Evidence from prospective epidemiologic studies as well as Mendelian randomization studies is in favor of an independent and causal association of elevated lipoprotein(a) (Lp(a)) concentrations with atherosclerotic cardiovascular disease (ASCVD) including coronary artery disease (CAD), ischemic stroke (IS), peripheral arterial disease (PAD), and cardiovascular as well as all-cause mortality 1, 2, 3, 4. In addition, recent studies have also suggested an association with the risk of incident and more rapid hemodynamic progression of calcific aortic valve stenosis (AVS) [5]. Median Lp(a) concentrations in European populations are around 22-24 nmol/l (10-11 mg/dl), but individual concentrations can range from <0.2 to >645 nmol/l (<0.1 to >300 mg/dl) mainly due to genetic variability observed at the LPA locus. A variable number of kringle-IV (KIV) type 2 repeats, causing a copy number variation in the LPA gene, is the basis for a protein size polymorphism with more than 40 isoforms [6]. Therefore, Lp(a) is regarded as a therapeutic target with the potential to lower ASCVD risk and prevent clinical events.

Lipoprotein apheresis (LA) is an effective option for lowering plasma concentrations of atherogenic lipoproteins in patients with severe hypercholesterolemia in situations of insufficient or poorly tolerated drug treatment 7, 8. The German Federal Joint Committee (GBA) approved high Lp(a) associated with clinically progressive ASCVD as an indication for regular LA with reimbursement in 2008 [9]. To become eligible for treatment, the Lp(a) concentration should exceed 60 mg/dl or as equivalent 120 nmol/l, LDL-C concentration should be in normal range, i.e. close to current treatment targets with maximally tolerated lipid lowering medication, and ASCVD should be progressive despite optimal treatment of all other cardiovascular risk factors.

Aim of the Pro(a)LiFe (Prospective Documentation of Isolated Lipoprotein(a)-Elevation with Progressive Cardiovascular Disease and Lipoprotein Apheresis for Effective Treatment of Hyperlipoproteinemia) study was to characterize this clinically selected high-risk patient population comparing the mean cardiovascular events rates before and after commencing regular LA 9, 10. Characterization of apo(a) genotypes and phenotypes showed that 95.3% of patients expressed at least one small apo(a) isoform [10]. Here we report the follow-up of these patients after completion of 12 years of regular LA (Pro(a)LiFe extension) to assess long-term sustainability of the preventive effect. In addition, the Pro(a)LiFe cohort was compared to corresponding clinical trajectories of an appropriate and well-characterized UK-Biobank cohort (UKBBC) with established ASCVD and verified risk enhancement due to elevated Lp(a) to confirm the efficacy of LA [11].