Zero Coronary Artery Calcium as a Marker of Vascular Resilience in High-Risk Adults

Area of Science:

• Cardiology
• Preventive Medicine
• Medical Imaging

Background:

• Atherosclerotic cardiovascular disease (ASCVD) prevention relies on accurate risk estimation.
• The Pooled Cohort Equations (PCE) identify high-risk adults (≥20% 10-year risk).
• Coronary heart disease (CHD) event rates vary significantly within the high-risk group, suggesting a potential 'resilient' phenotype.

Purpose of the Study:

• To determine if a coronary artery calcium (CAC) score of zero identifies a resilient, lower-risk subgroup among individuals with high calculated ASCVD risk.
• To compare the risk factor profiles of individuals with CAC = 0 versus those with CAC > 0.

Main Methods:

• Analysis of Multi-Ethnic Study of Atherosclerosis (MESA) participants with PCE-estimated ASCVD risk ≥20% and available CAC data.
• Comparison of baseline characteristics using standardized mean differences.
• 10-year CHD events analyzed using Kaplan-Meier methods and Cox models, adjusting for age, sex, and race/ethnicity.

Main Results:

• Among 1,608 high-risk adults, 22.3% had a CAC score of 0.
• Risk factor profiles (blood pressure, lipids, diabetes, BMI) were similar between CAC = 0 and CAC > 0 groups.
• 10-year hard CHD incidence was significantly lower in the CAC = 0 group (3.52 per 1,000 person-years) compared to the CAC > 0 group (13.46 per 1,000 person-years).
• CAC = 0 was associated with substantially lower CHD risk (HR: 0.27; 95% CI: 0.15-0.49).
• A significant interaction between CAC and age indicated stronger risk reduction from CAC = 0 at older ages.

Conclusions:

• Approximately one-quarter of adults classified as high ASCVD risk by PCE possess a CAC score of 0.
• Individuals with CAC = 0 experience significantly fewer CHD events, despite having similar traditional risk factor burdens.
• A CAC score of zero may represent a resilient phenotype that warrants further mechanistic investigation for ASCVD prevention strategies.