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The implication of cardio-oncology on Parkinson's disease: answers begin to emerge

Fulvio A. Scorza Antonio-Carlos G. de Almeida Josef Finsterer Ludhmila A. Hajjar About the authors

Parkinson's Disease (PD) is a progressive, incurable, and symptomatically devastating neurodegenerative disease.11 Seo HG, Byun SJ, Oh BM, Park SJ. Ten-Year relative survival from the diagnosis of Parkinson's disease: a nationwide database study. J Am Med Dir Assoc 2021;22(8):1757–61., 22 Scorza FA, Fiorini AC, Scorza CA, Finsterer J. Cardiac abnormalities in Parkinson's disease and Parkinsonism. J Clin Neurosci 2018;53:1–5., 33 Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, et al. Parkinson disease. Nat Rev Dis Primers 2017;3:17013. PD is the second most common neurodegenerative disease affecting up to ten million people worldwide.44 Han SA, Semilan SLA, Hong PK. Systematic review on Parkinson's Disease Medications, emphasizing on three recently approved drugs to control Parkinson's symptoms. Int J Environ Res Public Health 2021;19(1):364. Clinically, PD presents with tremor, rigidity, bradykinesia/akinesia, and postural instability due to the progressive loss of neurons in the Substantia Nigra pars compacta (SNpc) and extensive intracellular aggregation of α-synuclein.33 Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, et al. Parkinson disease. Nat Rev Dis Primers 2017;3:17013., 44 Han SA, Semilan SLA, Hong PK. Systematic review on Parkinson's Disease Medications, emphasizing on three recently approved drugs to control Parkinson's symptoms. Int J Environ Res Public Health 2021;19(1):364., 55 Balestrino R, Schapira AHV. Parkinson disease. Eur J Neurol 2020;27(1):27–42. In addition, molecular mechanisms such as mitochondrial dysfunction, excitotoxicity, impaired autophagy, oxidative stress, and genetic mutations are implicated in the degeneration of dopaminergic neurons in PD.66 Leong YQ, Lee SWH, Ng KY. Cancer risk in Parkinson disease: an updated systematic review and meta-analysis. Eur J Neurol 2021;28(12):4219–37. Available therapies for PD only affect the symptoms of the disease and mainly focus on the dopaminergic pathway.22 Scorza FA, Fiorini AC, Scorza CA, Finsterer J. Cardiac abnormalities in Parkinson's disease and Parkinsonism. J Clin Neurosci 2018;53:1–5.,33 Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, et al. Parkinson disease. Nat Rev Dis Primers 2017;3:17013.,55 Balestrino R, Schapira AHV. Parkinson disease. Eur J Neurol 2020;27(1):27–42.,77 Kalia LV, Lang AE. Parkinson's disease. Lancet 2015;386(9996):896-912. The most common non-motor symptoms associated with PD involve neurobehavioral complications, sensory problems, and auto-nomic dysfunction.66 Leong YQ, Lee SWH, Ng KY. Cancer risk in Parkinson disease: an updated systematic review and meta-analysis. Eur J Neurol 2021;28(12):4219–37. Several studies have found autonomic dysfunction to be a valuable predictor of cardiovascular morbidity and mortality in PD patients.88 Farrell MC, Shibao CA. Morbidity and mortality in orthostatic hypotension. Auton Neurosci 2020;229:102717.,99 Cuenca-Bermejo L, Almela P, Navarro-Zaragoza J, Fernandez Villalba E, González-Cuello AM, Laorden ML, et al. Cardiac changes in Parkinson's disease: lessons from clinical and experimental evidence. Int J Mol Sci 2021;22(24):13488. Despite the tremendous clinical and epidemiological relevance of these studies, Sudden Death in PD (SUDPAR), a rare but fatal event, contributes to the increased mortality in PD patients.22 Scorza FA, Fiorini AC, Scorza CA, Finsterer J. Cardiac abnormalities in Parkinson's disease and Parkinsonism. J Clin Neurosci 2018;53:1–5.,1010 Scorza FA, Almeida ACG, Scorza CA, Finsterer J. Prevention of Parkinson's disease-related sudden death. Clinics 2021;76:e3266.

Although the authors experienced an enlightening phase in PD research in the last decade,22 Scorza FA, Fiorini AC, Scorza CA, Finsterer J. Cardiac abnormalities in Parkinson's disease and Parkinsonism. J Clin Neurosci 2018;53:1–5.,33 Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, et al. Parkinson disease. Nat Rev Dis Primers 2017;3:17013. data on the influence of comorbidities on morbidity and mortality in PD are still lacking. Previous studies showed that hypertension, back problems, arthritis, dementia, cataracts, diabetes mellitus type II, non-specific hyperlipidemia, depressive disorder, atrial fibrillation, and urinary incontinence were the most common comorbidities in PD patients.1111 Wang X, Zeng F, Jin WS, Zhu C, Wang QH, Bu XL, et al. Comorbidity burden of patients with Parkinson's disease and Parkinsonism between 2003 and 2012: a multicentre, nationwide, retrospective study in China. Sci Rep 2017;7(1):1671., 1212 Gil-Prieto R, Pascual-Garcia R, San-Roman-Montero J, Martinez-Martin P, Castrodeza-Sanz J, Gil-de-Miguel A. Measuring the Burden of Hospitalization in Patients with Parkinsons Disease in Spain. PLoS One 2016;11(3):e0151563., 1313 Pohar SL, Allyson Jones C. The burden of Parkinson disease (PD) and concomitant comorbidities. Arch Gerontol Geriatr 2009;49(2):317–21. There is also growing evidence that PD and cancer may be closely linked.1414 Zhang X, Guarin D, Mohammadzadehhonarvar N, Chen X, Gao X. Parkinson's disease and cancer: a systematic review and meta-analysis of over 17 million participants. BMJ Open2021;11(7):e046329.,1515 Ejma M, Madetko N, Brzecka A, Guranski K, Alster P, Misiuk-Hojlo M, et al. The links between Parkinson's disease and cancer. Biomedicines 2020;8(10):416. In fact, cancer incidence increases with age, as does the incidence of PD.1414 Zhang X, Guarin D, Mohammadzadehhonarvar N, Chen X, Gao X. Parkinson's disease and cancer: a systematic review and meta-analysis of over 17 million participants. BMJ Open2021;11(7):e046329.,1616 Kendal WS. Dying with cancer: the influence of age, comorbidity, and cancer site. Cancer 2008;112:1354–62. On the one hand, an increased incidence of melanoma and other skin tumors, brain cancer, thyroid, and breast cancer has been demonstrated in PD patients.66 Leong YQ, Lee SWH, Ng KY. Cancer risk in Parkinson disease: an updated systematic review and meta-analysis. Eur J Neurol 2021;28(12):4219–37.,1717 Li Z, Zheng Z, Ruan J, Li Z, Tzeng CM. Chronic inflammation links cancer and Parkinson's disease. Front Aging Neurosci 2016;á:126. On the other hand, other studies showed that PD is associated with a significantly reduced risk of lung cancer, genitourinary cancers, gastrointestinal cancers, and hematological cancers.66 Leong YQ, Lee SWH, Ng KY. Cancer risk in Parkinson disease: an updated systematic review and meta-analysis. Eur J Neurol 2021;28(12):4219–37.,1717 Li Z, Zheng Z, Ruan J, Li Z, Tzeng CM. Chronic inflammation links cancer and Parkinson's disease. Front Aging Neurosci 2016;á:126. Although these data are controversial, there is a putative link between PD and cancer that requires much caution and further studies.66 Leong YQ, Lee SWH, Ng KY. Cancer risk in Parkinson disease: an updated systematic review and meta-analysis. Eur J Neurol 2021;28(12):4219–37.,1717 Li Z, Zheng Z, Ruan J, Li Z, Tzeng CM. Chronic inflammation links cancer and Parkinson's disease. Front Aging Neurosci 2016;á:126. Based on all these data and the worrying situation, the authors think it is appropriate to relate PD to the multidisciplinary specialty known as cardio-oncology.1818 Wickramasinghe CD, Nguyen KL, Watson KE, Vorobiof G, Yang EH. Concepts in car-dio-oncology: definitions, mechanisms, diagnosis and treatment strategies of cancer therapy-induced cardiotoxicity. Future Oncol 2016;12(6):855–70. In particular, the main goal of cardio-oncology is the prevention and treatment of cancer therapy-related cardiotoxicity to optimize cardiovascular health outcomes in cancer patients or after cancer.1818 Wickramasinghe CD, Nguyen KL, Watson KE, Vorobiof G, Yang EH. Concepts in car-dio-oncology: definitions, mechanisms, diagnosis and treatment strategies of cancer therapy-induced cardiotoxicity. Future Oncol 2016;12(6):855–70.,1919 Fradley MG, Beckie TM, Brown SA, Cheng RK, Dent SF, Nohria A, et al. Recognition, prevention, and management of arrhythmias and autonomic disorders in cardio-oncology: a scientific statement from the American Heart Association. Circulation. 2021;144(3):e41–55. In fact, it is already recognized that some cancer treatments can lead to atrial tachyarrhythmias, ventricular arrhythmias, and bradyarrhythmias.1919 Fradley MG, Beckie TM, Brown SA, Cheng RK, Dent SF, Nohria A, et al. Recognition, prevention, and management of arrhythmias and autonomic disorders in cardio-oncology: a scientific statement from the American Heart Association. Circulation. 2021;144(3):e41–55. Therefore, based on the authors’ experience of more than a decade with the cardio-oncology program in Brazil,2020 Hajjar LA, Mathias C. Cardio-Oncology in Brazil: The Dimensions of a New Era in the care of patients. JACC CardioOncol 2020;2(2):340–2. it is necessary to apply this knowledge to patients with PD as well. Certainly, the authors fully agree1818 Wickramasinghe CD, Nguyen KL, Watson KE, Vorobiof G, Yang EH. Concepts in car-dio-oncology: definitions, mechanisms, diagnosis and treatment strategies of cancer therapy-induced cardiotoxicity. Future Oncol 2016;12(6):855–70. that this valuable clinical convergence will enable us to identify PD patients at risk for cardiac complications and to develop precise cardioprotective strategies.

What lessons have the authors learned overall in recent years? Firstly, with an aging population and rising life expectancy worldwide, PD is estimated to increase by more than 50% by 2030.22 Scorza FA, Fiorini AC, Scorza CA, Finsterer J. Cardiac abnormalities in Parkinson's disease and Parkinsonism. J Clin Neurosci 2018;53:1–5.,77 Kalia LV, Lang AE. Parkinson's disease. Lancet 2015;386(9996):896-912. Second, PD is a systemic disease with cases of premature death. SUDPAR is a rare event, but it is common in PD patients with positive family history and risk factors for cardiovascular disease. Third, several studies suggest that cancer may be associated with PD. Furthermore, as extraordinary advances in translational neuroscience have changed our understanding of PD in the last decade,22 Scorza FA, Fiorini AC, Scorza CA, Finsterer J. Cardiac abnormalities in Parkinson's disease and Parkinsonism. J Clin Neurosci 2018;53:1–5. it is extremely important to integrate the concept of cardio-oncology in centers for movement disorders. In fact, as cancer survival has increased over time due to improvements in treatment, it is reasonable to expect that the significant risk of cardiovascular complications for survivors will remain high in the near future.2121 Adhikari BB, Shi S, Dimond EP, Shelburne N, Desvigne-Nickens P, Minasian LM. Spectrum of national institutes of health-funded research in cardio-oncology: a basic, clinical, and observational science perspective. Heart Fail Clin 2022;18(3):515–28. In these lines, the authors are in agreement that new lines of research should converge the research expertise of not only cardiologists and oncologists, but potentially others, including neurologists, and those with translational research experience.2121 Adhikari BB, Shi S, Dimond EP, Shelburne N, Desvigne-Nickens P, Minasian LM. Spectrum of national institutes of health-funded research in cardio-oncology: a basic, clinical, and observational science perspective. Heart Fail Clin 2022;18(3):515–28. Finally, all medical specialties must work together in research, education, and collaboration to ensure healthy lives of the patients in cardio-oncology.

Acknowledgments

The present studies are supported by the following grants: FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo); CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior).

References

  • 1
    Seo HG, Byun SJ, Oh BM, Park SJ. Ten-Year relative survival from the diagnosis of Parkinson's disease: a nationwide database study. J Am Med Dir Assoc 2021;22(8):1757–61.
  • 2
    Scorza FA, Fiorini AC, Scorza CA, Finsterer J. Cardiac abnormalities in Parkinson's disease and Parkinsonism. J Clin Neurosci 2018;53:1–5.
  • 3
    Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, et al. Parkinson disease. Nat Rev Dis Primers 2017;3:17013.
  • 4
    Han SA, Semilan SLA, Hong PK. Systematic review on Parkinson's Disease Medications, emphasizing on three recently approved drugs to control Parkinson's symptoms. Int J Environ Res Public Health 2021;19(1):364.
  • 5
    Balestrino R, Schapira AHV. Parkinson disease. Eur J Neurol 2020;27(1):27–42.
  • 6
    Leong YQ, Lee SWH, Ng KY. Cancer risk in Parkinson disease: an updated systematic review and meta-analysis. Eur J Neurol 2021;28(12):4219–37.
  • 7
    Kalia LV, Lang AE. Parkinson's disease. Lancet 2015;386(9996):896-912.
  • 8
    Farrell MC, Shibao CA. Morbidity and mortality in orthostatic hypotension. Auton Neurosci 2020;229:102717.
  • 9
    Cuenca-Bermejo L, Almela P, Navarro-Zaragoza J, Fernandez Villalba E, González-Cuello AM, Laorden ML, et al. Cardiac changes in Parkinson's disease: lessons from clinical and experimental evidence. Int J Mol Sci 2021;22(24):13488.
  • 10
    Scorza FA, Almeida ACG, Scorza CA, Finsterer J. Prevention of Parkinson's disease-related sudden death. Clinics 2021;76:e3266.
  • 11
    Wang X, Zeng F, Jin WS, Zhu C, Wang QH, Bu XL, et al. Comorbidity burden of patients with Parkinson's disease and Parkinsonism between 2003 and 2012: a multicentre, nationwide, retrospective study in China. Sci Rep 2017;7(1):1671.
  • 12
    Gil-Prieto R, Pascual-Garcia R, San-Roman-Montero J, Martinez-Martin P, Castrodeza-Sanz J, Gil-de-Miguel A. Measuring the Burden of Hospitalization in Patients with Parkinsons Disease in Spain. PLoS One 2016;11(3):e0151563.
  • 13
    Pohar SL, Allyson Jones C. The burden of Parkinson disease (PD) and concomitant comorbidities. Arch Gerontol Geriatr 2009;49(2):317–21.
  • 14
    Zhang X, Guarin D, Mohammadzadehhonarvar N, Chen X, Gao X. Parkinson's disease and cancer: a systematic review and meta-analysis of over 17 million participants. BMJ Open2021;11(7):e046329.
  • 15
    Ejma M, Madetko N, Brzecka A, Guranski K, Alster P, Misiuk-Hojlo M, et al. The links between Parkinson's disease and cancer. Biomedicines 2020;8(10):416.
  • 16
    Kendal WS. Dying with cancer: the influence of age, comorbidity, and cancer site. Cancer 2008;112:1354–62.
  • 17
    Li Z, Zheng Z, Ruan J, Li Z, Tzeng CM. Chronic inflammation links cancer and Parkinson's disease. Front Aging Neurosci 2016;á:126.
  • 18
    Wickramasinghe CD, Nguyen KL, Watson KE, Vorobiof G, Yang EH. Concepts in car-dio-oncology: definitions, mechanisms, diagnosis and treatment strategies of cancer therapy-induced cardiotoxicity. Future Oncol 2016;12(6):855–70.
  • 19
    Fradley MG, Beckie TM, Brown SA, Cheng RK, Dent SF, Nohria A, et al. Recognition, prevention, and management of arrhythmias and autonomic disorders in cardio-oncology: a scientific statement from the American Heart Association. Circulation. 2021;144(3):e41–55.
  • 20
    Hajjar LA, Mathias C. Cardio-Oncology in Brazil: The Dimensions of a New Era in the care of patients. JACC CardioOncol 2020;2(2):340–2.
  • 21
    Adhikari BB, Shi S, Dimond EP, Shelburne N, Desvigne-Nickens P, Minasian LM. Spectrum of national institutes of health-funded research in cardio-oncology: a basic, clinical, and observational science perspective. Heart Fail Clin 2022;18(3):515–28.

Publication Dates

  • Publication in this collection
    09 Sept 2022
  • Date of issue
    2022

History

  • Received
    21 June 2022
  • Accepted
    04 July 2022
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