Value of Measuring Lipoprotein(a) During Cascade Testing for Familial Hypercholesterolemia

• Published in: Journal of the American College of Cardiology 2019-03, Vol.73 (9), p.1029-1039
• Main Authors: Ellis, Katrina L., Pérez de Isla, Leopoldo, Alonso, Rodrigo, Fuentes, Francisco, Watts, Gerald F., Mata, Pedro
• Format: Article
• Language: English
• Subjects: Adult; Age; Arteriosclerosis; Atherosclerosis; atherosclerotic cardiovascular disease; Biomarkers - blood; Cardiology; Cardiovascular disease; Cardiovascular diseases; cascade screening; Cholesterol; Diabetes; DNA - genetics; DNA Mutational Analysis; familial hypercholesterolemia; Family medical history; Female; Follow-Up Studies; Genetic Testing - methods; Hereditary diseases; Humans; Hypercholesterolemia; Hyperlipoproteinemia Type II - blood; Hyperlipoproteinemia Type II - epidemiology; Hyperlipoproteinemia Type II - genetics; Hypertension; Hypotheses; Lipids; lipoprotein(a); Lipoprotein(a) - blood; Low density lipoprotein; Male; Middle Aged; Mutation; Pedigree; Prevalence; Prospective Studies; Receptors, LDL - genetics; Receptors, LDL - metabolism; Risk analysis; Risk Factors; Screening; Spain - epidemiology
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2018.12.037

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). This study investigated whether testing for Lp(a) was effective in detecting and risk stratifying individuals participating in an FH cascade screening program. 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. 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. 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).