Cardiovascular disease and diagnosis of amyotrophic lateral sclerosis: A population based study

Kioumourtzoglou, Marianthi-Anna; Seals, Ryan; Gredal, Ole; Mittleman, Murray A.; Hansen, Johnni; Weisskopf, Marc G.

doi:10.1080/21678421.2016.1208247

Cited by 24 publications

(23 citation statements)

References 27 publications

(40 reference statements)

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“…We estimated the risk of psychiatric disorders and CVD before ALS diagnosis date in those with ALS and their matched controls (table 4). We found an increased risk of CVD (RR) of (1.21; 95% CI, 1.15-1.27, p = 6 × 10 −15 ) in those with ALS compared with those without (as previously reported 16 ), but the increased risk was not significant for MI (RR = 1.08; 95% CI, 0.96-1.22, p = 0.19). We also found an increased risk of all psychiatric disorders (RR = 1.18; 95% CI, 1.09-1.29, p = 1.3 × 10 −4 ) likely reflecting an increased risk in affective disorders excluding bipolar disorder (RR = 1.20; 95% CI, 1.03-1.40, p = 0.019).…”

Section: Cross-trait Analyses Within Individual and For Relativessupporting

confidence: 78%

“…By contrast, we found no increase in the rate of CVD among relatives of those with ALS, despite high rates in firstdegree relatives of both the cases and controls (;35%). This may suggest broad lifestyle factors, rather than a genetic relationship, and explain the observed increased rates of CVD in those with ALS, 16 which would be consistent with the genetic correlation estimates from GWAS data between ALS and CVD that were not different from zero. 15 Alternatively, the high rate of CVD recorded before ALS diagnosis may reflect the increased medical surveillance in those in the early stages of disease.…”

Section: Discussionsupporting

confidence: 58%

“…32 We found increased rates of recorded cardiovascular disease (CVD) before diagnosis of ALS (RR = 1.21; 95% CI, 1.15-1.27), as previously reported. 16 This association, however, was not detected in the narrow definition of heart disease; MI. By contrast, we found no increase in the rate of CVD among relatives of those with ALS, despite high rates in firstdegree relatives of both the cases and controls (;35%).…”

Section: Discussionmentioning

confidence: 97%

“…14 By contrast, the estimated genetic correlation with cardiovascular disease (CVD) was not different from zero, 15 despite increased rates of CVD in those with ALS. 16 Here, we apply genetic epidemiology approaches to population records of ALS from Denmark with the objective to provide independent evidence for genetic associations between ALS and other disorders.…”

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confidence: 99%

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ALS in Danish Registries

et al. 2020

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ObjectiveTo investigate the genetic contribution to amyotrophic lateral sclerosis (ALS) and the phenotypic and genetic associations between ALS and psychiatric and cardiovascular disorders (CVD) we used the national registry data from Denmark linked to first-degree relatives to estimate heritability and cross-trait parameters.MethodsALS cases and 100 sex and birth-matched controls per case from the Danish Civil Registration System were linked to their records in the Danish National Patient Registry. Cases and controls were compared for (1) risk of ALS in first-degree relatives, used to estimate heritability, (2) comorbidity with psychiatric disorders and CVD, and (3) risk of psychiatric disorders and CVD in first-degree relatives.Results5,808 ALS cases and 580,800 controls were identified. Fifteen percent of cases and controls could be linked to both parents and full siblings, whereas 70% could be linked to children. (1) We estimated the heritability of ALS to be 0.43 (95% CI, 0.34–0.53). (2) We found increased rates of diagnosis of mental disorders (risk ratio = 1.18; 95% CI, 1.09–1.29) and CVD in those later diagnosed with ALS. (3) In first-degree relatives of those with ALS, we found increased rate of schizophrenia (1.17; 95% CI, 0.96–1.42), but no evidence for increased risk CVD.ConclusionsHeritability of ALS is lower than commonly reported. There is likely a genetic relationship between ALS and schizophrenia, and a nongenetic relationship between ALS and CVD.

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Section: Cross-trait Analyses Within Individual and For Relativessupporting

confidence: 78%

Section: Discussionsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

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ALS in Danish Registries

et al. 2020

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“…Previous epidemiological studies have explored the role of blood lipids in the pathogenesis of ALS. These observational studies have yielded controversial results, with many reporting that hyperlipidemia increases disease risk and others suggesting the opposite . In addition to being underpowered, much of this previous research was based on blood‐lipid profiles obtained after diagnosis of ALS when ancillary factors may be influencing these levels …”

Section: Discussionmentioning

confidence: 99%

Shared polygenic risk and causal inferences in amyotrophic lateral sclerosis

Bandrés‐Ciga

Noyce

Hemani

et al. 2019

Annals of Neurology

130

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Objective: To identify shared polygenic risk and causal associations in amyotrophic lateral sclerosis (ALS). Methods: Linkage disequilibrium score regression and Mendelian randomization were applied in a large-scale, datadriven manner to explore genetic correlations and causal relationships between >700 phenotypic traits and ALS. Exposures consisted of publicly available genome-wide association studies (GWASes) summary statistics from MR Base and LD-hub. The outcome data came from the recently published ALS GWAS involving 20,806 cases and 59,804 controls. Multivariate analyses, genetic risk profiling, and Bayesian colocalization analyses were also performed. Results: We have shown, by linkage disequilibrium score regression, that ALS shares polygenic risk genetic factors with a number of traits and conditions, including positive correlations with smoking status and moderate levels of physical activity, and negative correlations with higher cognitive performance, higher educational attainment, and light levels of physical activity. Using Mendelian randomization, we found evidence that hyperlipidemia is a causal risk factor for ALS and localized putative functional signals within loci of interest. Interpretation: Here, we have developed a public resource (https://lng-nia.shinyapps.io/mrshiny) which we hope will become a valuable tool for the ALS community, and that will be expanded and updated as new data become available. Shared polygenic risk exists between ALS and educational attainment, physical activity, smoking, and tenseness/ restlessness. We also found evidence that elevated low-desnity lipoprotein cholesterol is a causal risk factor for ALS. Future randomized controlled trials should be considered as a proof of causality.

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Erythrocytes' surface properties and stiffness predict survival and functional decline in ALS patients

Lopes,

Pronto‐Laborinho,

Conceição

et al. 2023

BioFactors

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Erythrocytes play a fundamental role in oxygen delivery to tissues and binding to inflammatory mediators. Evidences suggest that dysregulated erythrocyte function could contribute to the pathophysiology of several neurodegenerative diseases. We aimed to evaluate changes in morphological, biomechanical, and biophysical properties of erythrocytes from amyotrophic lateral sclerosis (ALS) patients, as new areas of study in this disease. Blood samples were collected from ALS patients, comparing with healthy volunteers. Erythrocytes were assessed using atomic force microscopy (AFM) and zeta potential analysis. The patients' motor and respiratory functions were evaluated using the revised ALS Functional Rating Scale (ALSFRS‐R) and percentage of forced vital capacity (%FVC). Patient survival was also assessed. Erythrocyte surface roughness was significantly smoother in ALS patients, and this parameter was a predictor of faster decline in ALSFRS‐R scores. ALS patients exhibited higher erythrocyte stiffness, as indicated by reduced AFM tip penetration depth, which predicted a faster ALSFRS‐R score and respiratory subscore decay. A lower negative charge on the erythrocyte membrane was predictor of a faster ALSFRS‐R and FVC decline. Additionally, a larger erythrocyte surface area was an independent predictor of lower survival. These changes in morphological and biophysical membrane properties of ALS patients' erythrocytes, lead to increased cell stiffness and morphological variations. We speculate that these changes might precipitate motoneurons dysfunction and accelerate disease progression. Further studies should explore the molecular alterations related to these observations. Our findings may contribute to dissect the complex interplay between respiratory function, tissue hypoxia, progression rate, and survival in ALS.

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Cardiovascular disease and diagnosis of amyotrophic lateral sclerosis: A population based study

Cited by 24 publications

References 27 publications

ALS in Danish Registries

ALS in Danish Registries

Shared polygenic risk and causal inferences in amyotrophic lateral sclerosis

Erythrocytes' surface properties and stiffness predict survival and functional decline in ALS patients

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