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Hyperlipoproteinaemia(a) is a common cause of autosomal dominant hypercholesterolaemia

  • Original Article
  • Published:
Journal of Inherited Metabolic Disease

Summary

Autosomal dominant hypercholesterolaemias (ADH) are a heterogeneous group of monogenic lipid disorders. The plasma level of lipoprotein(a) (Lp(a)) is a heritable trait associated with increased coronary heart disease (CHD) risk.

Objective

To evaluate the frequency of elevated Lp(a) as a cause of ADH and the characteristics of subjects with high Lp(a) (hyperLp(a)).

Material and methods

200 healthy subjects and 933 unrelated Spanish subjects with a clinical diagnosis of ADH who were screened for low-density lipoprotein receptor (LDLR) and apolipoprotein B (APOB) gene mutations. Standard cardiovascular risk factors and blood lipid levels, including Lp(a), were evaluated. HyperLp(a) was defined as Lp(a) levels ≥95th centile of control values.

Results

Lp(a) was higher in 263 subjects without LDLR or APOB mutations (nonLDLR/nonAPOB group) than in 670 subjects with mutations (FH group): 40.0 mg/dl (interquartile range (IR) 15.0–89.0) versus 31.0 mg/dl (IR 11.0–73.7) respectively, p=0.002. HyperLp(a) was present in 23% of ADH subjects (odds ratio (OR) 5.6 (95% CI, 2.9 to 10.7) versus controls) and 29% of nonLDLR/nonAPOB subjects (OR 7.7; 3.9 to 15.4). After adjusting for Lp(a), LDL cholesterol levels were <95th centile in 28 (10.6%) nonLDLR/nonAPOB subjects and in 9 (1.3%) FH subjects. Lp(a) levels were nonsignificantly higher in ADH subjects with early-onset CHD than in those without (43.5 mg/dl, (IR, 12.0–82.0) versus 31.7 mg/dl (11.8–76.5), respectively).

Conclusions

HyperLp(a) is responsible for ADH in approximately 6% of nonLDLR/nonAPOB subjects. HyperLp(a) would not appear to be a risk factor for early-onset CHD in ADH, independently of whether genetic defects have or have not been demonstrated.

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Authors and Affiliations

  1. Lipid Unit and Molecular Research Laboratory, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud, Avda Isabel La Católica 1–3, 50009, Zaragoza, Spain

    E. Meriño-Ibarra, E. Jarauta, A. Cenarro, D. Recalde, Á. L. García-Otín & F. Civeira

  2. Lipid Unit, Hospital San Jorge, Huesca, Spain

    J. Puzo

  3. Lipid Clinic, Institut d’Investigacions Biomèdiques August Pi Sunyer, Hospital Clínic, Barcelona, Spain

    E. Ros & D. Zambón

  4. Lipid Unit, Hospital Son Llàtzer, Palma de Mallorca, Spain

    E. Martorell

  5. Lipid & Atherosclerosis Unit, Hospital de Bellvitge, Barcelona, Spain

    X. Pintó

  6. Lipid Unit, Hospital Santa Cruz y San Pablo, Barcelona, Spain

    M. Franco

  7. Lipid Unit, Hospital San Millán, Logroño, Spain

    Á. Brea

  8. Department of Biochemistry, Molecularand Cellular Biology, Zaragoza University, Zaragoza, Spain

    M. Pocoví

Authors
  1. E. Meriño-Ibarra
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  2. J. Puzo
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  3. E. Jarauta
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  4. A. Cenarro
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  5. D. Recalde
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  6. Á. L. García-Otín
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  7. E. Ros
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  8. E. Martorell
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  9. X. Pintó
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  10. M. Franco
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  11. D. Zambón
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  12. Á. Brea
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  13. M. Pocoví
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  14. F. Civeira
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Corresponding author

Correspondence to F. Civeira.

Additional information

Communicating editor: Robert Steiner

Competing interests: None declared

References to electronic databases: Familial hypercholesterolaemia: OMIM #143890. Familial defective apo B: OMIM #144010. PCSK9: OMIM *607786. Neural apoptosis-regulated convertase 1: OMIM *607786. Lipoprotein(a): OMIM +152200.

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Meriño-Ibarra, E., Puzo, J., Jarauta, E. et al. Hyperlipoproteinaemia(a) is a common cause of autosomal dominant hypercholesterolaemia. J Inherit Metab Dis 30, 970–977 (2007). https://doi.org/10.1007/s10545-007-0585-z

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  • DOI: https://doi.org/10.1007/s10545-007-0585-z

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