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Lower levels of high-density lipoprotein cholesterol (HDL-C) and greater HDL-C variability were linked to higher incidence of Parkinson's disease, a population-based longitudinal study in Korea showed.

Older adults with the lowest quartile of baseline HDL-C showed higher Parkinson's incidence over 5 years (adjusted HR 1.20, 95% CI 1.08-1.34) compared with those in the highest quartile group, according to Do-Hoon Kim, MD, PhD, of Korea University College of Medicine in Ansan, and co-authors.

Those with the highest levels of HDL-C variability also had greater likelihood of incident Parkinson's disease (adjusted HR 1.19, 95% CI, 1.06-1.33) than those with the least variability. People who had both risk factors -- lowest baseline HDL-C and highest variability -- had the highest risk of Parkinson's (adjusted HR 1.6, 95% CI 1.31-1.96), the researchers reported in .

Lipids may disease, but the connection between HDL-C and Parkinson's is unclear, Kim and colleagues noted. "Previous studies reported inconsistent results with positive or null associations. Only a few small studies have suggested an association between HDL-C and Parkinson's disease but did not exclude the possibility of reverse causality."

The study looked at 380,404 people ages 65 and older who had at least three health exams provided by the Korean National Health Insurance System from 2008 to 2013, following them until 2017. People with a history of Parkinson's disease were excluded. About 62% of participants were men.

The researchers assessed HDL-C variability using three indices including variability independent of the mean (VIM). Mean baseline HDL-C was 53.1 ± 13.0 mg/dL, and median HDL-C variability, measured with VIM, was 7.6. Mean ages ranged from 69.8 in the lowest HDL-C variability group to 70.5 in the highest.

People in the higher quartile of HDL-C variability were older, had lower income, were more likely to be current smokers, and had lower rates of alcohol consumption and regular exercise than other groups. They also had higher mean body mass index, waist circumference, and fasting plasma glucose levels; a higher prevalence rate of hypertension, diabetes mellitus, and chronic kidney disease; and were more likely to use lipid-lowering medications.

With median follow-up of 5.03 years, 2,733 people were newly diagnosed with Parkinson's disease. People with a baseline HDL-C under 40 mg/dL were more likely to develop Parkinson's than those with HDL-C of 60 mg/dL or more (HR 1.21, 95% CI 1.07-1.37).

The data confirm previous findings "and showed for the first time that an increased temporal variability of serum HDL was an independent predictor of Parkinson's disease development, after adjusting for relevant potential confounders," wrote Gian Pietro Sechi, MD, of the University of Sassari in Italy, and co-authors, in an .

How variability in HDL-C may be linked to Parkinson's is unknown, but it may account for some discordant results observed in prior studies, the editorialists noted. Besides the anti-oxidative and anti-inflammatory properties of HDL-C, "a direct interaction between alpha-synuclein and cholesterol may be hypothesized, which may influence alpha-synuclein aggregation and accumulation," Sechi and co-authors said.

"Also, the possibility of a yet unidentified confounding factor linked to both HDL cholesterol levels and Parkinson's disease might also explain the proposed association found in this report, and deserves to be mentioned," the editorialists added.

They noted that the study did not find substantial differences in outcomes by sex, which may be due to a unique preponderance of Parkinson's in women in Asian populations, as well as lower mean HDL cholesterol levels in Korean women after age 70. The study also may have other unique limitations, including a possible association between HDL-C levels and genetic variants like mutations in the cholesterol ester transfer protein, which are frequent in Asian populations.

While patients with a prior diagnosis of Parkinson's disease 4 years before the study started were not included, reverse causality still is possible due to Parkinson's long prodromal phase, the editorialists pointed out: "The question may arise whether the altered HDL cholesterol profile is a mere epiphenomenon of Parkinson's disease, a disorder with evident features of systemic involvement."

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