In a recent innovative study, researchers have uncovered compelling evidence suggesting a potential causal relationship between Major Depressive Disorder (MDD) and Peripheral Artery Disease (PAD). Employing advanced genetic analysis techniques, the research sheds light on the intricate interplay between mental health and cardiovascular outcomes, emphasizing the importance of a holistic approach to disease management. The study suggests that effective interventions for cardiovascular diseases, including PAD, may necessitate a combined focus on both physical and mental health.

The study results were published in the Journal of The American Heart Association.
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Major depressive disorder (MDD) has been recognized as a contributing risk factor for various cardiovascular diseases. While observational findings have associated MDD with peripheral artery disease (PAD), there is a lack of conclusive causal evidence establishing this relationship. Hence researchers conducted a study to test the association between genetic liability for MDD and genetic liability for PAD. The study utilized Inverse Variance Weighted 2‐Sample Mendelian Randomization, a method that employs genetic information to explore causation rather than relying solely on observational data.
Findings:
The findings revealed a significant association between genetic predisposition for MDD and an increased likelihood of genetic susceptibility to PAD, with an odds ratio of 1.17 (95% CI, 1.06–1.29) and a p-value of 2.6×10^−3.
However, the research delved deeper, uncovering intermediate risk factors that appear to play a crucial role in this relationship.
Genetic predisposition for MDD was found to be linked to several lifestyle factors, including an increased genetic propensity for lifetime smoking (β=0.11; P=1.2×10^−12), reduced alcohol intake (β=−0.078; P=0.043), and elevated body mass index (β=0.10; P=1.8×10^−2).
These intermediate risk factors, in turn, were individually associated with an elevated risk of PAD.
Smoking, for instance, showed a substantial odds ratio of 2.81 (95% CI, 2.28–3.47; P=9.8×10^−22), while reduced alcohol intake exhibited a protective effect with an odds ratio of 0.77 (95% CI, 0.66–0.88; P=1.8×10^−4).
Similarly, an increased body mass index was associated with a heightened odds ratio of 1.61 (95% CI, 1.52–1.7; P=1.3×10^−57).
To further validate the causal link between MDD and PAD, researchers employed multivariable Mendelian randomization, controlling for the intermediate risk factors.
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Remarkably, the association between genetic predisposition for MDD and PAD was entirely attenuated, highlighting the pivotal role of these lifestyle factors in mediating the relationship. These findings carry significant implications for the field of cardiovascular health, emphasizing the need for a comprehensive approach to disease management. The study suggests that effective interventions for cardiovascular diseases, including PAD, may necessitate a combined focus on both physical and mental health. By addressing not only the cardiovascular risk factors but also the mental health components, healthcare professionals may enhance the overall efficacy of preventive and therapeutic strategies. In conclusion, this study adds a new dimension to our understanding of the complex relationship between depression and cardiovascular health. By unraveling the genetic and lifestyle factors at play, it paves the way for future research and underscores the importance of an integrated approach to healthcare that considers both mental and physical well-being.
Further reading: Major Depressive Disorder Impacts Peripheral Artery Disease Risk Through Intermediary Risk Factors. Doi: https://doi.org/10.1161/JAHA.123.030233