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AIM: Factors associated with unexpected absence or presence of coronary atherosclerosis in individuals at high/low estimated cardiovascular (CV) risk are largely unexplored. We assessed two extreme phenotypes: 1) no coronary atherosclerosis despite very high CV risk; and 2) severe-extensive coronary atherosclerosis despite low CV risk.

METHODS: A multicenter, cross-sectional nationwide, population-based cohort of 30,154 randomly invited individuals (age 50-64 years; 51% women). Coronary plaque burden was assessed by coronary computed tomography angiography using coronary artery calcium score and segment involvement score. CVD risk was estimated by the Systematic Coronary Risk Evaluation (SCORE2) and SCORE2-Diabetes, as appropriate.

RESULTS: In total 10,628 individuals without and 189 with diabetes were eligible. Absence of coronary plaques despite high SCORE2-risk occurred in 1.2% non-diabetic and 14.0% diabetic subjects. Severe-extreme coronary plaques despite low SCORE2-risk occurred in 0.7% non-diabetic and 0.3% diabetic subjects. In non-diabetic subjects, severe-extensive coronary plaque burden despite low SCORE2-risk was more likely in men, with increasing age, more pack-years of smoking, previous smoking, hypertension, hyperlipidemia, family history of CVD, and higher systolic blood pressure (all p<0.002). A similar but reverse pattern was observed among subjects without coronary plaques despite high SCORE2-risk. In addition, diabetic subjects without coronary plaques and high SCORE2-risk demonstrated a higher likelihood of moderate physical activity, higher education levels, and lower body mass index (p<0.05).

CONCLUSION: SCORE2-risk correlated well with presence of coronary atherosclerosis, yet 1.9% non-diabetic subjects and 14.3% diabetic subjects display extreme coronary phenotypes with a mismatch between estimated cardiovascular risk and signs of coronary atherosclerosis.