Cardiovascular Disease Linked with Psoriasis, Not Other Immune Diseases

Researchers examined whether a person’s inherited susceptibility to cardiovascular disease (CVD) predisposes them to immune-mediated disorders (IMIDs) in a recent study that was published in JAMA Cardiology.

Context
Researchers associate systemic inflammatory processes with immune-mediated illnesses and CVD. Biological mechanisms, confounding factors, and causality are still unknown.

Since severe psoriasis is an independent risk factor for the development of cardiovascular disease, psoriasis is a great model to study this relationship. Obesity, dyslipidemia, and cardiovascular risk factors are prevalent in psoriasis patients, especially in those with severe cases.

The theory that this causal relationship is driven by systemic inflammation related to psoriasis is supported by mechanistic data. Some have called for early intervention to lower cardiovascular risks because of the overactivation of the interleukin 17/23 pathway, its presence in blood and carotid atherosclerotic plaques, and targeted blockage, which improve imaging-based indicators of subclinical coronary artery disease (CAD) in psoriasis patients.

About the Study

Researchers looked at the reciprocal relationships between genetic estimators of cardiovascular disease and IMIDs like psoriasis in the current genetic association study.

Mendelian randomizations (MR) evaluated the diseases’ causal relationships. For every variable, researchers used summary-level data from the UK Biobank genome-wide association meta-analytic studies (GWAS) to perform a two-sample MR evaluation.

Genetic estimators of stroke, CAD, psoriasis, and nine other IMIDs were among the research exposures. These comprised multiple sclerosis, rheumatoid arthritis, ulcerative colitis, Crohn’s disease, celiac disease, asthma, atopic dermatitis, acne, and inflammatory bowel disease.

The relationships between genetic estimators of stroke and coronary artery disease, as well as the risks of psoriatic disease and nine other IMIDs, were the main study outcomes. The relationships were found using inverse variance weighting (IVW) and Mendelian randomizations. The timeframe of data analysis spanned from January 2023 to May 2024.

For the analysis, the odds ratio (OR) was calculated by the researchers. The waist-to-hip ratio, blood pressure, BMI, smoking, glycated hemoglobin, LDL, total cholesterol, and triglycerides were all considered study variables.

In order to investigate connections particularly among Europeans, the researchers classified cardiovascular genetic risk variables by drugs, sex-related variations, human leukocyte antigen-C06:02 (HLA-C*06:02) status (primary allele for psoriasis susceptibility), and CAD patients (vs controls). They used MR-Egger, MR-PRESSO, MR-Lasso, weighted median, and simple median to perform sensitivity studies. The genetic instrument’s directionality was evaluated using MR-Steiger tests. Heterogeneity was demonstrated by Cochran Q statistics.

In conclusion
The results of the study demonstrated that there was no reciprocal relationship or correlation between genetic estimators of cardiovascular disease and an elevated risk of psoriasis, nor with other immune-mediated illnesses. Since inflammation plays a critical role in the pathogenesis of cardiovascular disease, there may be an inflammatory component to the underlying mechanism that unites these traits. The study suggests that the causal biology of psoriasis may be influenced by biological processes that also affect the risk of cardiovascular disease.

The results may have a big impact on how psoriasis patients manage and avoid cardiovascular disease. Treatment of the disease may benefit from early treatment to reduce the risk of cardiovascular disease in psoriasis patients and monitoring cardiovascular health.

The findings could speed up the identification of biomarkers and spur the creation of novel therapeutic approaches that focus on shared inflammatory pathways, which would be advantageous for the management of psoriasis and the prevention of cardiovascular disease.

For more information: Exploring the Link Between Genetic Predictors of Cardiovascular Disease and Psoriasis, JAMA Cardiology, 2024,

doi:10.1001/jamacardio.2024.2859