Introduction

Psoriasis, a chronic T-helper 17 (Th17)-driven inflammatory disease, confers an elevated risk of cardiovascular events beyond traditional risk factors. Coronary microvascular dysfunction (CMD) is a potent predictor of adverse cardiac outcomes, yet the specific inflammatory pathways linking psoriasis to CMD remain incompletely characterised. The interplay between the interleukin (IL)-23/IL-17 axis and hemodynamic stressors like hypertension in driving microvascular injury is unknown.

Aim

To determine the association between circulating IL-23/IL-17 pathway cytokines and CMD in patients with moderate-to-severe psoriasis, and to rigorously test the hypothesis that this relationship is independent of systemic hypertension.

Material and methods

Adenosine-stress transthoracic Doppler echocardiography was used to measure coronary flow reserve (CFR) in the left anterior descending artery in 140 patients with moderate-to-severe plaque psoriasis (Psoriasis Area and Severity Index [PASI] ≥ 10) and 70 age- and sex-matched healthy controls. For categorical analyses, CMD was operationally defined as CFR < 2.5. Multivariable logistic regression was used to test independent associations in normotensive individuals.

Results

Psoriasis patients showed significantly elevated levels of IL-23 (median 285 vs. 64 pg/ml), IL-17A (18.4 vs. 2.1 pg/ml), and IL-22 (42.1 vs. 11.5 pg/ml) in comparison with healthy individuals (all p < 0.001). Prevalence of CMD was significantly higher among patients with psoriasis (38%) in comparison with controls (7%; p < 0.001). In the whole study population, multivariate analyses indicated that IL-17A (OR per quartile: 2.9, 95% CI: 1.8–4.7) and IL-23 (OR = 2.1, 95% CI: 1.4–-3.3) independently predicted CMD in a model adjusted for all variables; the relationship was also valid in the model additionally adjusted for hypertension. Importantly, among 102 patients with psoriasis without hypertension, high quartiles of IL-17A increased the risk of CMD by 4.5-fold (95% CI: 1.9–10.5).

Conclusions

Activation of the IL-23/IL-17 pathway is independently associated with coronary microvascular dysfunction in patients with moderate-to-severe psoriasis, including those without diagnosed hypertension and with normal office blood pressure. These findings identify a potential inflammatory CMD phenotype and support further investigation of whether targeted cytokine inhibition can modify coronary microvascular function.