Numerous studies have confirmed that lipoproteins containing apolipoprotein B (apoB), such as low-density lipoproteins (LDL), very low-density lipoproteins (VLDL) and their remnants, intermediate density lipoproteins (IDL), and lipoprotein(a) (Lp(a)), play a direct role in the onset of atherosclerotic cardiovascular disease (ASCVD).1 Lp(a), a molecule that is similar to low-density lipoprotein cholesterol (LDL-C), has been identified as a risk factor for ASCVD via induction of inflammation, atherogenesis, and thrombosis.2,3 Increased levels of Lp(a) (i.e., >30 mg/dL) have been suggested as prominent single gene lipid disorder, as it is estimated that about 20–30 % of people worldwide have high levels of Lp(a),4 while current rates suggest that Lp(a) affects cardiovascular health in 1 out of 4 individuals, globally.5 Even though Lp(a) is under strong genetic regulation, the extensive variability in Lp(a) levels between individuals and population groups cannot be fully explained by genetic factors. Several non-genetic factors, such as dietary habits, engagement in physical activity, and various clinical conditions, as well as pharmaceutical treatment may also influence its levels.6, 7, 8, 9

Various risk prediction tools have been developed to assess an individual's risk of developing ASCVD event; the Framingham Heart Study Risk Score was a pioneer tool in the 1990s,10 the Pooled Cohort Equations (PCE) in 2000s11 and more recently the SCORE2 risk tool proposed by the European Society of Cardiology (ESC).12 Although, the updated algorithm of SCORE2 enhances the identification of individuals at higher risk of developing ASCVD,12 the problem of misclassification remains, suggesting the addition of novel markers to improve goodness-of-fit of the risk models. Recent more inclusive scores, such as HellenicSCORE II+, show that stratification by Lp(a) levels may assist to better identify individuals at high ASCVD risk.13 In an updated consensus statement in 2022, the European Atherosclerosis Society (EAS) recommended a one-time Lp(a) level test for adults and introduced a novel risk calculator that incorporates Lp(a) levels. The statement highlighted that individuals with high or extremely high Lp(a) concentrations might have a substantially underestimated risk that could potentially impact the accuracy of ASCVD risk predictions and subsequent therapeutic strategies.14

Although Lp(a) concentrations are associated with incident ASCVD, mainly in primary prevention context, there is a lack of long-term studies on whether Lp(a) levels may confer to a considerable improvement in ASCVD risk prediction. Thus, the aim of the present work was to evaluate the discrimination and net-reclassification of Lp(a) levels on estimating 20-year ASCVD incidence, in a sample of apparently healthy adults from the general population.