title: Beneficial vascular risk profile is associated with amyotrophic lateral sclerosis.
abstract: OBJECTIVE
  Reports of increased amyotrophic lateral sclerosis (ALS) with hyperlipidaemia and elevated plasma homocysteine levels as well as cigarette-smoking and polymorphisms in angiogenic genes suggest a role for altered vascular homeostasis in ALS pathogenesis. The authors assessed the association between vascular risk factors and ALS.
  
  
  METHODS
  Traditional cardiovascular risk factors (smoking, hypertension, hypercholesterolaemia, diabetes and body mass index (BMI)) and cardiovascular disease prior to ALS onset established by a questionnaire were compared in 334 patients and 538 age- and sex-matched controls. Biochemical assessments (total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), hs-CRP, and homocysteine) at diagnosis were measured in blood samples of 303 patients with ALS and compared with prospectively collected data from 2100 population-based controls.
  
  
  RESULTS
  Patients with ALS used cholesterol-lowering agents less frequently (OR=0.6, p=0.008) and had a lower BMI (OR=0.9, p=0.001), a lower LDL/HDL ratio (women: OR=0.5, p<0.001; men: OR=0.4, p<0.001) and lower homocysteine levels (women: OR=0.9, p=0.02; men: OR=0.9, p<0.001). The mean LDL and TC levels were significantly lower among patients with a lower functional vital capacity percentage of predicted (FVC). In the univariate analysis, a higher LDL/HDL ratio correlated with increased survival (HR=0.9, p=0.04); after adjusting for the confounders age, site and FVC, no difference was observed.
  
  
  CONCLUSIONS
  Vascular risk factors, measured clinically and biochemically, were not associated with increased ALS. Instead, patients reported less use of cholesterol-lowering medication and had a lower premorbid BMI and favourable lipid profile-all findings consistent with the hypothesis that a higher metabolic rate plays a role in ALS.
authors.affiliation: Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: N A
authors.initials: NA
authors.lastname: Sutedja
authors.forename: Y T
authors.initials: YT
authors.lastname: van der Schouw
authors.forename: K
authors.initials: K
authors.lastname: Fischer
authors.forename: E M
authors.initials: EM
authors.lastname: Sizoo
authors.forename: M H B
authors.initials: MH
authors.lastname: Huisman
authors.forename: J H
authors.initials: JH
authors.lastname: Veldink
authors.forename: L H
authors.initials: LH
authors.lastname: Van den Berg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood* / Q000150:complications / Q000401:mortality*; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood* / Q000150:complications; D002784:Cholesterol / Q000097:blood; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D057566:Self Report; D012907:Smoking / Q000009:adverse effects
chemical_list: D006710:Homocysteine; D002097:C-Reactive Protein; D002784:Cholesterol