the Harvard Alumni study, an analysis of nearly 17,000 men followed-up for 16 years revealed an inverse dose-response association between PA and allcause mortality rates, after controlling for high blood pressure, cigarette smoking, extreme bodyweight gains, and early parental death (Paffenbarger et al., 1986). The rates of all-cause
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mortality, primarily due to cardiovascular or respiratory causes, were 25–33% lower among participants who expended ≥2000 kcal during PA per week compared to less active alumni. More recently in one of the largest European-based PA cohort study, the European Prospective Investigation into Cancer and Nutrition Study (EPIC) investigated whether the association between PA and all-cause mortality was modified by adiposity (Ekelund et al., 2015). In an analysis that consisted of 334,161 men and women follow-uped for 12.4 years, the authors (2015) reported that PA was associated with lower al l-cause mortality at all levels of body mass index (BMI) and waist circumference. The researchers (2015) estimated that the number of early deaths would theoretically be reduced by ~7% if all inactive individuals were at least moderately inactive, , compared with a ~4% reduction in deaths if all individuals with a BMI above 30 kg/m2 had a BMI below 30. Many systematic reviews, pooled analyses, and meta-analyses have collated the epidemiological evidence and calculated average RR reductions in all -cause premature mortality and disease incidence and mortality associated with PA. Arem and colleagues (2015) pooled data taken from eight studies (661,137 participants) of the USA National Cancer Institute (NCI) Cohort Consortium. The authors (2015) reported that compared with participants performing no leisure-time moderate-to-vigorous PA (MVPA), participants performing some MVPA but less than the recommended USA PA guidelines (defined as ≥7.5 MET-h/week), and those achieving 1–2, 2–3, and 3–5 times the recommendation had 20%, 31%, 37%, and 39% reductions in all-cause premature mortality risk, respectively (see Figure 5.1). Similarly, based on six studies (654,827 participants) from the same NCI Cohort, compared with no leisure-time activity, PA below recommended levels (0.1–3.74 and 3.747.49 MET-h/week), 1–2 times the recommended level (7.5–14.9 MET-h/week), and
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exceeding 22.5 MET-h/week (or ≥450 min/week of brisk walking) was associated with a gain of 1.8, 2.5, 3.4, and 4.5 years in life expectancy, respectively (Moore et al., 2012). Hupin and co-workers (2015) noted similar findings in a meta-analysis of prospective cohort studies in older adults (≥60 years). Low MVPA (1-499 MET-min/week) was associated with a 22% reduction in all-cause mortality in older adults, whereas following the current PA recommendations (500–999 MET-min/week) and beyond (≥1000 MET-min/week) was related to higher risk reductions of 28% and 35%, respectively, compared with no MVPA. [[Insert Figure 5.1 here]] Figure 5.1: Multivariable-adjusted with body mass index hazard ratios (HRs) and 95% confidence intervals for leisure time moderate -to-vigorous intensity physical activity and premature mortality risk. Mortality risk is expressed as a HR, which is a measure of relative risk (RR) over time. An RR is the probability that a member of a group exposed to PA will develop a disease relative to the probability that a member of an unexposed group will develop that same disease. If RR = ~1.0, an association between exposure to PA and disease is unlikely to exist. If RR = >1.0, there is an increased risk of developing that disease in those who were exposed to PA, and if RR =
