Better characterization of ASCVD risk in children with FH by measuring Lp(a) levels
In pediatric familial hypercholesterolemia, lipoprotein(a) is more predictive than LDL-C for early onset of cardiovascular disease in family members
Literature - Zawacki AW, Dodge A, Woo KM et al. - J Clin Lipidol 2018; 12:1445–1451Introduction and methods
It is recommended to test lipoprotein(a) (Lp[a]) in pediatric patients with familial hypercholesterolemia (FH) [1]. These patients show higher average Lp(a) levels, compared to age-matched controls [2], which is associated with increased atherosclerotic cardiovascular disease (ASCVD) risk [3-10]. One study found that children with FH and Lp(a) >30 mg/dL were slightly more likely to have a parent with FH with premature onset of clinically apparent ASCVD [11]. However, it remains unknown whether Lp(a) levels in children with FH might further stratify their risk of early-onset ASCVD. Therefore, this study examined the relationship between Lp(a) and LDL-c levels in pediatric patients with established FH and the age of onset of ASCVD in family members.
For this retrospective review, 129 patients with FH were identified from the University of Wisconsin pediatric preventive cardiology clinic database from 2011 to 2017. FH was diagnosed in patients <18 years of age with peak LDL-c levels ≥160 mg/dL (4.14 mmol/L) on two lipid profiles with either a family history of high LDL-c or premature ASCVD in a parent or grandparent and in patients >18 years of age with personal or family history of ASCVD with peak LDL-C ≥190 mg/dL on two lipid profiles.
Lp(a) levels were categorized as follows: normal (<30 mg/dL [<75 nmol/L]), borderline (30–49 mg/dL [75–124 nmol/L]), or high (≥50 mg/dL [≥125 nmol/L]). Peak LDL-c levels were categorized into moderately elevated (160-189 mg/dL [4.14-4.9 mmol/L]) or highly elevated (≥190 mg/dL [≥4.92 mmol/L]). ASCVD (MI, PCI, coronary artery bypass surgery, cerebrovascular accident, or peripheral vascular disease) in relatives was categorized as early-onset when it occurred ≤50 years in men and ≤60 years in women, or late-onset. 129 Children from 109 families met inclusion criteria. In these families, 125 ASCVD events were reported, of which 78 were classified as early onset and 47 as late onset.
Main results
- 59.2% of families with an early-onset ASCVD event had a child with high Lp(a), while this was seen in 27.8% and 38.1% of families with a late-onset event and without an event, respectively.
- The OR for high Lp(a) levels in children was higher in families with an early-onset ASCVD event, compared to those in families with a late-onset event (OR: 3.77, 95%CI: 1.16–12.25, P=0.027).
- In multivariable analysis, increases in peak LDL-c (OR: 1.01, 95%CI: 1.00–1.02, P=0.30) and total cholesterol (TC) (OR: 1.00, 95%CI: 0.99–1.01, P=0.52) were not significantly associated with high Lp(a).
- The association between Lp(a) and age at onset of ASCVD in a relatives was maintained after correction for both peak LDL-c and TC levels.
- The OR for having elevated LDL-c did not differ between children from families with an early-onset ASCVD event and from those with a late-onset event (OR: 0.45, 95%CI: 0.11–1.80, P=0.26). This did not change when the mean or highest LDL-c levels among siblings were used (OR: 0.79, 95%CI: 0.24–2.61, P=0.70).
Conclusion
Children with FH and family history of early-onset ASCVD were more likely to have Lp(a) ≥50 mg/dL, compared with children with FH and family history of late-onset ASCVD. The odds of having elevated LDL-c, however, did not differ between children from families with an early-onset ASCVD event and from those with a late-onset event. These data suggest that measurements of Lp(a) in children with FH may better characterize CV risk and may identify children who could benefit from more aggressive management to reduce ASCVD risk, especially when information on family history is limited.
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