Related Experiment Video
Updated: Oct 9, 2025
Murine Left Anterior Descending LAD Coronary Artery Ligation: An Improved and Simplified Model for Myocardial Infarction
Published on: April 2, 2017
Stroke and Myocardial Infarction: A Bidirectional Mendelian Randomization Study
Wenxian Sun1, Luyang Zhang1, Weishi Liu1
1Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People's Republic of China.
Background:
Stroke and myocardial infarction (MI) are associated with each other, as demonstrated in observational studies. However, it is unclear whether this relationship is causal, and the purpose of this study was to explore the bidirectional causality between stroke and MI.
Methods:
Causality between stroke and MI was assessed using two-sample Mendelian randomization (MR). All genetic instruments related to stroke (40,585 cases; 406,111 controls) and MI (43,676 cases; 128,199 controls) were derived from large published genome-wide association study. The MR analysis was calculated with inverse-variance weighting, MR-Egger, weighted mode, weighted median, and simple mode methods, and sensitivity analyses are used to detect the heterogeneity or pleiotropy.
Results:
Genetically predicted large-artery stroke (LAS) was causally related to higher odds of MI (odds ratio [OR] = 1.13, 95% confidence interval [CI]: 1.06-1.20, p = 1.0×10-4), and the causal effect of LAS on MI was significantly weakened (OR = 1.09, 95% CI: 1.02-1.17, p = 0.017) after excluding the multipotent single-nucleotide polymorphisms (SNPs). MI phenotypes were genetically correlated with all ischemic strokes (OR = 1.15, 95% CI: 1.03-1.28, p = 0.013) and LAS (OR = 1.39, 95% CI: 1.14-1.71, p = 0.001); but a causal effect of MI on all ischemic strokes (OR = 1.00, 95% CI: 0.95-1.28, p = 0.219) and LAS (OR = 1.26, 95% CI: 0.93-1.69, p = 0.130) was not observed after excluding the multipotent SNPs.
Conclusion:
This MR analysis provides evidence to support the causal effect of LAS subtype on MI, and some factors act as confiding factors whereas others may act as mediators.
Insights
Large-artery stroke (LAS) causally increases myocardial infarction (MI) risk. While MI does not appear to cause stroke, understanding this link is crucial for cardiovascular health.
Area of Science:
- Cardiovascular epidemiology
- Genetic epidemiology
- Causal inference
Background:
- Observational studies suggest a link between stroke and myocardial infarction (MI).
- The causal nature of this association remains unclear.
- Bidirectional causality requires rigorous investigation.
Purpose of the Study:
- To investigate the bidirectional causal relationship between stroke and myocardial infarction (MI).
- To differentiate between association and causation using genetic data.
Main Methods:
- Two-sample Mendelian randomization (MR) was employed.
- Genetic instruments for stroke and MI were derived from large genome-wide association studies.
- Multiple MR methods and sensitivity analyses were used to ensure robustness.
Main Results:
- Genetically predicted large-artery stroke (LAS) showed a causal effect on increasing MI risk (OR = 1.13).
- MI phenotypes were genetically correlated with all ischemic strokes and LAS.
- No significant causal effect of MI on stroke subtypes was observed after sensitivity analyses.
Conclusions:
- Evidence supports a causal effect of large-artery stroke (LAS) on myocardial infarction (MI).
- Potential mediating or confounding factors warrant further investigation.
- Findings contribute to understanding the complex interplay between stroke and MI.
