Comparing the predictive value of genetic determinants and measured plasma levels of Lipoprotein(a) in cardiovascular risk assessment: evidence from a large-scale UK Biobank study

Introduction: Lipoprotein(a) [Lp(a)] is a genetically influenced lipoprotein causally associated with atherosclerotic cardiovascular disease risk. This study compares the predictive value of genetically determined versus directly measured Lp(a) levels for major coronary events (MCE). Methods: From UK Biobank data, participants with complete genetic and plasma Lp(a) data, including LPA variants rs3798220 and rs10455872, were selected. Cox proportional hazards models were employed to estimate the risk of MCE, associated with both Lp(a) genetic score (0, 1, or ≥2 minor alleles) and measured Lp(a) levels. Results: Among 410,194 participants (mean age 57.25, 54% females), both Lp(a) genetic score and measured levels were independently associated with a stepwise increase in MCE risk. Within each genetic score group, increasing measured Lp(a) quintiles were associated with higher MCE. However, for individuals with similar measured Lp(a), MCE risk did not differ by genetic score. Conclusions: Directly measured Lp(a) levels offer superior cardiovascular risk prediction, supporting the practice of measuring Lp(a) levels at least once in adulthood.