Nicola Gaibazzi, Davide Donelli, Pietro Renda, Marco Barbierato, Giovanni Di Salvo, Nino Carerj, Francesca Casadei, Antonella Moreo, Fausto Rigo
Background/Objectives: Conventional cardiovascular risk scores may provide only modest discrimination in asymptomatic individuals undergoing screening. Ultrasound markers, including resting left anterior descending coronary artery peak diastolic flow velocity (V-LAD), carotid plaque, and global longitudinal strain (GLS), may detect subclinical abnormalities not captured by standard clinical assessment. Methods: In this prospective single-centre screening study, 1100 consecutive asymptomatic adults underwent clinical evaluation, laboratory testing, transthoracic echocardiography with coronary Doppler and GLS analysis, carotid ultrasound, and treadmill exercise electrocardiography. The primary analysis used Cox regression for time to the first composite event of adjudicated new-onset angina, acute coronary syndrome, heart failure hospitalization, atrial fibrillation, or death. Hierarchical models sequentially added continuous V-LAD, carotid plaque, and GLS to an internal clinical reference model. Results: Among 1094 evaluable participants, 79 primary endpoints occurred over a median follow-up of 25 months. Harrell C-index was 0.653 for the clinical model and increased to 0.824 after addition of V-LAD. The combined V-LAD-plus-plaque model had a C-index of 0.816, V-LAD was independently associated with outcome (HR 1.32 per + 10 cm/s (95% CI 1.23-1.43), p < 0.001) and carotid plaque remained strongly associated (HR 4.19 (95% CI 2.37-7.41), p < 0.001). Adding plaque beyond V-LAD significantly improved model fit (likelihood ratio p < 0.001) but did not further improve discrimination. GLS added no incremental prognostic information. Conclusions: V-LAD provided the major incremental gain in discrimination beyond conventional clinical variables, while carotid plaque contributed independent prognostic information and improved overall model fit without a consistent further gain in discrimination beyond V-LAD alone. GLS provided limited incremental value.