The following is a summary of “Appraising the Causal Role of Risk Factors in Coronary Artery Disease and Stroke: A Systematic Review of Mendelian Randomization Studies,” published in the October 2023 issue of Cardiology by Georgiou et al.

The systematic review delved into Mendelian randomization (MR) studies, offering a robust method to explore potential causal links between various exposures and health outcomes like coronary artery disease and stroke. This comprehensive assessment aimed to consolidate and assess the evidence gleaned from prior MR investigations.

The review encompassed MR studies investigating genetically predicted exposures and their correlation with coronary artery disease or stroke. From the array of associations scrutinized, totaling 2,725, involving 535 diverse exposures, outcomes were classified into four categories, robust, probable, suggestive, and insufficient, based on the significance of the primary MR analysis and its coherence with sensitivity analyses. Among the vast pool of associations, 141 were deemed robust, 353 probable, and 110 suggestive, while evidence for 926 was insufficient. Notably, the strongest associations were evident between anthropometric traits, lipids, and lipoproteins, alongside type 2 diabetes with coronary artery disease. Additionally, clinical measurements with coronary artery disease and stroke and thrombotic factors with stroke showed noteworthy associations.

However, despite the extensive research efforts, only a few associations exhibited robust evidence, signaling a need for further comprehensive investigations. While nearly half of the studies reported associations and conducted MR sensitivity analyzes alongside the primary analysis, offering additional support for causality, the review underscores the necessity for more exhaustive evaluations in future research endeavors. These should encompass thorough assessments of sensitivity MR analyses and explore mediation effects or nonlinear associations to fortify the existing evidence base in this domain.

Source: ahajournals.org/doi/10.1161/JAHA.122.029040