Raised lipoprotein(a) could account for a quarter of FH cases

By Eleanor McDermid

High levels of lipoprotein(a) could account for a substantial proportion of cases of familial hypercholesterolaemia (FH), a large study shows.

"Although it could be argued that this finding is not surprising, the fact that high lipoprotein(a) concentration has a potentially causal association with clinical familial hypercholesterolaemia has not, to our knowledge, previously been recognised or shown", write the researchers in The Lancet Diabetes & Endocrinology.

The study involved participants of the Copenhagen General Population Study, of whom 184 had probable or definite FH and 3082 had possible FH, according to the Dutch Lipid Clinic Network criteria (not accounting for causative mutations).

These people had average low-density lipoprotein (LDL) cholesterol levels of 35 and 32 mg/dL, respectively, which were a significant 52% and 39% higher than the average 23 mg/dL among the 42,934 people considered unlikely to have FH.

However, after adjusting for lipoprotein(a) levels, LDL cholesterol no longer differed between the groups, at 21, 22 and 24 mg/dL among people classified as having definite/probable, possible and no FH, respectively. Furthermore, the LPA rs10455872 polymorphism was significantly more common among people with an FH diagnosis than those unlikely to have the condition.

When Børge Nordestgaard (Copenhagen University Hospital, Denmark) and co-researchers discounted lipoprotein(a) cholesterol from total and LDL cholesterol measurements, they found around a 25% reduction in the number of people diagnosed with definite/probable or possible FH. In other words, high lipoprotein(a) levels accounted for clinical FH in a quarter of participants.

The team observes that "if during genetic testing, a familial hypercholesterolaemia-causing mutation is not found in LDLR, APOB, or PCSK9, it might be that variation in the LPA gene is a major contributing cause of clinical familial hypercholesterolaemia."

And the finding even has treatment implications, they note, because FH caused primarily by lipoprotein(a) may be less responsive to statin treatment.

Indeed, elevated lipoprotein(a) levels were associated with an increased risk of myocardial infarction, with levels above 50 mg/dL raising the risk 1.4-fold in participants without FH and 5.3-fold in those with possible, probable or definite FH. Patients with possible or probable/definite FH but low lipoprotein(a) levels had a 3.2-fold increased risk.

In an accompanying commentary, Raul Santos (Hospital Israelita Albert Einstein, São Paulo, Brazil) says that the findings "reinforce the need" to measure lipoprotein(a) levels in patients with hypercholesterolaemia.

He says it will "be interesting to test whether treatments that reduce both LDL cholesterol and lipoprotein(a) concentrations, such as the PCSK9 inhibitors, will prevent cardiovascular disease beyond the expected reduction in LDL cholesterol alone".

"At any rate, one should be cautious of elevated lipoprotein(a) concentrations."

Licensed from medwireNews with permission from Springer Healthcare Ltd. ©Springer Healthcare Ltd. All rights reserved. Neither of these parties endorse or recommend any commercial products, services, or equipment.