Tiantian Ji1, Yingxin Zhao2, Juan Wang3, Yi Cui4, Dandan Duan2, Qiang Chai2, Hua Zhang2, Zhendong Liu5. 1. 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. 2. Cardio-Cerebrovascular Control and Research Center, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, Shandong, China. 3. Department of Cardiology, The Second Hospital of Shandong University, Jinan, Shandong, China. 4. Department of Radiology, Qilu Hospital of Shandong University, Jinan, Shandong, China. 5. Cardio-Cerebrovascular Control and Research Center, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, Shandong, China. Electronic address: zhendongliu876@126.com.
Abstract
OBJECTIVES: 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. DESIGN: A subgroup analysis of a randomized clinical trial. SETTING: Shandong area, China. PARTICIPANTS: Hypertensive patients aged ≥60 years were recruited from April 2008 to November 2010. MEASUREMENTS: 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. RESULTS: 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.
RCT Entities:
OBJECTIVES: To investigate the effect of low-dose statins and apolipoprotein E (APOE) genotypes on cerebral small vessel disease (CSVD) to prevent CSVD in older hypertensivepatients. DESIGN: A subgroup analysis of a randomized clinical trial. SETTING: Shandong area, China. PARTICIPANTS: Hypertensivepatients aged ≥60 years were recruited from April 2008 to November 2010. MEASUREMENTS: 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. RESULTS: 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 hypertensivepatients.
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