Association of Parkinson Disease With Risk of Cardiovascular Disease and All-Cause Mortality

HomeCirculationVol. 141, No. 14Association of Parkinson Disease With Risk of Cardiovascular Disease and All-Cause Mortality Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBAssociation of Parkinson Disease With Risk of Cardiovascular Disease and All-Cause MortalityA Nationwide, Population-Based Cohort Study Joo-Hyun Park, MD, PhD, Do-Hoon Kim, MD, PhD, Yong-Gyu Park, PhD, Do-Young Kwon, MD, PhD, Moonyoung Choi, MD, Jin-Hyung Jung and Kyungdo Han, PhD Joo-Hyun ParkJoo-Hyun Park Department of Family Medicine (J.-H.P., D.-H.K., M.C.), Korea University Ansan Hospital, Korea University College of Medicine. , Do-Hoon KimDo-Hoon Kim Do-Hoon Kim, MD, PhD, Department of Family Medicine, Korea University Ansan Hospital, Korea University College of Medicine, 123 Jeokgeum-ro, Danwon-gu, Ansan-si, Gyeonggi-do 15355, Republic of Korea. Email E-mail Address: [email protected] https://orcid.org/0000-0001-7421-4501 Department of Family Medicine (J.-H.P., D.-H.K., M.C.), Korea University Ansan Hospital, Korea University College of Medicine. , Yong-Gyu ParkYong-Gyu Park Yong-Gyu Park, PhD, Department of Biostatistics, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea. E-mail Address: [email protected] Department of Biostatistics, College of Medicine, The Catholic University of Korea, Seoul (Y.-G.P., J.-H.J.). , Do-Young KwonDo-Young Kwon Department of Neurology (D.-Y.K.), Korea University Ansan Hospital, Korea University College of Medicine. , Moonyoung ChoiMoonyoung Choi Department of Family Medicine (J.-H.P., D.-H.K., M.C.), Korea University Ansan Hospital, Korea University College of Medicine. , Jin-Hyung JungJin-Hyung Jung Department of Biostatistics, College of Medicine, The Catholic University of Korea, Seoul (Y.-G.P., J.-H.J.). and Kyungdo HanKyungdo Han Department of Statistics and Actuarial Science, Soongsil University, Seoul, Korea (K.H.). Originally published6 Apr 2020https://doi.org/10.1161/CIRCULATIONAHA.119.044948Circulation. 2020;141:1205–1207Parkinson disease (PD) is the second most common neurodegenerative disorder and affects 1% to 3% of people aged >65 years. As life expectancy increases, the prevalence and burden of PD increase worldwide.1 Although epidemiologic studies have consistently reported high PD-associated mortality,2 the relationship between PD and cardiovascular diseases (CVDs), the leading cause of death, remains unclear. CVDs, such as myocardial infarction (MI), ischemic stroke, and congestive heart failure (CHF), are the most common medical conditions in older people. Although several studies have investigated the relationship between PD and CVD, the results remain controversial. Therefore, we conducted a nationwide, population-based cohort study to evaluate the risk of MI, ischemic stroke, CHF, and all-cause mortality in PD patients.We obtained data from the National Health Insurance Service and national rare intractable disease registry database, which covers the entire Korean population. Patients newly diagnosed with PD and individuals without PD who were aged ≥40 years from 2010 to 2015 were included from the database. However, individuals previously diagnosed with MI, ischemic stroke, CHF, and PD before 2010 were excluded. Finally, the PD group was matched 1:5 with the non-PD group with respect to age and sex, and 25 624 and 128 120 individuals were included in the PD and non-PD groups, respectively. Each patient was observed until 2016, and occurrences of MI, ischemic stroke, CHF, and all-cause death were recorded. PD was identified based on the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) code for PD (G20) and the PD registration code (V124) in the registry of rare intractable diseases, whose uniform diagnostic criteria are almost identical to the United Kingdom Parkinson’s Disease Society Brain Bank diagnostic criteria. The definitions of outcomes were as follows: ICD-10-CM-codes I21 and I22 during hospitalization for MI, ICD-10-CM-codes I63 and I64 during hospitalization, with ≥1 brain computed tomography or magnetic resonance imaging for ischemic stroke, and ICD-10-CM-codes I50 for CHF.To evaluate the high risk of MI, ischemic stroke, CHF and all-cause mortality in PD patients, we determined hazard ratios (HRs) and 95% CIs using Cox proportional hazards regression model. We adjusted for the following covariates: age, sex, household income (lowest quartile and remaining quartiles), hypertension (ICD-10-CM-codes I10-13 and I15 and antihypertensive agents), diabetes mellitus (ICD-10-CM-codes E11–E14 and oral antidiabetic agents or insulin), dyslipidemia (ICD-10-CM-code E78 and agents for dyslipidemia), chronic obstructive pulmonary disease (ICD-10-CM-codes J41–J44), and end-stage renal disease (ICD-10-CM-codes N18, N19, Z49, Z940, Z90, and Z992 and claims for hemodialysis, peritoneal dialysis, or renal transplantation). All statistical analyses were performed using SAS version 9.4 (SAS Institute Inc, Cary, NC). The study was approved by the institutional review board of Korea University (IRB No. 2018AS0098).The mean age±standard deviation (69.0±10.2 years) and proportion of men (42.5%) were the same between the age- and sex-matched cohorts. Higher risk of MI (HR 1.43 [95% CI, 1.28–1.59]), ischemic stroke (HR 1.42 [95% CI, 1.31–1.54]), CHF (HR 1.65 [95% CI, 1.52–1.78]), and all-cause mortality (HR 2.7 [95% CI, 2.60–2.81]) was observed in the PD group than in the non-PD group after adjustment for multiple covariates during the 498 812 person-years of follow-up. The effects of PD on the development of MI and ischemic stroke were more significant in women than in men, and the effects of PD on the development of ischemic stroke, CHF, and all-cause mortality were more significant in the younger age group than in the older age group.In this large-scale, nationwide, age- and sex-matched cohort study, we demonstrated that PD patients had higher risks of MI, ischemic stroke, CHF, and all-cause mortality than non-PD patients. To our knowledge, this is the largest study to demonstrate the association between PD and CVD using validated nationwide data. The mechanisms underlying the association between PD and CVD remain unclear; however, cardiovascular autonomic dysfunctions, including orthostatic hypotension,3 oxidative stress, inflammation,4 anti-Parkinson medications,5 and concurrent comorbidities, may be contributing factors.The strength of our study is that it was a large-scale cohort study of data covering >97% of the entire Korean population. Because the National Health Insurance Service accurately tracked all medical records, we could identify all incident outcomes to evaluate the temporal relationship between PD and CVD. We also used reliable uniform diagnostic criteria for PD. Nevertheless, this study had potential limitations. Information on smoking habits, alcohol consumption, physical exercise, body mass index, family history, PD severity, medical records, or imaging data was unavailable in the database.In conclusion, PD was associated with the higher risk of developing CVD. Further studies are required to investigate the mechanisms underlying the association between PD and CVD. Physicians also need to pay attention to CVD prevention in PD patients.Download figureDownload PowerPointFigure. Hazard ratios of acute myocardial infarction, ischemic stroke, congestive heart failure, and all-cause mortality in the Parkinson disease (PD) group compared with those in the non-PD group. *Adjusted for age, sex, lowest quartile income, diabetes mellitus, hypertension, and dyslipidemia.Sources of FundingThis work was supported by a grant from Korea University in South Korea (Grant No. K1912691).DisclosuresNone.Footnotes*Drs Kim and Y.-G. Park contributed equally.https://www.ahajournals.org/journal/circData are available from the Korea the National Health Insurance Service Institutional Data Access for researchers who meet the access criteria for confidential data.Do-Hoon Kim, MD, PhD, Department of Family Medicine, Korea University Ansan Hospital, Korea University College of Medicine, 123 Jeokgeum-ro, Danwon-gu, Ansan-si, Gyeonggi-do 15355, Republic of Korea. Email [email protected]netYong-Gyu Park, PhD, Department of Biostatistics, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea. [email protected]ac.krReferences1. Macerollo A, Chen JC. Trends in the incidence of Parkinson disease.JAMA Neurol. 2016; 73:1497–1498. doi: 10.1001/jamaneurol.2016.3850CrossrefMedlineGoogle Scholar2. Dobkin BH. Orthostatic hypotension as a risk factor for symptomatic occlusive cerebrovascular disease.Neurology. 1989; 39:30–34. doi: 10.1212/wnl.39.1.30CrossrefMedlineGoogle Scholar3. Goldstein DS. Cardiovascular autonomic dysfunction in Parkinson’s diseaseParkinson’s Disease and Nonmotor Dysfunction: Springer; 2013: 201–212. doi: 10.1007/978-1-60761-429-6_13CrossrefGoogle Scholar4. Jenner P. Oxidative stress in Parkinson’s disease.Ann Neurol. 2003; 53Suppl 3:S26–36; discussion S36-8. doi: 10.1002/ana.10483CrossrefMedlineGoogle Scholar5. Mokhles MM, Trifirò G, Dieleman JP, Haag MD, van Soest EM, Verhamme KM, Mazzaglia G, Herings R, Luise Cd, Ross D, et al. 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April 7, 2020Vol 141, Issue 14 Advertisement Article InformationMetrics © 2020 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.119.044948PMID: 32250706 Originally publishedApril 6, 2020 Keywordsheart failurecardiovascular diseaseneurodegenerative diseasestrokemortalityParkinson diseasemyocardial infarctionPDF download Advertisement