Evaluation of ADMA and Galectin 3 Levels in Predicting Cardiovascular Disease Risk in Patients with Bipolar Disorder

Year 2025, Volume: 35 Issue: 5, 796 - 804, 28.10.2025

Gökçe Kavak Sinanoğlu , Kürşat Altınbaş , Sedat Abuşoğlu , Kenan Erdem

https://doi.org/10.54005/geneltip.1563734

Abstract

Objective: Bipolar disorder is a chronic disease that occurs in 1-5% of the population. It has been reported that bipolar disorder patients have approximately twice as many cardiovascular disease-related deaths as the general population. In recent years, it has been reported that Asymmetric Dimethylarginine (ADMA) and its metabolites can be biomarkers for determining the risk of cardiovascular disease, and galectin 3(Gal 3) levels can be biomarkers for determining the burden of disease in chronic diseases. Myocardial performance index (MPI) is an echocardiographic parameter used to evaluate left ventricular (LV) systolic and diastolic functions. It has been reported that MPI indicates the risk of cardiovascular mortality. This study aims to investigate the relationship between the sociodemographic and disease-related characteristics of patients diagnosed with bipolar disorder and the parameters that evaluate the risk of cardiovascular and chronic diseases.
Material and Methods: ADMA and N(G)-monometil L-arginin (L-NMMA) were measured from the serum samples remaining from routine blood tests of 75 patients diagnosed with bipolar disorder who applied to Selçuk University Faculty of Medicine Mazhar Osman Mood Center and who had been euthymic for at least 8 weeks, and simultaneously echocardiography was performed to obtain information about cardiac function and myocardial performance index was calculated.
Results: The study included 75 patients diagnosed with bipolar disorder. 48% (n: 39) of the patients were female and 48% (n: 36 ) were male. 54.9% (n: 39) of the patients had previously experienced psychotic symptoms, while 45.1% (n: 32 ) had not previously experienced psychotic symptoms. Half of the patients had family members with bipolar disorder. The mean plasma ADMA values of the patients were 0.26±0.10µM/l, the mean MPI values were 0.33±0.77, and the mean galectin 3 value was 895.66±721.29 pg/ml. There is a moderately significant positive correlation between the patient's age and the MPI value (r=0.588, p≤0.001). There is a moderately significant negative correlation between the patient's age and the Gal 3 value (r=-0.493, p≤0.001). No significant correlation was found between the patient's age and the ADMA values. No statistically significant difference was observed in the mean values of MPI, ADMA, Gal 3 according to the presence of psychotic symptoms.
Conclusion: In this study, no significant relationship was found between ADMA, which is important in determining the risk of cardiovascular disease, and the burden of illness and psychotic symptoms in bipolar disorder patients. The fact that bipolar disorder is a chronic disease and that the episodic course increases with age and the increase in MPI and galectin 3 parameters are consistent with the literature.

Keywords

ADMA , GALEKTİN3 , BİPOLAR DİSORDER , MYOCARDIAL PERFUSION INDEX , CARDIOVASCULAR RISK

References

• 1. Morgan VA, Mitchell PB, Jablensky AV. The epidemiology of bipolar disorder: sociodemographic, disability and service utilization data from the Australian National Study of Low Prevalence (Psychotic) Disorders. Bipolar disorders. 2005;7(4):326-37.
• 2. Cansız A, İnce B, Altinbas K, Kurt E. Evaluation of mortality causes among patients with bipolar disorder in a specialized mood clinic. 2018.
• 3. Roshanaei-Moghaddam B, Katon W. Premature mortality from general medical illnesses among persons with bipolar disorder: a review. Psychiatric services (Washington, DC). 2009;60(2):147-56.
• 4. Westman J, Hällgren J, Wahlbeck K, Erlinge D, Alfredsson L, Osby U. Cardiovascular mortality in bipolar disorder: a population-based cohort study in Sweden. BMJ open. 2013;3(4).
• 5. Høye A, Nesvåg R, Reichborn-Kjennerud T, Jacobsen B. Sex differences in mortality among patients admitted with affective disorders in North Norway: A 33-year prospective register study. Bipolar disorders. 2016;18:272-81.
• 6. Girouard H, Iadecola C. Neurovascular coupling in the normal brain and hypertension, stroke, and Alzheimer's disease. Journal of Applied Physiology (Bethesda, Md: 1985). 2006;100(1):328-35.
• 7. Tieu K, Ischiropoulos H, Przedborski S. Nitric oxide and reactive oxygen species in Parkinson's disease. IUBMB life. 2003;55(6):329-35.
• 8. Achan V, Broadhead M, Malaki M, Whitley G, Leiper J, MacAllister R, et al. Asymmetric dimethylarginine causes hypertension and cardiac dysfunction in humans and is actively metabolized by dimethylarginine dimethylaminohydrolase. Arteriosclerosis, thrombosis, and vascular biology. 2003;23(8):1455-9.
• 9. Deneva-Koycheva TI, Vladimirova-Kitova LG, Angelova EA, Tsvetkova TZ. Plasma asymmetric dimethylarginine levels in healthy people. Folia Medica. 2011;53(1):28-33.
• 10. Nayor M, Wang N, Larson MG, Vasan RS, Levy D, Ho JE. Circulating Galectin-3 Is Associated With Cardiometabolic Disease in the Community. Journal of the American Heart Association. 2015;5(1).
• 11. Pugliese G, Iacobini C, Pesce CM, Menini S. Galectin-3: an emerging all-out player in metabolic disorders and their complications. Glycobiology. 2015;25(2):136-50.
• 12. Karabulut A, Doğan A, Tuzcu AK. Myocardial Performance Index for Patients with Overt and Subclinical Hypothyroidism. Medical science monitor: international medical journal of experimental and clinical research. 2017;23:2519-26.
• 13. Tei C, Ling LH, Hodge DO, Bailey KR, Oh JK, Rodeheffer RJ, et al. A new index of combined systolic and diastolic myocardial performance: a simple and reproducible measure of cardiac function--a study in normals and dilated cardiomyopathy. Journal of cardiology. 1995;26(6):357-66.
• 14. Weiner M, Warren L, Fiedorowicz JG. Cardiovascular morbidity and mortality in bipolar disorder. Annals of clinical psychiatry: official journal of the American Academy of Clinical Psychiatrists. 2011;23(1):40-7.
• 15. Braun D, Schlossmann J, Haen E. Asymmetric dimethylarginine in psychiatric disorders. Psychiatry Res. 2021;300:113901.
• 16. Ustundag MF, Ozcan H, Gencer AG, Yilmaz ED, Uğur K, Oral E, et al. Nitric oxide, asymmetric dimethylarginine, symmetric dimethylarginine, and L-arginine levels in psychotic exacerbation of schizophrenia and bipolar disorder manic episodes. Saudi Medical Journal. 2020;41(1):38-45.
• 17. Celik C, Cayci T, Ozdemir B, Akgul EO, Zincir S, Balikci A, et al. Plasma asymmetric dimethylarginine (ADMA) concentrations in patients with first and multiple episode schizophrenia. Psychiatry Res. 2011;190(2-3):177-80.
• 18. Zincir S, Zincir SB, Doruk A, Erdem M, Celik C, Ak M, et al. Asymmetric dimethylarginine (ADMA) and treatment response relationship in male patients with first-episode schizophrenia: a controlled study. Psychiatry Res. 2014;220(1-2):76-80.
• 19. Dong R, Zhang M, Hu Q, Zheng S, Soh A, Zheng Y, et al. Galectin-3 as a novel biomarker for disease diagnosis and a target for therapy (Review). International journal of molecular medicine. 2018;41(2):599-614.
• 20. Arnlöv J, Lind L, Andrén B, Risérus U, Berglund L, Lithell H. A Doppler-derived index of combined left ventricular systolic and diastolic function is an independent predictor of cardiovascular mortality in elderly men. American Heart Journal. 2005;149(5):902-7.