Extreme Coronary Atherosclerosis Phenotypes in Low- and High-Risk Patients

Overview

This study from the SCAPIS Extremes cohort identified rare but clinically significant mismatches between estimated cardiovascular risk and coronary atherosclerosis burden. Notably, some high-risk individuals lacked coronary plaques, while some low-risk individuals exhibited severe plaque burden, highlighting limitations of traditional risk algorithms.

Background

Cardiovascular disease risk assessment commonly relies on algorithms like SCORE2, which estimate 10-year risk based on traditional risk factors. However, these tools can misclassify individuals, leading to overtreatment or undertreatment. Coronary computed tomography angiography (CCTA) allows direct visualization of coronary plaque burden, providing an opportunity to study discrepancies between estimated risk and actual atherosclerosis. Understanding these extreme phenotypes may improve risk stratification and reveal protective or predisposing factors beyond traditional metrics.

Data Highlights

Key Findings

• 1. Among non-diabetics, 1.2% had no coronary plaques despite very high cardiovascular risk, while 0.7% had severe plaques despite low risk.
• 2. Among diabetics, 14.0% lacked plaques despite high risk, and 0.3% had severe plaques despite low risk.
• 3. Severe plaque burden in low-risk non-diabetics was associated with male sex, older age, smoking history, hypertension, hyperlipidemia, family history of CVD, and higher systolic blood pressure.
• 4. The inverse pattern was observed in high-risk individuals without plaques, suggesting protective factors.
• 5. Diabetic individuals without plaques despite high risk were more likely to have moderate physical activity, higher education, and lower BMI.
• 6. SCORE2 risk correlated well with coronary atherosclerosis overall but failed to predict these extreme phenotypes in a small subset.

Clinical Implications

Clinicians should recognize that traditional risk scores like SCORE2 may not fully capture individual coronary atherosclerosis burden, especially in patients with diabetes. Incorporating imaging modalities such as CCTA may help identify patients with discordant risk and plaque burden, guiding personalized management. Additionally, lifestyle factors and socio-demographic variables may influence these extreme phenotypes and warrant further consideration.

Conclusion

The SCAPIS Extremes study reveals that a small but important proportion of individuals exhibit a mismatch between estimated cardiovascular risk and coronary plaque burden. Further research is needed to elucidate mechanisms underlying these extreme phenotypes to improve risk prediction and preventive strategies.

References

1. Björnsson et al. 2024 -- Extreme Cases of Coronary Atherosclerosis in Low-Risk Patients and Its Absence in High-Risk Individuals: Insights from the SCAPIS Extremes Study