Obesity paradox

The obesity paradox is a medical hypothesis which holds that obesity (and high cholesterol, when the more global term reverse epidemiology is used) may, counterintuitively, be protective and associated with greater survival in certain groups of people, such as very elderly individuals or those with certain chronic diseases. It further postulates that normal to low body mass index or normal values of cholesterol may be detrimental and associated with higher mortality in asymptomatic people.

Description

The terminology reverse epidemiology was first proposed by Kamyar Kalantar-Zadeh in the journal Kidney International in 2003[1] and in the Journal of the American College of Cardiology in 2004.[2] It is a contradiction to prevailing concepts of prevention of atherosclerosis and cardiovascular disease; however, active prophylactic treatment of heart disease in otherwise healthy, asymptomatic people is and has been controversial in the medical community for several years.[3][4]

The mechanism responsible for this reversed association is unknown, but it has been suggested that, in chronic kidney disease patients, "The common occurrence of persistent inflammation and protein energy wasting in advanced CKD [chronic kidney disease] seems to a large extent to account for this paradoxical association between traditional risk factors and CV outcomes in this patient population."[5] Other research has proposed that the paradox may be explained by adipose tissue storing lipophilic chemicals that would otherwise be toxic to the body.[6]

The obesity paradox (excluding cholesterol paradox) was first described in 1999 in overweight and obese people undergoing hemodialysis,[7] and has subsequently been found in those with heart failure,[2][8][9] myocardial infarction,[10] acute coronary syndrome,[11] older nursing home residents,[12] and chronic obstructive pulmonary disease (COPD).[13]

In people with heart failure, those with a body mass index between 30.0–34.9 had lower mortality than those with what would normally be considered an ideal weight. This has been attributed to the fact that people often lose weight as they become progressively more ill.[14] Similar findings have been made in other types of heart disease. People with class I obesity and heart disease do not have greater rates of further heart problems than people of normal weight who also have heart disease. In people with greater degrees of obesity, however, risk of further events is increased.[15][16] Even after cardiac bypass surgery, no increase in mortality is seen in the overweight and obese.[17] One study found that the improved survival could be explained by the more aggressive treatment obese people receive after a cardiac event.[18] Another found that if one takes into account COPD in those with peripheral artery disease, the benefit of obesity no longer exists.[19]

Criticisms

The obesity paradox has been criticized on the grounds of being an artifact arising from biases in observational studies. Strong confounding by smoking has been noted by several researchers.[20][21] Since smokers, who are subject to higher mortality rates, also tend to be leaner, inadequate adjustment for smoking would lead to underestimations of the risk ratios associated with the overweight and obese categories of BMI. In an analysis of 1.46 million individuals, restriction to never-smoking participants greatly reduced the mortality estimates in the underweight group, as well as strengthening the estimates in the overweight and obese groups.[22]

Another concern is reverse causation due to illness-induced weight loss. That is, it may not be low BMI that is causing death (and thereby making obesity seem protective) but rather imminent death causing low BMI. Indeed, unintentional weight loss is an extremely significant predictor of mortality.[23] Sick individuals often undergo weight loss before death, and classifying those individuals as lean greatly inflates the mortality rate in the normal and underweight categories of BMI, while lowering the risk in the higher BMI categories. Studies that employ strategies to reduce reverse causation such as excluding sick individuals at baseline and introducing time lag to exclude deaths at the beginning of follow-up[24] have yielded estimates of increased risk for body mass indices above 25 kg/m2. Critics of the "paradox" have also argued that studies supporting its existence almost always use BMI as the only measure of obesity. However, because BMI is an imperfect method of measuring obesity, critics argue that studies using other measures of obesity in addition to BMI, such as waist circumference and waist to hip ratio, render the existence of the "paradox" questionable.[25]

References

  1. ↑ Kalantar-Zadeh, Kamyar; Block, Gladys; Humphreys, Michael H.; Kopple, Joel D. (2003). "Reverse epidemiology of cardiovascular risk factors in maintenance dialysis patients". Kidney International. 63 (3): 793–808. doi:10.1046/j.1523-1755.2003.00803.x. PMID 12631061.
  2. 1 2 Kalantar-Zadeh, Kamyar; Block, Gladys; Horwich, Tamara; Fonarow, Gregg C (2004). "Reverse epidemiology of conventional cardiovascular risk factors in patients with chronic heart failure". Journal of the American College of Cardiology. 43 (8): 1439–44. doi:10.1016/j.jacc.2003.11.039. PMID 15093881.
  3. ↑ Naghavi, Morteza; Falk, Erling; Hecht, Harvey S.; Shah, Prediman K.; Shape Task Force (2006). "The First SHAPE (Screening for Heart Attack Prevention and Education) Guideline". Critical Pathways in Cardiology. 5 (4): 187–90. doi:10.1097/01.hpc.0000249784.29151.54. PMID 18340236.
  4. ↑ Pearson, T. A. (2007). "The Prevention of Cardiovascular Disease: Have We Really Made Progress?". Health Affairs. 26 (1): 49–60. doi:10.1377/hlthaff.26.1.49. PMID 17211013.
  5. ↑ Vascular disease and chronic renal failure: new insights
  6. ↑ Hong, N-S; Kim, K-S; Lee, I-K; Lind, P M; Lind, L; Jacobs, D R; Lee, D-H (27 September 2011). "The association between obesity and mortality in the elderly differs by serum concentrations of persistent organic pollutants: a possible explanation for the obesity paradox". International Journal of Obesity. 36 (9): 1170–1175. doi:10.1038/ijo.2011.187.
  7. ↑ Schmidt, Darren S.; Salahudeen, Abdulla K. (2007). "CARDIOVASCULAR AND SURVIVAL PARADOXES IN DIALYSIS PATIENTS: Obesity-Survival Paradox-Still a Controversy?". Seminars in Dialysis. 20 (6): 486–92. doi:10.1111/j.1525-139X.2007.00349.x. PMID 17991192.
  8. ↑ Sharma, A; Lavie, CJ; Borer, JS; Vallakati, A; Goel, S; Lopez-Jimenez, F; Arbab-Zadeh, A; Mukherjee, D; Lazar, JM (15 May 2015). "Meta-analysis of the relation of body mass index to all-cause and cardiovascular mortality and hospitalization in patients with chronic heart failure.". The American journal of cardiology. 115 (10): 1428–34. doi:10.1016/j.amjcard.2015.02.024. PMID 25772740.
  9. ↑ Padwal, R; McAlister, F A; McMurray, J J V; Cowie, M R; Rich, M; Pocock, S; Swedberg, K; Maggioni, A; Gamble, G; Ariti, C; Earle, N; Whalley, G; Poppe, K K; Doughty, R N; Bayes-Genis, A (31 October 2013). "The obesity paradox in heart failure patients with preserved versus reduced ejection fraction: a meta-analysis of individual patient data". International Journal of Obesity. 38 (8): 1110–1114. doi:10.1038/ijo.2013.203.
  10. ↑ Wang, L; Liu, W; He, X; Chen, Y; Lu, J; Liu, K; Cao, K; Yin, P (4 September 2015). "Association of overweight and obesity with patient mortality after acute myocardial infarction: A meta-analysis of prospective studies.". International journal of obesity (2005). doi:10.1038/ijo.2015.176. PMID 26338077.
  11. ↑ Niedziela, J; Hudzik, B; Niedziela, N; Gąsior, M; Gierlotka, M; Wasilewski, J; Myrda, K; Lekston, A; Poloński, L; Rozentryt, P (November 2014). "The obesity paradox in acute coronary syndrome: a meta-analysis.". European Journal of Epidemiology. 29 (11): 801–12. doi:10.1007/s10654-014-9961-9. PMID 25354991.
  12. ↑ Veronese, N; Cereda, E; Solmi, M; Fowler, SA; Manzato, E; Maggi, S; Manu, P; Abe, E; Hayashi, K; Allard, JP; Arendt, BM; Beck, A; Chan, M; Audrey, YJ; Lin, WY; Hsu, HS; Lin, CC; Diekmann, R; Kimyagarov, S; Miller, M; Cameron, ID; Pitkälä, KH; Lee, J; Woo, J; Nakamura, K; Smiley, D; Umpierrez, G; Rondanelli, M; Sund-Levander, M; Valentini, L; Schindler, K; Törmä, J; Volpato, S; Zuliani, G; Wong, M; Lok, K; Kane, JM; Sergi, G; Correll, CU (November 2015). "Inverse relationship between body mass index and mortality in older nursing home residents: a meta-analysis of 19,538 elderly subjects.". Obesity Reviews. 16 (11): 1001–15. doi:10.1111/obr.12309. PMID 26252230.
  13. ↑ Cao, Chao; Wang, Ran; Wang, Jianmiao; Bunjhoo, Hansvin; Xu, Yongjian; Xiong, Weining; Simpson, Colin (24 August 2012). "Body Mass Index and Mortality in Chronic Obstructive Pulmonary Disease: A Meta-Analysis". PLoS ONE. 7 (8): e43892. doi:10.1371/journal.pone.0043892.
  14. ↑ Habbu, Amit; Lakkis, Nasser M.; Dokainish, Hisham (2006). "The Obesity Paradox: Fact or Fiction?". The American Journal of Cardiology. 98 (7): 944–8. doi:10.1016/j.amjcard.2006.04.039. PMID 16996880.
  15. ↑ Romero-Corral, Abel; Montori, Victor M; Somers, Virend K; Korinek, Josef; Thomas, Randal J; Allison, Thomas G; Mookadam, Farouk; Lopez-Jimenez, Francisco (2006). "Association of bodyweight with total mortality and with cardiovascular events in coronary artery disease: A systematic review of cohort studies". The Lancet. 368 (9536): 666–78. doi:10.1016/S0140-6736(06)69251-9. PMID 16920472.
  16. ↑ Oreopoulos, Antigone; Padwal, Raj; Kalantar-Zadeh, Kamyar; Fonarow, Gregg C.; Norris, Colleen M.; McAlister, Finlay A. (2008). "Body mass index and mortality in heart failure: A meta-analysis". American Heart Journal. 156 (1): 13–22. doi:10.1016/j.ahj.2008.02.014. PMID 18585492.
  17. ↑ Oreopoulos, Antigone; Padwal, Raj; Norris, Colleen M; Mullen, John C; Pretorius, Victor; Kalantar-Zadeh, Kamyar (2008). "Effect of Obesity on Short- and Long-term Mortality Postcoronary Revascularization: A Meta-analysis". Obesity. 16 (2): 442–50. doi:10.1038/oby.2007.36. PMID 18239657.
  18. ↑ Diercks, Deborah B.; Roe, Matthew T.; Mulgund, Jyotsna; Pollack, Charles V.; Kirk, J. Douglas; Gibler, W. Brian; Ohman, E. Magnus; Smith, Sidney C.; et al. (2006). "The obesity paradox in non–ST-segment elevation acute coronary syndromes: Results from the Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the American College of Cardiology/American Heart Association Guidelines Quality Improvement Initiative". American Heart Journal. 152 (1): 140–8. doi:10.1016/j.ahj.2005.09.024. PMID 16824844.
  19. ↑ "Obesity Paradox" in Chronic Obstructive Pulmonary Disease
  20. ↑ Stokes, Andrew (2015). "Smoking and reverse causation create an obesity paradox in cardiovascular disease.". Obesity. 23 (12): 2485–90. doi:10.1002/oby.21239. PMC 4701612Freely accessible. PMID 26421898.
  21. ↑ Preston, Samuel; Stokes, Andrew (2014). "Obesity Paradox: Conditioning on Disease Enhances Biases in Estimating the Mortality Risks of Obesity.". Epidemiology. 25 (3): 454–461. doi:10.1097/EDE.0000000000000075.
  22. ↑ Berrington de Gonzalez A, Hartge P, Cerhan JR, Flint AJ, Hannan L, MacInnis RJ, Moore SC, Tobias GS, Anton-Culver H, Freeman LB, Beeson WL, Clipp SL, English DR, Folsom AR, Freedman DM, Giles G, Hakansson N, Henderson KD, Hoffman-Bolton J, Hoppin JA, Koenig KL, Lee IM, Linet MS, Park Y, Pocobelli G, Schatzkin A, Sesso HD, Weiderpass E, Willcox BJ, Wolk A, Zeleniuch-Jacquotte A, Willett WC, Thun MJ (2010). "Body-mass index and mortality among 1.46 million white adults". The New England Journal of Medicine. 363 (23): 2211–9. doi:10.1056/NEJMoa1000367. PMC 3066051Freely accessible. PMID 21121834.
  23. ↑ Harrington, Mary; Gibson, Sigrid; Cottrell, Richard (2009). "A review and meta-analysis of the effect of weight loss on all-cause mortality risk.". Nutr Res Rev. 22 (1): 93–108. doi:10.1017/S0954422409990035. PMID 19555520.
  24. ↑ Prospective Studies Collaboration (2009). "Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies". The Lancet. 373 (9669): 1083–1096. doi:10.1016/S0140-6736(09)60318-4. PMC 2662372Freely accessible. PMID 19299006.
  25. ↑ Chrysant, Steven G.; Chrysant, George S. (January 2013). "New insights into the true nature of the obesity paradox and the lower cardiovascular risk". Journal of the American Society of Hypertension. 7 (1): 85–94. doi:10.1016/j.jash.2012.11.008.

Further reading

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