Global Variation in Lipoprotein(a) Levels Among Patients With Coronary Heart Disease: Insights From the INTERASPIRE Study and Implications for Emerging Lp(a)-Lowering Therapies

Background: Lipoprotein(a) [Lp(a)] is a common risk factor for atherosclerotic cardiovascular disease, potentially more atherogenic per particle than low-density lipoprotein. An estimated 1.5 billion individuals globally have elevated levels ≥125 nmol/L, considered as a risk-enhancing threshold. Although Lp(a) levels vary by ethnicity, ongoing trials of novel therapies in predominantly secondary prevention patients use fixed Lp(a) enrollment thresholds. Objectives: The purpose of this study was to assess Lp(a) levels in coronary heart disease (CHD) patients across geographical regions, providing inference on the proportions potentially eligible for future Lp(a)-lowering therapies and whether these vary by region and country. Methods: INTERASPIRE (International Action on Secondary Prevention through Intervention to Reduce Events)enrolled adults hospitalized with CHD in the previous 6 to 24 months. Lp(a) levels were available in 13 countries across 6 World Health Organization (WHO) regions: Africa (Kenya, Nigeria, Tanzania), Americas (Argentina, Colombia), Eastern Mediterranean (UAE), Europe (Poland, Portugal), South-East Asia (Indonesia), and Western Pacific (China, Malaysia, Philippines, Singapore). Lp(a) measurements were performed once and centrally in Helsinki using an isoform-independent assay for 11 countries, and locally in Indonesia and China with standardization to the core laboratory. Lp(a) levels are reported as median (Q1-Q3) and proportions above different thresholds. Results: Lp(a) results were available for 3,928 patients from 13 countries (mean age: 60.2 ± 10.2 years; 21.1% women). Median Lp(a) was 32 nmol/L (Q1-Q3: 11-89 nmol/L) overall, with 17.6% having levels ≥125 nmol/L. Median levels varied by region—highest in Africa (62 nmol/L) and lowest in Western Pacific (22 nmol/L)—and also between countries within regions: Europe (Portugal: 59 nmol/L vs Poland: 19.5 nmol/L), South America (Colombia: 46 nmol/L vs Argentina: 32 nmol/L) and Western Pacific (Malaysia: 39.5 nmol/L vs Philippines: 14 nmol/L). Overall, the proportions of patients with Lp(a) ≥150, 175, and 200 nmol/L (hence eligibility for future Lp(a)-lowering therapies) were 13.0%, 9.3%, and 6.2%, respectively, with eligibility also varying among countries: highest in Portugal (25.5%, 18.3%, and 11.6%) and lowest in Philippines (4.3%, 2.5%, and 1.3%). Conclusions: The vast majority of patients with CHD have Lp(a) levels far below what is considered a typical risk-enhancing threshold, suggesting that the attributable risk from Lp(a) is more complex than previously perceived. Furthermore, wide geographical variations in Lp(a) levels above entry criteria for ongoing trials could impact equitable access to therapies, if these trials are positive.