INTRODUCTION: Serum levels of CA125 are often high in advanced heart failure (AHF) patients. AIM: To determine the predictive value of CA125 in forecasting the occurrence of death or cardiac transplantation in an AHF population. METHODS: 88 AHF patients referred for heart transplantation were divided into 2 groups based on CA125 levels: normal (CA125/=38 U/mL). Events (death or heart transplant) were monitored over a period of 13+/-7 months after CA125 determination. RESULTS: Patients with elevated CA125 (n=65) had significantly lower blood pressure, body mass index, serum sodium and peak exercise oxygen consumption, while B-type natriuretic peptide levels were significantly higher. The combined primary endpoint (death or heart transplant) rate was 39.4% and 62.3% in normal and elevated CA125 groups, respectively (p=0.029). Multivariate regression analysis showed that CA125 and sodium levels were the only independent predictors of the combined endpoint. CONCLUSION: In AHF patients, plasma CA125 was an effective prognostic marker. Its determination may contribute to better risk stratification in this population

Coelho, L

Costa, S

Franco, F

Monteiro, P

Monteiro, S

Oliveira, L

Providência, LA

Vieira, H

Repositório Institucional dos Hospitais da Universidade de Coimbra

International Journal of Cardiology xx (2009) xxx–xxxIJCA-11304; No of Pages 4www.elsevier.com/locate/ijcardARTICLE IN PRESSLetter to the EditorPrognostic value of CA125 in advanced heart failure patientsSílvia Monteiro a,⁎, Fátima franco a, Susana Costa a, Pedro Monteiro a,b, Henrique Vieira a,Lourenço Coelho a, Luís Oliveira a, Luís A. Providência a,ba Cardiology Department of Coimbra University Hospital, Portugalb Coimbra Medical School, PortugalReceived 27 April 2008; received in revised form 17 August 2008; accepted 1 November 2008AbstractIntroduction: Serum levels of CA125 are often high in advanced heart failure (AHF) patients.Aim: To determine the predictive value of CA125 in forecasting the occurrence of death or cardiac transplantation in an AHF population.Methods: 88 AHF patients referred for heart transplantation were divided into 2 groups based on CA125 levels: normal (CA125b38 U/mL)and elevated (≥38 U/mL). Events (death or heart transplant) were monitored over a period of 13±7 months after CA125 determination.Results: Patients with elevated CA125 (n=65) had significantly lower blood pressure, body mass index, serum sodium and peak exerciseoxygen consumption, while B-type natriuretic peptide levels were significantly higher. The combined primary endpoint (death or hearttransplant) rate was 39.4% and 62.3% in normal and elevated CA125 groups, respectively (p=0.029). Multivariate regression analysisshowed that CA125 and sodium levels were the only independent predictors of the combined endpoint.Conclusion: In AHF patients, plasma CA125 was an effective prognostic marker. Its determination may contribute to better risk stratificationin this population.© 2008 Elsevier Ireland Ltd. All rights reserved.Keywords: CA125; Advanced heart failure; Cardiac transplantation; Prognostic markerTable 1Clinical characteristics of the study population of advanced heart failurepatients (n=88)Age (years) 53.5±13.8Men/women 62 (70%)/26 (30%)Body mass index (kg/m2) 24.0±5.0LVEF (%) 24.5±11.2NYHA functional class (%)III 58.1IV 41.9Aetiology (%)Dilated cardiomyopathy 49Coronary artery disease 40Hypertensive heart disease 101. IntroductionAdvanced heart failure (AHF) is associated with highmorbidity and mortality rates [1–3], unless cardiac trans-plantation is performed. Risk stratification of AHF patients isa critical component of the transplant candidate selectionprocess; therefore, search for new prognostic markers inAHF has recently been intensified.Carbohydrate antigen 125 (CA125) is a tumour markerclassically associated with ovarian cancer [4]; recently severalstudies reported increased serum CA125 levels in HF patients[5–15].⁎ Corresponding author. Tel.: +351966556027; fax: +351239084893.E-mail address: silvia.reis.monteiro@gmail.com (S. Monteiro).Other 1Data are presented as the mean value±SD, number or percentage of patients.LVEF — left ventricular ejection fraction; NYHA — New York HeartAssociation.0167-5273/$ - see front matter © 2008 Elsevier Ireland Ltd. All rights reserved.doi:10.1016/j.ijcard.2008.11.023Please cite this article as: Monteiro S, et al., Prognostic value of CA125 in advanced heart failure patients, Int J Cardiol (2009), doi:10.1016/j.ijcard.2008.11.023Table 2Clinical, laboratory and echocardiographic parameters of advanced heartfailure patients, classified according to CA125 levelsCA125b38 U/mL CA125≥38 U/mL pHeart rate (bpm) 73.8±11.5 83.1±15.3 0.015SBP (mmHg) 109.8±17.7 97.0±14.6 0.006DBP (mmHg) 66.1±13.8 56.7±10.3 0.01Body mass index (kg/m2) 24.8±6.5 23.4±3.2 0.04Serum Sodium (mmol/L) 135.9±4.5 133.9±4.1 0.04Serum creatinine (mg/dL) 1.4±0.5 1.7±1.7 0.80BNP (pg/mL) 593.4±554.9 2180.1±1468.7 b0.001LVEF (%) 24.7±11.5 24.3±11.1 0.92Peak VO2 (mL/kg/min) 16.0±5.1 13.8±3.4 0.049SBP— systolic blood pressure; DBP— diastolic blood pressure; BNP— Btype natriuretic peptide; LVEF — left ventricular ejection fraction; PeakVO2 — peak exercise oxygen consumption.2 S. Monteiro et al. / International Journal of Cardiology xx (2009) xxx–xxxARTICLE IN PRESSHowever, it is still a matter of debate if CA125 is a potentialprognostic marker for AHF and also if it is useful forevaluating and managing pre-transplant patients.The aim of the present studywas to determine the predictivevalue of plasma CA125 in forecasting the occurrence of deathor cardiac transplantation in an AHF patient population.1.1. Patients and methodsThis study included 88 consecutive AHF patients referredfor heart transplantation (62 male, mean age 53.5±13.8years) — Table 1.CA125 assayswere performed during clinic visits or duringhospitalization for HF, after clinical stabilization (7±3 days).Serum levels of CA125weremeasured by chemiluminescence(BRAHMSCA125 II KRYPTOR), with an upper normal limitFig. 1. Kaplan–Meier cumulative event-free survivaPlease cite this article as: Monteiro S, et al., Prognostic value of CA125 iijcard.2008.11.023of 38 U/mL. Population was divided into two groupsaccording to CA125 levels: normal (CA125b38 U/mL) andelevated (≥38 U/mL).Patients were followed for a mean period of 13±7 monthsafter CA125 assessment; the study primary endpoint wasdeath or heart transplant.1.2. Statistical analysisData are presented as the mean value±SD. Analysis ofgroups differences was performed using the Mann–WhitneyU test for continuous variables and χ2 test for categoricalvariables. A p valueb0.05 was considered statistically sig-nificant. Survival curves were constructed by the Kaplan–Meier method and were compared using the log-rank test.Multivariate regression analysis was then performed todetermine the independent predictors of the primary endpoint.2. ResultsTwenty-three patients had normal CA125 (15.3±6.1U/mL),while 65 had elevated levels (215.6±260.2 U/mL). Groupswere similar regarding demographic characteristics, HFaetiology and medication.Compared to the normal group, patients with elevatedCA125 had significantly lower systolic and diastolic bloodpressure, body mass index, serum sodium and peak oxygenconsumption in the cardio–respiratory stress test. B-typenatriuretic peptide (BNP) levels were also significantlyhigher in this group (Table 2).In elevated CA125 group, 38% of patients had pleuraleffusion versus none in normal CA125 group (p=0.014).l curves separated according to CA125 levels.n advanced heart failure patients, Int J Cardiol (2009), doi:10.1016/j.Table 3Multiple regression analysisVariables Beta p-value ORCA125≥38 U/mL 1.152 0.032 3.163 (1.107–9.036)NA≤132.5 mmol/L 1.339 0.041 3.817 (1.056–13.799)c-statistic 0.728.3S. Monteiro et al. / International Journal of Cardiology xx (2009) xxx–xxxARTICLE IN PRESSEvent rate was significantly lower in patients with normalCA125 levels: 2 versus 15 died, 11 versus 19were transplantedand 13 versus 27 were readmitted for worsening HF. Thecombined primary endpoint (death or heart transplant) ratewas39.4% in patients with normal CA125 values and 62.3% in theelevated CA125 group (p=0.029)— Fig. 1.Multivariate regression analysis showed that CA125 andsodium levels were the only independent predictors of thecombined endpoint (Table 3).3. DiscussionNumerous studies showed increased CA125 levels inCHF patients and a relationship between these values and HFseverity [5–15]. In the present study, we investigated theprognostic value of CA125 levels in an AHF population.According to our results, serum CA125 was elevated inmost AHF patients and its levels were significantly related toblood pressure, bodymass index, serum sodium, peak exerciseoxygen consumption and BNP levels (established markers ofseverity and prognosis in HF).We did not find significant differences in LVEF betweenpatients with normal and elevated CA125, probably becauseour population included mainly severe AHF patients withlow LVEF (24.5±11.2%) and LVEF is not a good marker tostratify AHF patients [1].Our data clearly demonstrated that CA125 is a markerof adverse outcome in AHF patients, associated with in-creased mortality, transplant and hospital readmission rates.Multivariate analysis identified CA125 as an indepen-dent predictor for the combined endpoint death or hearttransplant.In several reports high CA125 was associated with serosaleffusions, suggesting that the presence of serosal fluids maystimulate its release [8–10].However, other investigators showed increased CA125levels in HF patients without serosal effusion, indicating that anacute congestion may not be the sole cause of CA125 secretion[6,7].The majority of our patients with high CA125 did not havepleural effusion, either because they were clinically stable orbecause many AHF patients do not have serosal effusions.Recently, Kosar [16] demonstrated that high CA125levels in HF patients were correlated with inflammatory cyto-kines levels, suggesting a relationship between CA125 andcytokines.As in our study CA125 was measured during routineclinic visits or in hospitalized patients (but after clinicalPlease cite this article as: Monteiro S, et al., Prognostic value of CA125 iijcard.2008.11.023stabilization), our results support the hypothesis that CA125is an effective marker of AHF severity and prognosis, even incompensated phases of the disease.4. ConclusionIn AHF patients, CA125 is an independent predictorof worse prognosis, associated with a higher event rateand increased mortality. Even in stable patients CA125 is auseful marker of AHF severity and prognosis, which can beused to improve risk stratification and guide therapeuticdecisions.AcknowledgementThe authors of this manuscript have certified that theycomply with the Principles of Ethical Publishing in theInternational Journal of Cardiology [17].References[1] The task force for the diagnosis and treatment of chronic heart failureof the European society of cardiology. Guidelines for the diagnosis andtreatment of chronic heart failure: executive summary (update 2005).Eur Heart J 2005;26:1115–40.[2] Hunt SA, Abraham WT, Chin MH, et al. ACC/AHA 2005 guidelineupdate for the diagnosis and management of chronic heart failure in theadult. Circulation 2005;112:154–235.[3] Mosterd A, Hoes AW, de Bruyne MC, et al. Prevalence of heart failureand left ventricular dysfunction in the general population. Eur Heart J1999;20:447–55.[4] Bast RC, Badgwell D, Lu Z, et al. New tumour markers: CA125 andbeyond. Int J Gynecol Cancer 2005;15:274–81.[5] Nagele H, Bahlo M, Klapdor R, Schaeperkoetter D, Rodiger W. CA125and its relation to cardiac function. Am Heart J 1999;137:1044–9.[6] D'Aloia A, Faggiano P, Aurigemma G, et al. Serum levels of carbo-hydrate antigen 125 in patients with chronic heart failure. Relationto clinical severity hemodynamic and doppler echocardiographicabnormalities, and short-term prognosis. J Am Coll Cardiol 2003;41:1805–11.[7] Kouris NT, Zacharos ID, Kontogianni DD, et al. The significance ofCA125 levels in patients with chronic congestive heart failure.Correlation with clinical and echocardiographic parameters. Eur JHeart Fail 2005;7:199–203.[8] Varol E, Ozaydin M, Dogan A, Kosar F. Tumour marker levels inpatients with chronic heart failure. Eur J Heart Fail 2005;7:840–3.[9] Seo T, Ikeda Y, Onaka H, et al. Usefulness of serum CA125 measure-ment for monitoring pericardial effusion. Jpn Circ J 1993;57:489–94.[10] Turk HM, Pekdemir H, Buyukberber S, et al. Serum CA125 levels inpatients with chronic heart failure and accompanying pleural fluid.Tumour Biol 2003;24:172–5.[11] Duman C, Ercan E, Tengiz I, Bozdemir H, Ercan HE, Nalbantgil I.Elevated serum CA125 levels in mitral stenotic patients with heartfailure. Cardiology 2003;100:7–10.[12] Skorzynska H, Solski J, Gernand W, Matras P, Gniwek M, Sokol M.Estimation of CA125 concentration in patients with congestive heartfailure. Ann Univ Mariae Curie Sklodowska[Med] 2004;59:261–4.[13] Sugishita H, Imagawa H, Kawachi K, Takano S, Tsunooka N, ShikataF. Normalization of cancer antigen 125 after mitral valve replacementin a patient with congestive heart failure due to mitral valve endo-carditis. Jpn J Thorac Cardiovasc Surg 2005;53:486–9.[14] Kouris NT, Kontogianni DD, Papoulia EP, et al. Clinical andprognostic value of elevated CA125 levels in patients withn advanced heart failure patients, Int J Cardiol (2009), doi:10.1016/j.4 S. Monteiro et al. / International Journal of Cardiology xx (2009) xxx–xxxARTICLE IN PRESScongestive heart failure. Hellenic J Cardiol (Greece) 2006;47(5):269–742.[15] Antonini-Canterin F, Popescu BA, Popescu AC, et al. Heart failure inpatients with aortic stenosis: clinical and prognostic significance ofcarbohydrate antigen 125 and brain natriuretic peptide measurement.Int J Cardiol 2008;128(3):406–12.Please cite this article as: Monteiro S, et al., Prognostic value of CA125 iijcard.2008.11.023[16] Kosar F, AksoyY,OzguntekinG,Ozerol I, Varol E.Relationship betweencytokines and tumourmarkers in patients with chronic heart failure. Eur JHeart Fail 2006;8:270–4.[17] Coats AJ. Ethical authorship and publishing. Int J Cardiol 2009;131:149–50.n advanced heart failure patients, Int J Cardiol (2009), doi:10.1016/j.

Prognostic value of CA125 in advanced heart failure patients

INTRODUCTION: Serum levels of CA125 are often high in advanced heart failure (AHF) patients. AIM: To determine the predictive value of CA125 in forecasting the occurrence of death or cardiac transplantation in an AHF population. METHODS: 88 AHF patients referred for heart transplantation were divided into 2 groups based on CA125 levels: normal (CA125<38 U/mL) and elevated (>/=38 U/mL). Events (death or heart transplant) were monitored over a period of 13+/-7 months after CA125 determination. RESULTS: Patients with elevated CA125 (n=65) had significantly lower blood pressure, body mass index, serum sodium and peak exercise oxygen consumption, while B-type natriuretic peptide levels were significantly higher. The combined primary endpoint (death or heart transplant) rate was 39.4% and 62.3% in normal and elevated CA125 groups, respectively (p=0.029). Multivariate regression analysis showed that CA125 and sodium levels were the only independent predictors of the combined endpoint. CONCLUSION: In AHF patients, plasma CA125 was an effective prognostic marker. Its determination may contribute to better risk stratification in this population

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Prognostic value of CA125 in advanced heart failure patients

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