School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Zhangqiu, Shandong, China; Cardio-Cerebrovascular Control and Research Center, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, Shandong, China.
Cardio-Cerebrovascular Control and Research Center, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, Shandong, China.
J Am Med Dir Assoc. 2018 Nov;19(11):995-1002.e4. doi: 10.1016/j.jamda.2018.05.025. Epub 2018 Jul 10.
To investigate the effect of low-dose statins and apolipoprotein E (APOE) genotypes on cerebral small vessel disease (CSVD) to prevent CSVD in older hypertensive patients.
A subgroup analysis of a randomized clinical trial.
Shandong area, China.
Hypertensive patients aged ≥60 years were recruited from April 2008 to November 2010.
Patients were randomly assigned to rosuvastatin (10 mg/day) or placebo groups. APOE genotypes were categorized as ε4 carriers and non-ε4 carriers. White matter hyperintensities (WMH), Fazekas scale, lacunes, and microbleeds were assessed.
After an average of intervention period of 61.8 months, WMH volume increased 1.45 ± 0.52 mL. There were 107 new-incident Fazekas scale ≥2, 65 new-incident lacunes, and 63 new-incident microbleeds. The increase in WMH volume was significantly lower in the rosuvastatin group than in the placebo group and was higher in APOE ε4 carriers than in non-ε4 carriers (all adjusted P < .001). The risk of new-incident Fazekas scale ≥2 was higher in the placebo group than in the rosuvastatin group (hazard ratio 2.150, 95% confidence interval 1.443-3.203; P < .001). APOE ε4 carriers were associated with an increased risk of new-incident Fazekas scale ≥2 compared with non-ε4 carriers (hazard ratio 1.973, 95% confidence interval 1.334-2.920; P = .001). There were no statistically significant differences in the risk of new-incident cerebral microbleeds between the rosuvastatin and placebo groups or between APOE ε4 carriers and non-ε4 carriers. There were no significant interactions between rosuvastatin use and APOE ε4 status regarding increased WMH volume (F = 1.020, P = .313) or for new-incident Fazekas scale ≥2 (P = .377), lacunes (P = .232), and microbleeds (P = .362).
CONCLUSIONS/IMPLICATIONS: Low-dose rosuvastatin is an effective and safe therapy for CSVD. The presence of APOE ε4 allele may not be able to predict rosuvastatin treatment outcomes for preventing and/or treating CSVD in older hypertensive patients.
探讨小剂量他汀类药物和载脂蛋白 E（APOE）基因型对脑小血管病（CSVD）的影响，以预防老年高血压患者的 CSVD。
一项随机临床试验的亚组分析。
中国山东地区。
招募了年龄≥60 岁的高血压患者，时间为 2008 年 4 月至 2010 年 11 月。
患者被随机分配到瑞舒伐他汀（10mg/天）或安慰剂组。APOE 基因型分为 ε4 携带者和非 ε4 携带者。评估了脑白质高信号（WMH）、Fazekas 量表、腔隙和微出血。
在平均 61.8 个月的干预期后，WMH 体积增加了 1.45±0.52mL。新出现 Fazekas 量表≥2 的有 107 例，新出现腔隙 65 例，新出现微出血 63 例。瑞舒伐他汀组的 WMH 体积增加明显低于安慰剂组，APOE ε4 携带者高于非 ε4 携带者（所有调整 P<.001）。与瑞舒伐他汀组相比，安慰剂组新出现 Fazekas 量表≥2 的风险更高（风险比 2.150，95%置信区间 1.443-3.203；P<.001）。与非 ε4 携带者相比，APOE ε4 携带者新出现 Fazekas 量表≥2 的风险更高（风险比 1.973，95%置信区间 1.334-2.920；P=.001）。瑞舒伐他汀组和安慰剂组之间，以及 APOE ε4 携带者和非 ε4 携带者之间，新出现脑微出血的风险无统计学差异。瑞舒伐他汀使用与 APOE ε4 状态之间对 WMH 体积增加（F=1.020，P=.313）或新出现 Fazekas 量表≥2（P=.377）、腔隙（P=.232）和微出血（P=.362）无显著交互作用。
结论/意义：小剂量瑞舒伐他汀是治疗 CSVD 的有效且安全的方法。APOE ε4 等位基因的存在可能无法预测瑞舒伐他汀治疗老年高血压患者 CSVD 的效果，无论是预防还是治疗。
