Abstract
ObjectivesObservational studies have shown that elevated circulating cardiac troponin I (cTnI) concentrations were linked to higher risk of stroke and atrial fibrillation, but the causality remains unclear. Therefore, we used mendelian randomization to assess the potential causal effects of cTnI concentrations on the risk of stroke, its subtypes and atrial fibrillation. Materials and methodsThe instrumental variables for circulating cTnI concentrations were selected from a genome-wide association study meta-analysis of 48,115 European individuals. We examined the associations of circulating cTnI concentrations with stroke, ischemic stroke, ischemic stroke subtypes (cardioembolic, large artery, small vessel stroke), intracerebral hemorrhage and atrial fibrillation. ResultsGenetically predicted elevated circulating cTnI concentrations were associated with higher risk of cardioembolic stroke (odds ratio [OR], 1.80; 95% confidence interval [CI], 1.20–2.68; P = 0.004), but not associated with large artery stroke, small vessel stroke, total stroke, ischemic stroke and intracerebral hemorrhage. Additionally, we also found that elevated cTnI concentrations were causally linked to higher risk of atrial fibrillation (OR, 1.30; 95% CI, 1.10–1.53; P = 0.003). ConclusionsThis study provides evidence that genetically predicted circulating cTnI concentrations are causally linked to higher risk of cardioembolic stroke and atrial fibrillation.
Highlights
Stroke is a common cause of death and disability worldwide
The single nucleotide polymorphisms (SNPs) rs8039472 was used as a proxy for rs8024538 (r2 = 0.92), because rs8024358 was not available in the stroke ((total stroke, ischemic stroke (IS), IS subtypes and intracerebral hemorrhage (ICH)) outcome dataset
Mendelian randomization (MR)-PRESSO identified a outlier for CES outcome (Supplementary Table 2), and no outlier was identified for other stroke outcome (LAS, SVS, stroke, IS and ICH)
Summary
Stroke is a common cause of death and disability worldwide. many risk factors for stroke have been established, a substantial proportion of stroke risk factors remain unknown.[16]. Much of the available evidence for the causal association between cTnI concentrations and risk of stroke comes from observational studies, which may be affected by confounding and reverse causality. Whether cTnI concentrations are causally associated with the risk of stroke remains unknown. Observational studies have shown that elevated circulating cardiac troponin I (cTnI) concentrations were associated with higher risk of stroke and atrial fibrillation, but the causality remains unclear. We conducted a two-sample mendelian randomization study to evaluate the causal effects of cTnI concentrations on the risk of stroke subtypes and atrial fibrillation
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