Subclinical Atherosclerosis Links Premature and Late-Onset Coronary Artery Disease

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Abstract

Background

Despite established relationship between atherosclerosis and coronary artery disease (CAD), evidence on subclinical atherosclerosis and its differential associations with premature coronary artery disease (PCAD) versus late-onset coronary artery disease (LCAD) remains limited.

Aims

This study aims to delve deeper into the associations between subclinical atherosclerosis and the incidence risk of both PCAD and LCAD.

Methods

Using UK Biobank data, we identified PCAD (male <55/female <65 years; n=7,398) and LCAD (male ≥55/female ≥65 years; n=39,085) cohorts. Conditional inference tree classification optimized carotid intima-media thickness (cIMT) stratification in both cohorts.

Results

Conditional inference tree categorized the PCAD cohort into two subgroups: cIMT ≤700μm and cIMT >700μm, with the latter demonstrating a HR of 2.079 for cardiovascular risk. In the LCAD cohort, four cIMT strata were identified: ≤ 620μm, 620–763μm (HR=1.401), 763–1054μm (HR=1.810), and >1054μm (HR=2.850). Multivariable-adjusted Cox models demonstrated significant associations between subclinical atherosclerosis and PCAD (HR=2.079, 95%CI:1.477-2.925) and LCAD (HR=1.776, 95%CI:1.455-2.169), highlighting the prognostic value of cIMT stratification in coronary artery disease risk assessment.

Conclusions

A UK Biobank prospective cohort study revealed subclinical atherosclerosis significantly associated with PCAD and LCAD risks. Even within conventional cIMT “safe thresholds”, incremental increases predicted elevated risks, underscoring limitations of current thresholds. Future research need to develop multimodal frameworks integrating dynamic cIMT trajectories to refine risk stratification and early interventions.

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