Case-finding and genetic testing for familial hypercholesterolaemia in primary care

Nadeem Qureshi, Ralph Kwame Akyea, Brittany Dutton, Steve E Humphries, Hasidah Abdul Hamid, Laura Condon, Stephen F Weng, Joe Kai, FAMCAT study, Paul Roderick, Dermot Neely, Andrew Neil, Simon Williams, Matthew Jones, Kate Walters, Katherine Payne, Barbara Hanratty, Phil Rowlands, Mark Fishers, Pankaj Gupta, Roger Stanworth, Tony Wierzbicki, Maggie Williams, Nadeem Qureshi, Ralph Kwame Akyea, Brittany Dutton, Steve E Humphries, Hasidah Abdul Hamid, Laura Condon, Stephen F Weng, Joe Kai, FAMCAT study, Paul Roderick, Dermot Neely, Andrew Neil, Simon Williams, Matthew Jones, Kate Walters, Katherine Payne, Barbara Hanratty, Phil Rowlands, Mark Fishers, Pankaj Gupta, Roger Stanworth, Tony Wierzbicki, Maggie Williams

Abstract

Objective: Familial hypercholesterolaemia (FH) is a common inherited disorder that remains mostly undetected in the general population. Through FH case-finding and direct access to genetic testing in primary care, this intervention study described the genetic and lipid profile of patients found at increased risk of FH and the outcomes in those with positive genetic test results.

Methods: In 14 Central England general practices, a novel case-finding tool (Familial Hypercholetserolaemia Case Ascertainment Tool, FAMCAT1) was applied to the electronic health records of 86 219 patients with cholesterol readings (44.5% of total practices' population), identifying 3375 at increased risk of FH. Of these, a cohort of 336 consenting to completing Family History Questionnaire and detailed review of their clinical data, were offered FH genetic testing in primary care.

Results: Genetic testing was completed by 283 patients, newly identifying 16 with genetically confirmed FH and 10 with variants of unknown significance. All 26 (9%) were recommended for referral and 19 attended specialist assessment. In a further 153 (54%) patients, the test suggested polygenic hypercholesterolaemia who were managed in primary care. Total cholesterol and low-density lipoprotein-cholesterol levels were higher in those patients with FH-causing variants than those with other genetic test results (p=0.010 and p=0.002).

Conclusion: Electronic case-finding and genetic testing in primary care could improve identification of FH; and the better targeting of patients for specialist assessment. A significant proportion of patients identified at risk of FH are likely to have polygenic hypercholesterolaemia. There needs to be a clearer management plan for these individuals in primary care.

Trial registration number: NCT03934320.

Keywords: electronic health records; genetics; hyperlipidemias.

Conflict of interest statement

Competing interests: NQ has received honoraria and travel costs for lectures from AMGEN and grants from National Institute for Health Research Health Technology Assessment Programme during the conduct of the study, SW reports personal fees from AMGEN, personal fees from Quealth outside the submitted work and was a member of Clinical Practice Research Datalink Independent Scientific Advisory Committee (ISAC). SEH reports grants from British Heart Foundation during the conduct of the study.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

Figures

Figure 1
Figure 1
Study flow diagram. FH, familial hypercholesterolaemia. *Lost to follow up includes: 42 participants did not respond to genetic test invite and 11 left the practice before genetic test invite was sent.
Figure 2
Figure 2
Graphical display of key findings. *Ever had total cholesterol >7.5 or LDL-C >4.9 mmol/L. CVD, cardiovascular disease; EHR, electronic health record; FH, familial hypercholesterolaemia; GP, general practitioner; S-B, Simon-Broome; VUS, variants of unknown significance.

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