Elevated CA-125 as Humoral Biomarker of Congestive Heart Failure: Illustrative Cases and a Short Review of Literature

Abstract

Despite the recent, remarkable achievements in cardiology, heart failure (HF) remains a major public health problem due to its increasing prevalence, frequent hospitalizations, and significant mortality. Humoral biomarkers in HF are capable to reflect different aspects of the cardiac morpho-functional changes and the related pathophysiological processes and could have important diagnostic, prognostic, and therapeutical roles. CA-125 is a well-known tumor marker (mainly for ovarian cancer), and also a useful, but less applied cardiac biomarker. Practical aspects, possible pitfalls related with increased CA-125 levels are illustrated by two cases, both with HF, with the biomarker determined for other reasons and having high levels in the context of the cardiac decompensation. The paper presents a short review of the main biochemical, pathophysiological, and clinical data linked to CA-125, with special accent on its utility in patients with HF.

The role of carbohydrate antigen 125 in COVID-19

“…Although CA-125 and natriuretic peptides have different pathophysiological mechanisms and half-lives (BNP ∼ 20-30 minutes), significant correlations have been identified between them in the presence of heart failure. Moreover, strong associations of CA-125 with inflammatory stimuli, echocardiographic and hemodynamic parameters, mortality or re-hospitalization risk of patients during follow-up have been reported [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [25] , [26] , [27] , [28] , [29] , [31] , [37] , [39] , [45] . An improvement in LVEF with a marked decrease in CA 125 levels after treatment in heart failure patients, the observation of reductions in pericardial effusion, and also the ability to monitor treatments that affect cytokine levels through CA-125 levels make it a valuable marker [4] , [10] , [17] , [19] , [21] , [25] , [26] , [37] .…”

“…As the physiological role of CA-125 is considered to protect the epithelial lumen surfaces from physical stress through the process of hydration or lubrication [15] , [16] , [17] . Pathophysiological mechanisms that cause serum levels to increase are expressed as activation of mesothelial cells in response to stimuli such as oxidative stress, mechanical stress (fluid overload and tissue stretching) and systematic inflammatory process (cytokine activation) [15] , [16] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] .…”

“…Congestion is a hemodynamic parameter and causes the disease to progress by integrating into the circle of inflammatory process defined in heart failure. The most important determinants of the expression of CA-125 in heart failure are factors such as serosal fluid overload, congestion and also positive correlations with various inflammatory cytokines have been detected [15] , [19] , [20] , [21] , [22] , [23] , [26] , [28] , [29] , [37] . Considering that CA-125 is a surrogate marker for both congestion and systemic inflammation that can be considered that in COVID-19 patients may have high serum levels by a multifactorial mechanism in the complications that occur.…”

“…Findings in the literature supporting this hypothesis demonstrating the clinical usefulness of CA-125 are: (I) Positive correlations were reported between serum CA- 125 levels and CRP/hs-CRP, BNP/NT-proBNP, cytokines (TNF-α, IL-1, IL-6, IL-10) [17] , [18] , [19] , [25] , [30] , [37] , [38] , [39] ; (II) Elevated CA-125 levels were associated with the severity of diastolic and systolic dysfunctions in many studies supplemented by echocardiographic data. Positive and significant correlations also were found with left ventricular ejection fraction (LVEF), systolic pulmonary artery pressure (SPAP), right atrial pressure, pulmonary artery wedge pressure, left atrial volumes [15] , [16] , [17] , [18] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [30] , [31] , [37] , [39] ; (III) A positive correlation was detected between CA-125 and ventricular remodeling. Thus, It was suggested that high serum CA-125 levels in coronary heart patients may help predict the risk of short-term heart failure and death [24] ; (IV) It was reported that patients with increased CA-125 levels have a higher risk of developing atrial fibrillation [15] , [17] , [18] , [27] ; (V) Elevated CA-125 levels were also observed in other cardiac pathologies such as tricuspid stenosis, mitral stenosis, mitral valve endocarditis, atrial septal defect, pulmonary hypertension, aortic stenosis, and acute coronary syndromes [25] , [27] , [37] ; (VI) There is evidence that changes in serum CA-125 levels as a result of the therapy protocol used heal the clinical course [37] .…”

Expression of Circulating MicroRNA-141 in Epithelial Ovarian Cancer

“…Although CA-125 is upregulated in the serum of most women with ovarian cancer, around 50% of stage I ovarian cancer cases have serum CA-125 level below the conventional cut-off of 35 U/mL ( 73 ). Besides that, there have also been reports of elevated serum CA-125 level in some cancers ( 74 ), liver disease ( 75 ), congestive heart failure ( 76 ) and also in infectious diseases such as tuberculosis ( 77 , 78 ). Our study demonstrates that miR-141 was upregulated significantly in the blood plasma of patients with EOC.…”