Background and Aims

Background:Lipoprotein(a) [Lp(a)] is a recognized cardiovascular risk factor. Lp(a) concentration in heterozygous familial hypercholesterolemia (heFH) is not well established. Whether the genetic defect responsible for heFH plays a role in determining Lp(a) concentration is unknown.

Aims:To study Lp(a) concentration in subjects genetically diagnosed with heFH and to assess the influence of the genetic defect responsible for heFH on its concentration.

Methods

Methods: Cross-sectional study, performed in a lipid clinic in Spain. We studied 511 heFH adults according to the responsible gene (LDLR, APOB, APOE and PCSK9). We selected 443 subjects LDLR, 27 subjects APOB, 37 subjects carriers of the p.(Leu167del) mutation in APOE, and 4 subjects PCSK9.

Results

Results:

Lipid levels differed across gene groups after adjusting for age, sex, and BMI.Lp(a) concentration differed among subjects with LDLR, APOB, and APOE mutation(p <0.001).Median Lp(a) concentration was greatest in APOB-dependent FH 36.5 mg/dL(IQR 22.0,60.8),intermediate in LDLR-dependent FH,21.7 mg/dL (IQR 17.9, 26.4)(and independent on the affected LDL receptor protein domain) and lowest in carriers of the p.(Leu167del) mutation in APOE, 7.9 mg/dL (IQR 4.9,12.7).Lp(a) geometric means, adjusted for age, sex, and BMI differed significantly. The geometric mean of LPA KIV-2 repeats did not differ among the FH gene subgroups and the estimations and differences for Lp(a) remained unchanged after adjustment for the number of KIV-2 repeats.

Conclusions

Conclusions: The concentration of Lp(a) in heFH is depending on the responsible gene. Lp(a) concentration was gratest in APOB- dependent FH. In LDLR-dependent, FH Lp(a) levels are not different depending on the affected protein domain.

Background and Aims

Background:Lipoprotein(a) [Lp(a)] is a recognized cardiovascular risk factor. Lp(a) concentration in heterozygous familial hypercholesterolemia (heFH) is not well established. Whether the genetic defect responsible for heFH plays a role in determining Lp(a) concentration is unknown.

Aims:To study Lp(a) concentration in subjects genetically diagnosed with heFH and to assess the influence of the genetic defect responsible for heFH on its concentration.

Methods

Methods: Cross-sectional study, performed in a lipid clinic in Spain. We studied 511 heFH adults according to the responsible gene (LDLR, APOB, APOE and PCSK9). We selected 443 subjects LDLR, 27 subjects APOB, 37 subjects carriers of the p.(Leu167del) mutation in APOE, and 4 subjects PCSK9.

Results

Results:

Lipid levels differed across gene groups after adjusting for age, sex, and BMI.Lp(a) concentration differed among subjects with LDLR, APOB, and APOE mutation(p <0.001).Median Lp(a) concentration was greatest in APOB-dependent FH 36.5 mg/dL(IQR 22.0,60.8),intermediate in LDLR-dependent FH,21.7 mg/dL (IQR 17.9, 26.4)(and independent on the affected LDL receptor protein domain) and lowest in carriers of the p.(Leu167del) mutation in APOE, 7.9 mg/dL (IQR 4.9,12.7).Lp(a) geometric means, adjusted for age, sex, and BMI differed significantly. The geometric mean of LPA KIV-2 repeats did not differ among the FH gene subgroups and the estimations and differences for Lp(a) remained unchanged after adjustment for the number of KIV-2 repeats.

Conclusions

Conclusions: The concentration of Lp(a) in heFH is depending on the responsible gene. Lp(a) concentration was gratest in APOB- dependent FH. In LDLR-dependent, FH Lp(a) levels are not different depending on the affected protein domain.