Editorial
Cachexia as major underestimated unmet medical need: Facts and numbers

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Introduction

Cachexia is a serious, however underestimated and underrecognized medical consequence of malignant cancer, chronic heart failure (CHF), chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), cystic fibrosis, rheumatoid arthritis, Alzheimer's disease, infectious diseases and many other chronic illnesses. The prevalence of cachexia is high, ranging from 5 to 15% in CHF or COPD to 60–80% in advanced cancer. By population prevalence, the most frequent cachexia subtypes are in order: COPD cachexia, cardiac cachexia (in CHF), cancer cachexia and CKD cachexia. In industrialized countries (North America, Europe, Japan), the overall prevalence of cachexia (due to any disease) is growing and currently about 1%, i.e. about 9 million patients. The relative prevalence of cachexia is somewhat less in Asia, but is a growing problem there as well. In absolute terms cachexia is in Asia (due to the larger population) as least as big a problem as in the Western world. Cachexia is also a big medical problem in South America and Africa, but data are scarce.

A consensus statement was recently proposed to diagnose cachexia in chronic diseases when there is weight loss exceeding 5% within the previous 3–12 months combined with symptoms characteristic for cachexia (e.g. fatigue), loss of skeletal muscle and biochemical abnormalities (e.g. anaemia or inflammation). Treatment approaches using anabolics, anti-catabolic therapies, appetite stimulants and nutritional interventions are under development. A more thorough understanding of the pathophysiology of cachexia development and progression is needed that likely will lead to combination therapies being developed.

These efforts are greatly needed as presence of cachexia is always associated with high mortality and poor symptom status and dismal quality of life. It is thought that in cancer more than 30% of patients die due to cachexia and more than 50% of patients with cancer die with cachexia being present. In other chronic illnesses one can estimate that up to 30% of patients die with some degree of cachexia being present. Mortality rates of patients with cachexia range from 10 to 15% per year (COPD), to 20–30% per year (CHF, CKD) and to 80% in cancer.

Cachexia has been known for centuries. Hippocrates wrote that “the flesh is consumed and becomes water,… the abdomen fills with water, the feet and legs swell, the shoulders, clavicles, chest, and thighs melt away… The illness is fatal.” [1]. The term cachexia has Greek roots, a combination of the words kakós (bad) and hexis (condition or appearance) [2]. It is not exactly clear who suggested to use the term cachexia to describe involuntary weight loss in the context of chronic illness, but the first written documentation of cardiac cachexia, for example, dates back to 1860 when Charles Mauriac, a French physician, described a “commonly observed secondary phenomenon in patients affected with diseases of the heart … a peculiar state of cachexia which is … conventionally designated cardiac cachexia” [2]. He was not the only one to acknowledge the importance of body wasting. Herta Müller, winner of the 2009 Nobel Prize for literature, wrote that “once the flesh has disappeared from the body, carrying the bones becomes a burden; it draws you down into the earth” [3].

Cachexia is a serious, however underestimated and underrecognized medical problem that is observed as a consequence of malignant cancer, chronic heart failure (CHF), chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), cystic fibrosis, rheumatoid arthritis, Alzheimer's disease, infectious diseases, and many other chronic illnesses. Death normally ensues when weight loss exceeds 30% [4], and it has been estimated that about 50% of patients with cancer have some degree of cachexia at the time of their death [5]. In starvation, weight loss exceeding 40% of body weight is not compatible with life [6]. Neither do we understand the pathophysiology of cachexia in its entirety, nor do we have approved treatments against involuntary weight loss other than appetite stimulants [7] and recombinant human growth hormone (somatropin) [8] in AIDS-associated body wasting. Studies are reporting, and potential therapeutic approaches differ across a broad range [9], [10], [11]. We believe that cachexia requires more attention, not only by physicians and other health care professionals, but also by the general public. Indeed, body weight is a dynamic parameter and has a certain rhythm over the lifespan [12], and public opinion is currently more concerned with weight gain than with weight loss. Public awareness in chronic diseases needs to be redirected, and people need to understand that weight gain may be beneficial in certain clinical situations.

Section snippets

What is cachexia?

An important consideration in understanding and managing cachexia is that many misconceptions exist with regards to weight loss. Laviano and colleagues recently suggested somewhat depressingly that cachexia represents a state in which “all you can eat is yourself” [13]. On the other hand, descriptive terms such as “cachexia”, “anorexia”, “sarcopenia”, “malnutrition” and even “hypercatabolism” are frequently regarded as synonyms by researchers and clinicians [14]. Whilst malnutrition is

Defining a frequent clinical problem

Many definitions used in studies of cachexia in different illnesses have focused on weight loss alone, and few acknowledged the importance of body composition or temporal components of weight change. In cardiac cachexia, for example, it is necessary to consider the presence of oedema, and only non-oedematous weight loss can be considered appropriate [21]. Changes in body composition are not easily detectable, and may require even advanced technologies such as dual energy X-ray absorptiometry

Acknowledgement

This article is largely a re-publication of a paper published previously in the Journal of Cachexia, Sarcopenia and Muscle [24], updated regarding factual contents and somewhat modified for style. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [23].

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