Pathophysiological mechanisms of cardiovascular disorders in Parkinson’s disease
https://doi.org/10.15829/1560-4071-2025-6401
EDN: HYYUQH
Abstract
Parkinson’s disease is the second most common progressive neurodegenerative disease after Alzheimer’s disease, characterized by selective loss of dopaminergic neurons in the compact part of the substantia nigra. This leads to striatal dopamine deficiency and motor symptoms. Along with this, non-motor disorders, in particular cardiovascular dysfunctions, play a significant role in the pathogenesis of Parkinson’s disease, which have a significant impact on the quality of life of patients.
Neurogenic mechanisms include pathological accumulation and aggregation of alpha-synuclein with the formation of Lewy bodies and neurites, detected in both the central and peripheral autonomic nervous systems, including the heart sympathetic innervation. Additionally, non-neurogenic factors (decreased intravascular volume due to dysphagia and inadequate fluid intake, heart failure, and antiparkinsonian-induced hypotension) contribute to orthostatic hypotension and other cardiovascular events, increasing the risk of stroke and other complications.
In addition to autonomic and motor manifestations, mental and cognitive impairment is of paramount importance in Parkinson’s disease. Depression, anxiety, and dementia are found in 40-50% of patients, often in the early stages of the disease, and through activation of the sympathoadrenal system, increased cortisol levels, and baroreflex dysfunction can exacerbate arrhythmias, ischemic episodes, and other cardiac events. In addition, decreased motivation and adherence to therapy with mental symptoms further increases the risk of adverse cardiovascular outcomes in this group of patients.
About the Authors
F. A. YusupovKyrgyzstan
Osh
M. Sh. Abdykadyrov
Kyrgyzstan
Osh
References
1. Yusupov FA, Ydyrysov IT, Abdykadyrov MSh, Yusupova TF. Age and gender aspects of Parkinson’s disease. Clin Med. 2025;103(1):13-22. (In Russ.) doi:10.30629/0023-2149-2025-103-1-13-22.
2. Yusupov FA, Yuldashev AA, Nurmatov TA. Biomarkers of early diagnosis of Parkinson’s disease. Bull Sci Pract. 2024;10(7):309-23. (In Russ.) doi:10.33619/2414-2948/104/33.
3. Sahoo TA, Chand J, Kandy AT, et al. Unravelling the Proteinopathic Engagement of α-Synuclein, Tau, and Amyloid Beta in Parkinson’s Disease: Mitochondrial Collapse as a Pivotal Driver of Neurodegeneration. Neurochemical research. 2025;50(3):145. doi:10.1007/s11064-025-04399-7.
4. Gómez-Benito M, Granado N, García-Sanz P, et al. Modeling Parkinson’s Disease With the Alpha-Synuclein Protein. Frontiers in Pharmacology. 2020;11. doi:10.3389/fphar.2020.00356.
5. Kopylova LI, Nikolaeva TY, Tappakhov AA, Popova TE. Influence of non-motor symptoms of Parkinson’s disease on patients’ quality of life. Zabaikal Med Bull. 2024;(1):56-61. (In Russ.) doi:10.52485/19986173_2022_1_56.
6. Pfeiffer RF. Autonomic Dysfunction in Parkinson’s Disease. Neurotherapeutics. 2020;17(4): 1464-79. doi:10.1007/s13311-020-00897-4.
7. Katunina EA, Ilina EP, Sadekhova GI, Gaisenuk EI. Approaches to early diagnosis of Parkinson’s disease. S. S. Korsakov J Neurol Psychiatry. 2019;119(6):119-27. (In Russ.)doi:10.17116/jnevro2019119061119.
8. Kincl V, Panovský R, Bočková M, et al. Parkinson´s Disease Cardiovascular Symptoms: A New Complex Functional and Structural Insight. European Journal of Neurology. 2024;31(2):e16110. doi:10.1111/ene.16110.
9. Grosu L, Grosu AI, Crisan D, et al. Parkinson’s Disease and Cardiovascular Involvement: Edifying Insights (Review). Biomedical Reports. 2023;18(3):25. doi:10.3892/br.2023.1607.
10. Litvinenko IV, Dynin PS, Yanishevsky SN, et al. Neurogenic cardiovascular disorders in α-synucleinopathies: complex diagnostic and therapeutic challenges. Arter Hypertens. 2021;27(5):509-21. (In Russ.) Литвиненко И. В., Дынин П. С., Янишевский С. Н. и др. Нейрогенные сердечно-сосудистые нарушения при α-синуклеинопатиях: сложные вопросы диагностики и терапии. Артериальная гипертензия. 2021;27(5):509-21. doi:10.18705/1607-419X-2021-27-5-509-521.
11. Yakovenko EV, Abbasov FA. Piribedil in the treatment of mental and cognitive disorders in Parkinson’s disease. Neurol Neuropsychiatry Psychosomatics. 2022;14(4):103-7. (In Russ.) doi:10.14412/2074-2711-2022-4-103-107.
12. Husnu D, Eftal Murat B, Hikmet H. Cardiac Effects of Parkinson’s Disease. Open Journal of Parkinson’s Disease and Treatment. 2020;006-7. doi:10.17352/ojpdt.000009.
13. Zhu S, Li H, Xu X, et al. The Pathogenesis and Treatment of Cardiovascular Autonomic Dysfunction in Parkinson’s Disease: What We Know and Where to Go. Aging and Disease. 2021;12(7):1675-92. doi:10.14336/AD.2021.0214.
14. Lamotte G, Lenka A. Orthostatic Hypotension in Parkinson Disease: What Is New? Neurology. Clinical Practice. 2022;12(5):e112-e115. doi:10.1212/CPJ.0000000000200068.
15. Xue T, Cui Y, Kan Y, et al. Value of Multi-Parameter 123I-MIBG Scintigraphy in the Differential Diagnosis of Parkinson’s Disease. EJNMMI Research. 2025;15(1):7. doi:10.1186/s13550-025-01197-8.
16. Palma JA, Kaufmann H. Orthostatic Hypotension in Parkinson Disease. Clinics in Geriatric Medicine. 2020;36(1):53-67. doi:10.1016/j.cger.2019.09.002.
17. Venda LL, Cragg SJ, Buchman VL, Wade-Martins R. α-Synuclein and Dopamine at the Crossroads of Parkinson’s Disease. Trends in Neurosciences. 2010;33(12):559-68. doi:10.1016/j.tins.2010.09.004.
18. Sabino-Carvalho JL, Fisher JP, Vianna LC. Autonomic Function in Patients With Parkinson’s Disease: From Rest to Exercise. Frontiers in Physiology. 2021;12. doi:10.3389/fphys.2021.626640.
19. Cuenca-Bermejo L, Almela P, Navarro-Zaragoza J, et al. Cardiac Changes in Parkinson’s Disease: Lessons from Clinical and Experimental Evidence. International Journal of Molecular Sciences. 2021;22(24):13488. doi:10.3390/ijms222413488.
20. Bujala N, Javeid A, Javeid J, et al. Parkinson’s and Cardiovascular Disease-Related Mortality Trends in the United States and the Impact of COVID-19: A 24-Year Analysis. Neurology. 2025;104(7_Supplement_1). doi:10.1212/wnl.0000000000211991.
21. Suri JS, Paul S, Maindarkar MA, et al. Cardiovascular/Stroke Risk Stratification in Parkinson’s Disease Patients Using Atherosclerosis Pathway and Artificial Intelligence Paradigm: A Systematic Review. Metabolites. 2022;12(4):312. doi:10.3390/metabo12040312.
22. Bellini G, D’Antongiovanni V, Palermo G, et al. α-Synuclein in Parkinson’s Disease: From Bench to Bedside. Medicinal Research Reviews. 2025;45(3):909-46. doi:10.1002/med.22091.
23. Dickson DW. Neuropathology of Parkinson’s Disease and Parkinsonism. Cold Spring Harbor Perspectives in Medicine. 2025;a041610. doi:10.1101/cshperspect.a041610.
24. Totsune T, Baba T, Hasegawa T, Takeda A. The Heart of the Matter: Cardiac Denervation Casts Doubt on the Brain-First Versus Body-First Hypothesis of Parkinson’s Disease. Movement Disorders. 2025;40(5):807-12. doi:10.1002/mds.30174.
25. Serrano GE, Shprecher D, Callan M, et al. Cardiac Sympathetic Denervation and Synucleinopathy in Alzheimer’s Disease with Brain Lewy Body Disease. Brain Communications. 2020;2(1):fcaa004. doi:10.1093/braincomms/fcaa004.
26. Tripodi G, Lombardo M, Kerav S, et al. Nitric Oxide in Parkinson’s Disease: The Potential Role of Dietary Nitrate in Enhancing Cognitive and Motor Health via the Nitrate-Nitrite-Nitric Oxide Pathway. Nutrients. 2025;17(3):393. doi:10.3390/nu17030393.
27. Caproni S, Di Fonzo A, Colosimo C. Oxidative Stress: A New Pathophysiological Pathway in Parkinson’s Disease and a Potential Target of the Brain-Sport Crosstalk. Parkinson’s Disease. 2025;6691390. doi:10.1155/padi/6691390.
28. Pajares M, Rojo AI, Manda G, et al. Inflammation in Parkinson’s Disease: Mechanisms and Therapeutic Implications. Cells. 2020;9(7):1687. doi:10.3390/cells9071687.
29. Hu Y, Xu S. Association Between Parkinson’s Disease and the Risk of Adverse Cardiovascular Events: A Systematic Review and Meta-Analysis. Frontiers in Cardiovascular Medicine. 2023;10:1284826. doi:10.3389/fcvm.2023.1284826.
30. Basri AM, Turki AF. Evaluating Heart Rate Variability as a Biomarker for Autonomic Function in Parkinson’s Disease Rehabilitation: A Clustering-Based Analysis of Exercise-Induced Changes. Medicina. 2025;61(3):527. doi:10.3390/medicina61030527.
31. Fedorova DN, Solovyeva AE, Fudim M, et al. Frequency of hemodynamic response and symptoms in orthostasis in chronic heart failure with low ejection fraction: associations with clinical blood pressure. Russ J Cardiol. 2022;27(2S):5005. (In Russ.) doi:10.15829/1560-4071-2022-5005.
32. Goldman JG. Non-motor Symptoms and Treatments in Parkinson’s Disease. Neurologic clinics. 2025;43(2):291-317. doi:10.1016/j.ncl.2024.12.008.
33. Xu Y, Chen D, Dong M, et al. Bidirectional relationship between depression and activities of daily living and longitudinal mediation of cognitive function in patients with Parkinson’s disease. Frontiers in aging neuroscience, 2025;17:1513373. doi:10.3389/fnagi.2025.1513373.
34. Mujahid BIM, Holla VV, Kamble N, et al. Non-motor fluctuations in Parkinson’s disease: frequency and clinical correlate. Journal of neural transmission 2025. doi:10.1007/s00702-025-02908-0.
35. Tulbă D, Tănăsoiu AC, Constantinescu AM, et al. Cardiovascular Dysautonomia in Patients with Parkinson’s Disease and Hypertension: A Cross-Sectional Pilot Study. Journal of clinical medicine. 2025;14(7):2225. doi:10.3390/jcm14072225.
36. Degirmenci Y, Angelopoulou E, Georgakopoulou VE, Bougea A. Cognitive Impairment in Parkinson’s Disease: An Updated Overview Focusing on Emerging Pharmaceutical Treatment Approaches. Medicina (Kaunas, Lithuania), 2023;59(10):1756. doi:10.3390/medicina59101756.
Supplementary files
Review
For citations:
Yusupov F.A., Abdykadyrov M.Sh. Pathophysiological mechanisms of cardiovascular disorders in Parkinson’s disease. Russian Journal of Cardiology. 2025;30(9S):6401. (In Russ.) https://doi.org/10.15829/1560-4071-2025-6401. EDN: HYYUQH







































