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Abstract
Objective Familial hypercholesterolaemia (FH) is a common inherited disorder causing premature coronary heart disease (CHD) and death. We have developed the novel Familial Hypercholesterolaemia Case Ascertainment Tool (FAMCAT 1) case-finding algorithm for application in primary care, to improve detection of FH. The performance of this algorithm was further improved by including personal history of premature CHD (FAMCAT 2 algorithm). This study has evaluated their performance, at 95% specificity, to detect genetically confirmed FH in the general population. We also compared these algorithms to established clinical case-finding criteria.
Methods Prospective validation study, in 14 general practices, recruiting participants from the general adult population with cholesterol documented. For 260 participants with available health records, we determined possible FH cases based on FAMCAT thresholds, Dutch Lipid Clinic Network (DLCN) score, Simon-Broome criteria and recommended cholesterol thresholds (total cholesterol >9.0 mmol/L if ≥30 years or >7.5 mmol/L if <30 years), using clinical data from electronic and manual extraction of patient records and family history questionnaires. The reference standard was genetic testing. We examined detection rate (DR), sensitivity and specificity for each case-finding criteria.
Results At 95% specificity, FAMCAT 1 had a DR of 27.8% (95% CI 12.5% to 50.9%) with sensitivity of 31.2% (95% CI 11.0% to 58.7%); while FAMCAT 2 had a DR of 45.8% (95% CI 27.9% to 64.9%) with sensitivity of 68.8% (95% CI 41.3% to 89.0%). DLCN score ≥6 points yielded a DR of 35.3% (95% CI 17.3% to 58.7%) and sensitivity of 37.5% (95% CI 15.2% to 64.6%). Using recommended cholesterol thresholds resulted in DR of 28.0% (95% CI 14.3% to 47.6%) with sensitivity of 43.8% (95% CI 19.8% to 70.1%). Simon-Broome criteria had lower DR 11.3% (95% CI 6.0% to 20.0%) and specificity 70.9% (95% CI 64.8% to 76.5%) but higher sensitivity of 56.3% (95% CI 29.9% to 80.2%).
Conclusions In primary care, in patients with cholesterol documented, FAMCAT 2 performs better than other case-finding criteria for detecting genetically confirmed FH, with no prior clinical review required for case finding.
Trial registration number NCT03934320.
- electronic health records
- hyperlipidemias
- delivery of health care
Data availability statement
No data are available. We do not have consent from participants to share their data for the purposes of future research.
This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.
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Data availability statement
No data are available. We do not have consent from participants to share their data for the purposes of future research.
Supplementary materials
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Footnotes
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NQ and RKA contributed equally.
SW and JK contributed equally.
Collaborators Dr Pankaj Gupta, Dr Roger Stanworth, Professor Tony Wierzbicki, Dr Maggie Williams, Dr Matthew Jones, Dr Kate Walters, Professor Katherine Payne, Professor Barbara Hanratty.
Contributors NQ, SW and JK were involved in the study conception, study design and securing funding. Analysis by SW and RKA. BD was responsible for data curation and collection. The manuscript was first drafted by SW and NQ, and subsequent iterations were revised by RKA, JK and JL-B. All authors reviewed and approved the final manuscript. NQ is the guarantor of the manuscript.
Funding This study is funded by the National Institute for Health Research (NIHR) School for Primary Care Research (project reference FR12-332).
Disclaimer The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.
Competing interests NQ was a member of the NICE Familial Hypercholesterolaemia & Lipid Modification Guideline Development Groups (CG71 & CG181). SW is a member of the Clinical Practice Research Datalink (CPRD) Independent Scientific Advisory Committee (ISAC), academic advisor to Quealth, and has received independent research grant funding from AMGEN. NQ and SW have previously received honorarium from AMGEN. RKA currently holds an NIHR-SPCR funded studentship (2018-2021). The remaining authors have no competing interests.
Provenance and peer review Not commissioned; externally peer reviewed.