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EAS2019 Congress: Failure to diagnose familial hypercholesterolaemia results in worse outcome

Wednesday 29 May 2019   (0 Comments)
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Results from an analysis of more than 1.7 million patient records show that patients who are likely to have familial hypercholesterolaemia (FH, inherited high cholesterol) based on cholesterol and family history criteria, but are not diagnosed as FH, are twice as likely to die earlier than individuals who have a FH diagnosis.1 The study was reported by Professor Kausik Ray (Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College London, UK).

FH is a common inherited lipid disorder which is thought to affect about one in 200-250 people in Europe.2 Untreated, FH confers a high burden of premature cardiovascular disease due to cumulative long-term exposure to high levels of low-density lipoprotein cholesterol (LDL-C).3 With early identification, however, ideally in children, individuals with FH can be treated with effective LDL-C-lowering therapy to manage the increased risk.4 Consequently, early screening is imperative for a healthy outcome.

This retrospective cohort analysis compared outcomes among patients with a coded diagnosis of FH versus patients with potential FH but no diagnosis and those in whom FH was unlikely, using data from the UK CPRD general practice data base. In total, 1,729,046 patient records were evaluated, of whom 0.4% (n=6,843) had a coded FH diagnosis while 0.8% (n=13,459) were indicated as potential FH based on at least one LDL-C measurement. These two groups were categorised as definite or probable FH based on Dutch Lipid Clinic Network or EUROASPIRE criteria, and the remaining patients did not meet the criteria for FH. Patients with cardiovascular disease at baseline were excluded from the analysis.

There were differences between the groups in baseline characteristics. Patients with a definite or potential FH diagnosis had higher baseline LDL-C levels than those unlikely to have FH (4.8 mmol/L and 5.6 mmoL/L versus 3.0 mmol/L, respectively). Interestingly, statin prescription in patients with a potential FH diagnosis was twice that in those with definite or unlikely FH (67.5% versus 33.3% and 23.9%), respectively). Patients with definite or potential FH had a higher risk of cardiovascular events, than those unlikely to have FH. Compared with the group with a definite FH diagnosis, patients with potential FH were twice as likely to die prematurely.

Despite the limitations of a retrospective design, the results provide further compelling evidence for screening early to identify and treat individuals with FH early and thus improve long-term health outcomes. Yet the clinical reality, as shown again by this study, is that very few individuals with FH are recognised. The global EAS FH Studies Collaboration (FHSC) was initiated to address this gap in FH care, with the ultimate mission of ensuring that screening for FH is recognised as part of the World Health Organisation Non-Communicable Disease Programme. To facilitate this, the EAS FHSC recently announced a collaboration with the patient representative network, FH Europe, to ensure that there is now one voice for FH in Europe.

To the video interview with Professor Ray >>

Other news from the Late Breaking Session

Understanding the genetics of lipid species offers information beyond that provided by routine lipid screening, and can help improve risk prediction and treatment, according to results from a genetic investigation of detailed lipidomic profiles.5 The study was presented by Dr. Rubina Tabassum (Institute for Molecular Medicine Finland, University of Helsinki, Finland). Using an omics approach, the investigators integrated information from genomics, lipidomics and phenomics in 511,700 individuals for 35 lead genetic variants and 37 disease outcomes. The investigators highlighted three key findings, as summarised below.

  • Lipid species are heritable, with the highest heritability in lipids containing polyunsaturated fatty acids.

  • Ten of the variants investigated (in APOA5, ABCG5/8, BLK, LPL, FADS2, COL5A1, GALNT16, GLTPD2, MBOAT7 and SPTLC3 genes) were associated with cardiovascular disease. In addition, gene variants at the BLK, GALNT16 and LPL genes were associated with type 2 diabetes.

  • The study also provided clues to the underlying mechanisms of well-known lipid loci on cardiovascular disease risk. Notably, the association of reduced cardiovascular risk with the rs11570891 variant in the intron of the gene encoding lipoprotein lipase (LpL) might be mediated by increased activity of LpL.

In another report,6 data from the Ludwigshafen Risk and Cardiovascular Health Study showed that an NLRP3 variant (rs10754555) was associated with higher inflammation but not traditional cardiovascular risk factors, suggesting further investigation of its potential in therapeutic targeting.


1. Ray KK, Pillas D, Khunti K, Kondapally R, Hadjiphilippou S, Vallejo-Vaz A, Neasham D.  Premature morbidity and mortality among diagnosed and potentially undiagnosed familial hypercholesterolemia patients in the general population: an observational study of over 1.7 million health records.  Abstract EAS19-1126.

2. Benn M, Watts GF, Tybjærg-Hansen A, Nordestgaard BG. 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 2016;37:1384-94.

3. Nordestgaard BG, Chapman MJ, Humphries SE et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J 2013;34:3478-90a.

4. Wiegman A, Gidding SS, Watts GF et al. Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. Eur Heart J 2015;36:2425-37.

5. Tabassum R, Rämö JT, Ripatti P, Koskela JT, Kurki M, Karjalainen J, Palta P, Hassan S, Nunez-Fontarnau J, Kiiskinen TTJ, Söderlund S, Matikainen N, Gerl MJ, Surma MA, Klose C, Stitziel NO, Laivuori H, Havulinna AS, Service SK, Salomaa V, Pirinen M, FinnGen Project T, Jauhiainen M, Daly MJ, Freimer N, Palotie A, Taskinen MR, Simons K, Ripatti S. Genetics of human plasma lipidome and its link to diseases susceptibility. Abstract EAS19-1105.

6. März W, Zewinger S, Kleber MK, Schunk SJ, Triem S, Lars W, Trompet S, Jukema JW, Sattar N, Koenig W, Fliser D, Laufs U, Speer T. Common variant in the NLRP3 inflammasome locus associates with mortality. Abstract EAS- 1116.

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