Three new modifiable correlates of coronary artery calcium beyond age and male sex: uric acid, sleep apnoea severity, and vitamin D from 34-biomarker statin-free phenotyping

Background Coronary artery calcium (CAC) is the strongest subclinical atherosclerosis imaging marker, yet which modifiable factors independently associate with calcification in statin-free populations remains unclear. We assessed 34 candidate biomarkers across 7 domains against CAC in a statin-excluded cohort from the STELA nurse-led digital preventive cardiology platform. Methods Cross-sectional analysis of the Centre of Preventive Medicine STELA registry (nurse-led two-day cardiovascular assessment, Czech Republic). Of 543 sessions, 209 statin-free adults were analysed (12 statin users excluded via NLP-verified medication screening). Thirty-four predictors across 7 domains were assessed: lipids, glycaemia, inflammatory/metabolic biomarkers, ApoE genotype, bioimpedance body composition, spiroergometry, overnight polysomnography, psychological questionnaires, and Agatston CAC. Logistic regression with sequential model building, interaction testing (LRT), bootstrap validation (500 iterations), and reclassification (NRI, IDI) were applied. Results Among 209 statin-free adults (54.5% female; mean age 46.7 ± 9.7 years), 46 (22.0%) had CAC > 0, with zero prevalence below age 40. Age and sex alone yielded AUC 0.870 (bootstrap-corrected 0.862; 95% CI 0.774–0.933). Adding all 34 biomarkers achieved maximum AUC 0.874 (ΔAUC +0.004); continuous NRI was −0.50 and IDI 0.004 (Figure 1). Of 34 variables, only uric acid (adjusted OR 1.01 per µmol/L, p = 0.022), apnoea–hypopnoea index (adjusted OR 1.06 per event/h, p = 0.048; CAC prevalence 11%→27%→53%→100% across severity), and vitamin D (adjusted OR 0.98 per nmol/L, p = 0.028) retained significance after age-sex adjustment (Figure 1). All lipid markers including LDL-C (p = 0.71) and ApoB (p = 0.91), all glycaemic indices including HOMA-IR (p = 0.57) and HbA1c (p = 0.17), and all psychological measures were non-significant. ApoE ε2 carriers had lowest LDL (2.85 mmol/L) yet highest CAC prevalence (31.8% vs 21.1% in E3/E3; age-matched; Figure 2). Conclusions In statin-free adults, age and sex eclipsed 34 biomarkers for CAC discrimination. Uric acid, sleep apnoea severity, and vitamin D emerged as sole independent modifiable correlates, warranting evaluation as intervention targets in primary prevention.