Does Familial Hypercholesterolemia Cause Elevated Lipoprotein(a)?

Does Familial Hypercholesterolemia Cause Elevated Lipoprotein(a)?:Elevated lipoprotein(a) levels were not found to be caused by familial hypercholesterolemia (FH), but may help with clinical recognition of genetic FH, according to study results published in Journal of the American College of Cardiology.

Patients diagnosed with FH have elevated lipoprotein(a) levels, but the cause of this elevation remains unclear.

Genotypic information and lipoprotein(a) levels of patients with FH were obtained from the British Columbia Familial Hypercholesterolemia cohort, which consists of patients (n=391; 52.4% women) clinically diagnosed with FH. Data for patients with non-FH dyslipidemia (n=245; 35.5% women) were obtained from the Familial Combined Hyperlipidemia cohort. Samples were genotyped at the rs10455872 and rs3798220 loci in the lipoprotein(A) gene (LPA), which are associated with increased risk for elevated lipoprotein(a) levels.

Lipoprotein(a) levels, as well as low-density lipoprotein cholesterol (LDL-C) levels, the prevalence of premature coronary artery or cerebrovascular disease, and the prevalence of parental history of cardiovascular disease or stroke, were also compared between genotypes in the general population using data from the United Kingdom Biobank (UK Biobank) cohort (n=37,486).

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Patients with clinically diagnosed FH had higher lipoprotein(a) levels (median, 28.7 mg/dL) than patients with non-FH dyslipidemia (median, 13.0. mg/dL; P =.0008) or the general population.

In the clinically diagnosed FH cohort, there was no significant difference in log-transformed lipoprotein(a) levels between carriers of pathogenic gene variants associated with FH relative to noncarriers. Similar results were seen within the UK Biobank cohort, in which there was no significant difference observed in lipoprotein(a) levels between patients with vs without genetically predicted FH.

Increased lipoprotein(a) levels in the clinically diagnosed FH vs non-FH dyslipidemia cohort were accounted for by an increased frequency of the rs10455872-G allele (15.1% vs (8.8%, respectively; P <.05).

In the UK Biobank cohort, the number of rs10455872-G risk alleles were found to be associated with lipoprotein(a) levels, LDL-C levels, premature coronary artery disease, premature cerebrovascular disease, and a parental history of heart disease (P <.0001 for all).

The researchers noted that the cohorts used in the study are largely of European ancestry and that results may not be representative of all populations.

“[L]ipoprotein(a) levels are elevated in patients with FH due to increased frequency of LPA variants contributing to increased levels of reported LDL-C, premature coronary artery disease, and a positive family history for heart disease that leads to ascertainment bias,” the study authors concluded. “Clinical and laboratory investigations for differentiating FH, elevated lipoprotein(a), or the combination of both are important for accurate diagnosis, risk stratification, and treatment strategies.” Does Familial Hypercholesterolemia Cause Elevated Lipoprotein(a)?

Disclosures: Dr Mancini reported affiliations with the pharmaceutical industry. Please see the original reference for a full list of disclosures.

Reference

Trinder M, DeCastro ML, Azizi H, et al. Ascertainment bias in the association between elevated lipoprotein(a) and familial hypercholesterolemia. J Am Coll Cardiol. 2020;75(21):2682‐2693. doi:10.1016/j.jacc.2020.03.065

This article originally appeared on The Cardiology Advisor