Lipoprotein(a) Levels in Familial Hypercholesterolemia: An Important Predictor for Cardiovascular Disease Independent of the Type of LDL-Receptor Mutation

Study Questions:

What is the relationship between lipoprotein a [Lp(a)] levels and cardiovascular disease (CVD) in patients with heterozygous familiar hypercholesterolemia (FH)?

Methods:

Plasma levels of Lp(a) were measured in 1,960 FH and 957 non-FH relatives recruited for a long-term observational cohort study.

Results:

FH patients had higher Lp(a) plasma levels compared with their unaffected relatives (p < 0.001). In multivariate analysis, Lp(a) was an independent predictor for CVD. Patients carrying low-density lipoprotein (LDL) receptor null-mutations and Lp(a) levels >50 mg/dl showed the highest CV risk compared with patients carrying the same mutations and Lp(a) <50 mg/dl.

Conclusions:

The authors concluded that Lp(a) is an independent predictor of CVD in subjects with FH.

Perspective:

Several studies have demonstrated an association between levels of Lp(a) and risk for CV complications. However, this association in patients with FH is controversial. In this study, FH patients with CVD had Lp(a) levels that were twice as high compared to those in FH and non-FH relatives without CVD. This suggests that there may be clinical utility in measuring Lp(a) in certain high-risk patient groups, especially since emerging lipid-lowering drugs such as PCSK9 inhibitors effectively reduce Lp(a) levels.

Keywords: Mutation, Lipoproteins, LDL, Multivariate Analysis, Lipoprotein(a), Hyperlipoproteinemia Type II, Heterozygote, Cardiovascular Diseases, Receptors, LDL, Hypercholesterolemia


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