Cor Vasa 2026, 68(4):404-409 | DOI: 10.33678/cor.2025.134

Endothelial Dysfunction in Non-Diabetic Patients and Coronary Calcification: A Different Pathway to Coronary Artery Disease?

Jan Pudil^a, Tasneem Faheem^b, Štěpán Jeřábek^c, David Zemánek^a, Kristýna Bayerová^a, Tomáš Kovárník^a

^a 2nd Department of Medicine - Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, the Czech Republic

^b First Faculty of Medicine, Charles University in Prague, the Czech Republic

^c Department of Cardiology, Institute for Clinical and Experimental Medicine, Prague, the Czech Republic

Objective: To evaluate whether endothelial dysfunction (ED) in patients with coronary artery disease (CAD) is associated with a lower prevalence of coronary macrocalcifications (CMC), a marker of more advanced and typically more stable plaque remodelling.

Methods: This secondary analysis included 77 consecutive patients enrolled in the FIGARO trial. Endothelial function was evaluated using the EndoPAT 2000 device, with ED defined as RHI < 1.67. Coronary angiograms were re-assessed by blinded reviewers for the presence of angiographically visible macrocalcification. Patients were categorised into three predefined groups: diabetics, non-diabetics with preserved endothelial function (RHI ≥ 1.67), and non-diabetics with ED. Clinical characteristics, risk factors, and angiographic findings
were compared across groups. Logistic regression was used to identify independent predictors of CMC.

Results: ED was present in 21 patients (27.3%), and diabetes mellitus in 24 (31.2%). Overall, CMC was identified in 22.1% of the cohort. Among non-diabetic patients, the prevalence of CMC differed markedly across endothelial phenotypes: 31.6% in non-diabetics with preserved endothelial function versus only 8.8% in non-diabetics with ED (p = 0.04). Despite similar age and risk-factor burden, non-diabetic patients with ED had the lowest prevalence of CMC. In non-diabetics, preserved endothelial function independently predicted the presence of CMC (OR 4.77, 95% CI 1.03–22.0; p = 0.045). This association remained significant in multivariable analysis adjusting for age, dyslipidaemia, arterial hypertension, CKD, and active smoking (OR 6.96, 95% CI 1.27–38.19; p = 0.026).

Conclusions: Among non-diabetic patients with CAD, endothelial dysfunction is associated with a markedly lower prevalence of coronary macrocalcification, indicating a non-calcified atherosclerotic phenotype. These findings support the concept of divergent atherosclerotic pathways, in which ED without metabolic abnormalities reflects earlier, inflammation-driven vascular pathology rather than calcific remodelling. Non-invasive endothelial function testing may help refine risk stratification by identifying patients more likely to harbour non-calcified and potentially vulnerable plaques, thereby providing complementary information beyond traditional cardiovascular risk factors.

Keywords: Coronary artery disease, Coronary calcification, Coronary pathophysiology, Endothelial dysfunction

Received: December 6, 2025; Revised: December 6, 2025; Accepted: December 14, 2025; Prepublished online: August 11, 2026; Published: August 31, 2026  Show citation