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Aims The objective of this study was to evaluate if vascular age derived from coronary artery calcium (CAC) score improves atherosclerosis cardiovascular disease (ASCVD) risk discrimination in primary prevention asymptomatic heterozygous familial hypercholesterolaemia (FH) patients undergoing standard lipid-lowering therapy. Methods and results Two hundred and six molecularly confirmed FH individuals (age 45 ± 14 years, 36% males, baseline LDL-cholesterol 6.2 ± 2.2 mmol/L; 239 ± 85mg/dL) were followed by 4.4 ± 2.9 years (median: 3.7 years, interquartile ranges 2.7–6.8). CAC measurement was performed, and lipid-lowering therapy was optimized according to FH guidelines. Vascular age was derived from CAC and calculated according to the Multi Ethnic Study of Atherosclerosis algorithm. Risk estimation based on the Framingham equations was calculated for both biological (bFRS) and vascular (vaFRS) age. During follow-up, 15 ASCVD events (7.2%) were documented. The annualized rate of events for bFRS &amp;lt;10%, 10–20%, and &amp;gt;20% was respectively: 8.45 [95% confidence interval (CI) 3.17–22.52], 23.28 (95% CI 9.69–55.94), and 28.13 (95% CI 12.63–62.61) per 1000 patients. The annualized rate of events for vaFRS &amp;lt;10%, 10–20%, and &amp;gt;20% was respectively: 0, 0, and 50.37 (95% CI 30.37–83.56) per 1000 patients. vaFRS presented a better discrimination for ASCVD events compared to bFRS 0.7058 (95% CI 0.5866–0.8250) vs. vaFRS 0.8820 (95% CI 0.8286–0.9355), P = 0.0005. Conclusion CAC derived vascular age can improve ASCVD risk discrimination in primary prevention FH subjects. This tool may help further stratify risk in FH patients already receiving lipid-lowering medication who might be candidates for further treatment with newer therapies.

Vascular age derived from coronary artery calcium score on the risk stratification of individuals with heterozygous familial hypercholesterolaemia