👤 Albert Wiegman

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

Cost-effectiveness of Lipoprotein(a) [Lp(a)] testing is not established. We aimed to evaluate the cost-effectiveness of Lp(a) testing in the cardiovascular disease (CVD) primary prevention population from healthcare and societal perspectives. We constructed and validated a multi-state microsimulation Markov model for a population of 10,000 individuals aged between 40 and 69 years without CVD, selected randomly from the UK Biobank. The model evaluated Lp(a) testing in individuals not initially classified as high-risk based on age, diabetes status, or the SCORE-2 algorithm. Those with an Lp(a) level ≥105 nmol/L (50 mg/dL) were treated as high risk (initiation of a statin plus blood pressure lowering). The Lp(a) testing intervention was compared to standard of care. The primary analyses were conducted from the Australian and UK healthcare perspectives in 2023AUD/GBP. A cost adaptation method estimated cost-effectiveness in multiple European countries, Canada, and the USA. Among 10,000 individuals, 1,807 had their treatment modified from Lp(a) testing. This led to 217 and 255 quality-adjusted life years gained in Australia and the UK, respectively, with corresponding incremental cost-effectiveness ratios of 12,134 (cost-effective) and -3,491 (cost-saving). From a societal perspective, Lp(a) testing saved $85 and £263 per person in Australia and the UK, respectively. Lp(a) testing was cost-saving among all countries tested in the cost adaptation analysis. Lp(a) testing in the primary prevention population to reclassify CVD risk and treatment is cost-saving and warranted to prevent CVD. Show less

Lipoprotein lipase (LPL) deficiency, a rare inherited metabolic disorder, is characterized by high triglyceride (TG) levels and life-threatening acute pancreatitis. Current treatment for pediatric patients involves a lifelong severely fat-restricted diet, posing adherence challenges. Volanesorsen, an EMA-approved RNA therapy for adults, effectively reduces TG levels by decreasing the production of apolipoprotein C-III. This 96-week observational open-label study explores Volanesorsen's safety and efficacy in a 13-year-old female with LPL deficiency. The patient, with a history of severe TG elevations, 53 hospital admissions, and life-threatening recurrent pancreatitis despite dietary restrictions, received weekly subcutaneous Volanesorsen injections. We designed a protocol for this investigator-initiated study, primarily focusing on changes in fasting TG levels and hospital admissions. While the injections caused occasional pain and swelling, no other adverse events were observed. TG levels decreased during treatment, with more measurements below the pancreatitis risk threshold compared to pre-treatment. No hospital admissions occurred in the initial 14 months of treatment, contrasting with 21 admissions in the 96 weeks before. In the past 10 months, two pancreatitis episodes may have been linked to dietary noncompliance. Dietary restrictions were relaxed, increasing fat intake by 65% compared to baseline. While not fully reflected in the PedsQL, both parents and the patient narratively reported an improved quality of life. This study demonstrates, for the first time, that Volanesorsen is tolerated in a pediatric patient with severe LPL deficiency and effectively lowers TG levels, preventing life-threatening complications. This warrants consideration for expanded access in this population. Show less