Two Sides of the Same Curve: Targets, Reduction, and LDL-C Burden

The relationship between low-density lipoprotein cholesterol (LDL-C) and atherosclerotic cardiovascular disease (ASCVD) has traditionally been discussed in terms of achieved LDL-C levels.Decades of clinical trials have firmly established that lower LDL-C levels are associated with lower cardiovascular risk, leading to increasingly stringent LDL-C targets in contemporary guidelines.However, from a biological perspective, atherosclerosis develops as a consequence of cumulative exposure to circulating LDL particles 1 , 2) .This concept raises an important question: should clinicians focus primarily on the LDL-C level ultimately achieved, or on the magnitude of LDL-C reduction achieved through treatment?In recent years, international lipid-management strategies have increasingly incorporated both concepts.The 2019 ESC/EAS guidelines recommend not only achieving LDL-C levels below specified thresholds but also reducing LDL-C by at least 50% from baseline in very high-risk patients 3 ) .Similarly, the ACC/AHA guidelines emphasize percentage LDL-C reduction as an important therapeutic goal 4 ) .In contrast, the 2022 Japan Atherosclerosis Society (JAS) Guidelines continue to focus primarily on achieved LDL-C levels, providing clinicians with a relatively simple and practical treat-to-target approach 5 ) .Against this background, Morishita et al. examined the association between relative LDL-C reduction and cardiovascular outcomes after PCI in a real-world Japanese cohort 6 ) .Their study demonstrated a graded association between larger LDL-C reductions and lower cardiovascular risk and further showed that patients achieving both LDL-C ＜55 mg/dL and ≥ 50% LDL-C reduction