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Vol. 61. Issue 6.
Pages 653 (June 2008)
DOI: 10.1016/S1885-5857(08)60192-9
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The Obesity Paradox or Vulnerability of the Underweight
Paradoja de la obesidad o susceptibilidad del bajo peso
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Alberto Morales Salinasa
a Servicio de Cardiología, Cardiocentro Ernesto Che Guevara, Santa Clara, Cuba
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To the Editor:

In response to the interesting articles from Zamora1 and Artham,2 we would like to comment on the controversial issue of the obesity paradox.

Advances in pharmacological treatments have been the main reason for the reduction in mortality associated with acute myocardial infarction (AMI) between 1975 and 1995.3 It is therefore surprising that the studies reporting on different aspects of reverse epidemiology, within the context of polypharmacy and haemodynamic instability, as well as acute coronary syndrome (ACS) and acute cardiac failure (ACF), all under-utilise pharmacological variables and are limited to a general analysis of the percentage of drugs used.1,4

Another element to be highlighted is the high percentage of patients excluded from these researches since their weight and/or size is not provided.4 This would seem to suggest that, in particular during the first stages of a cardiological emergency, there are failures in taking the patient's anthropometric measurements, which may lead to an incorrect pharmacological dose.4

Unfortunately, drugs which have proven to be beneficial in reducing cardiovascular morbimortality can also have very serious adverse effects if the correct dose is not given.5 In this way, subjects with reduced body mass have greater "pharmacological susceptibility,"5 which is perhaps related to older age1,6 and comorbidity, as well as a reduced "therapeutic window."

Therapeutic intervals are directly and proportionately related to body mass index (BMI) and are influenced by multiple factors, such as age, sex, and renal function. This relationship is not taken into account in the exclusive analysis of the percentage of drugs used. Fonarow recently recognised the need to include more complex pharmacological variables such as: dose, tolerability and adverse effects.7

It is also to be noted that the insufficiencies indicated have been concluded from studies based on hospital records4,5 and that the situation in practice may be much more critical.

Moreover, markers should not be confused with risk factors.2 The obesity paradox does not fit the causality criteria, since on analysing the strength of the association, severe obesity does not yield better outcomes, in particular when compared to overweight and slightly obese patients.2 While the paradox is not detected or even disappears ("reversal of the reversal epidemiology")8 in situations where the importance of quantifying the acute pharmacological management is "reduced," as is the case of sudden death1,2,6 (in particular where this occurs outside the hospital), stable coronary heart disease,9 long-term monitoring (>5 years) of heart failure6,8 or heart failure with ejection fraction >40%1,2 and heart transplant.8

Finally, we believe that the risk factors can never be separated from the constant of cardiovascular risk, rather they are associated with ACS and ACF in a much more complex maze of causality than we have been able to quantify and in which medical treatment plays a leading role.4

In conclusion, we have put forward a theory that pharmacological variables are the main confounding factors in reverse epidemiology and suggest caution on accepting the validity of the obesity paradox, until more evidence is acquired.

Bibliography
[1]
Zamora E, Lupón J, Urrutia A, González B, Mas D, Pascual T..
??El ??ndice de masa corporal influye en la mortalidad de los pacientes con insuficiencia cardiaca? Rev Esp Cardiol, 60 (2007), pp. 1127-34
[2]
Artham SM, Ventura HO..
Insuficiencia cardiaca y la «paradoja de la obesidad»: la historia continúa..
Rev Esp Cardiol, 60 (2007), pp. 1113-7
[3]
Heidenreich PA, McClellan M..
Trends in treatment and outcomes for acute myocardial infarction: 1975-1995..
Am J Med, 110 (2001), pp. 165-74
[4]
Morales A, Lopez G, Ramos R..
Replay..
Am Heart J, 155 (2008), pp. e1
[5]
Curtis JP, Alexander JH, Huang Y, Wallentin L, Verheugt F, Armstrong PW, et al..
Efficacy and safety of two unfractionated heparin dosing strategies with tenecteplase in acute myocardial infarction (results from Assessment of the Safety and Efficacy of a New Thrombolytic Regimens 2 and 3)..
Am J Cardiol, 94 (2004), pp. 279-83
[6]
Horwich TB, Fonarow GC, Hamilton MA, MacLellan WR, Woo MA, Tillisch JH..
The relationship between obesity and mortality in patients with heart failure..
J Am Coll Cardiol, 38 (2001), pp. 789-95
[7]
Fonarow G..
Reply..
Am Heart J, 154 (2007), pp. e21
[8]
Kalantar-Zadeh K, Block G, Horwich T, Fonarow GC..
Reverse epidemiology of conventional cardiovascular risk factors in patients with chronic heart failure..
J Am Coll Cardiol, 43 (2004), pp. 1439-44
[9]
Domanski MJ, Jablonski KA, Murguia-Rice M, Fowler SE, Braunwald E..
Obesity and cardiovascular events in patients with established coronary disease Eur Heart J, 27 (2006), pp. 1416-22
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Revista Española de Cardiología (English Edition)

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