Premature morbidity and mortality associated with potentially undiagnosed familial hypercholesterolemia in the general population

Background: Familial hypercholesterolemia (FH) is common, but underdiagnosed, and few systematic early screening programs exist. Objective: To assess health outcomes among those with a recorded diagnosis of FH and potential cases of FH with no recorded diagnosis. Methods: Retrospective cohort study using the UK Clinical Practice Research Datalink. Records of adults were classified as diagnosed FH (FHCoded), or via accepted algorithms using LDL-C and clinical characteristics as potential FH (FHPotential) or unlikely FH (FHUnlikely) using the DLCN or EUROASPIRE criteria (but no record of FH). Outcomes assessed were premature cardiovascular (CV) events, premature deaths and life expectancy. Results: Among 1,729,046 individuals free from CV events, a record of FHCoded before the age of 40 was 0.3/1000 (IQR 0.3–0.4) and increased with age. Where LDL-C levels were available, 1.8/1000 (IQR 1.6–2.0) could be classified as FHPotential. LDL-C was higher for both FHCoded and FHPotential vs FHUnlikely (185.6 and 216.6 vs 116 mg/dL, respectively, p