Key result
PCSK9 gain-of-function FH mutations are linked to roughly fourfold higher serum Lp(a) levels.
Why the study?
Are serum Lp(a) levels elevated in patients with familial hypercholesterolemia caused by PCSK9 gain-of-function mutations compared to controls?
Observational (n=4,255)
Are serum Lp(a) levels elevated in patients with familial hypercholesterolemia caused by PCSK9 gain-of-function mutations compared to controls?
Absolute Event Rate: 21.1% vs 5%
p-value: p=0.002
Serum Lp(a) is elevated in patients with familial hypercholesterolemia caused by PCSK9 gain-of-function mutations to a similar extent as in those with LDLR mutations.
Background:It has been shown that serum lipoprotein(a) [Lp(a)] is elevated in familial hypercholesterolemia (FH) with mutation(s) of the LDL receptor (LDLR) gene. However, few data exist regarding Lp(a) levels in FH with gain-of-function mutations of the PCSK9 gene.Methods and Results:We evaluated 42 mutation-determined heterozygous FH patients with aPCSK9gain-of-function mutation (FH-PCSK9, mean age 52, mean LDL-C 235 mg/dl), 198 mutation-determined heterozygous FH patients with aLDLRmutation (FH-LDLR, mean age 44, mean LDL-C 217 mg/dl), and 4,015 controls (CONTROL, mean age 56, mean LDL-C 109 mg/dl). We assessed their Lp(a), total cholesterol, triglycerides, HDL-C, LDL-C, use of statins, presence of hypertension, diabetes, chronic kidney disease, smoking, body mass index (BMI) and coronary artery disease (CAD). Multiple regression analysis showed that HDL-C, use of statins, presence of hypertension, smoking, BMI, and Lp(a) were independently associated with the presence of CAD. Under these conditions, the serum levels of Lp(a) in patients with FH were significantly higher than those of the CONTROL group regardless of their causative genes, among the groups propensity score-matched (median Lp(a) 12.6 mg/dl [IQR:9.4–33.9], 21.1 mg/dl [IQR:11.7–34.9], and 5.0 mg/dl [IQR:2.7–8.1] in the FH-LDLR, FH-PCSK9, and CONTROL groups, respectively, P=0.002 for FH-LDLR vs. CONTROL, P=0.002 for FH-PCSK9 vs. CONTROL).Conclusions:These data demonstrate that serum Lp(a) is elevated in patients with FH caused by PCSK9 gain-of-function mutations to the same level as that in FH caused by LDLR mutations. (Circ J 2016; 80: 512–518)
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Tada et al. (2016) conducted an observational in Familial Hypercholesterolemia (n=4,255). PCSK9 gain-of-function mutations vs. Controls and LDLR mutations was evaluated on Serum Lp(a) levels (p=0.002). Serum Lp(a) levels were significantly elevated in patients with FH caused by PCSK9 gain-of-function mutations (median 21.1 mg/dl) compared to controls (5.0 mg/dl; P=0.002).
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