Kuwabara Masanari, Sasaki Jun, Ouchi Yasuyoshi, Oikawa Shinichi, Nakagawa Kiyotaka, Sato Masao, Koba Shinji, Kono Suminori, Saikawa Tetsunori, Arai Hidenori
Toranomon Hospital Tokyo Japan.
International University of Health and Welfare Fukuoka Japan.
J Am Heart Assoc. 2024 Feb 6;13(3):e031865. doi: 10.1161/JAHA.123.031865. Epub 2024 Jan 19.
Higher cholesterol absorption has been reported to be related to a higher incidence of cardiovascular events (CVEs). The KEEP (Kyushu Elderly Ezetimibe Phytosterol) study, a substudy of the EWTOPIA 75 (Ezetimibe Lipid-Lowering Trial on Prevention of Atherosclerotic Cardiovascular Disease in 75 or Older) study, investigated the relationships of cholesterol absorption and synthesis markers with CVEs in older old individuals with hypercholesterolemia, particularly in relation to ezetimibe treatment.
Eligible patients were those aged ≥75 years who had low-density lipoprotein cholesterol ≥140 mg/dL, no history of coronary artery disease, and no recent use of lipid-lowering drugs. Participants were randomly assigned into a diet-only or diet-plus-ezetimibe group. Baseline and 24-week follow-up blood samples were analyzed for cholesterol absorption (eg, campesterol) and synthesis markers (eg, lathosterol). Of 1287 patients, 1061 patients with baseline measurement were analyzed. Over a median follow-up of 4.0 years, 64 CVEs occurred. Higher campesterol levels at baseline were significantly associated with a lower risk of CVEs. After adjustment for sex, age, and treatment, the hazard ratios for the lowest to highest quartile categories of baseline campesterol were 1.00 (reference), 0.59 (95% CI, 0.30-1.17), 0.44 (95% CI, 0.21-0.94), and 0.44 (95% CI, 0.21-0.93), respectively (trend =0.01). This association persisted after further adjustment for hypertension, diabetes, and other cardiovascular risk factors. Neither interactions with ezetimibe treatment nor mediating effects of the changes in cholesterol absorption markers were observed.
The KEEP study indicated that higher campesterol levels without lipid-lowering drugs were associated with a lower incidence of CVEs in older old individuals with hypercholesterolemia who were subsequently treated with diet or ezetimibe.
URL: https://www.umin.ac.jp; unique identifier: UMIN000017769.
据报道，较高的胆固醇吸收与心血管事件（CVE）的较高发生率相关。KEEP（九州老年人依折麦布植物甾醇）研究是EWTOPIA 75（依折麦布预防75岁及以上人群动脉粥样硬化性心血管疾病降脂试验）研究的一项子研究，调查了高胆固醇血症老年个体中胆固醇吸收和合成标志物与CVE的关系，特别是与依折麦布治疗的关系。
符合条件的患者为年龄≥75岁、低密度脂蛋白胆固醇≥140mg/dL、无冠状动脉疾病史且近期未使用降脂药物的患者。参与者被随机分为单纯饮食组或饮食加依折麦布组。对基线和24周随访的血样进行胆固醇吸收（如菜油甾醇）和合成标志物（如羊毛甾醇）分析。在1287例患者中，对1061例有基线测量值的患者进行了分析。在中位随访4.0年期间，发生了64例CVE。基线时较高的菜油甾醇水平与较低的CVE风险显著相关。在调整性别、年龄和治疗后，基线菜油甾醇最低至最高四分位数类别的风险比分别为1.00（参考值）、0.59（95%CI，0.30 - 1.17）、0.44（95%CI，0.21 - 0.94）和0.44（95%CI，0.21 - 0.93）（趋势 = 0.01）。在进一步调整高血压、糖尿病和其他心血管危险因素后，这种关联仍然存在。未观察到与依折麦布治疗的相互作用，也未观察到胆固醇吸收标志物变化的中介作用。
KEEP研究表明，在随后接受饮食或依折麦布治疗的高胆固醇血症老年个体中，未使用降脂药物时较高的菜油甾醇水平与较低的CVE发生率相关。
