Premature morbidity and mortality associated with potentially undiagnosed familial hypercholesterolemia in the general population

Kausik K Ray; Demetris Pillas; Savvas Hadjiphilippou; Kamlesh Khunti; Sreenivasa Rao Kondapally Seshasai; Antonio J Vallejo-Vaz; David Neasham; Janet Addison

doi:10.1016/j.ajpc.2023.100580

Premature morbidity and mortality associated with potentially undiagnosed familial hypercholesterolemia in the general population

Am J Prev Cardiol. 2023 Sep 6:15:100580. doi: 10.1016/j.ajpc.2023.100580. eCollection 2023 Sep.

Authors

Kausik K Ray¹, Demetris Pillas², Savvas Hadjiphilippou¹, Kamlesh Khunti³, Sreenivasa Rao Kondapally Seshasai⁴, Antonio J Vallejo-Vaz^{1

5

6}, David Neasham², Janet Addison⁷

Affiliations

¹ Imperial Centre for Cardiovascular Disease Prevention (ICCP), Dept. of Primary Care and Public Health, School of Public Health, Imperial College London, Charing Cross Campus, The Reynolds Building, St Dunstan's Road, London W6 8RP, United Kingdom.
² Amgen Ltd, Uxbridge, United Kingdom.
³ University of Leicester, Leicester, United Kingdom.
⁴ Cardiovascular Clinical Academic Group, Molecular and Clinical Sciences Research Institute, St George's, University of London and St George's University Hospitals NHS Foundation Trust, London, United Kingdom.
⁵ Department of Medicine, Faculty of Medicine, University of Seville, Seville, Spain.
⁶ Clinical Epidemiology and Vascular Risk, Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocío/Universidad de Sevilla/CSIC. Seville, Spain.
⁷ Biogen Idec Ltd, Maidenhead, United Kingdom.

Abstract

Background: Familial hypercholesterolemia (FH) is common, but underdiagnosed, and few systematic early screening programs exist.

Objective: To assess health outcomes among those with a recorded diagnosis of FH and potential cases of FH with no recorded diagnosis.

Methods: Retrospective cohort study using the UK Clinical Practice Research Datalink. Records of adults were classified as diagnosed FH (FH_Coded), or via accepted algorithms using LDL-C and clinical characteristics as potential FH (FH_Potential) or unlikely FH (FH_Unlikely) using the DLCN or EUROASPIRE criteria (but no record of FH). Outcomes assessed were premature cardiovascular (CV) events, premature deaths and life expectancy.

Results: Among 1,729,046 individuals free from CV events, a record of FH_Coded before the age of 40 was 0.3/1000 (IQR 0.3-0.4) and increased with age. Where LDL-C levels were available, 1.8/1000 (IQR 1.6-2.0) could be classified as FH_Potential. LDL-C was higher for both FH_Coded and FH_Potential vs FH_Unlikely (185.6 and 216.6 vs 116 mg/dL, respectively, p<0.001). Compared to FH_Unlikely both FH_Coded and FH_Potential cohorts had a higher risk of premature cardiovascular events (both p<0.001) with highest rates among FH_Coded. Risk of premature deaths did not differ between FH_Coded and FH_Unlikely, but was 1.88 (95% CI 1.27-2.78, p = 0.002) for FH_Potential vs FH_Coded and 2.40 (95% CI 1.57-3.67, p<0.001) for FH_Potential vs FH_Unlikely. At age 18, the FH_Potential cohort had a life expectancy 16 years lower than the FH_Coded cohort (p<0.001).

Conclusions: Potential cases of FH had a doubling in risk of premature death and a large reduction in life expectancy compared to individuals with a recorded diagnosis of FH. These findings strengthen the critical importance of identifying potential cases of FH early and early treatment.

Keywords: Cardiovascular disease prevention; Familial hypercholesterolemia; LDL-C; Screening.