Exploring the Genetic Link Between Cardiovascular Disease and Psoriasis

Although genetic predictors of cardiovascular disease (CVD) were associated with an increased risk of psoriasis, there was no reciprocal effect of psoriasis on CVD, a study has found.¹ Furthermore, no associations were found between cardiovascular genetic predictors and other immune-mediated inflammatory diseases (IMIDs).

These study findings reveal a 1-way relationship between cardiovascular disease and psoriasis, with no impact on other immune-mediated inflammatory diseases. | Image credit: Elena - stock.adobe.com

These results could help guide future research into shared genetic mechanisms and treatment strategies for psoriasis and CVD.

This genetic association study is published in JAMA Dermatology.

“Our findings are consistent with genetic predictors of CVD associating with increased psoriasis risk with no reciprocal effect,” wrote the researchers of the study. “This suggests that pathways influencing CVD risk may also contribute to the causal biological pathways of psoriasis.”

Previous studies have identified a link between psoriasis and CVD. Psoriasis is an autoimmune disease, which is known to cause inflammation that is not only visibly on the skin, but with other parts of the body, including the heart.² Researchers have identified several possible factors for this, including shared genetics and common inflammatory pathways.

In this study, the researchers aimed to determine the bidirectional relationship between genetic predictors of psoriasis with 2 major forms of CVD, coronary artery disease (CAD) and stroke, and the association between genetic predictors of CVD with 9 other IMIDs.¹

The researchers utilized a 2-sample mendelian randomization (MR) approach to analyze summary-level data from large-scale genome-wide association studies, which included data on individuals of European descent and covered information on CAD, stroke, psoriasis, and 9 other IMIDs: acne, atopic dermatitis, asthma, celiac disease, Crohn disease, inflammatory bowel disease multiple sclerosis, rheumatoid arthritis, or ulcerative colitis.

The primary outcomes were the associations of genetic predictors of CAD and stroke with the risk of psoriasis and the other IMIDs using inverse-variance weighted estimation to determine the direction and strength of associations, while adjusting for potential confounding variables. Data were analyzed from January 2023 to May 2024.

The study included 181,249 cases and 1,165,690 controls with CAD; 110,182 cases and 1,503,898 controls with stroke; and 36,466 cases and 458,078 controls with psoriasis.

Contrary to prior assumptions, genetic predictors of psoriasis were not associated with an increased risk of CAD or stroke. However, in the reverse direction, genetic predictors of both CAD (OR, 1.07; 95% CI, 1.04-1.10; P = .003) and stroke (OR, 1.22; 95% CI, 1.05-1.41; P = .01) were significantly associated with a higher risk of developing psoriasis.

After adjusting for stroke, the association between CAD genetic predictors and psoriasis risk became nonsignificant, indicating a shared genetic effect between CAD and stroke that increases psoriasis risk. Importantly, no significant associations were found between cardiovascular genetic predictors and other common IMIDs, suggesting that this genetic link may be specific to psoriasis.

The researchers noted several limitations to the study, First, they were unable to empirically confirm that the second and third instrumental variable assumptions had not been violated, as this relied on the researchers’ judgment. Second, the bidirectional MR method may have led to bias estimates and reduced the power of the analysis. Third, although the study was able to identify moderate to large effects between CVD genetic predictors and other IMIDs, it may have been unable to identify smaller effect sizes.

Despite these limitations, the researchers believe the study suggests an association between genetic predictors of CVD with increased psoriasis risk with no reciprocal effect or associations with other IMIDs.

“This knowledge could help expedite biomarker discovery to improve cardiovascular risk prediction in the psoriasis population and lead to the development of novel therapeutic strategies that target common inflammatory pathways, potentially offering dual benefits in treating psoriasis and preventing CVD,” wrote the researchers.

References

1. Ramessur R, Saklatvala J, Budu-Aggrey A, et al. Exploring the link between genetic predictors of cardiovascular disease and psoriasis. JAMA Cardiol. Published online September 18, 2024. doi:10.1001/jamacardio.2024.2859

2. Ellis RR. Psoriasis and heart disease. WebMD. Published March 12, 2024. Accessed October 9, 2024. https://www.webmd.com/skin-problems-and-treatments/psoriasis/psoriasis-heart-disease.