Risk factor paradox in wasting diseases.
OBJECTIVE
Emerging data indicate that conventional cardiovascular risk factors (e.g. hypercholesterolemia and obesity) are paradoxically associated with better survival in distinct populations with wasting. We identify these populations and review survival paradoxes and common pathophysiologic mechanisms.


RESULTS
A 'reverse epidemiology' of cardiovascular risk is observed in chronic kidney disease, chronic heart failure, chronic obstructive lung disease, cancer, AIDS and rheumatoid arthritis, and in the elderly. These populations apparently have slowly progressive to full-blown wasting and significantly greater short-term mortality than the general population. The survival paradoxes may result from the time differential between the two competing risk factors [i.e. over-nutrition (long-term killer but short-term protective) versus undernutrition (short-term killer)]. Hemodynamic stability of obesity, protective adipokine profile, endotoxin-lipoprotein interaction, toxin sequestration of fat, antioxidation of muscle, reverse causation, and survival selection may also contribute.


CONCLUSIONS
The seemingly counterintuitive risk factor paradox is the hallmark of chronic disease states or conditions associated with wasting disease at the population level. Studying similarities among these populations may help reveal common pathophysiologic mechanisms of wasting disease, leading to a major shift in clinical medicine and public health beyond the conventional Framingham paradigm and to novel therapeutic approaches related to wasting and short-term mortality.
Kalantar-Zadeh
Kamyar
K
Harold Simmons Center for Kidney Disease Research and Epidemiology, Los Angeles Biomedical Research Center at Harbor-UCLA, Torrance, California 90509-2910, USA. kamkal@ucla.edu
Horwich
Tamara B
TB
Oreopoulos
Antigone
A
Kovesdy
Csaba P
CP
Younessi
Houman
H
Anker
Stefan D
SD
Morley
John E
JE
D002100:Cachexia / Q000378:metabolism / Q000401:mortality*; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000401:mortality*; D002908:Chronic Disease; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000401:mortality*; D009765:Obesity / Q000378:metabolism / Q000401:mortality*; D012307:Risk Factors; D016019:Survival Analysis; D019282:Wasting Syndrome / Q000378:metabolism / Q000401:mortality*