Multiple Sclerosis and the Risk of Cardiovascular Diseases: A Mendelian Randomization Study

Abstract

BackgroundObservational studies suggested that multiple sclerosis (MS) is associated with cardiovascular diseases (CVDs). However, the causal association has not been fully elucidated. Thus, we aim to assess the causality of the associations of MS with risk of CVDs.MethodsA two-sample Mendelian randomization (MR) study was performed to explore the causality. Genetic instruments were identified for MS from a genome-wide association study (GWAS) involving 115,803 individuals. Summary-level data for CVDs were obtained from different GWAS meta-analysis studies. MR analysis was conducted mainly using the inverse-variance weighted (IVW) method. Sensitivity analyses were further performed to ensure the robustness of the results.ResultsThis MR study found suggestive evidence that genetic liability to MS was associated with an increased risk of coronary artery disease (CAD) [odds ratio (OR), 1.02; 95% confidence interval (CI), 1.00–1.04; p = 0.03], myocardial infarction (MI) (OR, 1.03; 95% CI, 1.00–1.06; p = 0.01), heart failure (HF) (OR, 1.02; 95% CI, 1.00–1.04; p = 0.02), all-cause stroke (AS) (OR, 1.02; 95% CI, 1.00–1.05; p = 0.02), and any ischemic stroke (AIS) (OR, 1.02; 95% CI, 1.00–1.05; p = 0.04). The null-association was observed between MS and the other CVDs. Further analyses found little evidence of pleiotropy.ConclusionsWe provided suggestive genetic evidence for the causal associations of MS with increased risk of CAD, MI, HF, AS, and AIS, which highlighted the significance of active monitoring and prevention of cardiovascular risk to combat cardiovascular comorbidities in MS patients.

Etiology, effects and management of comorbidities in multiple sclerosis: recent advances

“…Recent evidence suggests that MS may directly cause some comorbidities, as identified using Mendelian randomization methods. One study suggested a causal effect of MS on lung cancer (odds ratio [OR] 1.07, p=0.0082) ( 19 ) and cardiovascular diseases, including IHD (OR 1.02, p=0.03) and myocardial infarction ( 25 , 26 ), but conflicting evidence for stroke ( 25 , 26 ). These findings are consistent with observations that the increased risk of IHD in persons with MS is not fully explained by traditional vascular risk factors ( 11 ).…”

Genetically predicted blood pressure, antihypertensive drugs and risk of heart failure: a Mendelian randomization study

“…For each study, further details of definitions used to assess heart failure status have been published previously [15] (Supplementary Table S2, http://links.lww.com/HJH/C74). The GWAS was used in many Mendelian randomization studies [23,24].…”

“…The GWAS [15] (Supplementary Table S2, http://links.lww.com/HJH/C74). The GWAS was used in many Mendelian randomization studies [23,24].…”

Antiplatelet drugs: Potential therapeutic options for the management of neurodegenerative diseases

“…Still, the recent finding establishes a strong association with cardiovascular diseases like myocardial infarction, heart failure, atrial fibrillation, and ischemic stroke. 33 As a pivotal contributor to cardiovascular impairments, the blood platelets significantly modulate the pathophysiology of MS. For example, an increased number of hyperactivated platelets expressing surface exposure of P-selectin are observed in the demyelinating lesions of the inflamed brain and spinal cord of MS patients. 15 Activated platelets in the brain may provide an additional source for the production of reactive oxygen species (ROS) as well as reactive nitrogen species (RNS).…”