Evaluation of Cascade Screening for Elevated Lipoprotein(a)

An elevated plasma level of lipoprotein(a) [Lp(a)] is an independent and causative risk factor for atherosclerotic cardiovascular disease. The Lp(a) plasma level is predominantly genetically determined via a complex hereditary pattern of the LPA gene, and remains relatively constant throughout an individual's entire life cycle. The relationship between plasma Lp(a) and the risk for a cardiovascular event has been shown to be linear.

Cascade screening, i.e. screening of biological relatives of the first detected patient (index) with a disease in a family, is an effective approach to identify and diagnose new patients with hereditary diseases. The method has been shown to be cost-effective for the most common genetically caused dyslipidemia, familial hypercholesterolemia, but the knowledge if cascade screening would be an effective method to screen for elevated plasma Lp(a) is not known.

The aim of the current project is to evaluate the penetrance of elevated plasma Lp(a) levels in patients with atherosclerotic coronary artery disease to their first- and second-degree biological relatives. The study will be based on results from a clinical health care development project in which patients who have had their plasma Lp(a) measured in the clinical routine will be asked to participate in the project. The participating patients invite their relatives to participate in the cascade screening and to measure their plasma Lp(a) levels. Six Swedish hospitals participate in the project and 750 patients with atherosclerotic coronary artery disease be included and divided into three strata according to their plasma Lp(a) level (low <70 nmol/L; intermediate 70-169 nmol/L; high >170 nmol/L). The indexes will in turn invite 1200 first- and second-degree relatives to have their plasma Lp(a) measured.

A scientific evaluation of the health care development project will be performed to study the penetrance of elevated plasma Lp(a) levels in indexes to their relatives.

Inclusion criteria

• participation in the clinical health care development project
• established atherosclerotic coronary artery disease

Exclusion criteria

• diagnosis of familial hypercholesterolemia
• chronic kidney disease stadium ≥4