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Ascertainment Bias in the Association Between Elevated Lipoprotein(a) and Familial Hypercholesterolemia

Trinder, Mark, DeCastro, Maria L., Azizi, Hawmid, Cermakova, Luba, Jackson, Linda M., Frohlich, Jiri, Mancini, G.B. John, Francis, Gordon A., Brunham, Liam R.·2020·Journal of the American College of Cardiology
DOI 10.1016/j.jacc.2020.03.065
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  • Other studies of individuals with Familial Hypercholesterolemia have not reported an increase in Lp(a) levels.

    “Some studies of individuals with Familial Hypercholesterolemia (FH) have reported an increase in Lp(a) levels40-42, but others have not43-45 and suggested that the former may have been confounded by diagnostic ascertainment bias and/or unequal distributions of LPA risk alleles between FH and non-FH populations44,45.”

    From Functional interrogation of cellular Lp(a) uptake by genome-scale CRISPR screening (2025) · cites this paper as [44]

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Research works printed but not linked: 41

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  2. Kamstrup, 2013, Extreme lipoprotein(a) levels and improved cardiovascular risk prediction, J Am Coll Cardiol, 61, 1146, 10.1016/j.jacc.2012.12.023 · DOI · Paper page
  3. Burgess, 2018, Association of LPA variants with risk of coronary disease and the implications for lipoprotein(a)-lowering therapies: a Mendelian randomization analysis, JAMA Cardiol, 3, 619, 10.1001/jamacardio.2018.1470 · DOI · Paper page
  4. Nordestgaard, 2010, Lipoprotein(a) as a cardiovascular risk factor: current status, Eur Heart J, 31, 2844, 10.1093/eurheartj/ehq386 · DOI · Paper page
  5. Boerwinkle, 1992, Apolipoprotein(a) gene accounts for greater than 90% of the variation in plasma lipoprotein(a) concentrations, J Clin Invest, 90, 52, 10.1172/JCI115855 · DOI
  6. Clarke, 2009, Genetic variants associated with Lp(a) lipoprotein level and coronary disease, N Engl J Med, 361, 2518, 10.1056/NEJMoa0902604 · DOI · Paper page
  7. Langsted, 2016, High lipoprotein(a) as a possible cause of clinical familial hypercholesterolaemia: a prospective cohort study, Lancet Diabetes Endocrinol, 4, 577, 10.1016/S2213-8587(16)30042-0 · DOI · Paper page
  8. Alonso, 2014, Lipoprotein(a) levels in familial hypercholesterolemia: an important predictor of cardiovascular disease independent of the type of LDL receptor mutation, J Am Coll Cardiol, 63, 1982, 10.1016/j.jacc.2014.01.063 · DOI · Paper page
  9. Li, 2017, Significance of lipoprotein(a) levels in familial hypercholesterolemia and coronary artery disease, Atherosclerosis, 260, 67, 10.1016/j.atherosclerosis.2017.03.021 · DOI
  10. Reyes-Soffer, 2017, The metabolism of lipoprotein (a): an ever-evolving story, J Lipid Res, 58, 1756, 10.1194/jlr.R077693 · DOI
  11. Benn, 2016, Mutations causative of familial hypercholesterolaemia: screening of 98,098 individuals from the Copenhagen General Population Study estimated a prevalence of 1 in 217, Eur Heart J, 37, 1384, 10.1093/eurheartj/ehw028 · DOI
  12. Akioyamen, 2017, Estimating the prevalence of heterozygous familial hypercholesterolaemia: a systematic review and meta-analysis, BMJ Open, 7, 10.1136/bmjopen-2017-016461 · DOI
  13. de Ferranti, 2016, Prevalence of familial hypercholesterolemia in the 1999 to 2012 United States National Health and Nutrition Examination Surveys (NHANES), Circulation, 133, 1067, 10.1161/CIRCULATIONAHA.115.018791 · DOI · Paper page
  14. Taylor, 2010, Mutation detection rate and spectrum in familial hypercholesterolaemia patients in the UK pilot cascade project, Clin Genet, 77, 572, 10.1111/j.1399-0004.2009.01356.x · DOI
  15. Ference, 2017, Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel, Eur Heart J, 38, 2459, 10.1093/eurheartj/ehx144 · DOI · Paper page
  16. Defesche, 2017, Familial hypercholesterolaemia, Nat Rev Dis Primer, 3, 17093, 10.1038/nrdp.2017.93 · DOI · Paper page
  17. Kraft, 2000, Lipoprotein(a) in homozygous familial hypercholesterolemia, Arterioscler Thromb Vasc Biol, 20, 522, 10.1161/01.ATV.20.2.522 · DOI · Paper page
  18. Raal, 2014, Reduction in lipoprotein(a) with PCSK9 monoclonal antibody evolocumab (AMG 145): a pooled analysis of more than 1,300 patients in 4 phase II trials, J Am Coll Cardiol, 63, 1278, 10.1016/j.jacc.2014.01.006 · DOI
  19. Rader, 1995, The low density lipoprotein receptor is not required for normal catabolism of Lp(a) in humans, J Clin Invest, 95, 1403, 10.1172/JCI117794 · DOI · Paper page
  20. Willeit, 2018, Baseline and on-statin treatment lipoprotein(a) levels for prediction of cardiovascular events: individual patient-data meta-analysis of statin outcome trials, Lancet, 392, 1311, 10.1016/S0140-6736(18)31652-0 · DOI · Paper page
  21. Tsimikas, 2019, Statin therapy increases lipoprotein(a) levels, Eur Heart J
  22. Brunham, 2017, Contemporary trends in the management and outcomes of patients with familial hypercholesterolemia in Canada: a prospective observational study, Can J Cardiol, 33, 385
  23. Holmes, 2005, Lipoprotein(a) is an independent risk factor for cardiovascular disease in heterozygous familial hypercholesterolemia, Clin Chem, 51, 2067, 10.1373/clinchem.2005.055228 · DOI
  24. Trinder, 2019, Risk of premature atherosclerotic disease in patients with monogenic versus polygenic familial hypercholesterolemia, J Am Coll Cardiol, 74, 512, 10.1016/j.jacc.2019.05.043 · DOI
  25. Umans-Eckenhausen, 2001, Review of first 5 years of screening for familial hypercholesterolaemia in the Netherlands, Lancet, 357, 165, 10.1016/S0140-6736(00)03587-X · DOI
  26. Jones, 2003, Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR∗ Trial), Am J Cardiol, 92, 152, 10.1016/S0002-9149(03)00530-7 · DOI
  27. Lanktree, 2009, Determination of lipoprotein(a) kringle repeat number from genomic DNA: copy number variation genotyping using qPCR, J Lipid Res, 50, 768, 10.1194/jlr.D800050-JLR200 · DOI
  28. Veerkamp, 2004, Nomogram to diagnose familial combined hyperlipidemia on the basis of results of a 5-year follow-up study, Circulation, 109, 2980, 10.1161/01.CIR.0000130646.93255.86 · DOI
  29. Bycroft, 2018, The UK Biobank resource with deep phenotyping and genomic data, Nature, 562, 203, 10.1038/s41586-018-0579-z · DOI · Paper page
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  31. Trinder, 2020, Association of monogenic vs polygenic hypercholesterolemia with risk of atherosclerotic cardiovascular disease, JAMA Cardiol, 10.1001/jamacardio.2019.5954 · DOI
  32. Khera, 2016, Diagnostic yield and clinical utility of sequencing familial hypercholesterolemia genes in patients with severe hypercholesterolemia, J Am Coll Cardiol, 67, 2578, 10.1016/j.jacc.2016.03.520 · DOI · Paper page
  33. Landrum, 2014, ClinVar: public archive of relationships among sequence variation and human phenotype, Nucleic Acids Res, 42, D980, 10.1093/nar/gkt1113 · DOI · Paper page
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  35. Brown, 2010, Management of Lp(a), J Clin Lipidol, 4, 240, 10.1016/j.jacl.2010.07.002 · DOI
  36. Virani, 2012, Associations between lipoprotein(a) levels and cardiovascular outcomes in black and white subjects, Circulation, 125, 241, 10.1161/CIRCULATIONAHA.111.045120 · DOI
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Metadata

Authors
Trinder, M., DeCastro, M. L., Azizi, H., Cermakova, L., Jackson, L. M., Frohlich, J., Mancini, G. B. J., Francis, G. A., & Brunham, L. R.
Venue
Journal of the American College of Cardiology
Publisher
Elsevier BV
Published
2020-06
Volume
75
Issue
21
Pages
2682-2693
ISSN
0735-1097
DOI
10.1016/j.jacc.2020.03.065
Cited by
76
References
3
Language
en
Licence

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