Systemic inflammation and subsequent risk of amyotrophic lateral sclerosis: prospective cohort study
Systemic inflammation and subsequent risk of amyotrophic lateral sclerosis: prospective cohort study
Background: while systemic inflammation has been implicated in the etiology of selected neurodegenerative disorders, its role in the development of amyotrophic lateral sclerosis (ALS), a condition with high case-fatality, is untested. Accordingly, we quantified the relationship of C-reactive protein (CRP), an acute-phase reactant and marker of systemic inflammation, with subsequent ALS occurrence.
Methods: we used data from UK Biobank, a prospective cohort study of 502,649 participants who were aged 37 to 73 years when examined at research centers between 2006 and 2010. Venous blood was collected at baseline in the full cohort and assayed for CRP, and repeat measurement was made 3-7 years later in a representative subgroup (N = 14,514) enabling correction for regression dilution. ALS was ascertained via national hospitalization and mortality registries until 2021. We computed multivariable hazard ratios with accompanying 95% confidence intervals for log-transformed CRP expressed as standard deviation and tertiles.
Results: in an analytical sample of 400,884 initially ALS-free individuals (218,203 women), a mean follow-up of 12 years gave rise to 231 hospitalizations and 223 deaths ascribed to ALS. After adjustment for covariates which included health behaviors, comorbidity, and socio-economic status, a one standard deviation higher log-CRP was associated with elevated rates of both ALS mortality (hazard ratios; 95% confidence intervals: 1.32; 1.13, 1.53) and hospitalizations (1.20; 1.00, 1.39). There was evidence of dose-response effects across tertiles of CRP for both outcomes (p for trend ≤ 0.05). Correction for regression dilution led to a strengthening of the relationship with CRP for both mortality (1.62; 1.27, 2.08) and hospitalizations (1.37; 1.05, 1.76).
Conclusions: higher levels of CRP, a blood-based biomarker widely captured in clinical practice, is associated with moderately increased future risk of amyotrophic lateral sclerosis.
Humans, Female, Amyotrophic Lateral Sclerosis/epidemiology, Prospective Studies, Biomarkers, C-Reactive Protein/metabolism, Inflammation/complications
46-51
Batty, G. David
894f5dad-375f-40b6-8936-d9143b49f169
Kivimäki, Mika
a5788d83-a59c-477e-9ae9-8b7896ed098a
Frank, Philipp
f6be60a4-15f0-41ce-a206-a6d10a84dcf7
Gale, Catharine R.
5bb2abb3-7b53-42d6-8aa7-817e193140c8
Wright, Liam
70a57885-1db5-4ae1-af6b-70e8f4bd8e75
11 August 2023
Batty, G. David
894f5dad-375f-40b6-8936-d9143b49f169
Kivimäki, Mika
a5788d83-a59c-477e-9ae9-8b7896ed098a
Frank, Philipp
f6be60a4-15f0-41ce-a206-a6d10a84dcf7
Gale, Catharine R.
5bb2abb3-7b53-42d6-8aa7-817e193140c8
Wright, Liam
70a57885-1db5-4ae1-af6b-70e8f4bd8e75
Batty, G. David, Kivimäki, Mika, Frank, Philipp, Gale, Catharine R. and Wright, Liam
(2023)
Systemic inflammation and subsequent risk of amyotrophic lateral sclerosis: prospective cohort study.
Brain, Behavior, and Immunity, 114, .
(doi:10.1016/j.bbi.2023.07.026).
Abstract
Background: while systemic inflammation has been implicated in the etiology of selected neurodegenerative disorders, its role in the development of amyotrophic lateral sclerosis (ALS), a condition with high case-fatality, is untested. Accordingly, we quantified the relationship of C-reactive protein (CRP), an acute-phase reactant and marker of systemic inflammation, with subsequent ALS occurrence.
Methods: we used data from UK Biobank, a prospective cohort study of 502,649 participants who were aged 37 to 73 years when examined at research centers between 2006 and 2010. Venous blood was collected at baseline in the full cohort and assayed for CRP, and repeat measurement was made 3-7 years later in a representative subgroup (N = 14,514) enabling correction for regression dilution. ALS was ascertained via national hospitalization and mortality registries until 2021. We computed multivariable hazard ratios with accompanying 95% confidence intervals for log-transformed CRP expressed as standard deviation and tertiles.
Results: in an analytical sample of 400,884 initially ALS-free individuals (218,203 women), a mean follow-up of 12 years gave rise to 231 hospitalizations and 223 deaths ascribed to ALS. After adjustment for covariates which included health behaviors, comorbidity, and socio-economic status, a one standard deviation higher log-CRP was associated with elevated rates of both ALS mortality (hazard ratios; 95% confidence intervals: 1.32; 1.13, 1.53) and hospitalizations (1.20; 1.00, 1.39). There was evidence of dose-response effects across tertiles of CRP for both outcomes (p for trend ≤ 0.05). Correction for regression dilution led to a strengthening of the relationship with CRP for both mortality (1.62; 1.27, 2.08) and hospitalizations (1.37; 1.05, 1.76).
Conclusions: higher levels of CRP, a blood-based biomarker widely captured in clinical practice, is associated with moderately increased future risk of amyotrophic lateral sclerosis.
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Accepted/In Press date: 30 July 2023
e-pub ahead of print date: 4 August 2023
Published date: 11 August 2023
Keywords:
Humans, Female, Amyotrophic Lateral Sclerosis/epidemiology, Prospective Studies, Biomarkers, C-Reactive Protein/metabolism, Inflammation/complications
Identifiers
Local EPrints ID: 490520
URI: http://eprints.soton.ac.uk/id/eprint/490520
ISSN: 0889-1591
PURE UUID: 6af5cbda-d326-40c3-89e6-e2c6b7569b02
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Date deposited: 29 May 2024 16:44
Last modified: 30 May 2024 01:34
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Contributors
Author:
G. David Batty
Author:
Mika Kivimäki
Author:
Philipp Frank
Author:
Liam Wright
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