Article Text
Abstract
Objective To investigate the theory of premorbid fitness in amyotrophic lateral sclerosis (ALS), we studied whether a common genetic profile for physical or cardiovascular fitness was manifest in progenitors leading to less cardiovascular death and a longer lifespan in parents of patients with ALS compared with parents of controls.
Methods Patient and disease characteristics, levels of physical activity, parental cause and age of death were obtained using a structured questionnaire from a population-based, case–control study of ALS in the Netherlands. Logistic regression was used for the analyses of parental cause of death and levels of physical activity. Cox proportional hazard models were applied to study the association between parental survival and ALS, or specific patient subgroups. All models were adjusted for age at inclusion, level of education, body mass index, diabetes, hypercholesterolaemia and hypertension.
Results 487 patients and 1092 controls were included. Parents of patients died less frequently from a cardiovascular disease compared with parents of controls (OR=0.78, p=0.009). Their survival, however, was neither significantly longer nor shorter. Neither rates of cardiovascular causes of death, nor survival of parents was related to the extent to which patients were physically active in leisure time (all p>0.05).
Conclusions Exploring the fitness hypothesis in the pathogenesis of ALS, our findings provide evidence for a shared mechanism underlying a favourable cardiovascular fitness profile and ALS susceptibility.
- Amyotrophic lateral sclerosis
- case-control studies
- epidemiology
- cardiovascular
- fitness
- motor neuron disease
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Footnotes
Funding This work was supported by the Netherlands ALS Foundation. LHvdB received a grant from the Netherlands Organisation for Health Research and Development (Vici scheme).
Competing interests AEV: Drafting the manuscript for content, including medical writing for content; study concept or design; analysis or interpretation of data; acquisition of data; statistical analysis. MS, AFCH, JAdG, AJvdK, JR, JHV: Revising the manuscript for content, including medical writing for content; study concept or design; acquisition of data. LHvdB: Revising the manuscript for content, including medical writing for content; study concept or design; analysis or interpretation of data; study supervision or coordination; obtaining funding.
Provenance and peer review Not commissioned; externally peer reviewed.
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