AUTHOR=Oosterwegel Max J. , Krijthe Jesse H. , den Brok Melina G. H. E. , van den Heuvel Lieneke , Richard Edo , Heskes Tom , Bloem Bastiaan R. , Evers Luc J. W. 

TITLE=The effect of cardiovascular risk on disease progression in de novo Parkinson's disease patients: An observational analysis

JOURNAL=Frontiers in Neurology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2023.1138546

DOI=10.3389/fneur.2023.1138546

ISSN=1664-2295

ABSTRACT=Background: Currently available treatment options for Parkinson’s disease are symptomatic and do not alter the course of the disease. Recent studies have raised the possibility that cardiovascular risk management may slow the progression of the disease. 
Objectives: We estimated the effect of baseline cardiovascular risk factors on the progression of Parkinson’s disease, using measures for PD-specific motor signs and cognitive functions. 
Methods: We used data from 424 de novo Parkinson’s disease patients and 199 age-matched controls from the observational, multicenter Parkinson’s Progression Markers Initiative (PPMI) study, which included follow-up of up to nine years. The primary outcome was the severity of PD-specific motor signs , assessed with the MDS-UPDRS part III. The secondary outcome was cognitive function, measured with the Montreal Cognitive Assessment, Symbol Digit Modalities Test, and Letter-Number Sequencing task. Exposures of interest were diabetes mellitus, hypertension, body mass index (BMI), cardiovascular event history and hypercholesterolemia, and a modified Framingham risk score, measured at baseline. The effect of each of these exposures on disease progression was modelled using linear mixed models, including adjustment for identified confounders. A secondary analysis on the Tracking Parkinson’s cohort including 1841 patients was performed to validate our findings in an independent cohort. 
Results: Mean age was 61.4 years, and the average follow-up was 5.5 years. We found no statistically significant effect of any individual cardiovascular risk factor on the MDS-UPDRS part III progression, with one exception: in the PD group, the estimated effect of a one-point increase in BMI was 0.059 points on the MDS-UPDRS part III per year (95% CI: 0.017 to 0.102). We found no evidence for an effect of any of the exposures on the rate of change in cognitive functioning in the PD group. Similar results were observed for the Tracking Parkinson’s cohort (all 95% CIs overlapped with PPMI), but the 95% CI of the effect of BMI on the MDS-UPDRS part III progression included zero.  
Conclusions: Based on this analysis of two large cohorts of de novo PD patients, we found no evidence to support clinically relevant effects of cardiovascular risk factors on the clinical progression of Parkinson’s disease.