Genetics
Nordestgaard-led study of 15 Danish lipid clinics finds elevated Lp(a) explains 27% of clinical familial hypercholesterolaemia diagnoses (J Clin Endocrinol Metab 2024)
Original title: High Lipoprotein(a) May Explain One-Quarter of Clinical Familial Hypercholesterolemia Diagnoses in Danish Lipid Clinics
Because cholesterol carried in Lp(a) adds to measured LDL cholesterol, it can artificially drive some clinical diagnoses of familial hypercholesterolaemia (FH). This study recruited 1,166 individuals referred to 15 Danish lipid clinics for suspected FH between September 2020 and November 2021, classifying them by Dutch Lipid Clinical Network criteria both before and after adjusting LDL-C for the 30% cholesterol content attributable to Lp(a). Median Lp(a) was 15 mg/dL, with 28% of referred individuals at or above 50 mg/dL and 2% at or above 180 mg/dL. Of the 206 individuals who fulfilled a clinical FH diagnosis, 55 (27%) did so partly because of elevated Lp(a) inflating their apparent LDL-C. The findings support considering the LPA gene an important causative factor in patients diagnosed with clinical FH, and reinforce the importance of measuring Lp(a) both when diagnosing FH and when stratifying cardiovascular risk more broadly.
Original abstract
Context: Cholesterol carried in lipoprotein(a) adds to measured low-density lipoprotein cholesterol (LDL-C) and may therefore drive some diagnoses of clinical familial hypercholesterolemia (FH).
Objective: We investigated plasma lipoprotein(a) in individuals referred to Danish lipid clinics and evaluated the effect of plasma lipoprotein(a) on a diagnosis of FH.
Methods: Individuals referred to 15 Danish lipid clinics who were suspected of having FH according to nationwide referral criteria were recruited between September 1, 2020 and November 30, 2021. All individuals were classified according to the Dutch Lipid Clinical Network criteria for FH before and after LDL-C was adjusted for 30% cholesterol content in lipoprotein(a). We calculated the fraction of individuals fulfilling a clinical diagnosis of FH partly due to elevated lipoprotein(a).
Results: We included a total of 1166 individuals for analysis, of whom 206 fulfilled a clinical diagnosis of FH. Median lipoprotein(a) was 15 mg/dL (29 nmol/L) in those referred and 28% had lipoprotein(a) greater than or equal to 50 mg/dL (105 nmol/L), while 2% had levels greater than or equal to 180 mg/dL (389 nmol/L). We found that in 27% (55/206) of those fulfilling a clinical diagnosis of FH, this was partly due to high lipoprotein(a).
Conclusion: Elevated lipoprotein(a) was common in individuals referred to Danish lipid clinics and in one-quarter of individuals who fulfilled a clinical diagnosis of FH, this was partly due to elevated lipoprotein(a). These findings support the notion that the LPA gene should be considered an important causative gene in patients with clinical FH and further support the importance of measuring lipoprotein(a) when diagnosing FH as well as for stratification of cardiovascular risk.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.