👤 Barbara A Hutten

Cascade screening can identify individuals with elevated lipoprotein(a) [Lp(a)], a causal risk factor for atherosclerotic cardiovascular disease (ASCVD). The aim of this study is to explore the effectiveness of cascade screening with asymptomatic children as index cases to identify family members with elevated Lp(a). In this retrospective study we used our database consisting of all children referred for a tentative diagnosis of hereditary dyslipidemia to the Amsterdam University Medical Centers pediatric lipid clinic (1989-2023). Elevated Lp(a) was defined as ≥30 mg/dL or ≥75 nmol/L. We evaluated two cascade screening approaches (opportunistic and systematic), calculated the number needed to screen (NNS) and repeated the analysis exclusively in children with FH as subgroup with particularly high cardiovascular risk. A total of 1,931 children were included (732 indexes, mean age (SD) 11.7 (4.5) years; 1,199 relatives, mean age (SD) 10.1 (4.4) years). In total, 480 (25%) of all children had elevated Lp(a) concentrations (≥30 mg/dL or ≥75 nmol/L). Both opportunistic (732 indexes) and systematic (316 indexes) cascade screening identified relatives with elevated Lp(a). The NNS was of 3.7 (95% CI 3.3-4.3) for the systematic approach and 4.1 (95% CI 3.8-4.6) for the opportunistic approach. In the FH subgroup, NNS were 3.9 (95% CI 3.4-4.5) and 4.3 (95% CI 3.9-4.8), respectively. Our findings suggest that cascade screening using children as index cases is an effective strategy to identify asymptomatic relatives at risk. Cardiovascular risk assessment should include Lp(a), especially in patients with FH who face an even higher cardiovascular risk. Until effective therapies become available, management should focus on modifiable risk factors. Show less

In mouse models, apolipoprotein A-V (apoA-V) exhibits triglyceride (TG)-lowering effects. We investigated the apoA-V/TG relationship and the association of apoA-V with coronary artery disease (CAD) risk by determining serum apoA-V levels and genotypes in a nested case-control (n = 1,034/2,031) study. Both univariate and multivariate apoA-V levels showed no association with future CAD (P = 0.4 and 0.5, respectively). Unexpectedly, there was a significant positive correlation between serum apoA-V and TG in men and women (r = 0.36 and 0.28, respectively, P < 0.001 each) but a negative correlation between apoA-V and LPL mass (r = -0.14 and -0.12 for men and women respectively, P < 0.001 each). The frequency of the c.56C>G polymorphism did not differ between cases and controls despite significant positive association of c.56G with both apoA-V and TG levels. For -1131T>C, the minor allele was significantly associated with lower apoA-V yet higher TG levels and was overrepresented in cases (P = 0.047). The association of -1131T>C with CAD risk, however, was independent of apoA-V levels and likely acts through linkage disequilibrium with APOC3 variants. The positive correlation of apoA-V levels with TG levels, negative correlation with LPL levels, and lack of association with CAD risk highlight the need for further human studies to clarify the role of apoA-V. Show less