Author + information
- Received July 12, 2018
- Revision received November 21, 2018
- Accepted December 3, 2018
- Published online March 4, 2019.
- Katrina L. Ellis, PhDa,b,∗∗ (, )@uwanews,
- Leopoldo Pérez de Isla, MD, PhDc,d,
- Rodrigo Alonso, MD, PhDd,e,
- Francisco Fuentes, MD, PhDf,g,
- Gerald F. Watts, DSc, PhDa,h and
- Pedro Mata, MD, PhDd,∗ (, )@FHFamiliar
- aSchool of Medicine, Faculty of Medicine and Health Sciences, University of Western Australia, Perth, Australia
- bSchool of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Western Australia, Perth, Australia
- cCardiology Department, Hospital Clínico San Carlos, IDISSC, Universidad Complutense, Madrid, Spain
- dFundación Hipercolesterolemia Familiar, Madrid, Spain
- eNutrition Department, Clínica las Condes, Santiago de Chile, Chile
- fLipid and Atherosclerosis Unit, IMIBIC/Hospital Universitario Reina Sofía/Universidad de Cordoba, Spain
- gCIBER Fisiopatologia Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
- hLipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital, Perth, Australia
- ↵∗Address for correspondence:
Dr. Pedro Mata, Fundación Hipercolesterolemia Familiar, C/General Álvarez de Castro 14, 28010 Madrid, Spain.
- ↵∗∗Dr. Katrina Ellis, School of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Western Australia, PO Box X2213, Perth, WA 6847, Australia.
Background Familial hypercholesterolemia (FH) and elevated lipoprotein(a) [Lp(a)] are inherited disorders associated with premature atherosclerotic cardiovascular disease (ASCVD). Cascade testing is recommended for FH, but there are no similar recommendations for elevated Lp(a).
Objectives This study investigated whether testing for Lp(a) was effective in detecting and risk stratifying individuals participating in an FH cascade screening program.
Methods Family members (N = 2,927) from 755 index cases enrolled in SAFEHEART (Spanish Familial Hypercholesterolemia Cohort Study) were tested for genetic FH and elevated Lp(a) via an established screening program. Elevated Lp(a) was defined as levels ≥50 mg/dl. The authors compared the prevalence and yield of new cases of high Lp(a) in relatives of FH probands both with and without high Lp(a), and prospectively investigated the association between elevated Lp(a) and ASCVD events among family members.
Results Systematic screening from index cases with both FH and elevated Lp(a) identified 1 new case of elevated Lp(a) for every 2.4 screened. Opportunistic screening from index cases with FH, but without elevated Lp(a), identified 1 individual for 5.8 screened. Over 5 years’ follow-up, FH (hazard ratio [HR]: 2.47; p = 0.036) and elevated Lp(a) (HR: 3.17; p = 0.024) alone were associated with a significantly increased risk of experiencing an ASCVD event or death compared with individuals with neither disorder; the greatest risk was observed in relatives with both FH and elevated Lp(a) (HR: 4.40; p < 0.001), independent of conventional risk factors.
Conclusions Testing for elevated Lp(a) during cascade screening for FH is effective in identifying relatives with high Lp(a) and heightened risk of ASCVD, particularly when the proband has both FH and elevated Lp(a).
This work was supported by Fundación Hipercolesterolemia Familiar, grant FIS PI12/01289 from the Instituto de Salud Carlos III, and grant 08-2008 from the Centro Nacional de Investigación Cardiovascular. Dr. Ellis was supported by a Royal Perth Hospital Medical Research Foundation Fellowship and a Raine Medical Research Foundation grant. Dr. Watts has received research grants from Regeneron, Sanofi, and Amgen; and has served on advisory boards for Regeneron, Sanofi, Gemphire, and Amgen. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Received July 12, 2018.
- Revision received November 21, 2018.
- Accepted December 3, 2018.
- 2019 American College of Cardiology Foundation
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