Mechanisms
Review weighs conflicting evidence on whether lowering LDL-C blunts the cardiovascular risk carried by elevated Lp(a) (Biomolecules 2025)
Original title: Interaction Between Lipoprotein(a) and Other Lipid Molecules: A Review of the Current Literature
This narrative review summarises current evidence on how Lp(a), an established causal cardiovascular risk factor by Mendelian randomisation and large epidemiological studies, interacts with other lipid molecules, particularly LDL-C. It highlights a synergistic atherogenic effect when elevated Lp(a) coincides with elevated LDL-C, but notes conflicting literature on whether the risk from elevated Lp(a) persists once LDL-C is well controlled (below 70 mg/dL): some studies find elevated Lp(a) remains significantly associated with cardiovascular events despite low LDL-C, while others report attenuation of Lp(a)-mediated risk at lower LDL-C. The relationship between Lp(a) and triglycerides, HDL and VLDL remains unclear. The authors call this an open question with direct relevance to how targeted Lp(a)-lowering therapies, now in development, should be positioned relative to LDL-C control.
Original abstract
Lipoprotein(a) [Lp(a)] is a well-established causal risk factor for cardiovascular diseases (CVDs), as reported by multiple Mendelian randomization studies and large epidemiological studies. When elevated Lp(a) is combined with other risk factors, most notably elevated low-density lipoprotein cholesterol (LDL-C), a synergistic atherogenic effect has been reported. However, the current literature is conflicting regarding how Lp(a) interacts in the context of controlled LDL-C levels (e.g., <70 mg/dL) and whether reducing LDL-C can modify the atherogenic effect of Lp(a). In some studies, elevated Lp(a) was still significantly associated with a higher risk of cardiovascular events, despite controlled levels of LDL-C. In contrast, multiple studies have reported attenuation of the cardiovascular risk mediated by elevated Lp(a) with lower LDL-C levels. Moreover, the relationship between Lp(a) and triglycerides, high-density lipoprotein, and very low-density lipoprotein remains unclear. In this literature review, we summarize and discuss the current evidence regarding the interactions between Lp(a) and other lipid molecules, how they contribute to the pathogenesis of CVD, and future perspectives, particularly in the current era where promising targeted Lp(a)-lowering therapies are under development.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.