Log in to MyACC
CAC Score to Predict CV Events in Familial Hypercholesterolemia
Quick Takes
- Heterozygous familial hypercholesterolemia (HeFH) results in a four-fold CV event rate at the same LDL-C level from 130-190 mg/dl and a 20-fold event rate at an LDL-C of 190 mg/dl compared to healthy persons with an LDL-C of 130 mg/dl.
- The Spanish SAFEHEART risk estimate is based on follow-up of genetically confirmed HeFH. It is unique and the best available, but rarely used because of the well known very high risk of ASCVD in HeFH in young and middle-aged persons, particularly with other risk factors.
- The study supports the use of coronary artery calcium (CAC) in persons with genetic evidence or high clinical suspicion of HeFH to decide early intervention and very high-intensity treatment for primary prevention. In the US guidelines, a CAC score >0 supports the use of maximal dosing of high-intensity statin and consideration of PCSK9 antibody treatment.
Study Questions:
What is the added value of coronary artery calcium (CAC) score in predicting cardiovascular (CV) events in patients with heterozygous familial hypercholesterolemia (HeFH)?
Methods:
REFERCHOL (French Registry of Familial Hypercholesterolemia) and SAFEHEART, two national registries on HeFH, were used to analyze data from primary prevention HeFH patients undergoing CAC quantification. Probability-weighted Cox proportional hazards models were used to estimate hazard ratios (HRs). Area under the receiver-operating characteristic curve (AUC) and net reclassification improvement were used to compare the incremental contribution of CAC score when added to the SAFEHEART-risk estimate (RE) for atherosclerotic cardiovascular disease (ASCVD) prediction. ASCVD was defined as coronary heart disease, stroke or transient ischemic attack, peripheral artery disease, resuscitated sudden death, and CV death. Low-density lipoprotein cholesterol (LDL-C) year (yr)-score was calculated as [LDL-C max x (age at diagnosis/initiation of statin) + [LDL-C at inclusion x (age at inclusion – age at diagnosis/initiation of statin)].
Results:
The study included 1,624 patients (mean age, 48.5 ± 12.8 years; men, 45.7%). Subjects who developed ASCVD were more likely men, older, diabetics, hypertensive, overweight, and had a higher lipoprotein(a), and lower HDL-C. Those who developed ASCVD had a much higher LDL-C yr-score in mg/dl-yr (ASCVD 14,695 vs. 11,448 mg/dl-yr, p < 0.0001). After a median follow-up of 2.7 years, ASCVD occurred in 81 subjects. Compared to CAC = 0, a score of 1-10 had an HR of 4.4 and >100 an HR of 32.05. Receiving-operating curve analysis showed a good performance of CAC score alone in ASCVD prediction (AUC: 0.860) The addition of log(CAC + 1) to SAFEHEART-RE resulted in a significantly improved prediction of ASCVD (AUC: 0.884 [for + log(CAC + 1) vs. AUC: 0.793 for SAFEHEART-RE; p < 0.001). These results were confirmed also when considering only hard CV 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 CV risk stratification and ASCVD prediction in statin-treated HeFH patients.
Perspective:
HeFH is present in about 15% of persons with a myocardial infarction <50 years old and prevalence is 1/250. The great majority have not been diagnosed or are undertreated. The standard 10-yr risk ASCVD estimates are not useful because HeFH is under-represented in the databases. The findings in this study support clinical practice based on expert opinion regarding the utility of CAC in HeFH. Persons with genetic confirmed HeFH are generally treated with a statin at any age. A CAC score >1 has been used to decide statin therapy in HeFH patients who are reluctant, women of child bearing age not on birth control, and intensifying LDL-C lowering with proprotein convertase subtilisin/kexin type 9 (PCSK9) antibody therapy.
Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Noninvasive Imaging, Prevention, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Advanced Lipid Testing, Lipid Metabolism, Nonstatins, Novel Agents, Primary Hyperlipidemia, Statins, Computed Tomography, Nuclear Imaging
Keywords: Atherosclerosis, Cholesterol, LDL, Coronary Disease, Death, Sudden, Diagnostic Imaging, Dyslipidemias, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hyperlipoproteinemia Type II, Ischemic Attack, Transient, Lipoprotein(a), Peripheral Arterial Disease, Plaque, Atherosclerotic, Primary Prevention, Risk Assessment, Stroke, Tomography, X-Ray Computed
< Back to Listings
