Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, 82 Gumi-ro 173beon-gil, Bundang-gu, Seongnam, 463-707, South Korea.
Department of Internal Medicine, Eulji General Hospital, Seoul, South Korea.
Cardiovasc Diabetol. 2017 Nov 9;16(1):146. doi: 10.1186/s12933-017-0629-0.
The cardiovascular benefits of statins have been proven, but their effect on circulation in small vessels has not been examined fully. We investigated the effect of 20 mg rosuvastatin on biomarkers, including paraoxonase-1 (PON-1) and asymmetric dimethylarginine (ADMA), and on microvascular reactivity.
We enrolled 20 dyslipidemic patients with type 2 diabetes and 20 age- and body mass index (BMI)-matched healthy controls. Rosuvastatin (20 mg/day) was given to the patient group for 12 weeks. Biochemical parameters, including PON-1 and ADMA, were compared between the patient and control groups, and before and after rosuvastatin treatment in the patient group. Fasting and 2 h postprandial levels of PON-1 and ADMA after mixed-meal challenge were also compared. Microvascular reactivity in a peripheral artery was examined using laser Doppler flowmetry.
The respective mean ± standard deviation of age and BMI were 50.1 ± 3.8 year and 25.8 ± 3.7 kg/m in the patients and 50.2 ± 3.2 year and 25.4 ± 3.4 kg/m in the controls. The patient group had worse profiles of cardiometabolic biomarkers, including PON-1 and ADMA, than the controls. In the patients treated with 20 mg rosuvastatin, low-density lipoprotein (LDL)-cholesterol decreased from 147.2 ± 26.5 to 68.3 ± 24.5 mg/dL and high-density lipoprotein (HDL)-cholesterol increased from 42.4 ± 5.2 to 44.7 ± 6.2 mg/dL (both P < 0.05). Both fasting and 2 h postprandial levels of PON-1 increased and those of ADMA decreased after treatment with rosuvastatin for 12 weeks. The changes in postprandial levels of both biomarkers were greater than those after fasting. Microcirculation assessed as reactive hyperemia in the patients after an ischemic challenge increased significantly from 335.3 ± 123.4 to 402.7 ± 133.4% after rosuvastatin treatment. The postprandial changes in the biomarkers were significantly associated with improvement of microvascular reactivity.
Rosuvastatin treatment for 12 weeks improved microvascular reactivity with concomitant beneficial changes in the postprandial levels of PON-1 and ADMA. These results suggest that rosuvastatin improves the postprandial cardiometabolic milieu in type 2 diabetes. Trial registration ClinicalTrials.gov: NCT02185963 (July 7, 2014).
他汀类药物的心血管益处已得到证实，但它们对小血管循环的影响尚未得到充分研究。我们研究了 20mg 瑞舒伐他汀对生物标志物（包括对氧磷酶-1（PON-1）和不对称二甲基精氨酸（ADMA））和微血管反应性的影响。
我们纳入了 20 例 2 型糖尿病伴血脂异常患者和 20 例年龄和体重指数（BMI）匹配的健康对照者。患者组给予瑞舒伐他汀（20mg/天）治疗 12 周。比较患者组与对照组、患者组治疗前后的生化参数，包括 PON-1 和 ADMA。比较混合餐挑战后空腹和餐后 2 小时的 PON-1 和 ADMA 水平。采用激光多普勒血流仪检测外周动脉的微血管反应性。
患者组的平均年龄和 BMI 分别为 50.1±3.8 岁和 25.8±3.7kg/m，对照组分别为 50.2±3.2 岁和 25.4±3.4kg/m。患者组的代谢生物标志物，包括 PON-1 和 ADMA，较对照组差。20mg 瑞舒伐他汀治疗后，患者组的低密度脂蛋白胆固醇（LDL-C）从 147.2±26.5mg/dL 降至 68.3±24.5mg/dL，高密度脂蛋白胆固醇（HDL-C）从 42.4±5.2mg/dL 升至 44.7±6.2mg/dL（均 P<0.05）。瑞舒伐他汀治疗 12 周后，空腹和餐后 2 小时的 PON-1 水平升高，ADMA 水平降低。餐后生物标志物的变化大于空腹。缺血性挑战后，患者的反应性充血评估的微循环从 335.3±123.4%显著增加至 402.7±133.4%。生物标志物的餐后变化与微血管反应性的改善显著相关。
瑞舒伐他汀治疗 12 周可改善微血管反应性，并伴有 PON-1 和 ADMA 餐后水平的有益变化。这些结果表明，瑞舒伐他汀改善了 2 型糖尿病的餐后代谢环境。
ClinicalTrials.gov：NCT02185963（2014 年 7 月 7 日）。
