In a recent study published in Scientific reportsinvestigators performed a Mendelian randomization (MR) evaluation of two samples to analyze the causal associations between Parkinson’s disease (PD) and heart problems.
Background
Bradykinesia, resting tremor and rigidity are clinical symptoms of Parkinson’s disease, a typical disease of old age. Cardiovascular disorders are also common and are the important reason for death within the elderly. Nevertheless, the connection between Parkinson’s disease and cardiovascular disorders is uncertain. Recent research indicates that cardiovascular dysfunction could also be a precursor to Parkinson’s disease, and its symptoms worsen because the disease progresses. Previous research has sparked considerable debate.
Concerning the study
On this study, researchers assessed the impact of Parkinson’s disease on heart problems.
Single nucleotide polymorphisms (SNPs) related to Parkinson’s disease were chosen from the publicly available International PD Genomics Consortium genome-wide association studies (GWAS) database, containing data from 482,730 Europeans, including 33,647 patients and 449,056 controls. The team analyzed five GWAS datasets to acquire the resulting SNP data.
Cardiocerebral disorders studied 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 brain (IS). CAD-related SNP dataset (29,319 CAD patients, 183,134 controls), AMI-related SNP dataset (CARDIOGRAMplusC4D study participants; 43,676 cases, 128,199 controls), AMI-related SNP dataset with AF (60,620 AF patients, 970,216 controls) and an HF-related SNP dataset (47,309 HF patients, 930,014 healthy controls) were analyzed.
Moreover, the team analyzed findings from the MEGASTROKE consortium to acquire data on stroke subtype. The team searched the phenotype database for the second phenotypes of the only nucleotide polymorphisms analyzed and excluded SNPs related to the ultimate data. The researchers performed MR evaluation using the inverse variance weighted (IVW), weighted median, and MR-Egger methods, in addition to inverse MR evaluation to evaluate reverse causality.
Cochran’s Q statistic values indicated heterogeneity. Regression evaluation was performed to calculate odds ratios (ORs), indicating the strength of the association between exposure and final result. The statistical significance of the outcomes was determined using the F statistic. Moreover, sensitivity analyzes were performed using the MR-PRESSO approach to evaluate horizontal pleiotropy and the single-out method to evaluate MR estimation error.
Results
A complete of 23 SNPs were significantly related to Parkinson’s disease (p-value lower than 5.0 × 10–8) and independent of one another (R2 below 0.001). The F statistic was above 10, indicating strong associations between SNPs and exposures within the study. Results of the first inverse variance weighted evaluation showed that Parkinson’s disease was related to an increased risk of coronary heart disease (OR, 1.1), stroke (OR, 1.0), IS (OR, 1.0), and CES (OR, 1 ,1). Other methods, i.e. Mendelian-Egger randomization, weighted average, and easy and weighted mode, showed similar results.
Nevertheless, no association has been found between Parkinson’s disease and other cardiovascular diseases. The team included 22, 16, 22, and 20 single-nucleotide polymorphisms within the IVW evaluation for 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 relationship with PD. Inverse MR evaluation showed similar results. Mendelian randomization-PRESSO evaluation showed no horizontal pleiotropy in integrated single-nucleotide polymorphisms, and Cochran’s Q values indicated no heterogeneity in Mendelian randomization evaluation estimates. Moreover, sensitivity evaluation showed reliable results. Elimination of single nucleotide polymorphisms from the baseline study had no significant impact on the outcomes.
PD, a Lewy body disease, is related to an increased incidence of coronary artery disease through several mechanisms. Excessive Lewy body deposition in PD patients may result in cardiac sympathetic denervation, decreased sympathetic innervation, and abnormal function of remnant noradrenergic terminals. Ankylosis, bradykinesia, tremor, dementia, and depression exacerbate the severe cardiac norepinephrine depletion reported in patients with Parkinson’s disease. Because the disease progresses, patient mobility increases the chance of CAD. Postural hypotension is related to the chance of developing CAD. PD affects lipid metabolism, which in turn affects the course of cardiovascular diseases.
Parkinson’s disease is related to an increased risk of stroke resulting from abnormalities within the metabolism of α-synuclein, which accumulates in excessive amounts in Lewy bodies and may cause ischemic brain damage. Alpha-synuclein causes neuronal death through inflammation, oxidative stress, mitochondrial damage and autophagy, increasing the chance of stroke. Glutathione peroxidase 7 (GPX7) expression in Parkinson’s disease patients is comparable to that in stroke patients, possibly aggravating endoplasmic reticulum oxidative stress and causing stroke. Iron metabolism in PD patients may play a job in the connection between PD and CES, causing the formation of fibrin-like substances and thrombosis.
Overall, the study results showed that PD is related to an increased risk of coronary heart disease, stroke, ischemic stroke, and cardioembolic stroke, consistent with previous animal studies and clinical observations. The outcomes indicate that early screening and treatment of stroke and CAD in patients with PD is crucial.