Lipoprotein(a) distributions and trial eligibility thresholds for Lp(a)-lowering therapies in the general population: The Rotterdam Study.

AIMS: General population distributions of lipoprotein(a) (Lp(a)) are well-characterized. However, less is known about its distributions and associated event rates within high-risk populations, including individuals with atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD) and varying levels of subclinical atherosclerosis and calcific aortic valve disease. Yet, such insights will facilitate clinical implementation of Lp(a) testing and enhance the design of clinical trials with Lp(a)-lowering agents. METHODS: Data from 5,129 participants in the population-based Rotterdam Study were used to assess Lp(a) distributions, prevalence of Lp(a) levels exceeding thresholds used in ongoing trials (i.e. >150, >175, and >200 nmol/L), accompanying numbers needed to screen (NNS), and major adverse cardiovascular event (MACE) rates across high-risk groups. RESULTS: Lp(a) distributions were right skewed across all groups. Among participants with ASCVD, 13.5% (11.9-15.3%) had Lp(a) >150 nmol/L and 6.5% (5.3-7.8%) had >200 nmol/L, with corresponding NNS 7.4 and 15.4. Similar distributions were observed between participants with coronary artery calcium (CAC) score >300 and participants with coronary heart disease (CHD). Prevalence in participants with aortic valve calcification (AVC) scores >300 was double that of the general population: 20.2% (13.0-27.4) at >150 nmol/L and 11.8% (6.6-19.0) at >200 nmol/L, with the lowest NNS across all groups (5.0-8.5). MACE rates varied by group and increased progressively with higher Lp(a) thresholds. CONCLUSIONS: Lp(a) distributions and MACE rates substantially vary across high-risk groups in the general population. These findings can facilitate design and recruitment strategies of studies with emerging Lp(a)-lowering therapies, while also aiding in identification of populations who may benefit from such therapies.