Parkinson 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.

Figure. 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.

This work was supported by a grant from Korea University in South Korea (Grant No. K1912691).

None.

*Drs Kim and Y.-G. Park contributed equally.

https://www.ahajournals.org/journal/circ

Data are available from the Korea the National Health Insurance Service Institutional Data Access for researchers who meet the access criteria for confidential data.

帕金森病（PD）是第二大最常见的神经退行性疾病，影响1岁至3％的65岁以上的人。随着预期寿命的增加，世界范围内PD的患病率和负担增加。¹尽管流行病学研究一直报告PD相关死亡率高，²PD与心血管疾病（CVD）之间的关系尚不清楚，心血管疾病是导致死亡的主要原因。CVD，例如心肌梗塞（MI），缺血性中风和充血性心力衰竭（CHF），是老年人中最常见的疾病。尽管有几项研究调查了PD和CVD之间的关系，但结果仍存在争议。因此，我们进行了一项基于人群的全国性队列研究，以评估PD患者的MI风险，缺血性中风，CHF和全因死亡率。

我们从国民健康保险局和全国罕见的难治性疾病登记数据库中获得了数据，该数据库涵盖了整个韩国人口。从数据库中收集了2010年至2015年新诊断为PD的患者和年龄≥40岁的无PD的患者。但是，排除了先前在2010年之前被诊断出患有MI，缺血性中风，CHF和PD的患者。最后，就年龄和性别而言，PD组与非PD组匹配为1：5，PD和非PD组分别包括25624和128120个人。观察每位患者直至2016年，并记录MI，缺血性中风，CHF和全因死亡的发生。PD是根据《国际疾病分类》（第10版）PD（G20）的临床修改（ICD-10-CM）代码和罕见难治性疾病注册表中的PD注册代码（V124），其统一诊断标准几乎与英国帕金森氏病学会脑库的诊断标准相同。结果的定义如下：住院期间，ICD-10-CM编码I21和I22，用于MI，住院期间ICD-10-CM编码I63和I64，对于缺血性卒中，≥1台计算机断层扫描或磁共振成像， CHF的ICD-10-CM代码I50。

为了评估PD患者的MI，缺血性中风，CHF和全因死亡率的高风险，我们使用Cox比例风险回归模型确定了风险比（HR）和95％CI。我们对以下协变量进行了调整：年龄，性别，家庭收入（最低四分位数和剩余四分位数），高血压（ICD-10-CM代码I10-13和I15和降压药），糖尿病（ICD-10-CM代码E11–E14和口服抗糖尿病药或胰岛素），血脂异常（ICD-10-CM代码E78和血脂异常药物），慢性阻塞性肺疾病（ICD-10-CM代码J41–J44）和终末期肾脏疾病（ICD-10-CM代码N18，N19，Z49，Z940，Z90和Z992，并要求进行血液透析，腹膜透析或肾移植）。所有统计分析均使用SAS版本9.4（SAS Institute Inc，Cary，NC）进行。

在年龄和性别匹配的队列中，平均年龄±标准差（69.0±10.2岁）和男性比例（42.5％）相同。MI（HR 1.43 [95％CI，1.28–1.59]），缺血性卒中（HR 1.42 [95％CI，1.31-1.54]），CHF（HR 1.65 [95％CI，1.52-1.78]）和更高的风险较高在对498 812人年的随访中进行了多个协变量调整后，PD组的全因死亡率（HR 2.7 [95％CI，2.60–2.81]）高于非PD组。女性对PD对MI和缺血性脑卒中发展的影响比男性更显着，而PD对较年轻年龄组对缺血性脑卒中，CHF和全因死亡率的影响更显着。年龄较大的人群。

在这项大规模的，全国性的，年龄和性别匹配的队列研究中，我们证明了PD患者比非PD患者有更高的MI，缺血性中风，CHF和全因死亡率风险。据我们所知，这是使用已验证的全国性数据来证明PD和CVD之间关联的最大研究。PD与CVD之间关联的潜在机制尚不清楚；但是，心血管自主神经功能障碍，包括体位性低血压，^3种氧化应激，炎症，^4种抗帕金森药物，^5种并发合并症，可能是造成这种情况的因素。

我们研究的优势在于，这是一项大规模的队列研究，数据覆盖了整个韩国人口的97％以上。由于国家健康保险局准确跟踪了所有医疗记录，因此我们可以确定所有事件结果，以评估PD和CVD之间的时间关系。我们还为PD使用了可靠的统一诊断标准。然而，这项研究有潜在的局限性。数据库中没有有关吸烟习惯，饮酒，体育锻炼，体重指数，家族史，PD严重程度，病历或影像数据的信息。

总之，PD与发生CVD的较高风险有关。需要进一步的研究来研究PD和CVD之间关联的潜在机制。医师还需要注意PD患者的CVD预防。

数字。 与非PD组相比，帕金森病（PD）组的急性心肌梗塞，缺血性中风，充血性心力衰竭和全因死亡率的危险比。*根据年龄，性别，最低四分位数收入，糖尿病，高血压和血脂异常进行调整。

这项工作得到了韩国高丽大学的资助（资助号：K1912691）。

没有。

*金博士和Y.-G. 朴树平也贡献了。

https://www.ahajournals.org/journal/circ

数据可从韩国国民健康保险服务机构数据访问权获得，其条件是符合机密数据访问标准的研究人员。