Objective: To determine whether genetic forms of Parkinson’s Disease (PD), such as LRRK2-mutated PD (LRRK2-PD) and GBA­-mutated PD (GBA­-PD), have a different vascular risk compared to idiopathic PD (iPD) and healthy controls (HCs).

Background: A recent meta-analysis described that PD is associated with an increased risk of ischemic stroke, however, no relationship between PD and cardiovascular events was found. It has been suggested that other aspects, different from the classical risk factors, might influence that link. To date, little is known about the influence of PD-related genes in vascular disease of those patients.

Method: We recruited 342 iPD patients, 30 GBA-PD patients (most frequent variant: p.N370S, 40%), 31 LRRK2-PD patients (p.G2019S: 90,3%;  p.R1441G: 9,7%) and 641 HCs. PD patients with mutations in other PD-related genes were not included. HCs were not considered if they had PD-related gene mutations. Demographical and clinical data were obtained.  The presence of vascular events (ischemic stroke and coronary artery disease) was determined in our cohort. Strokes were confirmed by the presence of radiological findings. Multivariate logistic regression and Kaplan Maier analyses were applied.

Results: LRRK2-PD had a female predominance (61%) whereas in GBA-PD, iPD and HCs there was a male predominance (73%, 61% and 55%, respectively). iPD was the oldest group (mean age: 66.37 ± 11.64 y) and GBA-PD the youngest (48.77 ± 24.48 y). No differences were found in vascular risk factors among groups. Neither disease severity nor levodopa equivalent daily dose differed among PD groups. The prevalence of ischemic stroke was significantly different among groups after adjusting by sex, age, and vascular risk factors. LRRK2-PD was the group with a higher proportion of stroke (16.1%), followed by iPD (4.7%). GBA­­-PD and HCs had lower stroke prevalence (3,3% and 3,1%, respectively). Kaplan-Maier survival curves showed a younger age of stroke in the LRRK2-PD cohort (log-rank test: Xi²=14.6, p= 0.002). Regarding coronary artery disease, no differences were found among groups.

Conclusion: In our population, LRRK2-PD patients showed an increased risk for ischemic stroke compared to the other groups. Besides, ischemic stroke in LRRK2-PD patients seemed to occur at a younger age. GBA-PD showed a similar stroke risk to HCs. Prospective and larger studies are needed to confirm these findings and to consider them in our routine clinical practice.

References: Alves M, Caldeira D, Ferro JM, et al. Does Parkinson’s disease increase the risk of cardiovascular events? A systematic review and meta‐analysis. Eur J Neurol 2020;27:288–96.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/increased-stroke-risk-in-parkinsons-disease-patients-with-lrrk2-mutations/