JNNP: Higher blood high-density lipoprotein and apolipoprotein A1 levels are associated with a reduced risk of amyotrophic lateral sclerosis

Except for a small number of single-gene variants that account for less than 15% of cases, the exact factors responsible for the development of the neurodegenerative disease amyotrophic lateral sclerosis (ALS) are unclear
.

The main theories at present are: accumulation of neurotoxic substances; free radicals damage nerve cell membranes; the lack of nerve growth factor prevents the continuous growth and development of nerve cells

The main theories at present are: accumulation of neurotoxic substances; free radicals damage nerve cell membranes; the lack of nerve growth factor prevents the continuous growth and development of nerve cells

Many epidemiological studies have considered the role of metabolic factors in the development of ALS
.

Relative cardiovascular health and low pre-morbid body mass index (BMI) are associated with an increased risk of ALS

Many epidemiological studies of ALS are based on case-control studies.
These studies have inherent risks of referral and recall bias.
These problems can be partially avoided by prospective cohort studies
.

This study aims to study the relationship between metabolic factors and ALS, including blood markers of lipid and carbohydrate metabolism, physical exercise and BMI

This article was published in " Journal of Neurology, Neurosurgery & Psychiatry " ( Journal of Neurology, Neurosurgery & Psychiatry )

Participants received a preliminary assessment from March 2006 to October 2010, and the median follow-up time was 11.
9 years
.

Participants provided demographic and health information, as well as donated blood for biochemical analysis

Participants received a preliminary assessment from March 2006 to October 2010, and the median follow-up time was 11.

Schoenfeld residuals of the variables included in the combined model

Schoenfeld residuals of the variables included in the combined model

Statistical analysis was performed in R
.

Only occasional ALS cases were included in the analysis, that is, participants who were diagnosed with ALS after sampling, did not report the ALS diagnosis at the baseline study visit, or confirmed the diagnosis through medical contact before sampling

Therefore, only the data of participants related to the diagnosis of ALS more than 5 years after the baseline study visit were used for the secondary analysis

The Cox proportional hazards model registered in the study was used to conduct the time-event analysis of ALS diagnosis

The relationship between low-density lipoprotein and high-density lipoprotein cholesterol, apolipoprotein B and apolipoprotein A1 and the diagnosis of ALS

The data analyzed 409 participants
.

A total of 343 participants were diagnosed with ALS during the follow-up period, and the rough incidence rate was 5.
85/100,000/year
.
Construct a Cox proportional hazard model to examine the association between individual metabolic markers and ALS events, and control age and gender
.
Increased levels of biomarkers or metabolic parameters
.
Combining all cases of ALS, high-density lipoprotein (HR 0.
84, p=0.
010) and high apolipoprotein A1 (HR 0.
83, p=0.
005) were associated with a lower risk of subsequent diagnosis of ALS
.
High-density lipoprotein (HR1.
17) is associated with an increased risk of ALS
.
The model that excludes participants diagnosed within 5 years after the first visit is basically the same as the model that includes all participants in the degree of association and direction
.
High-density lipoprotein (HR 0.
81, p=0.
022) and high apolipoprotein A1 (HR 0.
83, p=0.
043) were associated with a reduction in the risk of ALS
.
High total cholesterol: High-density lipoprotein (HR1.
19, p=0.
022) is associated with an increased risk of ALS
.

The model that excludes participants diagnosed within 5 years after the first visit is basically the same as the model that includes all participants in the degree of association and direction
.

Combine HDL and LDL, apolipoprotein A1 and apolipoprotein B, HbA1c, triglycerides, excess methionine, BMI, serum creatinine, gender and age to construct a combined model
.
Considering the correlation between vascular disease and ALS risk and blood lipid level, coronary artery and cerebrovascular disease are added as covariates.
Smoking is related to high-density lipoprotein cholesterol level and ALS risk and the use of statins.
It is used to treat hypercholesterolemia.
Symptoms are associated with high and low risks of ALS
.
Since total cholesterol is highly correlated with LDL, total cholesterol is excluded
.
High-density lipoprotein and apolipoprotein A1 levels are associated with a lower risk of ALS
.

Coronary artery and cerebrovascular diseases were added as covariates.
Smoking was associated with high-density lipoprotein cholesterol levels and ALS risk and statin use, used to treat hypercholesterolemia, and was associated with high and low risks of ALS
.
Since total cholesterol is highly correlated with LDL, total cholesterol is excluded
.
High-density lipoprotein and apolipoprotein A1 levels are associated with a lower risk of ALS
.

In conclusion, the association between high-density lipoprotein, apolipoprotein A1, and low-density lipoprotein levels and the risk of amyotrophic lateral sclerosis is helpful for the exploration of pre-symptomatic biomarkers and therapeutic targeting
.

Thompson  AG ,  Talbot  K ,  Turner MR Thompson  AGThompson Talbot  KTalbot Turner MRTurnerHigher blood high density lipoprotein and apolipoprotein A1 levels are associated with reduced risk of developing amyotrophic lateral sclerosisJournal of Neurology, Neurosurgery & Psychiatry  Published Online First:  13 September 2021 .
 Published Online First: doi:  10.
1136/jnnp-2021-327133doi:

 

 

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