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INTRODUCTION
Parkinson’s disease (PD) is a neurological disorder that worsens with time, which also affects the elderly population [4]. In past examinations, it was found that ischemic heart disease reflects the highest mortality rate in patients with PD [27,28]. A population-based with matched participants revealed that PD was linked to a greater chance of acute myocardial infarction (AMI) [17]. Other studies, however, discovered that PD patients adapted a reduced risk of ischemic heart disease-related death [2,25]. According to recent research, PD is linked to hypertension and diabetes and other vascular risk factors [3,26,34]. Since the two conditions are likewise AMI risk factors, these vascular comorbidities may defy the relationship between AMI and PD. In addition, earlier work focusing on the association between AMI and PD used a small size sample and the follow-up period was only 3 years [17]. This subsequent countrywide longitudinal research was not only based on how much data was available, but it was also adjusted to account for confounding variables such as hypertension, dyslipidemia, and diabetes. As a result, the goal of this cross-country study resulted in comparing the estimated percent of AMI in a PD group to a control group.
MATERIALS AND METHODS
The Review Committee of CHA Bundang Medical Center of CHA University gave us the rights to utilize it (IRB No. 2020-01-011).
Data source
South Korea’s health-care system is single-payer run by the National Health Insurance Sharing Service (NHISS) [1,14,15,23]. This service is operated through the medical claims that are submitted by health-care providers for a thorough review, as well as the numerous national health examinations provided bi-annually for office workers and annually for non-office workers, all aged ≥40 years. These two procedures allows the NHISS to make available a clear database of those engaging in national health examinations [32]. Such a database incorporates recent medical procedures, treatments, demographics, and diagnoses from the International Classification of Diseases (ICD-10) [13]. To make use of the following NHIS-HEALS database, researchers are strongly advised to get permission from the official review committee.
Study design and subjects
The aim of this sex and age coordinated cohort analysis is to determine the potential risks of AMI in patients with PD. The study’s subjects include a PD and control group. The Korea NIHSS cohort included 515547 participants, whose data have been in track until December 2015 (12 years). From this population, numerous factors such as age, income level, sex, ICD-10 disease codes, and preexisting comorbid medical disorders in the NHISS database played a role in classifying them into different categories [16,24]. After such an adjustment, their risk of AMI and co-morbidities of dyslipidemia, diabetes mellitus, and hypertension were evaluated.
Establishment of the study cohort
Six thousand four hundred seventy-five PD patients were drawn out from the 515547 patients exhibited in the NHISS database using the code G20 based on the ICD-10 code, which helps identify researchers the presence of PD. Five thousand four hundred thirty-six people who were hospitalized more than once or who visited an outpatient clinic more than two times were selected. In addition, after excluding 177 subjects with preexisting PD, 5259 patients who were newly diagnosed after January 1, 2004 remained. Furthermore, to classify the control group, 26295 individuals were chosen through 1 : 5 sex and age coordinated matching without replacement with ‘Match IT’, a R-package match algorithm [16]. The researchers have kept a close watch on both the PD and control groups until 31 December 2015 (Fig. 1).
Statistical analysis
To distinguish the mean differences in the control and PD groups’ demographic features and co-morbidities, a statistical analysis was done using the chi-square test and student’s t-test (Table 1). The Kaplan-Meier technique was used to look at the probability of surviving without an AMI. The Wilcoxon’s log rank test was then used to assess the distinctions in survival percents between the two groups. To account for the influence of PD on each subsequent incident, two Cox proportional-hazards regression models were utilized. Model 1 was modified for gender and age. In addition, in model 2, sex, age, low income, and other variables were changed. R software was used to examine such exams (version 3.3.3; R Foundation for Statistical Computing, Vienna, Austria).
RESULTS
Characteristics of the PD and control groups
There were notable distinctions in the PD and control groups in both of their low income (p<0.001), diabetes mellitus (p=0.001), and hypertension (p<0.001) (Table 2).
The data showed 5259 patients who have been newly diagnosed with PD. The population consisted of a mean age of 62.87±8.42 years, with 53.28% of them being male. The two groups were significantly different in terms of how common their low income (p<0.001), diabetes mellitus (p=0.001), and hypertension (p<0.001) were.
AMI in the PD and control groups
The chance of AMI in the PD group was significantly higher (p<0.001, Fig. 2) than in the control group, as demonstrated by the Kaplan-Meier curves. In addition, a closer look at Cox proportional-hazards regression model 1 reveals that the PD group’s AMI ratio was 3.603 (95% confidence interval [CI], 2.83–4.57; Table 3), whereas model 2’s ratio was 3.586 (95% CI, 2.82–4.55; Table 3).
Subgroup analysis of AMI incidence rate
The AMI rates in the control and PD groups were much unalike in the female and male subgroups (95% CI, 2.579–4.922 and 2.569–5.238, respectively; Table 1). Similarly, the same occurrence happened in the subgroups of age <65 and ≥65 (95% CI, 3.347–7.040 and 2.109–3.958, respectively; Table 1), non-diabetes and diabetes (95% CI, 2.346–4.185 and 2.922–6.916, respectively; Table 1), non-hypertension and hypertension (95% CI, 2.758–5.544 and 2.373–4.576, respectively; Table 1), non-dyslipidemia and dyslipidemia (95% CI, 3.725–4.874 and 1.783–5.102, respectively; Table 1).
DISCUSSION
In this nationwide cohort study based on the NHISS database, 5259 PD patients had a significantly more prone to AMI. One population-based follow-up study conducted in Taiwan claimed that the AMI rate of the PD group was higher by 1.67 times compared to a control group [17]. Our follow-up research, after modifying for important co-morbidities like age, sex, and income level, suggested that PD was affiliated with a 3.603-fold increased chance of AMI (Table 3). This data is synchronous with previous research that also studied factors that affected PD patients’ mortality rates and concluded that their death rates were linked to ischemic heart disease (hazard ratio, 2.3; 95% CI, 1.5–3.4).
The mechanism of increased AMI in PD patients is unclear. One reasonable theory is that oxidative stress is present in idiopathic PD, and these oxidative damage products interfere with cellular functions [9,12]. According to previous research, systemic inflammation and oxidative stress were linked to atherosclerosis development [9,18] and danger of coronary artery disease [8,10,21]. As having PD may point to a higher oxidative stress accumulation, it indicates a higher incidence rate of AMI.
Orthostatic hypotension, usually due to the autonomic dysfunction in PD, is commonly seen in patients’ cardiovascular systems [7,31] : a meta-analysis indicated that orthostatic hypotension is present in 30% of those with PD [35]. Likewise, another study suggested that 48% of PD patients who were diagnosed over 20 years also suffered from the same symptom [19]. Moreover, some research report that such a behavior is related to baroreflex failure, extracardiac noradrenergic denervation, and sympathetic denervation [11]. However, it is known by many that those with orthostatic hypotension are more prone to coronary heart disease : a condition that can appear when there is decreased diastolic perfusion pressure of the myocardial blood flow [6,20,29,36].
Despite such different findings, various limitations of this study should be mentioned. For instance, the pathogenesis of atherosclerosis and AMI [5,22,30,33], and the inflammatory markers and chronic infectious burden, like interleukin-6 and C-reactive protein, can be correlated with one another [5,22,30,33]. Nonetheless, since information about inflammatory markers are not much available in the database, it is tough to analyze the possible effects of it on the relationship between AMI and PD [16,32]. Nevertheless, though limitations can be seen, it is no doubt that this is the first longitudinal nationwide follow-up study that clearly assesses the relationship between AMI and PD in Korea.
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