Lipoprotein(a)-associated risk of atherosclerotic cardiovascular disease is independent of C-reactive protein

Genetically determined high lipoprotein(a) represents a common, causal, and increasingly recognized risk factor for atherosclerotic cardiovascular disease (ASCVD).1 While the lipoprotein(a)-associated risk is independent of conventional risk factors including low-density lipoprotein (LDL) cholesterol, recent studies have reached contrasting conclusions on whether systemic low-grade inflammation measured by elevated C-reactive protein (CRP) modifies the risk of ASCVD from high lipoprotein(a).2–8 In a contemporary general population setting (inclusion 2003–2015; n = 68 090; 5801 incident ASCVD; median follow-up 8.1 years), we demonstrated similar relative risk increases for incident ASCVD for high lipoprotein(a) regardless of CRP.2 Also, in a combined analysis of eight European population-based cohort studies (inclusion 1984–2010; 65 661 without/6017 with coronary heart disease (CHD) at baseline; follow-up 9.8/13.8 years), results were similar for participants without CHD.4 However, amongst 2641 participants with CHD and low CRP, risk estimates for recurrent CHD did not reach statistical significance when comparing top vs. bottom lipoprotein(a) quintiles (1.29 [0.98–1.71]), which led the authors to conclude that CRP modifies the lipoprotein(a)-associated risk of CHD. Thus, it remains a possibility that in a secondary prevention setting, absence of low-grade inflammation may attenuate the association of high lipoprotein(a) with increased risk of ASCVD.