In a recent study published in Scientific Reportsresearchers performed a two-sample Mendelian randomization (MR) analysis to investigate causal associations between Parkinson’s disease (PD) and cardiovascular diseases.
Record
Bradykinesia, resting tremor, and rigidity are clinical symptoms of PD, a common geriatric condition. Cardiovascular disorders, which are a leading cause of mortality in geriatric individuals, are also common. However, the relationship between PD and cardiovascular disorders is uncertain. Recent research suggests that cardiovascular dysfunction may be a precursor to Parkinson’s disease, with symptoms intensifying as the disease progresses. Previous research has generated considerable debate.
About the study
In the present study, the researchers evaluated the effect of PD on cardiovascular diseases.
Single nucleotide polymorphisms associated with PD were selected from the International PD Genomics Consortium (GWAS) database, which includes data from 482,730 Europeans, including 33,647 patients with 449,056 controls. The team analyzed five GWAS datasets to obtain SNP outcome data.
Cardiovascular disorders investigated included myocardial infarction (MI), coronary artery disease (CAD), heart failure (HF), atrial fibrillation (AF), stroke, cardioembolic stroke (CES), large-artery stroke (LAS), and ischemic stroke. ( IS). CAD-associated SNP dataset (29,319 CAD patients, 183,134 controls), MI-associated SNP dataset (CARDIOGRAMplusC4D study participants; 43,676 cases, 128,199 controls), AF-associated SNPs (60,620 controls, 60,620 6 AF patients), the HF-associated SNP dataset was analyzed (47,309 HF patients, 930,014 healthy subjects).
In addition, the team analyzed the findings of the MEGASTROKE consortium to obtain data on stroke subtype. The team searched the phenotype database for second single-nucleotide polymorphism phenotypes analyzed and excluded SNPs associated with outcome data. The researchers performed the MRI analysis using the inverse variance weighting (IVW), weighted median, and MR-Egger methods and inverse MRI analysis to assess reverse causality.
Cochran’s Q statistic values indicated heterogeneity. Regression analysis was performed to calculate odds ratios (ORs), indicating the robustness of the relationship between exposure and outcome. Statistical significance of findings was determined using the F statistic. Furthermore, sensitivity analyzes were performed using the MR-PRESSO approach to assess horizontal pleiotropy and the eliminate-one-out method to assess MR estimation bias.
Results
Overall, 23 SNPs were significantly associated with Parkinson’s disease (p-value below 5.0 × 10–8) and independent of each other (R2 below 0.001). The F statistic was above 10, indicating strong associations between SNPs and study exposure. Findings from the primary variance-weighted analysis showed that Parkinson’s disease was associated with an increased risk of coronary heart disease (OR, 1.1), stroke (OR, 1.0), IS (OR, 1.0), and CES ( OR, 1,1). The other methods, namely Mendelian-Egger randomization, weighted mean, and simple and weighted modes, showed similar results.
However, there were no associations between Parkinson’s disease and other cardiovascular diseases. The panel included 22, 16, 22, and 20 single nucleotide polymorphisms in the IVW analysis of LAS, HF, AF, and MI, respectively, and OR values of 0.98, 0.97, 0.97, and 1.1 for MI, AF, HF , and LAS, indicating no causal associations with PD. Inverse MRI analysis showed similar results. Mendelian randomization-PRESSO analysis showed no horizontal pleiotropy in integrated single nucleotide polymorphisms and Cochran’s Q values showed no heterogeneity in Mendelian randomization analysis estimates. In addition, sensitivity analysis showed reliable results. Eliminating a single nucleotide polymorphism from the primary study did not significantly affect the results.
PD, a Lewy body disease, is associated with an increased incidence of CAD due to several mechanisms. Excessive Lewy body deposition in PD patients may lead to cardiac sympathetic denervation, reduced sympathetic innervation, and abnormal function of residual noradrenergic endings. Ankylosis, bradykinesia, tremor, dementia, and depression exacerbate severe cardiac norepinephrine deficiencies reported in PD patients. As the disease progresses, the patient’s mobility increases the risk of CAD. Orthostatic hypotension is associated with a risk of developing CAD. PD affects lipid metabolism, which in turn affects the course of cardiovascular disease.
Parkinson’s disease is associated with an increased risk of stroke due to abnormalities in the metabolism of α-synuclein, which overaccumulates in Lewy bodies and can cause ischemic brain damage. Alpha-synuclein induces neuronal death through inflammation, oxidative stress, mitochondrial rupture and autophagy, increasing the risk of stroke. Glutathione peroxidase 7 (GPX7) expression in PD patients is comparable to that in stroke patients, possibly exacerbating endoplasmic reticulum oxidative stress and causing stroke. Iron metabolism in PD patients may play a role in the relationship between PD and CES, resulting in fibrin-like substance formation and thrombosis.
Overall, the study findings showed that PD is associated with an increased risk of coronary heart disease, stroke, ischemic stroke, and cardioembolic stroke, consistent with previous animal and clinical studies. The findings showed that it is crucial to achieve early control and treatment of stroke and CAD in patients with PD.
