EDITORIAL COMMENT
Obesity, Cardiology, and Beyond*
Maarten L. Simoons, MD ,* and
Luc Bonneux, MD
Thoraxcentrum, Department of Cardiology, Erasmus University Medical Center, Rotterdam, the Netherlands
Netherlands Interdisciplinary Demographic Institute, The Hague, the Netherlands
* Reprint requests and correspondence: Dr. Maarten L. Simoons, Erasmus Medical Center, Cardiology Thoraxcentre, Thoraxcenter H560, Gravendijkwal 230, Room BA.5.93, 3015CE Rotterdam, 3015 GD, the Netherlands (Email: m.simoons{at}erasmusmc.nl).
Key Words: obesity • mortality • atherosclerosis
Clinical trials and registries create extensive databases that might be explored by different analyses apart from the original purpose for which the databases were created. Such analyses often address the pathophysiology of the disease that has been studied or the mechanisms of specific drugs tested in a trial. Necessarily, the additional analyses are restricted to the data that have been collected or additional measurements from serum samples, and so on.
The CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines) registry provided an opportunity to investigate the relation between obesity (body mass index [BMI]) and age in patients admitted with a non–ST-segment elevation myocardial infarction (NSTEMI) (1). For this analysis 111,847 (59.2%) of the total of 189,075 patients in the databases were available. No data were available on patients with ST-segment elevation myocardial infarction. Body mass index was calculated from weight and height.
It should be appreciated that BMI is a poor predictor of mortality risk. A combination of waist circumference or waist-hip ratio as a marker for adiposity and middle arm muscle circumference as a marker for muscle mass is a far better predictor of mortality (2–4). However, such measurements were not available in the CRUSADE database.
The analysis from the CRUSADE registry in this issue of the Journal (1) reports a striking, stepwise lower age at first NSTEMI in patients with increasing BMI. Patients admitted with NSTEMI and BMI >40 kg/m2 (extreme obesity) were 15.9 years younger than patients with a first NSTEMI and BMI  18.5 kg/m2 (underweight) or 12.5 years younger than those with a normal weight (BMI 18.6 to 25.0 kg/m2). The relation between higher BMI and younger age at first NSTEMI was consistent after adjustment for other risk factors. These observations are in agreement with earlier reports of a higher risk for myocardial infarction and death from a cardiovascular cause in subjects with increasing body weight or BMI in different parts of the world (4–7). Also, in patients with known coronary artery disease, obesity—but only severe obesity (BMI >35 kg/m2)—has been associated with subsequent cardiovascular mortality (8,9). In fact, overweight and mild obesity showed better outcomes in many cardiovascular conditions (10–14).
Moreover, however important the heart might be to health, there is more to health than the heart.
In earlier times, overweight and mild obesity were symbols of well being, good health, and the blessing of the gods. Although the relationships among increasing body weight, BMI, hypertension, diabetes, and manifestations of cardiovascular disease are consistent, the relationships among body weight, BMI, and total mortality are far more complex, particularly in elderly persons. In many studies the mortality risk from any cause is approximately the same for subjects with BMI between 18.9 and 30.0 kg/m2 (normal and overweight) or even 35.0 kg/m2 (normal, overweight, and obese) (15,16). The mortality risk is increased in subjects with a low BMI (underweight, 18.5 kg/m2) not only in India (17) and China (6,7) but also in Europe (5) and the U.S., as shown in Figure 1
(16,18). For men, smokers, and patients with a clinical history of disease, mortality starts to increase at low normal weights of a BMI <23 kg/m2.
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Figure 1 Proportional Mortality Hazard Ratios by BMI
Proportional mortality hazard ratios by body mass index (BMI) (BMI 23 kg/m2 as reference), adjusted for age, smoking, and level of education. Symbols are BMI, lines are 5-point central moving averages weighted by SEMs. Willis J. Health and retirement study. Institutional Review Board (IRB) information. Sponsor: NIA U01 AG 09740: UM Health Sciences IRB Protocol H03-00002774-M8, 2005. Reprinted with permission from Bonneux and Reuser (18).
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The mortality risk also rises in severe obesity: BMI >35 kg/m2 in men or BMI >33 kg/m2 in women.
Our occupation as cardiologists, focusing on prevention, detection, and management of cardiovascular disease, should not lead to a preoccupation. Overweight and mild obesity increase the risk for hypertension, diabetes, and cardiovascular disease but also lower the risk for hip fracture (19). Overweight and obesity lower the risk of death in a wide range of conditions, including heart disease, where it is known as the obesity paradox (10–14). It should be appreciated that, when identified in a timely manner, the increased cardiovascular risk in overweight and obese subjects can be effectively reduced by lowering blood pressure, low-density lipoprotein cholesterol, and elevated glucose levels and by refraining from smoking.
The "ideal" BMI is different by age, gender, and disease status. It is different if we look at disability, mortality, or various causes of death. Indeed, in a large individual record meta-analysis, overweight increased cardiovascular mortality but lowered all-cause mortality (5). Overweight might, at the same time, extend total life expectancy but shorten life expectancy free from disability.
The CRUSADE registry provided an opportunity to once more call attention to the cardiovascular risks of obesity, in particular the risk for premature NSTEMI. This is appropriate, indeed, but also opportunistic. In aging populations, the measuring tape should complement the balance, because age-related muscle wasting might mask high body fat mass. Future research should aim to gain insight into the pathophysiology of obesity and the mechanisms that result in excess cardiovascular morbidity and mortality but at the same time reduce the risk for other (fatal) diseases. Particularly at older ages, enhancing moderate physical activity seems a more rewarding policy target than decreasing population BMI.
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Footnotes
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* Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology. 
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References
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1. Madala MC, Franklin BA, Chen AY, et al. Obesity and age of first non–ST-segment elevation myocardial infarction J Am Coll Cardiol 2008;52:979-985.[Abstract/Free Full Text]2. Visscher TL, Seidell JC, Molarius A, van der Kuip D, Hofman A, Witteman JC. A comparison of body mass index, waist-hip ratio and waist circumference as predictors of all-cause mortality among the elderly: the Rotterdam study Int J Obes Relat Metab Disord 2001;25:1730-1735.[CrossRef][Web of Science][Medline] 3. Wannamethee SG, Shaper AG, Lennon L, Whincup PH. Decreased muscle mass and increased central adiposity are independently related to mortality in older men Am J Clin Nutr 2007;86:1339-1346.[Abstract/Free Full Text] 4. Yusuf S, Yawken S, Ounpuu S, et al. Obesity and the risk of myocardial infarction in 27.000 participants from 52 countries: a case-control study Lancet 2005;366:1640-1649.[CrossRef][Web of Science][Medline] 5. McGee DL. Body mass index and mortality: a meta-analysis based on person-level data from twenty-six observational studies Ann Epidemiol 2005;15:87-97.[CrossRef][Web of Science][Medline] 6. Yuan JM, Ross RK, Gao YT, Yu MC. Body weight and mortality: a prospective evaluation in a cohort of middle-aged men in Shanghai, China Int J Epidemiol 1998;27:824-832.[Abstract/Free Full Text] 7. Gu D, He J, Duan X, et al. Body weight and mortality among men and women in China JAMA 2006;295:776-783.[Abstract/Free Full Text] 8. Romero-Coral A, Montori VM, Somers VK. Association of bodyweight with total mortality and with cardiovascular events in coronary artery disease: a systematic review of cohort studies Lancet 2006;368:666-678.[CrossRef][Medline] 9. Abdulla J, Kober L, Abildstrom SZ, Christensen E, James WP, Torp-Pedersen C. Impact of obesity as a mortality predictor in high-risk patients with myocardial infarction or chronic heart failure: a pooled analysis of five registries Eur Heart J 2008;29:594-601.[Abstract/Free Full Text] 10. Curtis JP, Selter JG, Wang Y, et al. The obesity paradox: body mass index and outcomes in patients with heart failure Arch Intern Med 2005;165:55-61.[Abstract/Free Full Text] 11. McAuley P, Myers J, Abella J, Froelicher V. Body mass, fitness and survival in veteran patients: another obesity paradox? Am J Med 2007;120:518-524.[CrossRef][Web of Science][Medline] 12. Mehta RH, Califf RM, Garg J, et al. The impact of anthropomorphic indices on clinical outcomes in patients with acute ST-elevation myocardial infarction Eur Heart J 2007;28:415-424.[Abstract/Free Full Text] 13. Oreopoulos A, Padwal R, Norris CM, Mullen JC, Pretorius V, Kalantar-Zadeh K. Effect of obesity on short- and long-term mortality postcoronary revascularization: a meta-analysis Obesity (Silver Spring) 2008;16:442-450.[Medline] 14. Uretsky S, Messerli FH, Bangalore S, et al. Obesity paradox in patients with hypertension and coronary artery disease Am J Med 2007;120:863-870.[CrossRef][Web of Science][Medline] 15. Flegal KM, Graubard BI, Williamson DF, Gail MH. Excess deaths associated with underweight, overweight, and obesity JAMA 2005;293:1861-1867.[Abstract/Free Full Text] 16. Reuser M, Bonneux L, Willekens F. The burden of mortality of obesity at middle and old age is small. A life table analysis of the US Health and Retirement Survey. Eur J Epidemiol 2008June 27;[E-pub ahead of print]. 17. Pednekar MS, Hakama M, Hebert JR, Gupta PC. Association of body mass index with all-cause and cause-specific mortality: findings from a prospective cohort study in Mumbai (Bombay), India Int J Epidemiol 2008;37:524-535.[Abstract/Free Full Text] 18. Bonneux L, Reuser M. Overweight and mortality risk: no connection between overweight in middle and older age groups and increased mortality(Dutch) Ned Tijdschr Geneeskd 2007;151:2764-2769.[Medline] 19. De Laet C, Kanis JA, Oden A, et al. Body mass index as a predictor of fracture risk: meta-analysis Osteoporos Int 2005;16:1330-1338.[CrossRef][Web of Science][Medline]
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Obesity and Age of First Non–ST-Segment Elevation Myocardial Infarction
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J. Am. Coll. Cardiol. 2008 52: 979-985.
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