Elsevier

JACC: Cardiovascular Imaging

Volume 14, Issue 12, December 2021, Pages 2414-2424
JACC: Cardiovascular Imaging

Original Research
The Added Value of Coronary Calcium Score in Predicting Cardiovascular Events in Familial Hypercholesterolemia

https://doi.org/10.1016/j.jcmg.2021.06.011Get rights and content
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Abstract

Objectives

This study aimed at investigating the additional contribution of coronary artery calcium (CAC) score to SAFEHEART (Spanish Familial Hypercholesterolemia Cohort Study) risk equation (SAFEHEART-RE) for cardiovascular risk prediction in heterozygous familial hypercholesterolemia (HeFH).

Background

Common cardiovascular risk equations are imprecise for HeFH. Because of the high phenotype variability of HeFH, CAC score could help to better stratify the risk of atherosclerotic cardiovascular disease (ASCVD).

Methods

REFERCHOL (French Registry of Familial Hypercholesterolemia) and SAFEHEART are 2 ongoing national registries on HeFH. We analyzed data from primary prevention HeFH patients undergoing CAC quantification. We used probability-weighted Cox proportional hazards models to estimate HRs. Area under the receiver-operating characteristic curve (AUC) and net reclassification improvement (NRI) were used to compare the incremental contribution of CAC score when added to the SAFEHEART-RE for ASCVD prediction. ASCVD was defined as coronary heart disease, stroke or transient ischemic attack, peripheral artery disease, resuscitated sudden death, and cardiovascular death.

Results

We included 1,624 patients (mean age: 48.5 ± 12.8 years; men: 45.7%) from both registries. After a median follow-up of 2.7 years (interquartile range: 0.4-5.0 years), ASCVD occurred in 81 subjects. The presence of a CAC score of >100 was associated with an HR of 32.05 (95% CI: 10.08-101.94) of developing ASCVD as compared to a CAC score of 0. Receiving-operating curve analysis showed a good performance of CAC score alone in ASCVD prediction (AUC: 0.860 [95% CI: 0.853-0.869]). The addition of log(CAC + 1) to SAFEHEART-RE resulted in a significantly improved prediction of ASCVD (AUC: 0.884 [95% CI: 0.871-0.894] for SAFEHEART-RE + log(CAC + 1) vs AUC: 0.793 [95% CI: 0.779-0.818] for SAFEHEART-RE; P < 0.001). These results were confirmed also when considering only hard cardiovascular endpoints. The addition of CAC score was associated with an estimated overall net reclassification improvement of 45.4%.

Conclusions

CAC score proved its use in improving cardiovascular risk stratification and ASCVD prediction in statin-treated HeFH.

Key Words

cardiovascular disease
coronary artery calcium
coronary imaging
familial hypercholesterolemia
genetic disease
risk prediction

Abbreviations and Acronyms

ASCVD
atherosclerotic cardiovascular disease
AUC
area under the receiver-operating characteristic curve
AVR
aortic valve replacement
CAC
coronary artery calcium
HeFH
heterozygous familial hypercholesterolemia
LDL-C
low-density lipoprotein cholesterol
LLT
lipid-lowering treatment
MI
myocardial infarction
NRI
net reclassification improvement
PCSK9
proprotein convertase subtilisin kexin 9
Q
quartile
RE
risk equation
SAFEHEART-RE
Spanish Familial Hypercholesterolemia Cohort Study risk equation

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The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.

Drs Gallo and Perez de Isla contributed equally to this work.