Skip Navigation

European Journal of Heart Failure 2005 7(5):840-843; doi:10.1016/j.ejheart.2004.12.008
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Varol, E.
Right arrow Articles by Kosar, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Varol, E.
Right arrow Articles by Kosar, F.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2005 European Society of Cardiology

Tumour marker levels in patients with chronic heart failure

Ercan Varola,*, Mehmet Ozaydinb, Abdullah Doganb and Feridun Kosarc

a Department of Cardiology, Isparta State Hospital Anadolu Mah. ESO (memur) Evleri C Blok No:5, 32200 Isparta, Turkey
b Department of Cardiology Süleyman Demirel University, Isparta, Turkey
c Department of Cardiology Inonü University, Malatya, Turkey

* Corresponding author. Tel.: +90 532 346 8258, +90 246 232 4510. E-mail address: adogan35{at}hotmail.com


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
Background: Carbohydrate Antigen 125 (CA 125), a marker for ovarian cancer has been reported to increase in relation to the severity of heart failure.

Objective: To evaluate the serum levels of CA 125 and other tumour markers, in patients with chronic heart failure.

Methods: Blood levels of CA 125 and other tumour markers were determined in 44 heart failure patients (16 males and 28 females; age 66.3±6.5 years) before and after optimal medical treatment. Levels were also evaluated in 30 healthy volunteers (11 males and 19 females; age 65.7±9.8 years). The results in the heart failure patients were grouped according to clinical status (New York Heart Association Class). The mean duration of follow-up was 3±1.5 months.

Results: The mean serum level of CA 125 was 81.9±91 in the patient group and 7.5±4.8 in control group (p<0.001). The mean CA 19-9 level in the patient group (16.8±16.6) was significantly higher than in the control group (4.5±2.6) (p<0.001). CA 125 levels increased as the New York Heart Association (NYHA) functional class increased (Class I/II: 17.7±22.4 U/ml; Class III: 99.6±92.1 U/ml; Class IV 136.4±102.8 U/ml; p<0.05). There were no significant differences in serum CA 125 and other tumour marker levels before and after optimisation of treatment. Significantly higher serum CA 125 levels were found in patients with pericardial effusion (p=0.002) when compared to patients without pericardial effusion.

Conclusion: Among the tumour markers evaluated, only CA 125 seems to be specifically related to the presence and severity of heart failure and also the presence of pericardial fluid. Therefore, measurements of CA 125 serum levels might be proposed for the serial assessment of heart failure. Whether CA 125 has a specific biological role in heart failure requires further investigation.

Key Words: CA 125 • Heart failure • Tumour markers

Received July 16, 2004; Revised December 14, 2004; Accepted December 20, 2004


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 References
 
Tumour markers are normally used to follow-up patients with cancer [1,2]. Clinical usage of tumour markers is limited due to low specificity. Carbohydrate Antigen 125 (CA 125) is a tumour marker of ovarian cancer [3,4], but is also increased in patients with heart failure [5,6]. It has also been reported that CA 125 is related to heart failure severity, pleural fluid involvement and short-term prognosis [7,8]. Whereas CA 19-9 and carcinoembryonic antigen levels were not influenced by circulatory disturbances in a previous study [9].

The aim of the present study was to measure the blood levels of CA 125 and other tumour markers in patients with symptomatic left ventricular dysfunction and to determine the potential relationship between tumour markers and the severity of heart failure. We also aimed to detect if there was a change in tumour marker levels after aggressive medical treatment.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 References
 
2.1. Patients
We prospectively evaluated 44 heart failure patients (16 male and 28 female; age 66.3±6.5 years) consecutively admitted to the Department of Cardiology, Isparta State Hospital, Turkey, over a period of 12 months.. The diagnosis of heart failure was based on clinical presentation and standard investigation. One patient was in New York Heart Association (NYHA) functional Class I, 13 were in Class II, 20 in Class III and 10 patients were in Class IV. The aetiology of heart failure was coronary artery disease in 64% of patients, dilated cardiomyopathy in 21%, hypertensive heart disease in 10% and 5% of patients had "other" aetiologies. Mean left atrial diameter was 4.1±0.2 cm. Mean left ventricular ejection fraction was 31.2±12% and 59% of patients had atrial fibrillation. Patient medication included ACE-inhibitors (95%), digitalis (64%), diuretics (86%), beta-blockers (45%) and spironolactone (45%). Mean serum sodium at baseline was 136.6±5.2 mmol/l and creatinine was 123.7±106.08 mmol/l. Most of the patients had at least one hospital admission with heart failure. Patients awaiting coronary artery bypass graft or valvular surgery, patients with recent acute coronary syndrome (<3 months) and those with any evidence of active infection, cancer, end stage liver disease or renal failure were excluded from the study. Thirty healthy age- and gender-matched volunteers were used as a control group (11 male and 19 female; age 65.7±9.8 years).

All patients and volunteers gave informed consent and the study was approved by the local ethics committee. Patients were hospitalized for treatment and further aetiologic investigation, the mean duration of hospitalisation was 6.3±2.7 days. All patients underwent clinical examination, telecardiography, two-dimensional Doppler echocardiographic examination and venous blood sampling for evaluation of CA 125 and other tumour markers on the day of admission. Two dimensional echocardiography was performed with commercially available equipment. The left ventricular ejection fraction was calculated using the Simpson method from the apical four-chamber view. The patients also underwent an ultrasonographic examination to determine the presence of fluid in the pleural cavity.

2.2. Measurement of serum tumour markers
CA 125, CA 15-3, CA 19-9, carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) tumour markers were measured with chemiluminescent enzyme immunoassay methods, using OM-MA, BR-MA, GI-MA, CEA and AFP commercial kits in sequence respectively (DPC, Los Angeles).

Clinical improvement was achieved after a mean of 6 days (range 3 to 15 days) of optimal medical treatment, and patients were discharged from the hospital. Tumour marker measurements were repeated on the day of discharge. All patients were followed up for 3 months (range 1 to 6 months). Clinical end-points included total mortality, cardiovascular mortality and hospitalization for any cardiovascular cause especially worsening heart failure.

2.3. Statistical analysis
All measurements are presented as mean±SD. The differences between the study groups were assessed using the student t test and one-way or two-way analysis of variance for repeated measures with post hoc Scheffé correction. A p value<0.05 was considered statistically significant.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 References
 
The mean serum level of CA 125 was 81.9±91 U/ml in the study group and 7.5±4.8 U/ml in the control group (p<0.001). The mean CA 19-9 level in study group (16.8±16.6 U/ml) was significantly higher than control group (4.5±2.6 U/ml) (p<0.001). There were no statistically significant differences in other tumour marker levels between two groups.

The mean CA 125 levels in NYHA Class III patients (99.6±92.1 U/ml, p=0.02) and Class IV patients (136.4±102.8 U/ml, p=0.004) was significantly higher than functional Class I/II group (17.7±22.4 U/ml) (Table 1). No statistically significant differences were found for CA 15-3, CA 19-9, CEA and AFP between functional class groups (Table 1).


View this table:
[in this window]
[in a new window]

  		Table 1 Serum tumour marker levels in the control group and in heart failure patients classified according to NYHA functional class

 
There were no statistically significant differences in serum tumour marker levels before and after optimisation of medical treatment.

There were no statistically significant differences in serum tumour marker levels between heart failure patients with and without pleural effusion. Significantly higher serum CA 125 levels were found in heart failure patients with pericardial effusion when compared to heart failure patients without pericardial effusion (188±122.1 U/ml vs. 61.9±69.3 U/ml, p=0.002) There were no statistically significant differences in other tumour marker levels between patients with and without pericardial effusion (Table 2).


View this table:
[in this window]
[in a new window]

  		Table 2 Serum tumour marker levels in CHF patients with and without pericardial effusion

 
The patients were followed for a mean period of 3±1.5 months, during this time 1 patient died and 6 were readmitted to hospital at least once for worsening heart failure. Serum levels of CA 125 above the normal range (≤16.3 U/ml) were found in 5 of the 6 patients who were readmitted to hospital.


   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
References
 
CA 125 is a sensitive but nonspecific tumour marker used in the follow-up of ovarian cancer to monitor the efficacy of therapy and for early detection of recurrence [10]. Recently, associations between clinical heart failure, hemodynamic data, patient outcome and CA 125 levels have been reported [6,7]. To our knowledge there is only one report concerning the levels of other tumour markers in heart failure [9].

The present study showed that serum CA 125 and CA19-9 levels were elevated in patients with heart failure. Among the tumour markers, only CA 125 levels correlated with baseline clinical status, but did not change with aggressive medical treatment in parallel with clinical improvements. Similarly, there was no significant change in other tumour marker levels following optimisation of medical treatment.

High CA 125 values have been observed in patients with lung, breast, uterine and gastrointestinal tract cancer [11]. Recent study has showed significantly higher serum CA-125 levels in case of ovarian cancer with ascites when compared with those without ascites [12]. Furthermore, it has been reported that some non-malignant diseases, such as chronic liver disease, nephrotic syndrome and chronic renal disease requiring hemodialysis, with concomitant serosal effusions (i.e., fluid accumulation in the pleural, peritoneal or pericardial space) may be associated with elevated serum levels of CA 125 [13–15]. It is well known from immunohistochemical studies that CA 125 is released from the pleura and peritoneum [16,17]. Seo et al. found significantly higher serum concentrations of CA 125 in 65% of 57 patients with pericardial effusion of different etiologies, including 25 with some degree of heart failure. Significantly higher values of CA 125 were found in subjects with larger effusion, as documented by echocardiography and were reported to decrease or even normalize along with a reduction or disappearance of effusion [18]. In the same study the pericardial tissue obtained at autopsy was stained with anti CA 125 antibodies in 17 patients. Serum and pericardial CA 125 levels were significantly higher in subjects with CA 125 positive stained pericardium, compared with those in whom the pericardium was negative for CA 125, suggesting a pericardial production of this marker. Watanabe et al. reported a case of lymphoma followed by cardiac tamponade in which CA 125 was highly elevated [19].

Non-malignant pleural fluid has also been found to be associated with high serum levels CA 125, suggesting that the presence of pleural fluid may stimulate its release rather than cytopathological content. Cacoub et al. reported two cases of chronic constrictive pericarditis with ascites and pleural fluid, in which extremely elevated serum CA 125 levels were detected and concluded that the presence of pleural fluid was the sole cause of high CA 125 levels [20]. Lindgren et al. found elevated serum CA 125 levels in 13 of 34 (38%) patients with benign diseases causing pleural effusion [21]. Recently Turk et al. investigated the effects of the presence of pleural fluid on serum CA 125 levels in patients with chronic heart failure. Significantly higher serum CA 125 levels were observed in patients with chronic heart failure and pleural fluids (100.06±129.46 U/ml) than in those without pleural fluid (36.59±35.29 U/ml p<0.05). However, in our study we did not find significant differences in serum CA 125 levels between patients with and without pleural fluid, perhaps reflecting a low incidence in this population.

Nagele et al. measured CA 125 serum levels in heart failure patients undergoing evaluation for cardiac transplantation and found an increase in CA 125 levels, not only in patients with advanced heart failure (functional Class III/IV) in whom some degree of fluid accumulation may be expected, but also in those with mild or no symptoms (functional Class I/II) in whom serosal effusion is unlikely [6]. The prevalence of pleural or pericardial effusion was not reported in this study. The significantly elevated serum CA 125 levels in patients with heart failure were found to be decreased to normal levels after heart transplantation in this study. D' Aloia et al. [7] found elevated serum CA 125 levels both in the few patients with pleural, pericardial or peritoneal effusion and in most patients with moderate to severe heart failure with no effusion. In this study, serum levels of CA 125 decreased significantly in patients showing a clinical improvement. In our study we did not find a significant change in CA 125 levels after optimal medical treatment, achieving clinical improvement. This may be due to short-term treatment (mean 6 days) compared to the study by D' Aloia et al., in which the mean duration of treatment was 18 days.

CA 125 might be produced from mesothelial cells regardless of classic stimuli (inflammation, stasis or other stimulatory mechanisms) and/or it might also be secreted by other cell lines. The biological role of CA 125 antigen in human pathophysiology remains obscure and needs to be elucidated. Interestingly, it has been reported that CA 125 is produced and released from ovarian cancer cells and lymphoma cells when stimulated by cytokines [22,23], such as tumour necrosis factor and interleukin-6, which are also elevated in heart failure [24–26]. Also, the relationship between CA 125 and long-term outcome should be investigated. In addition, heart failure may confound the use of some markers in patients with cancer. The small patient numbers and short-term follow-up are a limitation of this study.


   Acknowledgements
 
We thank to Fatma Güven MD for the help in the determination of tumour marker levels.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 

  1. Fritsche H.A. Serum tumor markers for patient monitoring: a case-oriented approach illustrated with carcinoembryonic antigen. Clin. Chem. (1993) 39:2431–2434.[Abstract]
  2. Bates S.E. Clinical applications of serum tumor markers. Ann. Intern. Med. (1991) 115:623–638.[Abstract/Free Full Text]
  3. Kenemans P., Yedema C.A., Bon G.G. CA 125 in gynecological pathology: a review. Eur. J. Obstet. Gynecol. Reprod. Biol. (1993) 49:115–124.[CrossRef][Web of Science][Medline]
  4. Vander Burg M.E., Lammes F.B., Verwei J.J. CA 125 in ovarian cancer. Neth. J. Med. (1992) 40:36–51.[Web of Science][Medline]
  5. Hopman E.H., Helmerhorst T.J., Bunfrer J.M., Ten Bukkel Huinink W.W. Highly elevated serum CA 125 levels in a patient with cardiac failure. Eur. J. Obstet. Gynecol. Reprod. Biol. (1993) 48:71–73.[CrossRef][Web of Science][Medline]
  6. Nägele H., Bahlu M., Klapdor R., Schaeperkoeter D., Rödiger W. CA 125 and its relation to cardiac function. Am. Heart J. (1999) 137:1044–1049.[CrossRef][Web of Science][Medline]
  7. A'loia D., Faggiano P., Aurigemma G., et al. Serum levels of carbohydrate Antigen 125 in patients with chronic heart failure. Relation to clinical severity, hemodynamic and Doppler echocardiographic abnormalities and short-term prognosis. J. Am. Coll. Cardiol. (2003) 41:1805–1811.[Abstract/Free Full Text]
  8. Turk H.M., Pekdemir H., Buyukberber S., et al. Serum CA 125 levels in patients with chronic heart failure and accompanying pleural fluid. Tumor Biol. (2003) 24:172–175.[CrossRef]
  9. Nagele H., Bahlo M., Klapdor R., Rodiger W. Fluctuations of tumor markers in heart failure patients pre and post heart transplantation. Anticancer Res. (1999) 19(4A):2531–2534.[Web of Science][Medline]
  10. Lavin P.T., Knapp R.C., Malkasion G., Whitney C.W., Berek J.C., Bast R.C. Jr. CA 125 for the monitoring of ovarian carcinoma during primary therapy. Obstet. Gynecol. (1987) 69:223–227.[Web of Science][Medline]
  11. Sjovall K., Nilsson B., Einhorn N. The significance of serum CA 125 elevation malignant and nonmalignant diseases. Gynecol. Oncol. (2002) 85:175–178.[CrossRef][Web of Science][Medline]
  12. Saygili U., Guclu S., Uslu T., Erten O., Dogan E. The effect of ascites, mass volume, and peritoneal carcinomatosis on serum CA 125 levels in patients with ovarian carcinoma. Int. J. Gynecol. Cancer (2002) 12:438–442.[CrossRef][Web of Science][Medline]
  13. Sevinç A., Buyukberber S., Sari R., Turk H.M., Ates M. Elevated serum CA 125 levels in patients with nephrotic syndrome induced ascites. Anticancer Res. (2000) 20:1201–1204.[Web of Science][Medline]
  14. Sevinc A., Buyukberber S., Sari R. Elevated serum CA 125 levels: hepatitis or ascites? Gynecol. Oncol. (2000) 76:141–142.[Web of Science][Medline]
  15. Sevinc A., Buukberber S., Sari R., Kinoglu Y., Turk H.M., Ates M. Elevated serum CA 125 levels in hemodialysis patients with peritoneal, pleural or pericardial fluids. Gynecol. Oncol. (2000) 76:141–142.[Web of Science][Medline]
  16. Epiney M., Bertussa C., Weil A., Campana A., Bishof P. CA 125 production by peritoneum: in-vitro and in-vivo studies. Hum. Reprod. (2000) 15:1261–1265.[Abstract/Free Full Text]
  17. Gullu I., Yalcin S., Tekuzman G. Tumour markers in effusions: a comparative study of tumour marker levels in sera and effusion. In: Use of biomarkers in assessing health and environmental impacts of chemical pollutants—Travis C.C., ed. (1993) New York: Plenum. 265–272.
  18. Seo T., Ikeda Y., Onaka H., et al. Usefulness of serum CA 125 measurement for monitoring pericardial effusion. Jpn. Circ. J. (1993) 57:489–494.[Medline]
  19. Watanabe M., Kanda T., Takatama M., Iwai T., Naito I., Fukuda T., et al. An autopsy case of malignant lymphoma with a high serum CA 125 level occurring only in the brain and the pericardium. J. Med. (1996) 27:221–227.[CrossRef][Web of Science][Medline]
  20. Cacoub P., Le Thi H.D., Wechesler B., Chapelon C., Auperin A., Gandjbakch I., et al. Chronic constrictive pericarditis responsible for an increase of CA 125 levels, two cases (in French). Presse Méd. (1990) 19:1712–1714.[Web of Science][Medline]
  21. Lindgren J., Kuusela P., Hellstrom P.E., Petterson T., Klockars M. The ovarian cancer associated antigen CA 125 in patients with pleural effusions. Eur. J. Cancer Clin. Oncol. (1988) 24:737–739.[CrossRef][Web of Science][Medline]
  22. Zeimet A.G., Offner F.A., Marth C., et al. Modulation of CA 125 release by inflammatory cytokines in human peritoneal mesothelial and ovarian cancer cells. Anticancer Res. (1997) 17:3129–3131.[Web of Science][Medline]
  23. Kubonishi I., Bandobaschi K., Murata N., Daibata H., Ido E., Sunobe H. High serum level of CA 125 and interleukin-6 in a patient with Ki-1 lymphoma. Br. J. Haematol. (1997) 98:450–452.[CrossRef][Web of Science][Medline]
  24. Mac Gowen G.A., Mann D.L., Kormos R.L., Feldman A.M., Murali S. Circulating interleukin-6 in severe heart failure. Am. J. Cardiol. (1997) 79:1128–1131.[CrossRef][Web of Science][Medline]
  25. Ferrari R., Bachetti T., Confortini R., et al. Tumor necrosis factor soluble receptors in patients with various degree of congestive heart failure. Circulation (1995) 92:1479–1486.[Abstract/Free Full Text]
  26. Kosar F., Varol E., Ileri M., et al. Circulating cytokines and complements in chronic heart failure. Angiology (1999) 50(5):403–408.[CrossRef][Web of Science][Medline]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Eur J Heart FailHome page
F. Kosar, Y. Aksoy, G. Ozguntekin, I. Ozerol, and E. Varol
Relationship between cytokines and tumour markers in patients with chronic heart failure
Eur J Heart Fail, May 1, 2006; 8(3): 270 - 274.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Varol, E.
Right arrow Articles by Kosar, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Varol, E.
Right arrow Articles by Kosar, F.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?