Genetic Liability for Chronic Pain Associated With Coronary Artery Disease Risk

A Mendelian randomization analysis found that multisite chronic pain increased risk for coronary artery disease (CAD) and that the relationship was partially mediated by body mass index (BMI), smoking, and depression. These findings were published in Pain.

Investigators from Hangzhou Medical College in China sourced data for this study from the UK Biobank. They first evaluated the relationship between multisite chronic pain and CAD, atrial fibrillation, and stroke. The cardiovascular diseases that were found to have a relationship with chronic pain were then evaluated for causal effects and potential mediators using data from 387,649 individuals.

High genetic liability for multisite chronic pain was found to be associated with increased risk for CAD (odds ratio [OR], 1.52; 95% CI, 1.19-1.95). No relationships were observed between genetic liability for chronic pain and atrial fibrillation (OR, 1.14; 95% CI, 0.81-1.61) or stroke (OR, 1.14; 95% CI, 0.93-1.41).

Increased genetic liability for chronic pain was also found to be associated with higher BMI (β, 0.198; 95% CI, 0.087-0.310), increased risk for smoking initiation (OR, 1.41; 95% CI, 1.15-1.73), and increased risk for major depressive disorder (OR, 1.91; 95% CI, 1.52-2.40).

Similarly, risk for CAD was found to be associated with genetically predicted higher BMI (OR, 1.53; 95% CI, 1.44-1.64), smoking initiation (OR, 1.23; 95% CI, 1.15-1.31), and major depressive disorder (OR, 1.14; 95% CI, 1.05-1.24).

In the multivariate analysis, the relationship between multisite chronic pain and CAD was partially attenuated after correcting for BMI (adjusted OR [aOR], 1.43; 95% CI, 1.05-1.93), smoking (aOR, 1.49; 95%. CI, 1.11-2.00), and major depressive disorder (aOR, 1.44; 95% CI, 1.03-2.01). The relationship was fully attenuated after correcting for all 3 covariates (aOR, 1.34; 95% CI, 0.88-2.05).

In the reverse Mendelian randomization analysis, predictors of multisite chronic pain included increased BMI (β, 0.178; 95% CI, 0.154-0.201), smoking initiation (β, 0.181; 95% CI, 0.157-0.204), and major depressive disorder (β, 0.176; 95% CI, 0.141-0.211).

This study may have been limited by methodological challenges of testing binary variables in Mendelian randomization analyses.

According to the researchers, “Our findings demonstrate that multisite chronic pain led to higher risk of coronary artery disease.” Additional study is needed to evaluate whether the mediators of this relationship — higher BMI, smoking, and depression — may be potential modifiable risk factors.