Lee Jaeoh, Bangalore Sripal, Yun Kyeong Ho, Lee Sang-Hyup, Lee Yong-Joon, Lee Seung-Jun, Hong Sung-Jin, Ahn Chul-Min, Kim Jung-Sun, Kim Byeong-Keuk, Ko Young-Guk, Choi Donghoon, Jang Yangsoo, Hong Bum-Kee, Hong Myeong-Ki
Division of Cardiology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA.
Yonsei Med J. 2025 Sep;66(9):537-544. doi: 10.3349/ymj.2024.0476.
We aimed to compare the visit-to-visit variability in low-density lipoprotein cholesterol (LDL-C) according to different lipid-lowering strategies and evaluate its prognostic implications using data from previous trials.
We analyzed two randomized clinical trials: the RACING trial and the LODESTAR trial. LDL-C variability was evaluated using standard deviation (SD), coefficient of variation, and variation independent of mean. The primary endpoint was a composite of death, myocardial infarction, stroke, or coronary revascularization.
Among the 6800 patients included, when compared with patients randomized to high-intensity statins, LDL-C variability was similar in the group randomized to moderate-intensity statin plus ezetimibe combination, but it was higher in those randomized to treat-to-target strategy. The variability in LDL-C (by SD) was a predictor of primary endpoint even after adjustment for lipid-lowering strategy and mean LDL-C (hazard ratio 1.024; 95% confidence interval 1.014 to 1.035; <0.001). Every 1-SD increase in LDL-C variability (SD) was also independently associated with higher risk of myocardial infarction by 2.1%, stroke by 3.5%, and coronary revascularization by 2.7%.
Compared to high-intensity statin therapy, LDL-C variability was not increased with the moderate-intensity statin plus ezetimibe combination therapy; however, it was increased in the treat-to-target strategy. Even among those treated with moderate- or high-intensity statins or statins with a target LDL-C levels of 50-70 mg/dL, increased LDL-C variability was associated with higher risk of adverse cardiovascular outcomes.
我们旨在根据不同的降脂策略比较低密度脂蛋白胆固醇（LDL-C）的就诊间变异性，并利用既往试验数据评估其预后意义。
我们分析了两项随机临床试验：RACING试验和LODESTAR试验。使用标准差（SD）、变异系数和与均值无关的变异来评估LDL-C变异性。主要终点是死亡、心肌梗死、中风或冠状动脉血运重建的复合终点。
在纳入的6800例患者中，与随机接受高强度他汀类药物治疗的患者相比，随机接受中等强度他汀类药物加依泽替米贝联合治疗的组中LDL-C变异性相似，但在随机接受达标治疗策略的组中更高。即使在调整了降脂策略和平均LDL-C后，LDL-C的变异性（以SD表示）仍是主要终点的预测指标（风险比1.024；95%置信区间1.014至1.035；P<0.001）。LDL-C变异性（SD）每增加1个标准差也与心肌梗死风险增加2.1%、中风风险增加3.5%和冠状动脉血运重建风险增加2.7%独立相关。
与高强度他汀类药物治疗相比，中等强度他汀类药物加依泽替米贝联合治疗未增加LDL-C变异性；然而，达标治疗策略增加了LDL-C变异性。即使在接受中等强度或高强度他汀类药物治疗或目标LDL-C水平为50 - 70 mg/dL的他汀类药物治疗的患者中，LDL-C变异性增加也与不良心血管结局风险较高相关。
