Prevalence and clinical correlates of familial hypercholesterolemia founder mutations in the general population

This study aimed to investigate the exact prevalence of familial hypercholesterolemia (FH) in the general population, taking advantage of the fact that five low-density lipoprotein receptor (LDLR) founder mutations account for 78% of FH cases in Finland.

Five LDLR founder mutations, FH-North Karelia, FH-Helsinki, FH-Pogosta, FH-Turku, and FH-Pori, were genotyped and serum lipid levels were measured in a large collection of Finnish population cohorts (n = 28,465), including the National FINRISK Study and the Health 2000 Study. Follow-up data were obtained from national healthcare registries.

The combined prevalence of three of the five FH founder mutations (FH-North Karelia, FH-Helsinki, and FH-Pogosta) was 0.12% (95% CI 0.07-0.16%), while FH-Turku and FH-Pori were not identified in the present sample cohort. Our data suggest that the estimated total prevalence of FH in Finland is at least 0.17%. Approximately half of the 35 FH mutation carriers used lipid-lowering medication at the time of the baseline investigation. LDL cholesterol levels were on average 2 mmol/L higher in mutation carriers than in non-carriers (p < 0.001) but did not differ between FH mutation carriers with and without lipid-lowering medication. During the follow-up for 13 years, one mutation carrier encountered a probable sudden cardiac death, two mutation carriers suffered from a stroke, and one from a myocardial infarction.

In Finland, at least 1 in 600 individuals is estimated to have FH. A marked undertreatment of FH was observed in LDLR mutation carriers.