- Email: [email protected]
Global trends in body-mass index – Authors' reply
Correspondence
*Erlend T Aasheim, Torgeir T Søvik [email protected] Imperial Weight Centre, Imperial College London, London SW6 8RF, UK (ETA); and Department of Gastrointestinal Surgery, Oslo University Hospital Aker, Oslo, Norway (TTS) 1
2
3
4
5
Finucane MM, Stevens GA, Cowan MJ, et al. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9·1 million participants. Lancet 2011; 377: 557–67. Whitlock G, Lewington S, Sherliker P, et al. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet 2009; 373: 1083–96. Sturm R. Increases in morbid obesity in the USA: 2000-2005. Public Health 2007; 121: 492–96. Flegal KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity among US adults, 1999-2008. JAMA 2010; 303: 235–41. Flum DR, Belle SH, King WC, et al. Perioperative safety in the longitudinal assessment of bariatric surgery. N Engl J Med 2009; 361: 445–54.
Mariel Finucane and colleagues1 provide important information about the alarming trends of increasing body-mass index (BMI) worldwide and highlight the effect of this development on the growing incidence of cardiovascular disease and type 2 diabetes. Additionally, they discuss the often low effectiveness of interventions to combat obesity and its metabolic consequences. Hence, to use the limited resources available in the most effective way, we need to identify who, for a given BMI, is at the highest risk of metabolic diseases. In this respect, we and others have found that about 25–30% of obese people might not be at increased risk of metabolic diseases.2,3 Consequently, we can identify people who are obese but remain insulin sensitive and have a reduced intima-media thickness of the carotid arteries (an early marker of atherosclerosis). Prospective studies have confirmed that the risk of allcause, cancer, and cardiovasculardisease mortality is not higher in metabolically healthy obese people than it is in non-obese individuals.4,5 What characterises this interesting phenotype? By use of precise metabolic imaging with magnetic resonance techniques, we found that decreased www.thelancet.com Vol 377 June 4, 2011
visceral fat mass, but, more importantly, lower ectopic fat accumulation in the skeletal muscle and predominantly in the liver, determined whether a metabolically benign or malign obesity is present.2 Certainly, such measurements could not be applied feasibly for routine diagnostic purposes; however, health-care professionals could perhaps focus not only on BMI but also on waist circumference, and particularly the presence of fatty liver, by use of more simple markers, when dealing with the problem of obesity. NS is supported by a Heisenberg-Grant of the Deutsche Forschungsgemeinschaft (STE 1096/1-1). We declare that we have no conflicts of interest.
*Norbert Stefan, Konstantinos Kantartzis, Jürgen Machann, Fritz Schick, Hans-Ulrich Häring [email protected] Department of Internal Medicine (NS, KK, H-UH) and Section of Experimental Radiology (JM, FS), University of Tübingen, 72076 Tübingen, Germany 1
2
3
4
5
Finucane MM, Stevens GA, Cowan MJ, et al. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 countryyears and 9·1 million participants. Lancet 2011; 377: 557–67. Stefan N, Kantartzis K, Machann J, et al. Identification and characterization of metabolically benign obesity in humans. Arch Intern Med 2008; 168: 1609–16. Wildman RP, Muntner P, Reynolds K, et al. The obese without cardiometabolic risk factor clustering and the normal weight with cardiometabolic risk factor clustering: prevalence and correlates of 2 phenotypes among the US population (NHANES 1999–2004). Arch Intern Med 2008; 168: 1617–24. Meigs JB, Wilson PW, Fox CS, et al. Body mass index, metabolic syndrome, and risk of type 2 diabetes or cardiovascular disease. J Clin Endocrinol Metab 2006; 91: 2906–12. Calori G, Lattuada G, Piemonti L, et al. Prevalence, metabolic features, and prognosis of metabolically healthy obese Italian individuals: the Cremona Study. Diabetes Care 2011; 34: 210–15.
Authors’ reply Estimates for diseases and risk factors at the national level have a range of applications (eg, in global benchmarking) but, by design, do not apply to subgroups, which might be based on socioeconomic status or geography.1,2 Although subgroup analysis would provide insight into within-country
disparities, doing subgroup analysis by socioeconomic status globally and over time is hindered by the incomparability of measures of socioeconomic status over time and across countries.3 Additionally, such an analysis would have to formally model the heterogeneities of the association between socioeconomic status and body-mass index (BMI) by region, national income, and time. Even if consistent and comparable estimates of BMI by socioeconomic status find a positive association in some lowincome countries, the association might attenuate or reverse with rising national income,4 as was the case for tobacco smoking. Finally, the absolute risk associated with raised BMI might be higher among groups with low socioeconomic status for two reasons: first, they have a higher background risk of disease owing to exposure to other risks and restricted access to health care;1,2 and second, they have lower access to treatment for the mediators of hazardous effects such as diabetes, high blood pressure, and high cholesterol. For all these reasons, curbing the global obesity epidemic, and those of the associated metabolic risk factors, with implementation taking into account within-country variations and disparities, will help to achieve both the aggregate and disparity benefits of prevention.1,2 Estimates of the full distribution of BMI, including the prevalence of extreme obesity, would indeed be valuable for understanding whether the rise in mean BMI is simply due to a distributional shift or whether there is an increase in the spread and skewness of the distribution. This issue is partly reflected (for all obesity) in figure 4 of our paper,5 and is a subject of continuing methodological and empirical research by the collaborating group. Novel markers of adiposity and obesity should also be pursued, although their application to population-based surveillance will 1917
Correspondence
only be possible if the cost is low and measurement can take place under field conditions. We declare that we have no conflicts of interest.
*Majid Ezzati, Gretchen A Stevens, Mariel M Finucane, Goodarz Danaei [email protected] MRC-HPA Centre for Environment and Health and Department of Epidemiology and Biostatistics, Imperial College London, London SW7 2AZ, UK (ME); Department of Health Statistics and Informatics, WHO, Geneva, Switzerland (GAS); and Department of Biostatistics (MMF) and Department of Epidemiology (GD), Harvard School of Public Health, Boston, MA, USA 1
2
3
4
5
Danaei G, Rimm EB, Oza S, Kulkarni SC, Murray CJ, Ezzati M. The promise of prevention: the effects of four preventable risk factors on national life expectancy and life expectancy disparities by race and county in the United States. PLoS Med 2010; 7: e1000248. Stevens G, Dias RH, Thomas KJ, et al. Characterizing the epidemiological transition in Mexico: national and subnational burden of diseases, injuries, and risk factors. PLoS Med 2008; 5: e125. Gakidou E, Vayena E. Use of modern contraception by the poor is falling behind. PLoS Med 2007; 4: e31. Monteiro CA, Conde WL, Lu B, Popkin BM. Obesity and inequities in health in the developing world. Int J Obes Relat Metab Disord 2004; 28: 1181–86. Finucane MM, Stevens GA, Cowan MJ, et al. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9·1 million participants. Lancet 2011; 377: 557–67.
C-reactive protein in the Heart Protection Study Although the Heart Protection Study (HPS) investigators report that baseline C-reactive protein (CRP) concentration does not modify the vascular benefits of statin therapy (Feb 5, p 469),1 readers should be aware that neither does baseline concentration of LDL cholesterol.2 Although not discussed, the data clearly show that CRP concentrations are in fact a predictor of absolute risk in HPS. The investigators elect not to address the hypothesis that on-treatment concentrations of CRP are associated with the magnitude of risk reduction (as reported in several previous statin 1918
trials3), arguing that such analyses are not randomised and thus potentially biased. Nonetheless, the investigators are comfortable concluding that the benefits of statin therapy accrue solely from on-treatment reductions in LDL cholesterol—analyses that by definition have the same limitations. Finally, the HPS trial was done almost entirely among those with a history of myocardial infarction, stroke, peripheral arterial disease, or diabetes and thus cannot be interpreted as a primary prevention trial, the setting in which CRP measurement has been shown to provide as much incremental information on vascular risk as does total and HDL cholesterol4 and where CRP measurement is recommended as a method to detect groups of patients who benefit from statin therapy but otherwise would not qualify for treatment on the basis of LDL cholesterol concentrations.5 PMR is listed as a co-inventor on patents held by the Brigham and Women’s Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease. WK and JJPK declare that they have no conflicts of interest.
*Paul M Ridker, Wolfgang Koenig, John J P Kastelein [email protected] Brigham and Women’s Hospital, Boston, MA 02215, USA (PMR); University of Ulm Medical Center, Ulm, Germany (WK); and Academic Medical Center, Amsterdam, Netherlands (JJPK) 1
2
3
4
5
Heart Protection Study Collaborative Group. C-reactive protein concentration and the vascular benefits of statin therapy: an analysis of 20 536 patients in the Heart Protection Study. Lancet 2011; 377: 469–76. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360: 7–22. Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008; 359: 2195–207. The Emerging Risk Factors Collaboration. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet 2010; 375: 132–40. Genest J, McPherson R, Frohlich J, et al. 2009 Canadian Cardiovascular Society/Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult—2009 recommendations. Can J Cardiol 2009; 25: 567–79.
Authors’ reply In the Heart Protection Study (HPS) of 20 536 patients at high risk of vascular events, reduction of LDL cholesterol with simvastatin reduced the incidence of major vascular events to a similar proportional extent irrespective of presenting CRP concentration1 (or, as previously reported, presenting LDL cholesterol concentration or other baseline features2). These results are reliable because they are based on randomised comparisons between patients with a wide range of presenting CRP concentrations in whom a large number of vascular events occurred. Hence, they provide a compelling refutation of the hypothesis—generated by studies involving far fewer vascular events—that CRP modifies the vascular protective effects of statin therapy. Meta-analyses of individual patients’ data from all of the large statin trials indicate that there is a linear association between the absolute LDL cholesterol reduction and the proportional reduction in vascular risk seen in each trial.3 Such analyses between trials retain the randomised nature of the comparisons because they are based on all patients allocated statin therapy versus all patients allocated control within each trial. By contrast, comparisons of outcome in patients allocated statin therapy who achieve particular CRP concentrations and outcome in those who do not versus outcome in all of the placebo-allocated participants are non-randomised (as was acknowledged previously by Paul Ridker4), and so were avoided in HPS. Although HPS involved patients with pre-existing vascular disease or diabetes, the results are likely to be generalisable to people without known vascular disease since the proportional benefits of statins have been shown to be similar in secondary and primary prevention.3 Indeed, the results are consistent with the equivalent analyses of the JUPITER trial,5 in which there was no evidence that the effect of rosuvastatin on vascular events differed according to baseline CRP concentration. www.thelancet.com Vol 377 June 4, 2011
*Erlend T Aasheim, Torgeir T Søvik [email protected] Imperial Weight Centre, Imperial College London, London SW6 8RF, UK (ETA); and Department of Gastrointestinal Surgery, Oslo University Hospital Aker, Oslo, Norway (TTS) 1
2
3
4
5
Finucane MM, Stevens GA, Cowan MJ, et al. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9·1 million participants. Lancet 2011; 377: 557–67. Whitlock G, Lewington S, Sherliker P, et al. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet 2009; 373: 1083–96. Sturm R. Increases in morbid obesity in the USA: 2000-2005. Public Health 2007; 121: 492–96. Flegal KM, Carroll MD, Ogden CL, Curtin LR. Prevalence and trends in obesity among US adults, 1999-2008. JAMA 2010; 303: 235–41. Flum DR, Belle SH, King WC, et al. Perioperative safety in the longitudinal assessment of bariatric surgery. N Engl J Med 2009; 361: 445–54.
Mariel Finucane and colleagues1 provide important information about the alarming trends of increasing body-mass index (BMI) worldwide and highlight the effect of this development on the growing incidence of cardiovascular disease and type 2 diabetes. Additionally, they discuss the often low effectiveness of interventions to combat obesity and its metabolic consequences. Hence, to use the limited resources available in the most effective way, we need to identify who, for a given BMI, is at the highest risk of metabolic diseases. In this respect, we and others have found that about 25–30% of obese people might not be at increased risk of metabolic diseases.2,3 Consequently, we can identify people who are obese but remain insulin sensitive and have a reduced intima-media thickness of the carotid arteries (an early marker of atherosclerosis). Prospective studies have confirmed that the risk of allcause, cancer, and cardiovasculardisease mortality is not higher in metabolically healthy obese people than it is in non-obese individuals.4,5 What characterises this interesting phenotype? By use of precise metabolic imaging with magnetic resonance techniques, we found that decreased www.thelancet.com Vol 377 June 4, 2011
visceral fat mass, but, more importantly, lower ectopic fat accumulation in the skeletal muscle and predominantly in the liver, determined whether a metabolically benign or malign obesity is present.2 Certainly, such measurements could not be applied feasibly for routine diagnostic purposes; however, health-care professionals could perhaps focus not only on BMI but also on waist circumference, and particularly the presence of fatty liver, by use of more simple markers, when dealing with the problem of obesity. NS is supported by a Heisenberg-Grant of the Deutsche Forschungsgemeinschaft (STE 1096/1-1). We declare that we have no conflicts of interest.
*Norbert Stefan, Konstantinos Kantartzis, Jürgen Machann, Fritz Schick, Hans-Ulrich Häring [email protected] Department of Internal Medicine (NS, KK, H-UH) and Section of Experimental Radiology (JM, FS), University of Tübingen, 72076 Tübingen, Germany 1
2
3
4
5
Finucane MM, Stevens GA, Cowan MJ, et al. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 countryyears and 9·1 million participants. Lancet 2011; 377: 557–67. Stefan N, Kantartzis K, Machann J, et al. Identification and characterization of metabolically benign obesity in humans. Arch Intern Med 2008; 168: 1609–16. Wildman RP, Muntner P, Reynolds K, et al. The obese without cardiometabolic risk factor clustering and the normal weight with cardiometabolic risk factor clustering: prevalence and correlates of 2 phenotypes among the US population (NHANES 1999–2004). Arch Intern Med 2008; 168: 1617–24. Meigs JB, Wilson PW, Fox CS, et al. Body mass index, metabolic syndrome, and risk of type 2 diabetes or cardiovascular disease. J Clin Endocrinol Metab 2006; 91: 2906–12. Calori G, Lattuada G, Piemonti L, et al. Prevalence, metabolic features, and prognosis of metabolically healthy obese Italian individuals: the Cremona Study. Diabetes Care 2011; 34: 210–15.
Authors’ reply Estimates for diseases and risk factors at the national level have a range of applications (eg, in global benchmarking) but, by design, do not apply to subgroups, which might be based on socioeconomic status or geography.1,2 Although subgroup analysis would provide insight into within-country
disparities, doing subgroup analysis by socioeconomic status globally and over time is hindered by the incomparability of measures of socioeconomic status over time and across countries.3 Additionally, such an analysis would have to formally model the heterogeneities of the association between socioeconomic status and body-mass index (BMI) by region, national income, and time. Even if consistent and comparable estimates of BMI by socioeconomic status find a positive association in some lowincome countries, the association might attenuate or reverse with rising national income,4 as was the case for tobacco smoking. Finally, the absolute risk associated with raised BMI might be higher among groups with low socioeconomic status for two reasons: first, they have a higher background risk of disease owing to exposure to other risks and restricted access to health care;1,2 and second, they have lower access to treatment for the mediators of hazardous effects such as diabetes, high blood pressure, and high cholesterol. For all these reasons, curbing the global obesity epidemic, and those of the associated metabolic risk factors, with implementation taking into account within-country variations and disparities, will help to achieve both the aggregate and disparity benefits of prevention.1,2 Estimates of the full distribution of BMI, including the prevalence of extreme obesity, would indeed be valuable for understanding whether the rise in mean BMI is simply due to a distributional shift or whether there is an increase in the spread and skewness of the distribution. This issue is partly reflected (for all obesity) in figure 4 of our paper,5 and is a subject of continuing methodological and empirical research by the collaborating group. Novel markers of adiposity and obesity should also be pursued, although their application to population-based surveillance will 1917
Correspondence
only be possible if the cost is low and measurement can take place under field conditions. We declare that we have no conflicts of interest.
*Majid Ezzati, Gretchen A Stevens, Mariel M Finucane, Goodarz Danaei [email protected] MRC-HPA Centre for Environment and Health and Department of Epidemiology and Biostatistics, Imperial College London, London SW7 2AZ, UK (ME); Department of Health Statistics and Informatics, WHO, Geneva, Switzerland (GAS); and Department of Biostatistics (MMF) and Department of Epidemiology (GD), Harvard School of Public Health, Boston, MA, USA 1
2
3
4
5
Danaei G, Rimm EB, Oza S, Kulkarni SC, Murray CJ, Ezzati M. The promise of prevention: the effects of four preventable risk factors on national life expectancy and life expectancy disparities by race and county in the United States. PLoS Med 2010; 7: e1000248. Stevens G, Dias RH, Thomas KJ, et al. Characterizing the epidemiological transition in Mexico: national and subnational burden of diseases, injuries, and risk factors. PLoS Med 2008; 5: e125. Gakidou E, Vayena E. Use of modern contraception by the poor is falling behind. PLoS Med 2007; 4: e31. Monteiro CA, Conde WL, Lu B, Popkin BM. Obesity and inequities in health in the developing world. Int J Obes Relat Metab Disord 2004; 28: 1181–86. Finucane MM, Stevens GA, Cowan MJ, et al. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9·1 million participants. Lancet 2011; 377: 557–67.
C-reactive protein in the Heart Protection Study Although the Heart Protection Study (HPS) investigators report that baseline C-reactive protein (CRP) concentration does not modify the vascular benefits of statin therapy (Feb 5, p 469),1 readers should be aware that neither does baseline concentration of LDL cholesterol.2 Although not discussed, the data clearly show that CRP concentrations are in fact a predictor of absolute risk in HPS. The investigators elect not to address the hypothesis that on-treatment concentrations of CRP are associated with the magnitude of risk reduction (as reported in several previous statin 1918
trials3), arguing that such analyses are not randomised and thus potentially biased. Nonetheless, the investigators are comfortable concluding that the benefits of statin therapy accrue solely from on-treatment reductions in LDL cholesterol—analyses that by definition have the same limitations. Finally, the HPS trial was done almost entirely among those with a history of myocardial infarction, stroke, peripheral arterial disease, or diabetes and thus cannot be interpreted as a primary prevention trial, the setting in which CRP measurement has been shown to provide as much incremental information on vascular risk as does total and HDL cholesterol4 and where CRP measurement is recommended as a method to detect groups of patients who benefit from statin therapy but otherwise would not qualify for treatment on the basis of LDL cholesterol concentrations.5 PMR is listed as a co-inventor on patents held by the Brigham and Women’s Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease. WK and JJPK declare that they have no conflicts of interest.
*Paul M Ridker, Wolfgang Koenig, John J P Kastelein [email protected] Brigham and Women’s Hospital, Boston, MA 02215, USA (PMR); University of Ulm Medical Center, Ulm, Germany (WK); and Academic Medical Center, Amsterdam, Netherlands (JJPK) 1
2
3
4
5
Heart Protection Study Collaborative Group. C-reactive protein concentration and the vascular benefits of statin therapy: an analysis of 20 536 patients in the Heart Protection Study. Lancet 2011; 377: 469–76. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360: 7–22. Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008; 359: 2195–207. The Emerging Risk Factors Collaboration. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet 2010; 375: 132–40. Genest J, McPherson R, Frohlich J, et al. 2009 Canadian Cardiovascular Society/Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult—2009 recommendations. Can J Cardiol 2009; 25: 567–79.
Authors’ reply In the Heart Protection Study (HPS) of 20 536 patients at high risk of vascular events, reduction of LDL cholesterol with simvastatin reduced the incidence of major vascular events to a similar proportional extent irrespective of presenting CRP concentration1 (or, as previously reported, presenting LDL cholesterol concentration or other baseline features2). These results are reliable because they are based on randomised comparisons between patients with a wide range of presenting CRP concentrations in whom a large number of vascular events occurred. Hence, they provide a compelling refutation of the hypothesis—generated by studies involving far fewer vascular events—that CRP modifies the vascular protective effects of statin therapy. Meta-analyses of individual patients’ data from all of the large statin trials indicate that there is a linear association between the absolute LDL cholesterol reduction and the proportional reduction in vascular risk seen in each trial.3 Such analyses between trials retain the randomised nature of the comparisons because they are based on all patients allocated statin therapy versus all patients allocated control within each trial. By contrast, comparisons of outcome in patients allocated statin therapy who achieve particular CRP concentrations and outcome in those who do not versus outcome in all of the placebo-allocated participants are non-randomised (as was acknowledged previously by Paul Ridker4), and so were avoided in HPS. Although HPS involved patients with pre-existing vascular disease or diabetes, the results are likely to be generalisable to people without known vascular disease since the proportional benefits of statins have been shown to be similar in secondary and primary prevention.3 Indeed, the results are consistent with the equivalent analyses of the JUPITER trial,5 in which there was no evidence that the effect of rosuvastatin on vascular events differed according to baseline CRP concentration. www.thelancet.com Vol 377 June 4, 2011