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Predicting cardiovascular events … How FIT is our crystal ball?
Atherosclerosis 241 (2015) 741e742
Contents lists available at ScienceDirect
Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis
Discussion
Predicting cardiovascular events … How FIT is our crystal ball? Clinton A. Brawner a, *, Haitham M. Ahmed b a b
Division of Cardiovascular Medicine, Henry Ford Hospital, 6525 Second Ave., Detroit, MI 48202, USA Ciccarone Center for the Prevention of Heart Disease, John Hopkins Hospital, 1800 Orleans St, Baltimore, MD 21287, USA
a r t i c l e i n f o Article history: Received 15 June 2015 Accepted 16 June 2015 Available online 17 June 2015 Keywords: Cardiorespiratory fitness Physical activity Prognosis Cardiovascular disease Diabetes
In spite of a declining rate of mortality from cardiovascular disease (CVD) over the past 50 years, CVD continues to be the underlying cause in one of three deaths in the United States [1] and is the number one cause of death among men and women worldwide [2]. Coronary heart disease (CHD) accounts for the largest proportion of CVD cases [1]. Physical inactivity is a major risk factor for CVD and is one of the American Heart Association's (AHA) seven components of ideal cardiovascular health. Although not currently endorsed as a major risk factor for CVD [1] and not included in the AHA and American College of Cardiology's (ACC) 2013 atherosclerotic CVD (ASCVD) risk calculator [3], cardiorespiratory fitness (CRF) is at least as strong of a predictor of CVD outcomes as traditional risk factors [1,4]. It is important to note that physical activity and CRF are two distinct attributes; the former a behavior and the latter a measure of physiologic performance. In recent years, much attention has also been directed toward coronary artery calcium (CAC) given its strong link to risk of CHD and death [5e8]. The presence of subintimal coronary calcium is characteristic of atherosclerosis. Following instability and rupture of an atheroma, there is subsequent calcification that forms as a part of the healing process [8]. Accordingly, CAC represents a usual
DOI of original article: http://dx.doi.org/10.1016/j.atherosclerosis.2015.06.020. * Corresponding author. Preventive Cardiology, Henry Ford Hospital, 6525 Second Ave., Detroit, MI 48202, USA. E-mail addresses: [email protected] (C.A. Brawner), [email protected] (H.M. Ahmed). http://dx.doi.org/10.1016/j.atherosclerosis.2015.06.015 0021-9150/© 2015 Elsevier Ireland Ltd. All rights reserved.
pattern of atherosclerotic progression between type IV (atheroma) and type V (fibroatheroma) lesions [8]. Several investigators have reported a significant inverse correlation between level of physical activity and CAC burden [9e12]. However, few studies have evaluated CRF relative to CAC and risk of CVD events. In the current issue of Atherosclerosis, Zafrir and colleagues [13] build on prior studies that support the important relationship between CRF and risk of morbidity and mortality. In a prospective cohort study of asymptomatic patients with type 2 diabetes mellitus (DM) and no history of CHD (n ¼ 600; 55 to 74 y; 53% female), they evaluated the incremental prognostic value of low CRF on the relationship between CAC and risk of a composite outcome that included all-cause mortality, myocardial infarction, and stroke. Using metabolic equivalents of task (METs) estimated from peak treadmill speed and grade achieved during a clinical exercise stress test, they defined low CRF as the lowest tertile based on percent of gender- and age-predicted METs achieved. After adjustment for traditional risk factors, low CRF was significantly associated with a 2.5-fold greater risk for the composite outcome. In the presence of CAC score and/or the United Kingdom Prospective Diabetes Study risk score, low CRF continued to be significantly associated with more than twice the risk for the composite outcome [13]. Although prior guideline statements [14] have considered the risk for a CVD-related event in patients with DM to be equivalent to a diagnosis of CHD, we now understand that risk among these patients is heterogeneous. CAC score adds to the CHD risk prediction of traditional risk factors, including DM. Based on data from the Multi-Ethnic Study of Atherosclerosis (MESA), the annual rate of a CHD event was <1% among individuals with DM (type 1 or 2) and a CAC score <100 which was comparable to those without DM [15]. Moreover, individuals with a CAC score <10 represent a very low risk subgroup of patients with type 2 DM [16]. In the study by Zafrir and colleagues [13] low CRF further stratified risk among patients with type 2 DM and either a CAC score <10 or 10 with a net reclassification index of 45%. In spite of data supporting the prognostic significance of both CAC score [17] and CRF [18], neither is included in the ACC/AHA ASCVD risk calculator due to insufficient data [3]. However, according to the ACC/AHA working group for the 2013 guidelines on CVD assessment, CAC score may be considered when treatment decision is uncertain based on risk score assessment alone [3]. On the other hand, data was insufficient to provide a recommendation
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C.A. Brawner, H.M. Ahmed / Atherosclerosis 241 (2015) 741e742
on the role of CRF in the risk assessment of CVD [3]. So where does this leave the clinician relative to the importance of CRF, physical activity habits, and clinical decisions? Among apparently healthy individuals and those with CVD, CRF is inversely related to all-cause and CVD-related mortality regardless of the CVD risk factor that might be present [4]. Among men and women, individuals with CRF below 6 METs are at highest risk [4]. Risk declines with higher CRF and levels off above 10 METs [4]. Importantly, increasing CRF, especially moving out of the lowest CRF category, and maintaining high CRF are associated with lower risk of mortality [4]. While genotype accounts for up to 50% of the exercise training response of CRF [19], physical activity is the only modifiable behavior that can affect CRF. In addition to improving CRF, regular physical activity accompanied with weight loss reduces the risk of developing type 2 DM among individuals with pre-DM [20]. A recent randomized controlled trial of physical activity and weight loss among patients with type 2 DM did not show an effect on clinical outcomes; however, a significant interaction was observed between patients with, versus those without, CVD at baseline [21]. In addition, structured physical activity through a supervised exercise training program reduces the risk for all-cause and CVD-related morbidity and mortality among patients with CHD [22] and patients with heart failure [23,24]. Occupational and leisure time physical activity are also related to mortality with higher volumes (e.g., total minutes per week) associated with lower risk [4]. According to both the World Health Organization [25] and US Health and Human Services [26], adults should achieve at least 150 min per week of moderate-to-vigorous physical activity or 75 min per week of vigorous activity. Additional benefits are likely with higher levels of activity. Moderate intensity is an activity equivalent to 3 to 6 METs and vigorous is > 6 METs. The goal is to exceed 7.5 MET-hours per week (i.e., METs of activity hours per week) through moderate and/or vigorous physical activity [25,26]. The Compendium of Physical Activities by Ainsworth et al. [27] can be a useful guide to estimate the METs associated with various activities (https://sites.google.com/site/ compendiumofphysicalactivities/Activity-Categories). Based on the Compendium, 3 METs is equivalent to walking on level ground at 4.0 kph (2.5 mph). Examples of vigorous activities include bicycling at 16 kph (10 mph; 6 METs), doubles tennis (6 METs), and casual soccer (7 METs). As a general rule, if an individual is unable or unwilling to participate in activities that exceed the absolute intensity of a walking pace, their physical activity goal should be at least 150 min per week. In summary, we commend Zafrir and colleagues [13] for their contribution to the literature on the important link between CRF and outcomes. Regardless of the availability of sufficient data on CRF to guide evidence-based ASCVD risk estimates, we believe it is prudent to use CRF to refine risk assessment and guide clinical decisions. Low CRF is associated with increased risk, regardless of age and comorbidities. Individuals with low CRF may benefit the most from supervised exercise training programs. Finally, all patients should be regularly queried and counseled on their physical activity habits. Conflicts of interest The authors have no conflicts to disclose. References [1] D. Mozaffarian, E.J. Benjamin, A.S. Go, et al., Heart disease and stroke statisticse2015 update: a report from the American Heart Association, Circulation 131 (2015) e29e322. [2] World Health Organization, Global Status Report on Noncommunicable Diseases 2014, 2014. Geneva.
[3] D.C. Goff Jr., D.M. Lloyd-Jones, G. Bennett, et al., 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, Circulation 129 (2014) S49eS73. [4] P. Kokkinos, J. Myers, Exercise and physical activity: clinical outcomes and applications, Circulation 122 (2010) 1637e1648. [5] H.M. Ahmed, M.J. Blaha, K. Nasir, et al., Low-risk lifestyle, coronary calcium, cardiovascular events, and mortality: results from MESA, Am. J. Epidemiol. 178 (2013) 12e21. [6] M. Blaha, M.J. Budoff, L.J. Shaw, et al., Absence of coronary artery calcification and all-cause mortality, JACC Cardiovasc. Imaging 2 (2009) 692e700. [7] M.J. Budoff, J.E. Hokanson, K. Nasir, et al., Progression of coronary artery calcium predicts all-cause mortality, JACC Cardiovasc. Imaging 3 (2010) 1229e1236. [8] J.W. McEvoy, M.J. Blaha, A.P. Defilippis, et al., Coronary artery calcium progression: an important clinical measurement? A review of published reports, J. Am. Coll. Cardiol. 56 (2010) 1613e1622. [9] A.G. Bertoni, M.C. Whitt-Glover, H. Chung, et al., The association between physical activity and subclinical atherosclerosis: the multi-ethnic study of atherosclerosis, Am. J. Epidemiol. 169 (2009) 444e454. [10] M. Hamer, M. Kivimaki, A. Lahiri, et al., Walking speed and subclinical atherosclerosis in healthy older adults: the Whitehall II study, Heart 96 (2010) 380e384. [11] K.K. Pettee, B.M. Larouere, A.M. Kriska, et al., Associations among walking performance, physical activity, and subclinical cardiovascular disease, Prev. Cardiol. 10 (2007) 134e140. [12] K.L. Storti, K.K. Pettee Gabriel, D.A. Underwood, et al., Physical activity and coronary artery calcification in two cohorts of women representing early and late postmenopause, Menopause 17 (2010) 1146e1151 (New York, N.Y.). [13] B. Zafrir, M. Azaiza, T. Gaspar, et al., Low cardiorepiratory fitness and coronary arter calcification: complementary cardiovascular risk predictors in asymptomatic type 2 diabetics, Atherosclerosis 241 (2015) 634e640. [14] National Cholesterol Education Program (NCEP) Expert Panel on Detection, E, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), Third report of the National Cholesterol Education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment Panel III) final report, Circulation 106 (2002), 3143e3421. [15] S. Malik, M.J. Budoff, R. Katz, et al., Impact of subclinical atherosclerosis on cardiovascular disease events in individuals with metabolic syndrome and diabetes: the multi-ethnic study of atherosclerosis, Diabetes Care 34 (2011) 2285e2290. [16] C.K. Kramer, B. Zinman, J.L. Gross, et al., Coronary artery calcium score prediction of all cause mortality and cardiovascular events in people with type 2 diabetes: systematic review and meta-analysis, BMJ 346 (2013) f1654. [17] A.J. Taylor, M. Cerqueira, J.M. Hodgson, et al., ACCF/SCCT/ACR/AHA/ASE/ASNC/ NASCI/SCAI/SCMR 2010 appropriate use criteria for cardiac computed tomography. A report of the American College of Cardiology Foundation appropriate Use criteria task Force, the Society of cardiovascular computed tomography, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the American Society of Nuclear Cardiology, the North American Society for Cardiovascular Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society for Cardiovascular Magnetic Resonance, J. Am. Coll. Cardiol. 56 (2010) 1864e1894. [18] R. Arena, J. Myers, M.A. Williams, et al., Assessment of functional capacity in clinical and research settings: a scientific statement from the American Heart Association Committee on exercise, rehabilitation, and prevention of the Council on Clinical Cardiology and the Council on Cardiovascular Nursing, Circulation 116 (2007) 329e343. [19] C. Bouchard, E.W. Daw, T. Rice, et al., Familial resemblance for VO2max in the sedentary state: the HERITAGE family study, Med. Sci. Sports Exercise 30 (1998) 252e258. [20] W.C. Knowler, E. Barrett-Connor, S.E. Fowler, et al., Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin, N. Engl. J. Med. 346 (2002) 393e403. [21] R.R. Wing, P. Bolin, F.L. Brancati, et al., Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes, N. Engl. J. Med. 369 (2013) 145e154. [22] A.S. Leon, B.A. Franklin, F. Costa, et al., Cardiac rehabilitation and secondary prevention of coronary heart disease: an American Heart Association scientific statement from the Council on Clinical Cardiology (Subcommittee on Exercise, Cardiac Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity), in collaboration with the American association of Cardiovascular and Pulmonary Rehabilitation, Circulation 111 (2005) 369e376. [23] R.S. Taylor, V.A. Sagar, E.J. Davies, et al., Exercise-based rehabilitation for heart failure, Cochrane Database Syst. Rev. 4 (2014) CD003331. [24] V.A. Sagar, E.J. Davies, S. Briscoe, et al., Exercise-based rehabilitation for heart failure: systematic review and meta-analysis, Open Heart 2 (2015) e000163. [25] World Health Organization, in: World Health Organization (Ed.), Global Recommendations on Physical Activity for Health, World Health Organization., Geneva, 2010, p. 60. [26] Physical Activity Guidelines Advisory Committee, Physical Activity Guidelines Advisory Committee Report, 2008, U.S. Department of Health and Human Services, 2008. [27] B.E. Ainsworth, W.L. Haskell, S.D. Herrmann, et al., 2011 Compendium of physical activities: a second update of codes and MET values, Med. Sci. Sports Exerc 43 (2011) 1575e1581.
Contents lists available at ScienceDirect
Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis
Discussion
Predicting cardiovascular events … How FIT is our crystal ball? Clinton A. Brawner a, *, Haitham M. Ahmed b a b
Division of Cardiovascular Medicine, Henry Ford Hospital, 6525 Second Ave., Detroit, MI 48202, USA Ciccarone Center for the Prevention of Heart Disease, John Hopkins Hospital, 1800 Orleans St, Baltimore, MD 21287, USA
a r t i c l e i n f o Article history: Received 15 June 2015 Accepted 16 June 2015 Available online 17 June 2015 Keywords: Cardiorespiratory fitness Physical activity Prognosis Cardiovascular disease Diabetes
In spite of a declining rate of mortality from cardiovascular disease (CVD) over the past 50 years, CVD continues to be the underlying cause in one of three deaths in the United States [1] and is the number one cause of death among men and women worldwide [2]. Coronary heart disease (CHD) accounts for the largest proportion of CVD cases [1]. Physical inactivity is a major risk factor for CVD and is one of the American Heart Association's (AHA) seven components of ideal cardiovascular health. Although not currently endorsed as a major risk factor for CVD [1] and not included in the AHA and American College of Cardiology's (ACC) 2013 atherosclerotic CVD (ASCVD) risk calculator [3], cardiorespiratory fitness (CRF) is at least as strong of a predictor of CVD outcomes as traditional risk factors [1,4]. It is important to note that physical activity and CRF are two distinct attributes; the former a behavior and the latter a measure of physiologic performance. In recent years, much attention has also been directed toward coronary artery calcium (CAC) given its strong link to risk of CHD and death [5e8]. The presence of subintimal coronary calcium is characteristic of atherosclerosis. Following instability and rupture of an atheroma, there is subsequent calcification that forms as a part of the healing process [8]. Accordingly, CAC represents a usual
DOI of original article: http://dx.doi.org/10.1016/j.atherosclerosis.2015.06.020. * Corresponding author. Preventive Cardiology, Henry Ford Hospital, 6525 Second Ave., Detroit, MI 48202, USA. E-mail addresses: [email protected] (C.A. Brawner), [email protected] (H.M. Ahmed). http://dx.doi.org/10.1016/j.atherosclerosis.2015.06.015 0021-9150/© 2015 Elsevier Ireland Ltd. All rights reserved.
pattern of atherosclerotic progression between type IV (atheroma) and type V (fibroatheroma) lesions [8]. Several investigators have reported a significant inverse correlation between level of physical activity and CAC burden [9e12]. However, few studies have evaluated CRF relative to CAC and risk of CVD events. In the current issue of Atherosclerosis, Zafrir and colleagues [13] build on prior studies that support the important relationship between CRF and risk of morbidity and mortality. In a prospective cohort study of asymptomatic patients with type 2 diabetes mellitus (DM) and no history of CHD (n ¼ 600; 55 to 74 y; 53% female), they evaluated the incremental prognostic value of low CRF on the relationship between CAC and risk of a composite outcome that included all-cause mortality, myocardial infarction, and stroke. Using metabolic equivalents of task (METs) estimated from peak treadmill speed and grade achieved during a clinical exercise stress test, they defined low CRF as the lowest tertile based on percent of gender- and age-predicted METs achieved. After adjustment for traditional risk factors, low CRF was significantly associated with a 2.5-fold greater risk for the composite outcome. In the presence of CAC score and/or the United Kingdom Prospective Diabetes Study risk score, low CRF continued to be significantly associated with more than twice the risk for the composite outcome [13]. Although prior guideline statements [14] have considered the risk for a CVD-related event in patients with DM to be equivalent to a diagnosis of CHD, we now understand that risk among these patients is heterogeneous. CAC score adds to the CHD risk prediction of traditional risk factors, including DM. Based on data from the Multi-Ethnic Study of Atherosclerosis (MESA), the annual rate of a CHD event was <1% among individuals with DM (type 1 or 2) and a CAC score <100 which was comparable to those without DM [15]. Moreover, individuals with a CAC score <10 represent a very low risk subgroup of patients with type 2 DM [16]. In the study by Zafrir and colleagues [13] low CRF further stratified risk among patients with type 2 DM and either a CAC score <10 or 10 with a net reclassification index of 45%. In spite of data supporting the prognostic significance of both CAC score [17] and CRF [18], neither is included in the ACC/AHA ASCVD risk calculator due to insufficient data [3]. However, according to the ACC/AHA working group for the 2013 guidelines on CVD assessment, CAC score may be considered when treatment decision is uncertain based on risk score assessment alone [3]. On the other hand, data was insufficient to provide a recommendation
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C.A. Brawner, H.M. Ahmed / Atherosclerosis 241 (2015) 741e742
on the role of CRF in the risk assessment of CVD [3]. So where does this leave the clinician relative to the importance of CRF, physical activity habits, and clinical decisions? Among apparently healthy individuals and those with CVD, CRF is inversely related to all-cause and CVD-related mortality regardless of the CVD risk factor that might be present [4]. Among men and women, individuals with CRF below 6 METs are at highest risk [4]. Risk declines with higher CRF and levels off above 10 METs [4]. Importantly, increasing CRF, especially moving out of the lowest CRF category, and maintaining high CRF are associated with lower risk of mortality [4]. While genotype accounts for up to 50% of the exercise training response of CRF [19], physical activity is the only modifiable behavior that can affect CRF. In addition to improving CRF, regular physical activity accompanied with weight loss reduces the risk of developing type 2 DM among individuals with pre-DM [20]. A recent randomized controlled trial of physical activity and weight loss among patients with type 2 DM did not show an effect on clinical outcomes; however, a significant interaction was observed between patients with, versus those without, CVD at baseline [21]. In addition, structured physical activity through a supervised exercise training program reduces the risk for all-cause and CVD-related morbidity and mortality among patients with CHD [22] and patients with heart failure [23,24]. Occupational and leisure time physical activity are also related to mortality with higher volumes (e.g., total minutes per week) associated with lower risk [4]. According to both the World Health Organization [25] and US Health and Human Services [26], adults should achieve at least 150 min per week of moderate-to-vigorous physical activity or 75 min per week of vigorous activity. Additional benefits are likely with higher levels of activity. Moderate intensity is an activity equivalent to 3 to 6 METs and vigorous is > 6 METs. The goal is to exceed 7.5 MET-hours per week (i.e., METs of activity hours per week) through moderate and/or vigorous physical activity [25,26]. The Compendium of Physical Activities by Ainsworth et al. [27] can be a useful guide to estimate the METs associated with various activities (https://sites.google.com/site/ compendiumofphysicalactivities/Activity-Categories). Based on the Compendium, 3 METs is equivalent to walking on level ground at 4.0 kph (2.5 mph). Examples of vigorous activities include bicycling at 16 kph (10 mph; 6 METs), doubles tennis (6 METs), and casual soccer (7 METs). As a general rule, if an individual is unable or unwilling to participate in activities that exceed the absolute intensity of a walking pace, their physical activity goal should be at least 150 min per week. In summary, we commend Zafrir and colleagues [13] for their contribution to the literature on the important link between CRF and outcomes. Regardless of the availability of sufficient data on CRF to guide evidence-based ASCVD risk estimates, we believe it is prudent to use CRF to refine risk assessment and guide clinical decisions. Low CRF is associated with increased risk, regardless of age and comorbidities. Individuals with low CRF may benefit the most from supervised exercise training programs. Finally, all patients should be regularly queried and counseled on their physical activity habits. Conflicts of interest The authors have no conflicts to disclose. References [1] D. Mozaffarian, E.J. Benjamin, A.S. Go, et al., Heart disease and stroke statisticse2015 update: a report from the American Heart Association, Circulation 131 (2015) e29e322. [2] World Health Organization, Global Status Report on Noncommunicable Diseases 2014, 2014. Geneva.
[3] D.C. Goff Jr., D.M. Lloyd-Jones, G. Bennett, et al., 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, Circulation 129 (2014) S49eS73. [4] P. Kokkinos, J. Myers, Exercise and physical activity: clinical outcomes and applications, Circulation 122 (2010) 1637e1648. [5] H.M. Ahmed, M.J. Blaha, K. Nasir, et al., Low-risk lifestyle, coronary calcium, cardiovascular events, and mortality: results from MESA, Am. J. Epidemiol. 178 (2013) 12e21. [6] M. Blaha, M.J. Budoff, L.J. Shaw, et al., Absence of coronary artery calcification and all-cause mortality, JACC Cardiovasc. Imaging 2 (2009) 692e700. [7] M.J. Budoff, J.E. Hokanson, K. Nasir, et al., Progression of coronary artery calcium predicts all-cause mortality, JACC Cardiovasc. Imaging 3 (2010) 1229e1236. [8] J.W. McEvoy, M.J. Blaha, A.P. Defilippis, et al., Coronary artery calcium progression: an important clinical measurement? A review of published reports, J. Am. Coll. Cardiol. 56 (2010) 1613e1622. [9] A.G. Bertoni, M.C. Whitt-Glover, H. Chung, et al., The association between physical activity and subclinical atherosclerosis: the multi-ethnic study of atherosclerosis, Am. J. Epidemiol. 169 (2009) 444e454. [10] M. Hamer, M. Kivimaki, A. Lahiri, et al., Walking speed and subclinical atherosclerosis in healthy older adults: the Whitehall II study, Heart 96 (2010) 380e384. [11] K.K. Pettee, B.M. Larouere, A.M. Kriska, et al., Associations among walking performance, physical activity, and subclinical cardiovascular disease, Prev. Cardiol. 10 (2007) 134e140. [12] K.L. Storti, K.K. Pettee Gabriel, D.A. Underwood, et al., Physical activity and coronary artery calcification in two cohorts of women representing early and late postmenopause, Menopause 17 (2010) 1146e1151 (New York, N.Y.). [13] B. Zafrir, M. Azaiza, T. Gaspar, et al., Low cardiorepiratory fitness and coronary arter calcification: complementary cardiovascular risk predictors in asymptomatic type 2 diabetics, Atherosclerosis 241 (2015) 634e640. [14] National Cholesterol Education Program (NCEP) Expert Panel on Detection, E, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), Third report of the National Cholesterol Education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment Panel III) final report, Circulation 106 (2002), 3143e3421. [15] S. Malik, M.J. Budoff, R. Katz, et al., Impact of subclinical atherosclerosis on cardiovascular disease events in individuals with metabolic syndrome and diabetes: the multi-ethnic study of atherosclerosis, Diabetes Care 34 (2011) 2285e2290. [16] C.K. Kramer, B. Zinman, J.L. Gross, et al., Coronary artery calcium score prediction of all cause mortality and cardiovascular events in people with type 2 diabetes: systematic review and meta-analysis, BMJ 346 (2013) f1654. [17] A.J. Taylor, M. Cerqueira, J.M. Hodgson, et al., ACCF/SCCT/ACR/AHA/ASE/ASNC/ NASCI/SCAI/SCMR 2010 appropriate use criteria for cardiac computed tomography. A report of the American College of Cardiology Foundation appropriate Use criteria task Force, the Society of cardiovascular computed tomography, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the American Society of Nuclear Cardiology, the North American Society for Cardiovascular Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society for Cardiovascular Magnetic Resonance, J. Am. Coll. Cardiol. 56 (2010) 1864e1894. [18] R. Arena, J. Myers, M.A. Williams, et al., Assessment of functional capacity in clinical and research settings: a scientific statement from the American Heart Association Committee on exercise, rehabilitation, and prevention of the Council on Clinical Cardiology and the Council on Cardiovascular Nursing, Circulation 116 (2007) 329e343. [19] C. Bouchard, E.W. Daw, T. Rice, et al., Familial resemblance for VO2max in the sedentary state: the HERITAGE family study, Med. Sci. Sports Exercise 30 (1998) 252e258. [20] W.C. Knowler, E. Barrett-Connor, S.E. Fowler, et al., Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin, N. Engl. J. Med. 346 (2002) 393e403. [21] R.R. Wing, P. Bolin, F.L. Brancati, et al., Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes, N. Engl. J. Med. 369 (2013) 145e154. [22] A.S. Leon, B.A. Franklin, F. Costa, et al., Cardiac rehabilitation and secondary prevention of coronary heart disease: an American Heart Association scientific statement from the Council on Clinical Cardiology (Subcommittee on Exercise, Cardiac Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity), in collaboration with the American association of Cardiovascular and Pulmonary Rehabilitation, Circulation 111 (2005) 369e376. [23] R.S. Taylor, V.A. Sagar, E.J. Davies, et al., Exercise-based rehabilitation for heart failure, Cochrane Database Syst. Rev. 4 (2014) CD003331. [24] V.A. Sagar, E.J. Davies, S. Briscoe, et al., Exercise-based rehabilitation for heart failure: systematic review and meta-analysis, Open Heart 2 (2015) e000163. [25] World Health Organization, in: World Health Organization (Ed.), Global Recommendations on Physical Activity for Health, World Health Organization., Geneva, 2010, p. 60. [26] Physical Activity Guidelines Advisory Committee, Physical Activity Guidelines Advisory Committee Report, 2008, U.S. Department of Health and Human Services, 2008. [27] B.E. Ainsworth, W.L. Haskell, S.D. Herrmann, et al., 2011 Compendium of physical activities: a second update of codes and MET values, Med. Sci. Sports Exerc 43 (2011) 1575e1581.