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EFFECT OF LIPID PROFILE ON PROGNOSIS IN THE PATIENTS WITH AMYOTROPHIC LATERAL SCLEROSIS
  1. Muhammad Rafiq,
  2. Ellen Lee,
  3. Michael Bradburn
  1. University of Sheffield

    Abstract

    Background The patients with Amyotrophic lateral sclerosis (ALS) are particularly predisposed to malnutrition for a variety of reasons which include dysphagia, fear of choking and aspiration, inability to feed themselves and high resting metabolic rate. Hence various defence mechanisms are likely to be activated in such patients to provide energy substrates e.g., gluconeogenesis, lipolysis, and ketogenesis. Higher weight in ALS is associated with a better outcome and it has been reported that patients with raised LDL/HDL ratio have a significantly improved survival. However, opposing view is that body mass index and not dislipidaemia is an independent predictor of survival in ALS. Like in normal population, of similar age, deranged lipid profile is commonly seen in the patients with ALS. An obvious explanation of it is being a defence mechanism to provide energy substrates. Another possible explanation is being a result of metabolic dysregulation or mitochondrial and/or endoplasmic reticulum (ER) stress. Mitochondrial and ER stress have been implicated in the pathogenesis of ALS. If it is a defence mechanism, then patients with a raised lipid profile may show a better prognosis. If it is a reflection of mitochondrial/ER dysfunction, then it could be associated with a poor outcome.

    Objective To determine: 1. The prevalence (by gender) of raised lipid profile (cholesterol, LDH, triglycerides) in a large cohort of patients with ALS. 2. The relationship of lipid profile with the body mass index (BMI) through the ALS disease course. 3. Does hyperlipidaemia develops with the progression of the disease or may be an early observation? 4. What are the implications (if any) of a raised lipid profile (cholesterol, LDH, triglycerides) on disease outcome or prognosis?

    Methods This is a prospective observational cohort study consisting of 512 ALS patients, recruited for TRO19622 (Olesoxime) investigational medicinal product trial. Fasting serum concentrations of total cholesterol (TC), low density lipoprotein cholesterol (LDL–C) and high density lipoprotein cholesterol (HDL–C) were measured during follow–up.

    Results 73% of the participants had hypercholesterolaemia on the screening visit. The prevalence of hypercholesterolaemia decreased with time and was 64% at 18 months follow up. On univariate analysis total cholesterol, LDL–C and LDL/HDL ratio had a statistically significant effect on survival (p=0.015, 0.003 and 0.027 respectively). On multivariate analysis, however, none of the lipids were found to have a statistically significant effect on survival.

    Conclusions This study does not provide evidence for lipid profile to be an independent prognostic factor in ALS.

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