Prediction of Familial Hypercholesterolemia in Patients at High Atherosclerotic Cardiovascular Disease Risk Using a Recently Validated Algorithm

Background The prevalence of heterozygous familial hypercholesterolemia (FH) is 1 of 250 in the general population and approximately 1 of 125 in patients with atherosclerotic cardiovascular disease (ASCVD), yet only a minority are diagnosed. The diagnostic criteria for FH rely on a point system using low-density lipoprotein cholesterol (LDL-C), family history, cutaneous manifestations, and molecular diagnosis. The aim of the present study was to determine the prevalence of FH in the R elating E vidence to A chieve C holesterol T argets (REACT) registry. Methods Patients were enrolled as ASCVD (n = 86) or FH (n = 109) and with an LDL-C level > 3.0 mmol/L despite maximally tolerated statin therapy. FH was diagnosed clinically using a validated clinical application integrating an imputation for baseline (untreated) LDL-C levels. Results There were 109 men and 86 women with a mean age of 63 ± 12 years. Diabetes (29.7%), hypertension (62.1%), smoking (37.9%), and family history of premature ASCVD (59.5%) were common. On-treatment LDL-C was 4.26 ± 0.94 mmol/L. On the basis of the dose and type of statin ± ezetimibe, imputed baseline LDL-C was 7.04 ± 2.90 mmol/L. A diagnosis of probable/definite FH was found in 54.7%, 49.5%, and 61.5% of patients according to the Simon Broome, Dutch Lipid Clinic Network criteria, and the new Canadian FH definition, respectively. Of note, 40% of patients in the ASCVD inclusion subgroup had probable or definite FH. Conclusions Our study reveals that a substantial proportion of patients with ASCVD whose LDL-C levels are > 3.0 mmol/L despite maximally tolerated statins have heterozygous FH. Clinicians should consider using the recently described algorithm to assess the possibility of FH in this high-risk population.