A role for cytokines has been suggested by the finding that tumour necrosis factor-alpha (TNF-á) is increased in

patients with severe chronic heart failure and cardiac cachexia[7–9].

[7] Levin B, Kalman J, Mayer L, Fillit HM, Packer M. Elevated

circulating levels of tumor necrosis factor in severe chronic
heart failure. N Engl Med 1990; 323: 236–41.
[8] McMurray J, Abdullah I, Dargie HJ, Shapiro D. Increased
concentrations of tumor necrosis factor in ‘cachectic’ patients
with severe chronic heart failure. Br Heart J 1991; 66: 356–8.
[9] Dutka DP, Elborn JS, Delamere F, Shale DJ, Morris GK.
Tumor necrosis factor a in severe congestive cardiac failure.
Br Heart J 1993; 70: 141–3.

Hasta seçiminde yazılabilecek bir yorum...

In the documentation of weight loss for the detection
of cachexia, special care was taken to ensure that no
patient had peripheral or pulmonary oedema, significant
elevation of jugular venous pressure, hepatomegaly or
ascites at the time of assessment.

Cachectic patients. The results for cachectic and noncachectic CHF patients are shown in Table 3 ⇑. The plasma
sodium concentration was decreased, and epinephrine, norepinephrine, cortisol, and TNF-α were
substantially increased in cachectic CHF patients (all P≤.0002 versus noncachectic CHF patients, all P≤.0015
versus control subjects). (kaynak:Hormonal Changes and Catabolic/Anabolic Imbalance in Chronic Heart
Failure and Their Importance for Cardiac Cachexia)

Cytokines and neurohormones relating to body

composition alterations in the wasting syndrome of
chronic heart failureThe possible role of cytokine inflammatory activation
(TNF-á, sTNFRs IL-â and interleukin-6) in severe
chronic heart failure and the development of cardiac
cachexia have been described (reviews[28,29]). The bulk of
evidence (mainly animal studies) suggests that cytokine
changes are causally related to loss of muscle or fat
tissue (TNF-á, interleukin-1) and bone tissue
(interleukin-6). Depending on the site of action, muscle
or brain, TNF-á caused muscle wasting or anorexia in
animal studies[30]. Interleukin-1 has been implicated as
important for muscle catabolism[31] and interleukin-6 as
mediating osteoclastogenesis[32], but two studies failed to
show increased levels of interleukin-1 or interleukin-6 in
stable heart failure patients[33,34]. The role of sTNFRs is
more controversial. They are either just a sensitive
marker of the disease process, an important TNFcounterregulatory
factor, or, by stabilizing the TNF
reservoir, are a factor that potentiates the long-term
actions of TNF-á. In the current study, significant
correlations between increased levels of TNF-á and
sTNFR-1 and reduced lean, fat or bone mass were
demonstrated. It was not possible to demonstrate such
relationships for interleukin-1 or interleukin-6. It is
recognized that this neither proves nor disproves a
causal relationship. It was not possible to measure
locally acting concentrations (28-34.kaynaklar;
[28] Mann DL, Young JB. Basic mechanisms in congestive heart
failure. Recognizing the role of proinflammatory cytokines.
Chest 1994; 105: 897–904.
[29] Packer M. Is tumor necrosis factor an important neurohormonal
mechanism in chronic heart failure? Circulation 1995;
92: 1379–82.
[30] Tracey KJ, Morgello S, Koplin B et al. Metabolic effects of
cachectin/tumor necrosis factor are modified by site of production:
Cachectin/tumor necrosis factor-secreting tumor in
skeletal muscle induces chronic cachexia, while implantation
in brain induces predominantly acute anorexia. J Clin Invest
86: 2014–24.
[31] Flores EA, Bistrian BR, Pomposelli JJ, Dinarello CA,
Blackburn GL, Istfan NW. Infusion of tumor necrosis factor/
cachectin promotes muscle catabolism in the rat. A synergistic
effect with interleukin 1. J Clin Invest 1989; 83: 1614–22.
[32] Bellido T, Jilka RL, Boyce BF et al. Regulation of
interleukin-6, osteoclastogenesis, and bone mass by androgens.
J Clin Invest 1995; 95: 2886–95.
[33] Katz SD, Rao R, Berman JW et al. Pathophysiological
correlates of increased serum tumor necrosis factor in patients
with congestive heart failure. Circulation 1994; 90: 12–6.
[34] Nozaki N, Yamaguchi S, Nakamura H, Takahashi K,
Tomoike H. Two types of soluble tumor necrosis factor
(TNF) receptors are increased in relation to severity in heart
failure (Abstr). Circulation 1994; 90: I-381.

Sonuç cümleleri
This study indicates that alterations of catabolism and
partly anabolism with neurohormonal and cytokine
activation are important markers of a wasting process
that finally leads to cardiac cachexia.

Levine ve arkadaşlarının yaptığı çalışmada TNF-Alfa düzeyinin kardiyak kaşeksili hastalarda arttığı gösterilmiştir.(figure 2)
( T he syndrome of cardiac cachexia 8.kaynak [8] Levine B, Kalman J, Mayer L, Fillit H, Packer M. Elevated
circulating levels of tumor necrosis factor in severe chronic heart
failure. N Engl J Med 1990;323:236–41.
The serum level of TNFαwas also higher in patients with CHF than in control subjects (5.9±0.7 vs
2.6±0.5 pg/ml; p<0.005). The serum level of TNFαwas increased in relation to the severity of CHF
(ANOVA; p<0.005). The level of TNFαin patients of NYHA classes III and IV (7.7±1.5 pg/ml) was
significantly higher than normal subjects (p<0.001). Kaynak çalışma adı::: (Anti-inflammatory
Cytokine Profile in Human Heart Failure Behavior of Interleukin-10 in Association With Tumor
Necrosis Factor-Alpha .................Minako Yamaoka, MD; Seiji Yamaguchi, MD; Masaki Okuyama,
MD; Hitonobu Tomoike, MD ...........Japanese Circulation Journal Vol.63, December 1999 )
Nutritional markers and prognosis in cardiac cachexia
3. Results
From the 358 records screened we found 38 (11%) cachecticpatients. The cachectic group (
n=38) had 11.0±4.4% documentedweight loss (minimum 7.6%, maximum 28.2%), during a mean
time of 28 months since CHF diagnosis. No significant differences concerning weight loss was
documented in the control group (n=56). Clinical characteristics and laboratory data of both groups
are shown and compared in Table 1. No significant differences concerning age, sex,time since CHF
diagnosis and severity of left ventricular dysfunction existed between groups. Heart failure was
predominantly non-ischemic in the cachectic group and no significant differences existedconcerning
comorbidities. Beta-blocker, aspirin and statin use were more prevalent in the non-cachectic group.
BNP was significantly higher in the cachectic group. Cachectic patients had higher levels of
catabolic hormones (cortisol, free T4) and lower levels of anabolic hormones (IGF-1, insulin). Proin
flammatory cytokines (hsCRP,serum amyloid A and TNF-α) were higher in the cachectic group.
Anthropometric evaluation, body composition analysis and markers of nutritionalstatus are
displayed inTable2.The lean(as assessedby arm muscle area) and the fat tissue (as assessed by
percent body fat) were significantly reduced in the cachectic patients. Pre-albumin, albumin,
haemoglobin, lymphocyte count and triglycerides were significantly lower in cachectics. Despite
the lower statin use, cholesterol levels were lower in the cachectic group.Table 3 displays univariate
and multivariate logistic regression analysis of all possible cachexia predictors in order to
investigateanalytical markers of cardiac cachexia. The odds ratios depicted
representtheassociationofeachvariablewiththeexistenceofcachexia. Low pre-albumin was the only
marker independently associated withcardiac cachexia occurrence [OR=1.08 (CI: 1.01–1.17)].
During a follow-up of 16.2±5.8 months, death occurred in 15 (39.4%) out of the 38 cachectic
patients and in 6 (10.7 %) out of the 56non-cachectic patients (p
-value b0.001).Fig. 1represents the corre-sponding Kaplan–Meier survival curve.Variables
associated with outcome in the subgroup of patients with cardiac cachexia are depicted inTable 4 .
In univariate Cox-regression analysis, pre-albumin, total cholesterol, IGF-1, insulin and BNP
predicted death. In a multivariate Cox-regression model,including these 5 variables, low cholesterol
was independently associated with worse outcome, performing even better than BNP.

There are some laboratory markers helpful in diagnosing cachexia, including prealbumin,
cholesterol, and C-reactive protein. Prealbumin is the best marker of cardiac cachexia as it indicates
protein-calorie malnutrition. C-reactive protein becomes elevated as a result of inflammation and is
generally a nonspecific indicator but can be helpful to confirm a presumptive diagnosis of cachexia.
Normal prealbumin levels are 16 to 35 mg/dL; a diagnosis of cardiac cachexia can be made when
levels are less than 16, or if albumin is less than 3.2 g/L. Cholesterol may be lower in cardiac
cachexia, and a total cholesterol level of less than 172 is associated with poor prognosis in cachectic
patients.[10] 10.Cavey J. Cardiac cachexia. J. Nurse Pract. 2011;7(7):578–581.