THE HIGH PREVALENCE OF FAMILIAL HYPERCHOLESTEROLEMIA IN A POPULATION OF ASCVD PATIENTS WITH LDL-C ABOVE TARGET: AN ANALYSIS FROM THE REACT REGISTRY

Abstract

Heterozygous familial hypercholesterolemia (FH) prevalence is 1/250 in the general population and 1/125 in ASCVD patients, yet only a minority of patients are formally diagnosed. FH rises significantly with baseline LDL-cholesterol (LDL-C) levels above 5 mmol/L. Early identification and aggressive lipid-lowering therapy is thought to have substantial benefit on prevention of cardiovascular morbidity and mortality. We used a validated imputation for baseline (untreated) LDL-C levels and determined the prevalence of FH in this group, based on accepted international criteria and a new Canadian definition for FH. We intended to prospectively enroll 1800 patients with either established atherosclerotic CV disease (ASCVD) or FH (diagnosed based on traditional criteria), with LDL-C level >3.0mmol/L despite maximally tolerated statin therapy, as part of a national registry (REACT program-Relating Evidence to Achieve Cholesterol Targets). The sponsor terminated funding prematurely, resulting in 195 enrolled patients. We used a validated imputation for baseline (untreated) LDL-C levels, along with other clinical criteria to determine prevalence of FH, using accepted international criteria and a new Canadian definition for FH. Patients were categorized by enrolling physicians as either ASCVD or FH. There were 109 men and 86 women (76% Caucasian), mean age was 63±12 years. Diabetes (29.7%), hypertension (62.1%), smoking (37.9%) and family history of premature ASCVD (59.5%) were common. Six patients (3%) were diagnosed by enrolling physicians as having FH, the remaining as ASCVD. On-treatment LDL-C was 4.26±0.94mmol/L (mean±SD). Based on the dose and type of statin, +/- ezetimibe, imputed baseline or untreated LDL-C was 7.06±2.94mmol/L. A computerized algorithm was used to determine a diagnosis of FH incorporating additional clinical criteria. Using a cut-point of LDL-C >5.0mmol/L, 140/195(72%) of patients had severe hypercholesterolemia, the threshold for considering a diagnosis of FH in adults. Using the Simon-Broome criteria, 47/140(34%) had definite or 24/140(17%) probable FH, and using the Dutch Lipid Clinic Network 48/140(34%) had definite, 5/140(4%) probable or 80/140(57%) possible FH. Results mirror the new Canadian FH definition with 48/140(34%) definite or 13/140(9%) probable FH. This REACT analysis reveals a substantial proportion of ASCVD patients whose LDL-C levels remain above target in fact have probable or definite FH. Appropriate diagnosis of FH in these patients not only guides aggressive therapy, but has important implications for cascade screening and prevention in first degree relatives. Use of an imputed LDL-C in statin treated patients, and simplified tools for FH diagnosis should enable clinicians to more easily identify FH patients in their practices.