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CAC and CV Events in Patients With HeFH
Study Questions:
Is coronary artery calcium (CAC) score a predictor of atherosclerotic cardiovascular disease (ASCVD) events in asymptomatic primary prevention molecularly proven heterozygous familial hypercholesterolemia (HeFH) patients receiving standard lipid-lowering therapy?
Methods:
Subjects with HeFH underwent CAC measurement and were followed prospectively. The association of CACs with ASCVD was evaluated using multivariate analysis. ASCVD was defined as fatal or not myocardial infarction, stroke, unstable angina requiring revascularization, and elective myocardial revascularization. Major CV risk factors, glucose, lipids, type of mutation, tendon xanthomas, corneal arcus, and statin use at baseline were available.
Results:
A total of 206 subjects (64% woman) had a mutation on low-density lipoprotein receptor (LDLR) (99.5%) or apolipoprotein B (0.5%). Mean age was 45 ± 14 years, baseline and on-treatment LDL cholesterol 269 ± 70 mg/dl and 150 ± 56 mg/dl, respectively; 69% were on statins at baseline and 96.6% at follow-up with a median of 3.7 years (interquartile range, 2.7-6.8 years). Ezetimibe was used in 64% at follow-up, which correlated with CACs. CAC was present in 105 (51%), and 15 ASCVD events (7.2%) were documented. Almost half of events were hard outcomes, and the others were elective coronary revascularizations. The annualized rates of events per 1,000 patients for CAC scores of 0 (n = 101 [49%]), 1-100 (n = 62 [30%]), and >100 (n = 43 [21%]) were (95% confidence interval) respectively, = 0, 26.4 (12.9-51.8), and 44.1 (26.0-104.1). In multivariate Cox regression analysis, log (CAC score ± 1) was independently associated with incident ASCVD events (hazard ratio, 3.33; 95% CI, 1.64-6.79; p = 0.001). On univariate analysis, ASCVD events were associated with male sex, family history of premature coronary heart disease, corneal arcus, high-density lipoprotein cholesterol, and log-transformed CAC. In the multivariate Cox regression model, only log-transformed CAC (p = 0.001) remained independently associated with incident ASCVD events.
Conclusions:
CAC was independently associated with ASCVD events in patients with HeFH receiving standard lipid-lowering therapy. This may help further stratify near-term risk in patients who might be candidates for further treatment with newer therapies.
Perspective:
This relatively large cohort of molecularly proven HeFH with documented risk factors, lipids, and CACs with reliable follow-up supports a strategy of using CAC to help risk stratification and decide treatment options. Men and women with genetically documented or definite or probable chance of HeFH using Simon Broome FH registry or Dutch Lipid Clinic criteria should be treated with a high-intensity statin with the addition of ezetimibe for those ages 40-79 years if the LDL cholesterol remains ≥70 mg/dl, and for those 18-39 years with an LDL cholesterol >100 mg. This study supports the option of avoiding statins in those who are reluctant or intolerant of statins, and in women in childbearing years who have no CAC score (known as ‘the power of zero’) with the intention of obtaining repeat CAC scores every 4 years. The CAC score aids in deciding who might benefit from the expensive proprotein convertase subtilisin/kexin type 9 (PCSK9) antibody class of drugs. The authors calculated that considering a 20% relative risk reduction in ASCVD events with the addition of a PCSK9 inhibitor to standard lipid-lowering therapy as seen in clinical trials, the 5-year numbers needed to treat of 38 and 23 would be estimated for CAC scores of 1-100 and >100, respectively.
Clinical Topics: Cardiac Surgery, Cardiovascular Care Team, Diabetes and Cardiometabolic Disease, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Cardiac Surgery and Arrhythmias, Lipid Metabolism, Nonstatins, Novel Agents, Primary Hyperlipidemia, Statins, Interventions and Imaging, Computed Tomography, Nuclear Imaging
Keywords: Angina, Unstable, Apolipoproteins, Atherosclerosis, Cholesterol, HDL, Cholesterol, LDL, Coronary Disease, Diagnostic Imaging, Glucose, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hyperlipoproteinemia Type II, Mutation, Myocardial Infarction, Myocardial Revascularization, Plaque, Atherosclerotic, Primary Prevention, Receptors, LDL, Stroke, Tomography, X-Ray Computed, Xanthomatosis, Vascular Calcification
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