Abstract
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 (FH(Coded)), or via accepted algorithms using LDL-C and clinical characteristics as potential FH (FH(Potential)) or unlikely FH (FH(Unlikely)) 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 FH(Coded) 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 FH(Potential). LDL-C was higher for both FH(Coded) and FH(Potential) vs FH(Unlikely) (185.6 and 216.6 vs 116 mg/dL, respectively, p<0.001). Compared to FH(Unlikely) both FH(Coded) and FH(Potential) cohorts had a higher risk of premature cardiovascular events (both p<0.001) with highest rates among FH(Coded). Risk of premature deaths did not differ between FH(Coded) and FH(Unlikely,) but was 1.88 (95% CI 1.27-2.78, p = 0.002) for FH(Potential) vs FH(Coded) and 2.40 (95% CI 1.57-3.67, p<0.001) for FH(Potential) vs FH(Unlikely). At age 18, the FH(Potential) cohort had a life expectancy 16 years lower than the FH(Coded) cohort (p<0.001). CONCLUSIONS: Potential cases of FH had a doubling in risk of premature death and a large reduction in life expectancy compared to individuals with a recorded diagnosis of FH. These findings strengthen the critical importance of identifying potential cases of FH early and early treatment.