Study Reveals Genetic Connection Between Cardiovascular Disease and Psoriasis, Paving the Way for New Therapies

"These findings indicate that the biological pathways affecting cardiovascular disease risk are linked to an increased risk of psoriasis, but not to other immune-mediated inflammatory diseases (IMIDs)," the researchers wrote.

Psoriasis, a chronic inflammatory skin disorder, affects millions worldwide and is known for its debilitating symptoms and impact on quality of life. Concurrently, cardiovascular disease remains a leading cause of morbidity and mortality globally.

The epidemiological connection between immune-mediated diseases and cardiovascular disease is frequently ascribed to systemic inflammation. However, the precise direction of causality and the biological mechanisms that link cardiovascular disease with IMIDs remain unclear. Given the strong epidemiological association and the increasing mechanistic evidence, psoriasis is suggested as an ideal model for investigating this relationship.

Against the above background, Ravi Ramessur, the King’s College London, London, United Kingdom, and colleagues aimed to evaluate the bidirectional relationships between genetic predictors of psoriasis and the two primary forms of cardiovascular disease: coronary artery disease (CAD) and stroke. Additionally, they examined the association between genetic predictors of cardiovascular disease and nine other immune-mediated inflammatory diseases.

For this purpose, the researchers conducted a genetic association study utilizing MR, a robust genetic tool that helps differentiate causation from mere associations found in epidemiological studies. This approach aimed to provide supportive evidence for causal relationships between various traits. The study employed two-sample MR analyses using summary-level data from extensive genome-wide association meta-analyses (GWAS) for each trait, focusing on individuals of European descent. The analysis included data related to CAD, stroke, psoriasis, and nine other IMIDs.

The exposures examined included genetic predictors associated with CAD, stroke, psoriasis, and the nine additional IMIDs. The primary outcomes of the study were the associations of genetic predictors of CAD and stroke with the risk of developing psoriasis and other IMIDs. These associations were determined using inverse-variance weighted (IVW) MR estimates.

The study revealed the following findings:

• The study included 181 249 cases and 1 165 690 controls with CAD, 110 182 cases and 1 503 898 controls with stroke, 36 466 cases and 458 078 controls with psoriasis, for a total of approximately 3 400 000 individuals, and nine other IMIDs.
• In contrast to previous assumptions, genetic predictors of psoriasis had no association with CAD or stroke.
• In the reverse direction, genetic predictors of both CAD (MR estimate IVW odds ratio [OR], 1.07) and stroke (IVW OR, 1.22) had risk-increasing associations with psoriasis.
• Adjusting for stroke rendered the associations of genetically predicted CAD with psoriasis risk nonsignificant (and vice versa), suggesting that a shared effect underlying genetic risk for CAD and stroke is associated with increased psoriasis risk.
• There were no risk-increasing associations for genetic predictors of cardiovascular disease with other common IMIDs, including rheumatoid arthritis and inflammatory bowel disease.

"The findings from this MR study suggest that genetic predictors of cardiovascular disease are linked to an elevated risk of psoriasis without any reciprocal effect or association with other immune-mediated diseases. Understanding the mechanisms behind this connection may pave the way for innovative therapeutic strategies for both conditions," the researchers concluded.

Reference:

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