Burden of elevated lipoprotein(a) among patients with atherosclerotic cardiovascular disease: Evidence from a systematic literature review and feasibility assessment of metaanalysis

Abstract

Background Elevated lipoprotein(a) [Lp(a)] level is an independent genetic risk factor that increases the risk of atherosclerotic cardiovascular disease (ASCVD) by 2-4 fold. We aimed to report the burden of clinically relevant elevated Lp(a) in secondary prevention ASCVD population as the evaluation of such evidence is lacking. Methods A systematic literature review (SLR) was conducted using Embase®, MEDLINE®, and MEDLINE ® In-Process databases to identify studies reporting burden of elevated Lp(a) levels from January 1, 2010, to March 28, 2022. Full-text, English-language studies including ≥500 participants with ≥1 Lp(a) assessment were included. Results Sixty-one studies reported clinical burden of elevated Lp(a). Of these, 25 observational studies and one clinical trial reported clinical burden of clinically relevant elevated Lp(a) levels. Major clinical outcomes included major adverse cardiovascular event (MACE; n = 20), myocardial infarction (MI; n = 11), revascularization (n = 10), stroke (n = 10), cardiovascular (CV) mortality (n = 9), and all-cause mortality (n = 10). Elevated Lp(a) levels significantly increased the risk of MACE (n = 15) and revascularization (n = 8), while they demonstrated a trend for positive association with remaining CV outcomes. Meta-analysis was not feasible for included studies due to heterogeneity in Lp(a) thresholds, outcome definitions, and patient characteristics. Three studies reported humanistic burden. Patients with elevated Lp(a) levels had higher odds of manifesting cognitive impairment (odds ratio [OR] [95% confidence interval; CI]: 1.62 [1.11-2.37]) and disability related to stroke (OR [95% CI]:1.46 [1.23-1.72)]) (n = 2). Elevated Lp(a) levels negatively correlated with health-related quality of life (R = -0.166, p = 0.014) (n = 1). A single study reported no association between elevated Lp(a) levels and economic burden. Conclusions This SLR demonstrated a significant association of elevated Lp(a) levels with major CV outcomes and increased humanistic burden in secondary prevention ASCVD population. These results reinforce the need to quantify and manage Lp(a) for CV risk reduction and to perform further studies to characterize the economic burden.