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Cardiovascular fitness attenuates obesity-related risk for chronic disease
Obesity Medicine 8 (2017) 23e26
Contents lists available at ScienceDirect
Obesity Medicine journal homepage: http://www.journals.elsevier.com/obesity-medicine
Cardiovascular fitness attenuates obesity-related risk for chronic disease Jacqueline Heath*, Ronald Maag, Andrew Foy Penn State M. S. Hershey Medical Center, Hershey, PA, USA
a r t i c l e i n f o Article history: Received 31 August 2017 Accepted 12 September 2017
1. Introduction It is widely known that obesity is a negative prognostic indicator in both men and women. Obesity has been linked to increased risk of all-cause mortality and even shortened life expectancy (Calle et al., 1999; Aune et al., 2016; Gu et al., 2006; Yan et al., 2006; Peeters et al., 2003). Additionally, overweight or obese Body Mass Index (BMI) has been linked to increased incidence of chronic conditions, including hypertension, diabetes and cardiovascular disease (Field et al., 2001), as well as increased risk of hospitalization secondary to such conditions (Yan et al., 2006). Fitness, on the other hand, has become a well-accepted positive prognostic health indicator. Increased cardiorespiratory fitness, as defined by maximal treadmill testing, has been linked with lower all-cause and cardiovascular disease mortality (Lee et al., 1998; Blair et al., 1989), independent of conventional coronary risk factors (Ekelund et al., 1988). These benefits have been shown in adults of all age groups and of both sexes. Physical activity has also been shown to particularly benefit individuals with overweight and obese BMI. Higher intensities of weekly activity have been associated with decreased mortality and hypertension in otherwise higher-risk, overweight and obese adults (Hu et al., 2004; Haapanen et al., 1997; Pereira et al., 1999). However, what is less understood is how cardiorespiratory fitness attenuates the risks of chronic conditions in overweight and obese adults. In some studies, it has been shown that overweight or obese adults with high cardiorespiratory fitness have a decreased risk of hypertension (HTN) (Rankinen et al., 2007), diabetes mellitus (DM) (Lee et al., 2009), hypercholesterolemia (HC) (Lee et al.,
* Corresponding author. E-mail address: [email protected] (J. Heath). http://dx.doi.org/10.1016/j.obmed.2017.09.001 2451-8476/© 2017 Published by Elsevier Ltd.
2012), or coronary artery disease (CAD) (McAuley et al., 2012) than their less fit counterparts. The aim of this study is to add to the available literature on fitness's ability to attenuate risks typically associated with increasing BMI. We hope, through this additional large-volume study, to confirm previous findings and shine further light on a relationship pertinent to the medical management of an increasingly obese US population (Ogden et al., 2014; Office of the Surgeon General, 2001). 2. Methods 2.1. Study population We performed a retrospective cohort study of all patients who underwent symptom-limited exercise stress echocardiography testing between the dates of January 1, 2010 through December 31, 2014. Inclusion for this analysis was not contingent upon the reason the test was ordered. The institutional review board of Penn State Health Milton S. Hershey Medical Center approved the study. 2.2. Exposures and outcomes Demographics, including age, weight, height, and comorbidities, including diabetes, hypertension, high cholesterol, and heart disease, were queried at the time of testing and recorded by the exercise physiologist who supervised the test on a standardized form. Individuals were divided into six prespecified groups based on BMI, which was computed using the weight and height information on the standardized forms (<20, 20e24.9, 25e29.9, 30e34.9, 35e39.9, >40). Single variable regression analyses were used to determine each group's odds for having DM, HTN and high cholesterol (HC), compared to the reference group (BMI 20e24.9). Due to differences in sample size across BMI subgroups, the particular BMI range of 20e34.9 kg/m2 will be the focus of our reported results. All subjects were divided into a ‘low fitness’ or ‘high fitness’ subgroup based on metabolic equivalents achieved on treadmill testing prior to test termination. METS was calculated for each subject using the X formula. Low fitness was defined as achieving <10 METS prior to test termination. High fitness was defined as achieving 10 METS prior to test termination. Within each subgroup, single variable regression analyses were performed to
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J. Heath et al. / Obesity Medicine 8 (2017) 23e26
determine the group's odds for having DM, HTN and high cholesterol, compared to the reference group (BMI 20e24.9). In this analysis, individuals who were classified as low fitness at any given BMI stratum were only compared to low fit subjects within the reference BMI stratum and vice versa. 3. Results There were 8674 subjects included in this analysis and the average age was 55 years. Nearly half of subjects were female (48%) and the other half were male (52%). The average METS achieved was 9.41. As shown in Table 1, 4094 (47%) subjects were characterized as low fitness while the remaining 4580 (53%) subjects met the prespecified criteria for high fitness. The average METS achieved by the low fitness subgroup was 6.95, while the average METS achieved by the high fitness subgroup was 11.62. 3.1. Coronary artery disease CAD was reported in 1132 (13%) subjects. Among all subjects, increasing BMI was associated with higher odds of CAD (Table 2). Subjects with BMI's 25e29.9 (OR 1.41; 95% CI 1.18e1.70) and 30e34.9 (OR 1.41; 95% CI 1.18e1.70) had higher odds of reporting CAD. This relationship did not reach statistical significance in the low fitness subgroup but was statistically significant in the high fitness subgroup with a BMI 25e29.9 (OR 1.30; 95% CI 1.12e1.51). Notably, high fitness subjects in this category were on average 2 years older than the reference group which could account for the increased rate. 3.2. Diabetes mellitus DM was reported in 1109 (13%) subjects. Among all subjects, increasing BMI was associated with higher odds of DM (Table 2). Subjects with BMI's 25e29.9 (OR 1.68; 95% CI 1.33e2.15) and 30e34.9 (OR 3.25; 95% CI 2.57e4.15) had higher odds of reporting DM compared to the reference group. This relationship was observed in the low fitness subgroup where those with BMI's 25e29.9 (OR 2.29; 95% CI 1.90e2.72) and 30e34.9 (OR 3.57; 95% CI 3.00e4.25) had higher odds of DM. However, higher BMI was not associated with higher odds of DM in the high fitness subgroup. In the high fitness subgroup, those with BMI's 25e29.9 (OR 0.32; 95% CI 0.26e0.39) and 30e34.9 (OR 0.63; 95% CI 0.51e0.78) had lower rates of DM compared to the reference group. 3.3. Hypertension HTN was reported in 4148 (48%) subjects. Among all subjects, increasing BMI was associated with higher odds of HTN (Table 2). Subjects with BMI's 25e29.9 (OR 1.79; 95% CI 1.60e2.04) and 30e34.9 (OR 2.55; 95% CI 2.23e2.92) had higher odds of reporting HTN compared to the reference group. This relationship was
Table 1 Demographics by BMI and fitness (METS). overall
METS<10
METS 10þ
BMI<20 BMI 20-24.9 BMI 25-29.9 BMI 30-34.9 BMI 35-39.9 BMI 40þ
191 1591 3139 2248 952 553
79 547 1183 1164 646 475
112 1044 1956 1084 306 78
Total
8674
4094
4580
*BMI¼ Body Mass Index, METS ¼ Metabolic Equivalents.
observed in the low fitness subgroup where those with BMI's 25e29.9 (OR 1.91; 95% CI 1.68e2.17) and 30e34.9 (OR 2.58; 95% CI 2.26e2.94) had higher odds of HTN. However, higher BMI was not associated with higher odds of HTN in the high fitness subgroup. In the high fitness subgroup, those with BMI's 25e29.9 (OR 0.62; 95% CI 0.56e0.69) and 30e34.9 (OR 0.79; 95% CI 0.70e0.91) had lower rates of HTN compared to the reference group. 3.4. High cholesterol HC was reported in 3937 (45%) subjects. Among all subjects, increasing BMI was associated with higher odds of HC (Table 2). Subjects with BMI's 25e29.9 (OR 1.68; 95% CI 1.48e1.90) and 30e34.9 (OR 1.83; 95% CI 1.60e2.09) had higher odds of reporting HC compared to the reference group. This relationship was observed in the low fitness subgroup where those with BMI's 25e29.9 (OR 1.57; 95% CI 1.38e1.78) and 30e34.9 (OR 1.68; 95% CI 1.48e1.91) had higher odds of HC. In the high fitness subgroup there was no statistically significant relationship between BMI group and odds of HC. 4. Discussion In this study of individuals who underwent stress echocardiography at a single center, increasing BMI was predictably associated with higher rates of self-reported CAD, DM, HTN and HC. However, when subjects were divided into low fitness and high fitness subgroups, this relationship between higher BMI and chronic disease was consistently observed only in the low fitness subgroup. These findings support the idea that cardiovascular fitness attenuates the relationship between obesity and chronic disease. These findings are hypothesis generating and support previous research. In 2001, Field, Coakley et al. published findings in the Archives of Internal Medicine, which showed a dose-response relationship between BMI and the risk of developing chronic diseases. Compared with same-sex peers of a normal-range BMI (18.5e24.9), those with BMI of 35.0 or more were approximately 20 times more likely to develop diabetes. Women with overweight BMI (25.0e29.9) were also significantly more likely than their leaner peers to develop hypertension, high cholesterol level, and heart disease; similar results were shown in men. During the 10 years of follow-up, the degree of overweight in both men and women were found to relate to the incidence of numerous health conditions and chronic diseases (Aune et al., 2016). In 2012, McAuley, Artero, Sui, et al. described the relationship between obesity and all-cause mortality in the Mayo Clinic Proceedings. After adjustment for age, examination year, and multiple baseline risk factors, men with low cardiorespiratory fitness were shown to have a higher risk of all-cause mortality in the BMI categories of normal-weight, obese class I, and obese class II/III, compared with the normal-weight and high-fitness reference group. Among men with high cardiorespiratory fitness, there were no significant differences in CVD and all-cause mortality risk across BMI categories. Cardiorespiratory fitness was shown to greatly modify the relationship between adiposity and mortality in men with documented coronary heart disease (Ekelund et al., 1988), (Mora et al., 2005). Also in 2012, Lee, Sui et al. proceeded to demonstrate the distinct influences that both fitness and fat gain had on cardiovascular disease risk factor development in adults, as published in the Journal of the American College of Cardiology. The particular cardiovascular disease risk factors investigated included, hypertension, metabolic syndrome, and hypercholesterolemia. During the 6-year follow-up, the increased risks associated with fat gain
J. Heath et al. / Obesity Medicine 8 (2017) 23e26
25
Table 2 BMI subgroups' age, METS and odds ratios of chronic diseases (CAD, DM, HTN, HC). Average Age
Overall BMI BMI BMI BMI BMI BMI
<20 20-24.9 25-29.9 30-34.9 35-39.9 40þ
Low Fit <10 METS BMI BMI BMI BMI BMI BMI
<20 20-24.9 25-29.9 30-34.9 35-39.9 40þ
High Fit 10þ METS BMI BMI BMI BMI BMI BMI
<20 20-24.9 25-29.9 30-34.9 35-39.9 40þ
Average METS
54.92
9.41
52.52 55.1 56.4 55.43 52.73 48.53
9.94 10.32 10 9 8.19 7.07
59.6
6.95
62.07 63.9 63.32 59.9 55.67 49.53
6.65 6.95 7.04 7.01 7.02 6.52
50.73
11.62
45.74 50.49 52.2 50.62 46.53 42.59
12.27 12.08 11.79 11.15 10.65 10.51
CAD (OR)
95% CI
DM (OR)
2.5%
97.5%
0.62 1 1.41 1.40 1.03 0.46
0.34 1 1.18 1.16 0.80 0.30
1.06 1 1.70 1.71 1.32 0.67
0.93 1 1.08 1.19 0.94 0.35
0.45 1 0.90 0.99 0.73 0.23
0.26 1 1.30 1.21 0.72 0.58
0.08 1 1.12 0.996 0.47 0.22
95% CI
HTN (OR)
2.5%
97.5%
0.88 1 1.68 3.25 4.44 5.13
0.42 1 1.33 2.57 3.43 3.86
1.64 1 2.15 4.15 5.79 6.85
1.73 1 1.29 1.42 1.19 0.52
1.38 1 2.29 3.57 4.12 4.50
0.61 1 1.90 3.00 3.35 3.57
0.62 1 1.51 1.45 1.05 1.22
0.09 1 0.32 0.63 0.90 0.58
0.02 1 0.26 0.51 0.64 0.26
95% CI
HC (OR)
2.5%
97.5%
0.80 1 1.79 2.55 3.35 3.83
0.57 1 1.80 2.23 0.83 3.13
1.11 1 2.04 2.92 3.96 4.70
0.09 1 2.72 4.25 5.07 5.65
0.92 1 1.91 2.58 2.94 3.01
0.57 1 1.68 2.26 2.48 2.47
0.29 1 0.39 0.78 1.23 1.14
0.24 1 0.62 0.79 1.00 1.09
0.15 1 0.56 0.70 0.80 0.70
95% CI 2.5%
97.5%
0.72 1 1.68 1.83 2.09 1.45
0.51 1 1.48 1.60 1.78 1.19
1.00 1 1.90 2.09 2.47 1.77
1.43 1 2.17 2.94 3.50 3.67
0.95 1 1.57 1.68 1.80 1.24
0.60 1 1.38 1.48 1.53 1.02
1.48 1 1.78 1.91 2.12 1.50
0.37 1 0.69 0.91 1.26 1.71
0.27 1 0.91 0.92 1.01 0.46
0.17 1 0.17 0.81 0.81 0.28
0.43 1 1.01 1.05 1.28 0.74
*OR¼ Odds Ratios, DM ¼ Diabetes Mellitus, HTN¼ Hypertension, HC¼ Hypercholesterolemia.
appeared attenuated, although not completely eliminated, when fitness was maintained or improved. Maintaining or improving fitness was associated with lower risk of developing each outcome, whereas increasing fatness was associated with higher risk of developing each outcome. This study showed that both fitness and fatness affected an individual's risk of developing cardiovascular risk factors (Blair et al., 1989). This study has several strengths including its large sample size and representative population. For example, among US adults aged 55e64 years of age, sampled as part of the National Blood Pressure Education Program (NBPEP), hypertension was reported in 43% compared to 48% in our cohort (Wolz et al., 2000). The Centers for Disease Control and Prevention reported that in 2014, 12% of adults between the ages of 45e64 had diabetes, compared to 13% in our cohort (Centers for Disease Control and Prevention, 2014). However, the rate of CAD in our sample was about twice as high as what is reported for a similar age range in the US (Mozaffarian et al., 2015). This is likely due to some selection bias for cardiac stress testing among patients with known heart disease. Another strength of this analysis is the use of self-report on a standardized form for capturing information on disease as well as the use of Bruce treadmill testing to capture information on fitness. The use of chart review to capture chronic disease diagnoses may underestimate or overestimate disease prevalence. Furthermore, commonly used indirect measures of fitness such as self-reported exercise duration and/or intensity may bear little relation to actual fitness level. Despite the strengths of this analysis and its provocative findings, important limitations must be acknowledged. First, it is a retrospective study and the primary data used to conduct the analysis was not systematically queried with the intention of hypothesis testing. Second, we cannot exclude that the selection of patients for cardiovascular stress testing does not make this sample different, in important ways, from the general population. Third, it is unknown whether fitness information derived from symptomlimited treadmill testing caries prognostic value comparable to that of maximal-tolerance testing. Fourth, we did not explicitly adjust for age and sex but instead, made inferences based on the
descriptive information available. Fifth, the prespecified cut-point of 10 METS used to divide low fitness from high fitness subjects is crude. A more precise analysis might utilize a metric such as age and sex-adjusted exercise capacity. Future investigations should consider re-analysis along these lines. In conclusion, among patients referred for symptom-limited stress echocardiography testing at a single center, increasing BMI is associated with higher rates of self-reported chronic disease. However, when cardiovascular fitness, based on METS achieved on Bruce treadmill testing, is accounted for, the relationship does not persist. This suggests that cardiovascular fitness is an important factor, even among overweight and obese individuals, affecting the development of chronic disease and that perhaps, cardiovascular fitness itself should be a target for intervention. References Aune, D., Sen, A., Prasad, M., et al., 2016. BMI and all cause mortality: systematic review and non-linear dose-response meta-analysis of 230 cohort studies with 3.74 million deaths among 30.3 million participants. BMJ 353, i2156. Blair, S.N., Kohl 3rd, H.W., Paffenbarger Jr., R.S., et al., 1989. Physical fitness and allcause mortality. A prospective study of healthy men and women. JAMA 262, 2395. Calle, E.E., Thun, M.J., Petrelli, J.M., et al., 1999. Body-mass index and mortality in a prospective cohort of U.S. adults. N. Engl. J. Med. 341, 1097. Centers for Disease Control and Prevention, 2014. National Diabetes Statistics Report: Estimates of Diabetes and its Burden in the United States. US Department of Health and Human Services, Atlanta, GA, 2014. Ekelund, L.G., Haskell, W.L., Johnson, J.L., et al., 1988. Physical fitness as a predictor of cardiovascular mortality in asymptomatic north American men. The lipid research clinics mortality follow-up study. N. Engl. J. Med. 319, 1379. Field, A.E., Coakley, E.H., Must, A., et al., 2001. Impact of overweight on the risk of developing common chronic diseases during a 10-year period. Arch. Intern. Med. 161, 1581. Gu, D., He, J., Duan, X., et al., 2006. Body weight and mortality among men and women in China. JAMA 295, 776. Haapanen, N., Miilunpalo, S., Vuori, I., Oja, P., Pasanen, M., 1997. Association of leisure time physical activity with the risk of coronary heart disease, hypertension and diabetes in middle-aged men and women. Int. J. Epidemiol. 26, 739e747. €l C., Tuomilehto, Jaakko, Lakka, Timo A., Nissinen, Aulikki, Hu, Gang, Barengo, Noe Jousilahti, Pekka, 2004. Relationship of physical activity and body mass index to the risk of hypertension: a prospective study in Finland. Hypertension 43, 25e30.
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Lee, C., Jackson, A., Blair, S., 1998. US weight guidelines: is it also important to consider cardiorespiratory fitness? Intern. J. Obes. Relat. Metab. Disord. 22, 2e7. Lee, D., Sui, X., Church, T.S., Lee, I.-M., Blair, S.N., 2009. Associations of cardiorespiratory fitness and obesity with risks of impaired fasting glucose and type 2 diabetes in men. Diabetes Care 32 (2), 257e262. http://dx.doi.org/10.2337/ dc08-1377. Lee, D.C., Sui, X., Church, T.S., Lavie, C.J., Jackson, A.S., Blair, S.N., 2012. Changes in fitness and fatness on the development of cardiovascular disease risk factors hypertension, metabolic syndrome, and hypercholesterolemia. J. Am. Coll. Cardiol. 59 (7), 665e672. McAuley, P.A., Artero, E.G., Sui, X., et al., 2012. The obesity paradox, cardiorespiratory fitness, and coronary heart disease. Mayo Clin. Proc. 87 (5), 443e451. http://dx.doi.org/10.1016/j.mayocp.2012.01.013. Mora, S., Redberg, R.F., Sharrett, A.R., Blumenthal, R.S., 2005. Enhanced risk assessment in asymptomatic individuals with exercise testing and Framingham risk scores. Circulation 112, 1566. Mozaffarian, D., Benjamin, E.J., Go, A.S., et al., 2015. Heart disease and stroke statistics- 2015 update: a report from the American Heart Association. Circulation 131 (4), e29ee322. Office of the Surgeon General (US) Office of Disease Prevention and Health
Promotion (US) Centers for Disease Control and Prevention (US) National Institutes of Health (US), 2001. The Surgeon General's Call to Action to Prevent and Decrease Overweight and Obesity, pp. 1e39. Rockville (MD). Ogden, C.L., Carroll, M.D., Flegal, K.M., 2014 Jul. Prevalence of obesity in the United States. J. Am. Med. Assoc. 312 (2), 189e190. http://dx.doi.org/10.1001/ jama.2014.6228. Peeters, A., Barendregt, J.J., Willekens, F., et al., 2003. Obesity in adulthood and its consequences for life expectancy: a life-table analysis. Ann. Intern Med. 138, 24. Pereira, M.A., Folsom, A.R., McGovern, P.G., Carpenter, M., Arnett, D.K., Liao, D., Szklo, M., Hutchinson, R.G., 1999. Physical activity and incident hypertension in black and white adults: the Atherosclerosis risk in communities study. Prev. Med. 28, 304e312. Rankinen, T., Church, T.S., Rice, T., Bouchard, C., Blair, S.N., 2007. Cardiorespiratory fitness, BMI, and risk of hypertension: the HYPGENE study. Med. Sci. Sports Exerc 39 (10), 1687e1692. Wolz, M., Cutler, J., Roccella, E.J., Rohde, F., Thom, T., Burt, V., 2000 Jan. 13. Statement from the national high Blood pressure education Program: prevalence of hypertension. Am. J. Hypertens. 1 (1), 103e104. Yan, L.L., Daviglus, M.L., Liu, K., et al., 2006. Midlife body mass index and hospitalization and mortality in older age. JAMA 295, 190.
Contents lists available at ScienceDirect
Obesity Medicine journal homepage: http://www.journals.elsevier.com/obesity-medicine
Cardiovascular fitness attenuates obesity-related risk for chronic disease Jacqueline Heath*, Ronald Maag, Andrew Foy Penn State M. S. Hershey Medical Center, Hershey, PA, USA
a r t i c l e i n f o Article history: Received 31 August 2017 Accepted 12 September 2017
1. Introduction It is widely known that obesity is a negative prognostic indicator in both men and women. Obesity has been linked to increased risk of all-cause mortality and even shortened life expectancy (Calle et al., 1999; Aune et al., 2016; Gu et al., 2006; Yan et al., 2006; Peeters et al., 2003). Additionally, overweight or obese Body Mass Index (BMI) has been linked to increased incidence of chronic conditions, including hypertension, diabetes and cardiovascular disease (Field et al., 2001), as well as increased risk of hospitalization secondary to such conditions (Yan et al., 2006). Fitness, on the other hand, has become a well-accepted positive prognostic health indicator. Increased cardiorespiratory fitness, as defined by maximal treadmill testing, has been linked with lower all-cause and cardiovascular disease mortality (Lee et al., 1998; Blair et al., 1989), independent of conventional coronary risk factors (Ekelund et al., 1988). These benefits have been shown in adults of all age groups and of both sexes. Physical activity has also been shown to particularly benefit individuals with overweight and obese BMI. Higher intensities of weekly activity have been associated with decreased mortality and hypertension in otherwise higher-risk, overweight and obese adults (Hu et al., 2004; Haapanen et al., 1997; Pereira et al., 1999). However, what is less understood is how cardiorespiratory fitness attenuates the risks of chronic conditions in overweight and obese adults. In some studies, it has been shown that overweight or obese adults with high cardiorespiratory fitness have a decreased risk of hypertension (HTN) (Rankinen et al., 2007), diabetes mellitus (DM) (Lee et al., 2009), hypercholesterolemia (HC) (Lee et al.,
* Corresponding author. E-mail address: [email protected] (J. Heath). http://dx.doi.org/10.1016/j.obmed.2017.09.001 2451-8476/© 2017 Published by Elsevier Ltd.
2012), or coronary artery disease (CAD) (McAuley et al., 2012) than their less fit counterparts. The aim of this study is to add to the available literature on fitness's ability to attenuate risks typically associated with increasing BMI. We hope, through this additional large-volume study, to confirm previous findings and shine further light on a relationship pertinent to the medical management of an increasingly obese US population (Ogden et al., 2014; Office of the Surgeon General, 2001). 2. Methods 2.1. Study population We performed a retrospective cohort study of all patients who underwent symptom-limited exercise stress echocardiography testing between the dates of January 1, 2010 through December 31, 2014. Inclusion for this analysis was not contingent upon the reason the test was ordered. The institutional review board of Penn State Health Milton S. Hershey Medical Center approved the study. 2.2. Exposures and outcomes Demographics, including age, weight, height, and comorbidities, including diabetes, hypertension, high cholesterol, and heart disease, were queried at the time of testing and recorded by the exercise physiologist who supervised the test on a standardized form. Individuals were divided into six prespecified groups based on BMI, which was computed using the weight and height information on the standardized forms (<20, 20e24.9, 25e29.9, 30e34.9, 35e39.9, >40). Single variable regression analyses were used to determine each group's odds for having DM, HTN and high cholesterol (HC), compared to the reference group (BMI 20e24.9). Due to differences in sample size across BMI subgroups, the particular BMI range of 20e34.9 kg/m2 will be the focus of our reported results. All subjects were divided into a ‘low fitness’ or ‘high fitness’ subgroup based on metabolic equivalents achieved on treadmill testing prior to test termination. METS was calculated for each subject using the X formula. Low fitness was defined as achieving <10 METS prior to test termination. High fitness was defined as achieving 10 METS prior to test termination. Within each subgroup, single variable regression analyses were performed to
24
J. Heath et al. / Obesity Medicine 8 (2017) 23e26
determine the group's odds for having DM, HTN and high cholesterol, compared to the reference group (BMI 20e24.9). In this analysis, individuals who were classified as low fitness at any given BMI stratum were only compared to low fit subjects within the reference BMI stratum and vice versa. 3. Results There were 8674 subjects included in this analysis and the average age was 55 years. Nearly half of subjects were female (48%) and the other half were male (52%). The average METS achieved was 9.41. As shown in Table 1, 4094 (47%) subjects were characterized as low fitness while the remaining 4580 (53%) subjects met the prespecified criteria for high fitness. The average METS achieved by the low fitness subgroup was 6.95, while the average METS achieved by the high fitness subgroup was 11.62. 3.1. Coronary artery disease CAD was reported in 1132 (13%) subjects. Among all subjects, increasing BMI was associated with higher odds of CAD (Table 2). Subjects with BMI's 25e29.9 (OR 1.41; 95% CI 1.18e1.70) and 30e34.9 (OR 1.41; 95% CI 1.18e1.70) had higher odds of reporting CAD. This relationship did not reach statistical significance in the low fitness subgroup but was statistically significant in the high fitness subgroup with a BMI 25e29.9 (OR 1.30; 95% CI 1.12e1.51). Notably, high fitness subjects in this category were on average 2 years older than the reference group which could account for the increased rate. 3.2. Diabetes mellitus DM was reported in 1109 (13%) subjects. Among all subjects, increasing BMI was associated with higher odds of DM (Table 2). Subjects with BMI's 25e29.9 (OR 1.68; 95% CI 1.33e2.15) and 30e34.9 (OR 3.25; 95% CI 2.57e4.15) had higher odds of reporting DM compared to the reference group. This relationship was observed in the low fitness subgroup where those with BMI's 25e29.9 (OR 2.29; 95% CI 1.90e2.72) and 30e34.9 (OR 3.57; 95% CI 3.00e4.25) had higher odds of DM. However, higher BMI was not associated with higher odds of DM in the high fitness subgroup. In the high fitness subgroup, those with BMI's 25e29.9 (OR 0.32; 95% CI 0.26e0.39) and 30e34.9 (OR 0.63; 95% CI 0.51e0.78) had lower rates of DM compared to the reference group. 3.3. Hypertension HTN was reported in 4148 (48%) subjects. Among all subjects, increasing BMI was associated with higher odds of HTN (Table 2). Subjects with BMI's 25e29.9 (OR 1.79; 95% CI 1.60e2.04) and 30e34.9 (OR 2.55; 95% CI 2.23e2.92) had higher odds of reporting HTN compared to the reference group. This relationship was
Table 1 Demographics by BMI and fitness (METS). overall
METS<10
METS 10þ
BMI<20 BMI 20-24.9 BMI 25-29.9 BMI 30-34.9 BMI 35-39.9 BMI 40þ
191 1591 3139 2248 952 553
79 547 1183 1164 646 475
112 1044 1956 1084 306 78
Total
8674
4094
4580
*BMI¼ Body Mass Index, METS ¼ Metabolic Equivalents.
observed in the low fitness subgroup where those with BMI's 25e29.9 (OR 1.91; 95% CI 1.68e2.17) and 30e34.9 (OR 2.58; 95% CI 2.26e2.94) had higher odds of HTN. However, higher BMI was not associated with higher odds of HTN in the high fitness subgroup. In the high fitness subgroup, those with BMI's 25e29.9 (OR 0.62; 95% CI 0.56e0.69) and 30e34.9 (OR 0.79; 95% CI 0.70e0.91) had lower rates of HTN compared to the reference group. 3.4. High cholesterol HC was reported in 3937 (45%) subjects. Among all subjects, increasing BMI was associated with higher odds of HC (Table 2). Subjects with BMI's 25e29.9 (OR 1.68; 95% CI 1.48e1.90) and 30e34.9 (OR 1.83; 95% CI 1.60e2.09) had higher odds of reporting HC compared to the reference group. This relationship was observed in the low fitness subgroup where those with BMI's 25e29.9 (OR 1.57; 95% CI 1.38e1.78) and 30e34.9 (OR 1.68; 95% CI 1.48e1.91) had higher odds of HC. In the high fitness subgroup there was no statistically significant relationship between BMI group and odds of HC. 4. Discussion In this study of individuals who underwent stress echocardiography at a single center, increasing BMI was predictably associated with higher rates of self-reported CAD, DM, HTN and HC. However, when subjects were divided into low fitness and high fitness subgroups, this relationship between higher BMI and chronic disease was consistently observed only in the low fitness subgroup. These findings support the idea that cardiovascular fitness attenuates the relationship between obesity and chronic disease. These findings are hypothesis generating and support previous research. In 2001, Field, Coakley et al. published findings in the Archives of Internal Medicine, which showed a dose-response relationship between BMI and the risk of developing chronic diseases. Compared with same-sex peers of a normal-range BMI (18.5e24.9), those with BMI of 35.0 or more were approximately 20 times more likely to develop diabetes. Women with overweight BMI (25.0e29.9) were also significantly more likely than their leaner peers to develop hypertension, high cholesterol level, and heart disease; similar results were shown in men. During the 10 years of follow-up, the degree of overweight in both men and women were found to relate to the incidence of numerous health conditions and chronic diseases (Aune et al., 2016). In 2012, McAuley, Artero, Sui, et al. described the relationship between obesity and all-cause mortality in the Mayo Clinic Proceedings. After adjustment for age, examination year, and multiple baseline risk factors, men with low cardiorespiratory fitness were shown to have a higher risk of all-cause mortality in the BMI categories of normal-weight, obese class I, and obese class II/III, compared with the normal-weight and high-fitness reference group. Among men with high cardiorespiratory fitness, there were no significant differences in CVD and all-cause mortality risk across BMI categories. Cardiorespiratory fitness was shown to greatly modify the relationship between adiposity and mortality in men with documented coronary heart disease (Ekelund et al., 1988), (Mora et al., 2005). Also in 2012, Lee, Sui et al. proceeded to demonstrate the distinct influences that both fitness and fat gain had on cardiovascular disease risk factor development in adults, as published in the Journal of the American College of Cardiology. The particular cardiovascular disease risk factors investigated included, hypertension, metabolic syndrome, and hypercholesterolemia. During the 6-year follow-up, the increased risks associated with fat gain
J. Heath et al. / Obesity Medicine 8 (2017) 23e26
25
Table 2 BMI subgroups' age, METS and odds ratios of chronic diseases (CAD, DM, HTN, HC). Average Age
Overall BMI BMI BMI BMI BMI BMI
<20 20-24.9 25-29.9 30-34.9 35-39.9 40þ
Low Fit <10 METS BMI BMI BMI BMI BMI BMI
<20 20-24.9 25-29.9 30-34.9 35-39.9 40þ
High Fit 10þ METS BMI BMI BMI BMI BMI BMI
<20 20-24.9 25-29.9 30-34.9 35-39.9 40þ
Average METS
54.92
9.41
52.52 55.1 56.4 55.43 52.73 48.53
9.94 10.32 10 9 8.19 7.07
59.6
6.95
62.07 63.9 63.32 59.9 55.67 49.53
6.65 6.95 7.04 7.01 7.02 6.52
50.73
11.62
45.74 50.49 52.2 50.62 46.53 42.59
12.27 12.08 11.79 11.15 10.65 10.51
CAD (OR)
95% CI
DM (OR)
2.5%
97.5%
0.62 1 1.41 1.40 1.03 0.46
0.34 1 1.18 1.16 0.80 0.30
1.06 1 1.70 1.71 1.32 0.67
0.93 1 1.08 1.19 0.94 0.35
0.45 1 0.90 0.99 0.73 0.23
0.26 1 1.30 1.21 0.72 0.58
0.08 1 1.12 0.996 0.47 0.22
95% CI
HTN (OR)
2.5%
97.5%
0.88 1 1.68 3.25 4.44 5.13
0.42 1 1.33 2.57 3.43 3.86
1.64 1 2.15 4.15 5.79 6.85
1.73 1 1.29 1.42 1.19 0.52
1.38 1 2.29 3.57 4.12 4.50
0.61 1 1.90 3.00 3.35 3.57
0.62 1 1.51 1.45 1.05 1.22
0.09 1 0.32 0.63 0.90 0.58
0.02 1 0.26 0.51 0.64 0.26
95% CI
HC (OR)
2.5%
97.5%
0.80 1 1.79 2.55 3.35 3.83
0.57 1 1.80 2.23 0.83 3.13
1.11 1 2.04 2.92 3.96 4.70
0.09 1 2.72 4.25 5.07 5.65
0.92 1 1.91 2.58 2.94 3.01
0.57 1 1.68 2.26 2.48 2.47
0.29 1 0.39 0.78 1.23 1.14
0.24 1 0.62 0.79 1.00 1.09
0.15 1 0.56 0.70 0.80 0.70
95% CI 2.5%
97.5%
0.72 1 1.68 1.83 2.09 1.45
0.51 1 1.48 1.60 1.78 1.19
1.00 1 1.90 2.09 2.47 1.77
1.43 1 2.17 2.94 3.50 3.67
0.95 1 1.57 1.68 1.80 1.24
0.60 1 1.38 1.48 1.53 1.02
1.48 1 1.78 1.91 2.12 1.50
0.37 1 0.69 0.91 1.26 1.71
0.27 1 0.91 0.92 1.01 0.46
0.17 1 0.17 0.81 0.81 0.28
0.43 1 1.01 1.05 1.28 0.74
*OR¼ Odds Ratios, DM ¼ Diabetes Mellitus, HTN¼ Hypertension, HC¼ Hypercholesterolemia.
appeared attenuated, although not completely eliminated, when fitness was maintained or improved. Maintaining or improving fitness was associated with lower risk of developing each outcome, whereas increasing fatness was associated with higher risk of developing each outcome. This study showed that both fitness and fatness affected an individual's risk of developing cardiovascular risk factors (Blair et al., 1989). This study has several strengths including its large sample size and representative population. For example, among US adults aged 55e64 years of age, sampled as part of the National Blood Pressure Education Program (NBPEP), hypertension was reported in 43% compared to 48% in our cohort (Wolz et al., 2000). The Centers for Disease Control and Prevention reported that in 2014, 12% of adults between the ages of 45e64 had diabetes, compared to 13% in our cohort (Centers for Disease Control and Prevention, 2014). However, the rate of CAD in our sample was about twice as high as what is reported for a similar age range in the US (Mozaffarian et al., 2015). This is likely due to some selection bias for cardiac stress testing among patients with known heart disease. Another strength of this analysis is the use of self-report on a standardized form for capturing information on disease as well as the use of Bruce treadmill testing to capture information on fitness. The use of chart review to capture chronic disease diagnoses may underestimate or overestimate disease prevalence. Furthermore, commonly used indirect measures of fitness such as self-reported exercise duration and/or intensity may bear little relation to actual fitness level. Despite the strengths of this analysis and its provocative findings, important limitations must be acknowledged. First, it is a retrospective study and the primary data used to conduct the analysis was not systematically queried with the intention of hypothesis testing. Second, we cannot exclude that the selection of patients for cardiovascular stress testing does not make this sample different, in important ways, from the general population. Third, it is unknown whether fitness information derived from symptomlimited treadmill testing caries prognostic value comparable to that of maximal-tolerance testing. Fourth, we did not explicitly adjust for age and sex but instead, made inferences based on the
descriptive information available. Fifth, the prespecified cut-point of 10 METS used to divide low fitness from high fitness subjects is crude. A more precise analysis might utilize a metric such as age and sex-adjusted exercise capacity. Future investigations should consider re-analysis along these lines. In conclusion, among patients referred for symptom-limited stress echocardiography testing at a single center, increasing BMI is associated with higher rates of self-reported chronic disease. However, when cardiovascular fitness, based on METS achieved on Bruce treadmill testing, is accounted for, the relationship does not persist. This suggests that cardiovascular fitness is an important factor, even among overweight and obese individuals, affecting the development of chronic disease and that perhaps, cardiovascular fitness itself should be a target for intervention. References Aune, D., Sen, A., Prasad, M., et al., 2016. BMI and all cause mortality: systematic review and non-linear dose-response meta-analysis of 230 cohort studies with 3.74 million deaths among 30.3 million participants. BMJ 353, i2156. Blair, S.N., Kohl 3rd, H.W., Paffenbarger Jr., R.S., et al., 1989. Physical fitness and allcause mortality. A prospective study of healthy men and women. JAMA 262, 2395. Calle, E.E., Thun, M.J., Petrelli, J.M., et al., 1999. Body-mass index and mortality in a prospective cohort of U.S. adults. N. Engl. J. Med. 341, 1097. Centers for Disease Control and Prevention, 2014. National Diabetes Statistics Report: Estimates of Diabetes and its Burden in the United States. US Department of Health and Human Services, Atlanta, GA, 2014. Ekelund, L.G., Haskell, W.L., Johnson, J.L., et al., 1988. Physical fitness as a predictor of cardiovascular mortality in asymptomatic north American men. The lipid research clinics mortality follow-up study. N. Engl. J. Med. 319, 1379. Field, A.E., Coakley, E.H., Must, A., et al., 2001. Impact of overweight on the risk of developing common chronic diseases during a 10-year period. Arch. Intern. Med. 161, 1581. Gu, D., He, J., Duan, X., et al., 2006. Body weight and mortality among men and women in China. JAMA 295, 776. Haapanen, N., Miilunpalo, S., Vuori, I., Oja, P., Pasanen, M., 1997. Association of leisure time physical activity with the risk of coronary heart disease, hypertension and diabetes in middle-aged men and women. Int. J. Epidemiol. 26, 739e747. €l C., Tuomilehto, Jaakko, Lakka, Timo A., Nissinen, Aulikki, Hu, Gang, Barengo, Noe Jousilahti, Pekka, 2004. Relationship of physical activity and body mass index to the risk of hypertension: a prospective study in Finland. Hypertension 43, 25e30.
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