Cardiac Troponin I and Risk of Stroke: A Mendelian Randomization Study

Area of Science:

• Cardiovascular Medicine
• Neurology
• Genetics

Background:

• Cardiac troponin I (cTnI) is a recognized biomarker for predicting stroke, particularly in individuals with pre-existing heart conditions.
• The precise causal link between circulating cTnI levels and the incidence of stroke remains incompletely understood.

Purpose of the Study:

• To investigate the potential causal effect of genetically predicted circulating cTnI levels on the risk of stroke and its various subtypes using Mendelian Randomization.
• To clarify the role of cTnI in stroke etiology, differentiating between direct causal effects and associations influenced by other risk factors.

Main Methods:

• Mendelian Randomization (MR) analysis was performed using summary-level data from genome-wide association studies.
• Single-nucleotide polymorphisms (SNPs) robustly associated with cTnI levels served as instrumental variables.
• Inverse-variance weighted (IVW) method was the primary analysis, supplemented by sensitivity and multivariable MR analyses to ensure result validity.

Main Results:

• Genetically elevated plasma cTnI showed a potential causal association with cardioembolic stroke (CES) (OR, 1.58; P = 0.003), though sensitivity analyses yielded broader confidence intervals.
• The association between cTnI and CES was attenuated after adjusting for atrial fibrillation and smoking, suggesting these factors mediate the effect.
• No significant causal effect of cTnI was observed for overall stroke risk or other stroke subtypes, including ischemic stroke, large artery stroke, small vessel stroke, and intracerebral hemorrhage.

Conclusions:

• This Mendelian Randomization study provides limited evidence for a direct causal relationship between increased serum cTnI levels and a higher risk of stroke.
• The findings suggest that the observed association between cTnI and stroke may be confounded by other factors like atrial fibrillation and smoking.