Smoking, high BMI drive relationship between PAD, major depressive disorder
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Key takeaways:
- Genetic major depressive disorder was linked to genetic liability for PAD.
- The association between genetic depression and PAD was entirely attenuated when adjusted for lifetime smoking and BMI.
The elevated propensity for peripheral artery disease in patients with major depression may be mediated by increased liability for lifetime smoking and BMI, according to research in the Journal of the American Heart Association.
Genetic liability for major depressive disorder was not linked to tendency for elevated alcohol intake, researchers reported.
“According to the World Health Organization, major depressive disorder is the leading cause of disability in the world affecting [more than] 300 million people. Multiple observational studies have linked depression and depressive symptoms to PAD and PAD outcomes, suggesting a comorbid nature between the two diseases,” Gabrielle Shakt, BS, of the department of surgery at the Corporal Michael J. Crescenz VA Medical Center in Philadelphia, and colleagues wrote. “Despite the observational evidence linking major depressive disorder to PAD and its risk factors, causal evidence for these associations is lacking.”
Shakt and colleagues conducted the present study using Mendelian randomization to test for causal associations between genetic propensity for major depressive disorder and that of PAD.
The study was conducted in three stages. In the first stage, the researchers tested the association between genetic liability for major depressive disorder and genetic liability for PAD; in the second stage, they tested for intermediaries linking major depressive disorder and PAD; and in the third stage, the researchers tested the independent association between genetic liability for major depressive disorder and genetic liability for PAD, adjusting for intermediaries identified in the second stage.
Data on major depressive disorder were acquired from the large Psychiatric Genomics Consortium analysis of more than 135,000 patients. PAD data were acquired from a genome- wide association study in the Veterans Affairs’ Million Veteran Program, which included 31,307 patients with PAD.
In the first stage of the study, Shakt and colleagues reported that genetic liability for major depressive disorder was associated with increased liability for PAD (OR = 1.17; 95% CI, 1.06-1.29; P = 2.64 x 10–3).
In the second stage, genetic liability for major depressive disorder was associated with increased genetically determined lifetime smoking (beta = 0.11; 95% CI, 0.078-0.14; P = 1.2 x 10–12) and BMI (beta = 0.1; 95% CI, 0.02-0.19; P = 1.8 x 10–2), which were each associated with genetic liability for PAD (OR for smoking = 2.81; 95% CI, 2.28-3.47; P = 9.8 x 10–22; OR for BMI = 1.61; 95% CI, 1.52-1.7; P = 1.3 x 10–57).
Genetic liability for major depressive disorder was not associated with elevated alcohol intake (beta = 0.078; 95% CI, 0.15 to 0; P = .043), which was therefore not linked to elevated liability for PAD (OR = 0.77; 95% CI, 0.66-0.88; P = 1.8 x 10–4).
In the third stage, after controlling for lifetime smoking, alcohol intake and BMI, the association between genetic liability for major depressive disorder and genetic liability for PAD was completely attenuated.
“As many as one in five individuals presenting with PAD have comorbid depression, which is associated with worse limb outcomes and higher all-cause mortality,” the researchers wrote. “Our results suggest that both addressing underlying depression and mental health, as well as addressing risk factors that are exacerbated by depression, offer opportunities to reduce the risk of PAD and improve patient outcomes.”
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