This cohort study's findings indicate that Parkinson's disease (PD) elevates the risk of both cardiovascular disease (CVD) mortality and overall mortality. The robustness of these results was confirmed through subgroup and sensitivity analyses.
Our findings on overall mortality rate are consistent with previous research findings.A historical cohort study spanning 11 years revealed a mortality rate of 1.64 (95% CI: 1.21-2.23) among patients with Parkinson's disease compared to the control group[16]. Similarly, the Sydney and Netherlands multicenter study reported a higher mortality rate in individuals with Parkinson's Disease (PD) compared to population data[17][18]. A meta-analysis concluded that cognitive impairment/dementia, ageing, late age of onset, male and gait disturbance are risk factors for mortality in PD patients[19].
The literature on cardiovascular disease mortality in people with PD is still limited and controversial. A previous study showed that the risk of ischemic heart disease and in Parkinson's disease patients remains unchanged compared to the general population (HR 1.1, 95% CI 0.6-2.0)[20]. Even some studies suggested that people with Parkinson's disease have a reduced overall incidence of both ischaemic stroke and heart attack[21][22]. However, previous studies have demonstrated that individuals with Parkinson's disease (PD) may encounter autonomic dysfunction, cardiomyopathy, coronary heart disease, arrhythmia, or sudden cardiac death (SCD), resulting in a higher prevalence of heart failure among PD patients[23][24]. In a recent study by Park et al[11]. in South Korea, a nationwide cohort analysis revealed that individuals with Parkinson's disease may face a greater probability of experiencing cardiovascular events and death compared to those without the condition,it was found that individuals with Parkinson's disease (PD) had a higher risk of myocardial infarction (HR 1.43 ,95% CI:1.28-1.59), ischemic stroke (HR 1.42,95% CI:1.31-1.54]), congestive heart failure (HR 1.65 ,95% CI:1.52-1.78). Our research findings also indicate that the cardiovascular mortality rate among Parkinson's patients is higher compared to non-Parkinson's patients.By utilizing a substantial sample size of American participants, our study contributes to enhancing the overall applicability of these results.
Autonomic dysfunction is frequently observed in Parkinson's disease (PD) and can manifest in the autonomic nervous system, including the heart[25]. In a study conducted on the heart tissue of Parkinson's disease patients in Japan, it was discovered that 9 out of 11 patients had Lewy bodies present in both tyrosine hydroxylase positive and negative neural processes, this suggests that the postganglionic sympathetic nervous system and intrinsic neurons in the heart play a role in the development of Parkinson's disease[26]. A prospective study conducted in Sweden revealed that diabetes and elevated fasting blood glucose levels were identified as risk factors for Parkinson's disease (PD). The study also found that a higher neutrophil to lymphocyte ratio (NLR) in the general population was linked to an increased risk of PD. Interestingly, diabetes, fasting glucose, and NLR are all associated with the risk of coronary events or ischemic stroke[12]. So,it is increasingly recognised that PD patients can develop coronary heart disease and ischemic stroke.Then,most Parkinson's disease patients receive levodopa treatment, which has been shown to increase homocysteine levels in the blood,elevated homocysteine levels have been associated with a higher incidence of cerebrovascular and cardiovascular diseases[19]. Some study also suggest that the relationship between Parkinson's disease and cardiovascular disease is complex, with overlapping biological mechanisms, including inflammation, insulin resistance, lipid metabolism, and oxidative stress[27]. These scientific discoveries corroborate our study's perspective, suggesting that Parkinson's disease (PD) increases the likelihood of mortality associated with cardiovascular disease (CVD).
In our stratified analysis, we identified several factors that influence the association between PD and cardiovascular disease mortality, such as older age, Non-Hispanic White,male, lower BMI, never smoking, and past or current alcohol consumption.Similar to a South Korea study found a negative dose-response relationship between BMI at diagnosis and mortality in patients with Parkinson's disease (PD), a 10% change in BMI was significantly linked to mortality outcomes[28]. One possible explanation for this negative correlation is that higher BMI affects insulin levels, which may play a beneficial role in dopaminergic neurodegeneration[29]. we identified a significant interaction regarding cardiovascular disease mortality among individuals with Parkinson's disease, distinguishing between the male and female subgroups.A retrospective study has analyzed the trend of Parkinson's disease (PD) mortality revealed that males had a mortality rate for PD that was twice as high as females[30]. The gender disparity in Parkinson's disease development could be attributed to the potential neuroprotective effect of female gonadotropins, especially circulating estradiol, on the dopaminergic system. Research indicates that men typically acquire Parkinson's disease at a younger age than women, leading to a higher mortality rate in men at an earlier stage, which may counterbalance other risk factors[31]. In the United States, there exists racial and ethnic disparities in access to neurological care, with black and Hispanic patients being less likely than white patients to consult outpatient neurologists. This discrepancy suggests that white patients have a greater likelihood of being diagnosed with Parkinson's disease[32], possibly attributed to their overall higher socioeconomic status in terms of education and income compared to minority populations. Consequently, this disparity may contribute to the higher cardiovascular disease mortality rates in white individuals with PD in comparison to other racial and ethnic groups.Numerous clinical studies have demonstrated a negative correlation between smoking and the occurrence of Parkinson's disease in both genders[33][34]. Smoking might have a protective effect against Parkinson's disease; however, the cause of the higher vulnerability to cardiovascular disease mortality in Parkinson's disease patients who have never smoked remains unclear.
Study strengths and limitations
This study is the first to examine cardiovascular disease mortality in Parkinson's disease patients using data from the NHANES. The sample size was both large and representative, allowing for a more comprehensive analysis. However there were some limitations to this study. Initially, it is critical to note that the determination of Parkinson's disease (PD) within our research was reliant on participants' self-reported medication usage, without corroboration through a formal medical diagnosis. This approach acknowledges the possibility that a subset of participants may be either unaware of their PD status or may exhibit milder symptoms not necessitating pharmacological intervention, potentially leading to an underrepresented sample.Moreover, we are mindful that patients with tremor-associated neurological conditions other than PD might be prescribed antiparkinsonian medications, yet lack a definitive PD diagnosis. Such instances could precipitate misclassification within our study, thereby introducing a bias into our research outcomes.To address these limitations, future investigations should endeavor to adopt more rigorous diagnostic methodologies. This might entail comprehensive clinical evaluations by specialists in movement disorders or the employment of standardized diagnostic instruments. By integrating these refined diagnostic practices, the accuracy of PD case identification can be enhanced, thereby mitigating the risk of misclassification.