Stroke: Cardiogenic risk factors for ischemic stroke

Cardiac disease is one of the major risk factors for stroke, and central atrial fibrillation (AF) and coronary artery disease (CAD) are representatives of systemic arteriosclerosis with indisputable roles
.

Recent observational studies suggest that other cardiac features, such as atrial cardiopathy, are also involved in stroke management
.
However, causal inference of observational findings remains controversial, with concerns about possible confounding, reverse causality, and other biases

Mendelian randomization (MR) can clarify potential causal relationships based on genetic data
.
Compared with observational studies, MR, especially multivariate MR, is less susceptible to confounding because genetic variants are randomly assigned at conception

With this, Simon Frerich et al.
from the University of Munich conducted a large-scale, systematic MR study of cardiac traits and their impact on stroke and stroke subtypes
.

They studied 66 cardiac traits, including cardiovascular disease, magnetic resonance imaging-derived cardiac imaging, echocardiographic imaging, and ECG measurements, and blood biomarkers by Mendelian randomization in 2 samples
.
In data from the MEGASTROKE consortium (40 585 cases/406 111 controls), the association of genetic predisposition for each trait with risk of stroke and stroke subtypes was explored

They observed a strong independent association between genetic susceptibility to atrial fibrillation and myocardial infarction stroke, as well as an association between genetic susceptibility to coronary artery disease as a proxy for atherosclerosis and large artery stroke
.

These data-driven analyses further suggest that a genetic predisposition to heart failure and lower resting heart rate is associated with stroke
.
However, these associations were explained by atrial fibrillation, coronary artery disease, and systolic blood pressure in multivariate analysis

Genetically predicted P-wave terminal force of V1, an ECG marker for atrial heart disease, was inversely associated with large-artery stroke
.

The significance of this study is its finding that existing genetic data do not support a substantial impact of cardiac characteristics on stroke
risk beyond known clinical risk factors .
These findings underscore the need to carefully control for confounders and other potential biases when investigating candidate cardiac risk factors for stroke

Original source:
[Frerich S, Malik R, Georgakis MK, et al.
Cardiac Risk Factors for Stroke: A Comprehensive Mendelian Randomization Study.
Stroke.