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Introduction
Studies on angiogenic factors have suggested a role for altered vascular homeostasis in amyotrophic lateral sclerosis (ALS) pathogenesis. In several human populations, vascular endothelial growth factor (VEGF) haplotypes associated with low VEGF levels are more prevalent among ALS patients, and mice expressing reduced VEGF levels develop motor neuron degeneration. 1-3 Moreover, the functionally similar angiogenin has been associated with ALS. 4-6 Vasculature damage may be an early pathological event leading to motor neuron degeneration in the transgenic mutated SOD1 mouse model of ALS. 7
Findings have suggested vascular risk factors to contribute to neurodegeneration in Alzheimer's disease. 8-11 Only one study examined the presence of multiple vascular risk factors in ALS patients 12 but remained inconclusive owing to a small study size. Other studies have focused on blood levels of specific vascular parameters: reports of higher plasma homocysteine 13 and higher lipid 14 levels seem to suggest atherogenic risk factors in ALS; however, the lack of association between lipid levels and ALS in a more recent study was not able to reinforce this hypothesis. 15 Moreover, the implication of the protective effect of higher lipid levels on disease progression found in one study, 14 but not in another study, 15 requires further elucidation. These different results have been suggested to be partly explained by an association of lower lipid status with lower respiratory function. 15
The aim of the present study was to assess the hypothesis that a higher risk profile for vascular disease, measured by clinical and biochemical indicators, was associated with susceptibility for developing ALS and to assess the association with survival in patients, after adjusting for confounders.
Methods
Patients
Between 1 July 2004 and 1 July 2009, patients diagnosed as having sporadic ALS at the University Medical Centre Utrecht, a tertiary referral clinic in The Netherlands, were recruited. Diagnosis was made according to the El Escorial Criteria after exclusion of other conditions. Patients diagnosed as having possible, probable or definite ALS according to the El Escorial criteria were included. The age and site of onset of disease were recorded. The onset of disease was defined as the time of initial weakness, dysarthria or dysphagia. The study protocol was approved by the institutional ethical committee of the University Medical Centre Utrecht.
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