Abstract 14601: Increased Risk of Major Adverse Cardiovascular Events Attributed to Lipoprotein(a) Across Current Atherosclerotic Cardiovascular Disease Risk Categories

Introduction: AHA guidelines recommend measurement of lipoprotein(a) [Lp(a); an inherited, causal risk factor for atherosclerotic cardiovascular disease (ASCVD)] in individuals with a family or personal history of premature ASCVD. Lp(a) measurement is also recommended for recalibrating the 10-year risk score for borderline or intermediate risk individuals. However, there is limited evidence on the risk of MACE attributed to elevated Lp(a) across ASCVD risk categories.

Hypothesis: To assess the impact of elevated Lp(a) levels on MACE across ASCVD 10-year risk categories.

Methods: This observational, retrospective study included a primary prevention cohort of Caucasian and Black ethnicities from the UK Biobank (2006-2020). Associations of Lp(a) level (categories of 105-150, 150-190, 190-215, and 215-260 nmol/L were compared to Lp(a) <105 nmol/L) with time to first MACE and MI were assessed using Cox proportional hazard models adjusted for age, sex, and ethnicity, stratified by ASCVD 10-year risk score category.

Results: The cohort (N=362,061) included 55.2% female, 94.3% Caucasian and 1.6% Black. MACE incidence rates (IR, per 100 person/years) increased with 10-year ASCVD risk score: low risk IR=0.14 (n=161,183), intermediate risk IR=0.72 (n=121,272) and high-risk IR=1.52 (n=27,733). Within and across these risk categories, elevated Lp(a) conferred a significant increase in risk of MACE and myocardial infarction (MI). In the low-risk category, HRs ranged from 1.15-1.55 (MACE) and 1.32-1.72 (MI), in the intermediate risk category HRs ranged from 1.19-1.51 (MACE) and 1.37-1.77 (MI), and in the high-risk category HRs ranged from 1.12-1.55 (MACE) and 1.14-1.76 (MI) (Figure 1).

Conclusions: Our study demonstrates that elevated Lp(a) increases the risk of MACE independently of ASCVD risk score. Measuring and considering elevated Lp(a) levels as part of individual ASCVD risk assessment in routine clinical practice may help improve the risk predication.