What is Lp(a)?

• Lp(a) is a unique lipoprotein that may play a role in hemostasis, help promote tissue repair, and wound healing²

• Lp(a) is prothrombotic, proinflammatory, and ~6-fold more atherogenic than LDL-C per particle basis^3-5†‡ 

Figure: Lp(a) levels are ~90% determined by genetics. Lp(a) concentrations have been found to be inversely related to the number of copies in the kringle IV type 2 (KIV-2) domain of Apo(a).⁶

*Retrospective cohort study of patients with ASCVD and an Lp(a) level (N=11,310) using US electronic medical records from January 2014-June 2023. Of those with premature ASCVD (n=2684), 29.7% had elevated Lp(a). Premature ASCVD was defined as MI, IS, or a PAD-related diagnosis/procedure before age 55 in males or 65 in females on or after first ASCVD diagnosis. Due to inherent limitations of EMR data and a predominately Caucasian cohort, findings should be cautiously interpreted and may lack generalizability.¹

^†Clinical relevance is unknown.

^‡Atherogenicity was defined as the difference in CHD risk per unit difference in Lp(a) or LDL particle number (molar concentration). This study was based on the UK Biobank population (>502,000 UK residents) who were predominately of European ancestry. The generalizability of the findings was tested in a replication cohort: the CARDIoGRAMplusC4D (Coronary ARtery DIsease Genome wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease Genetics) data set. Study did not differentiate between subjects with or without CHD at baseline. Analysis focused on the ApoB component of Lp(a).⁵

Lp(a) levels are ~90% genetically determined^3,7

• Elevated Lp(a) levels are defined as ≥50 mg/dL or ≥125 nmol/L⁸

• ~1 in 5 people worldwide may have elevated Lp(a)^4,9

• Elevated Lp(a) has emerged as one of the strongest single genetic drivers of CAD^7,10

• Higher Lp(a) levels are associated with a greater risk for MI¹¹

The risk for CV events from elevated Lp(a) is lifelong and cumulative over time¹²

• Lp(a) levels are typically established by 5 years of age and remain relatively consistent over time^12,13

• Lp(a) levels are generally not impacted by diet or lifestyle^7,12,13

• Risk for a CV event from elevated Lp(a) is cumulative over time¹²

Elevated Lp(a) can increase risk for CV events¹²

• Elevated Lp(a) can increase risk for peripheral artery disease, CAD, MI, and stroke^10,12

• Baseline risk for a lifetime major CV event increases with increasing Lp(a) levels¹²

• In one retrospective cohort study of patients who did not have prior ASCVD, the increased risk from elevated Lp(a) for a first acute myocardial infarction (MI) was shown to be similar to having 2 standard modifiable risk factors^14§

Elevated Lp(a) is an independent driver of CV risk^3,8,16,17

• The risk from elevated Lp(a) is independent of other CV risk factors^3,8,16,17 

Patients with elevated Lp(a) who have had a CV event are at increased risk for a recurrence^15,16,18,19

• The absolute risk of major adverse CV events in patients with CVD has been found to increase with increasing levels of Lp(a)^16||

^||Based on a prospective cohort study of white adults of Danish descent with CVD from the Copenhagen General Population Study (N=2527). Major adverse cardiovascular event (MACE) was defined as CV death, nonfatal MI, coronary artery bypass graft, percutaneous coronary intervention, and stroke. Those with Lp(a) <10 mg/dL (<18 nmol/L), 10 to 49 mg/dL (18–104 nmol/L), 50 to 99 mg/dL (105–213 nmol/L), and ≥100 mg/dL (≥214 nmol/L) had incidence rates of 29 (95% CI, 25–34), 35 (30–41), 42 (34–51), and 54 (42–70) per 1000 person years for MACE, respectively. Generalizability of results to other ethnicities is limited.¹⁶

Some people may have higher Lp(a) levels than others

For people of African ancestry^20,21:

• Median Lp(a) levels were shown to be higher when compared with other racial subgroups

For people of South Asian ancestry^22,23:

• Some studies have shown median Lp(a) levels were second highest after those of African ancestry