Baseline coronary computed tomography angiography and polygenic risk profiles in adults with type 2 diabetes: a cross-sectional analysis from the VOLTAIRE study

Type 2 diabetes mellitus (T2D) is associated with elevated cardiovascular risk, yet coronary atherosclerotic burden and inherited genetic risk vary substantially between individuals, limiting the precision of conventional risk stratification.

To describe baseline clinical characteristics, CT coronary angiography (CTCA) findings, and polygenic risk score (PRS) distributions in participants enrolled in the VOLTAIRE study.

This cross-sectional analysis included adults with T2D who completed baseline CTCA and PRS assessment prior to randomisation in the VOLTAIRE study (Evaluation of polygenic scores and CT imaging in risk factor modification in type 2 diabetes). Coronary atherosclerotic burden was characterised using coronary artery calcium (CAC) scores and CTCA-reported luminal stenosis severity. Polygenic risk for coronary artery disease was assessed using a genome-wide PRS and categorised for descriptive analyses.

Among 126 participants (mean age 57.5 ± 8.7 years; 62.7% male), coronary anatomy was highly heterogeneous. Over one-third had no detectable coronary calcification (CAC=0), while 18.7% demonstrated severe calcification (CAC ≥400). Moderate-to-severe luminal stenosis (≥50%) was present in 40.5% of participants, including 20.4% classified as low clinical cardiovascular risk. PRS distribution was also variable (low 37.3%, intermediate 35.7%, high 27.0%). Across PRS strata, moderate-to-severe stenosis was observed in 50.0% of those with high PRS, 48.9% with intermediate PRS, and 25.5% with low PRS, indicating incomplete alignment between inherited and anatomical risk. Concordance across risk domains was limited, with only 8.7% of participants simultaneously classified as high risk by anatomical (≥50% stenosis), genetic (PRS ≥67), and clinical (5-year CVD risk ≥15%) criteria, highlighting frequent discordance between risk assessment modalities.

Baseline findings demonstrate substantial heterogeneity and limited concordance between anatomical, genetic, and clinical risk measures in adults with T2D. These results underscore the multidimensional nature of cardiovascular risk and support the rationale for integrated, personalised risk assessment strategies to better inform prevention and management.