University Hospitals Cleveland Medical Center, Cleveland, OH, USA; Rainbow Babies and Children's Hospital, Cleveland, OH, USA; Case Western Reserve University, Cleveland, OH, USA.
Case Western Reserve University, Cleveland, OH, USA.
Atherosclerosis. 2017 Nov;266:74-80. doi: 10.1016/j.atherosclerosis.2017.09.030. Epub 2017 Sep 28.
Asymmetric dimethylarginine (ADMA) is an inhibitor of nitric oxide and an independent risk factor for cardiovascular disease. We examined the effect of statin on ADMA in HIV + patients on stable ART, and whether such an effect contributes to the favorable changes on carotid intima media thickness.
This is a secondary analysis of SATURN-HIV, in which HIV + adults on stable ART with HIV-1 RNA< 1000 copies/mL and LDL-cholesterol <130 mg/dL were randomized to 10 mg daily rosuvastatin or placebo. Arginine metabolites, ADMA, and markers of inflammation were assessed at baseline and 48 weeks. Carotid intima media thickness (c-IMT) was measured at baseline, 48 and 96 weeks. Spearman correlations, and linear mixed-effect models were used to study relationships among variables.
Overall, 79% were male, 68% African Americans, with a median age of 46 years. In the statin arm, no change in ADMA levels was observed at 48 weeks (0.70%), whereas a trend towards an increase in ADMA levels (23.78%) was observed in the placebo group (p = 0.06). Elevated baseline ADMA (highest tertile) was associated with a 0.04 mm increase in c-IMT (p = 0.03) after adjusting for statin and study duration. No interaction was seen between baseline ADMA and statin randomization on change in c-IMT (p = 0.21).
In HIV + subjects on ART, rosuvastatin suppressed the increase over time in ADMA levels. Elevated baseline levels of ADMA were associated with increases in c-IMT, regardless of statin assignment. The favorable effect of rosuvastatin on c-IMT appears to be independent of the arginine pathway.
不对称二甲基精氨酸（ADMA）是一氧化氮的抑制剂，也是心血管疾病的独立危险因素。我们研究了他汀类药物对接受稳定抗逆转录病毒治疗（ART）的 HIV 阳性患者 ADMA 的影响，以及这种影响是否有助于颈动脉内膜中层厚度（c-IMT）的有利变化。
这是 SATURN-HIV 的二次分析，其中 HIV 阳性且接受稳定 ART 的成年人，HIV-1 RNA<1000 拷贝/ml 且 LDL-胆固醇<130mg/dL，随机分为每日 10mg 瑞舒伐他汀或安慰剂组。在基线和 48 周时评估精氨酸代谢物、ADMA 和炎症标志物。在基线、48 周和 96 周时测量 c-IMT。采用 Spearman 相关分析和线性混合效应模型研究变量之间的关系。
总体而言，79%为男性，68%为非裔美国人，中位年龄为 46 岁。在他汀组，48 周时 ADMA 水平无变化（0.70%），而安慰剂组 ADMA 水平呈上升趋势（23.78%）（p=0.06）。校正他汀和研究持续时间后，基线 ADMA 升高（最高三分位）与 c-IMT 增加 0.04mm（p=0.03）相关。在基线 ADMA 与他汀随机分组对 c-IMT 变化的相互作用无差异（p=0.21）。
在接受 ART 的 HIV 阳性患者中，瑞舒伐他汀抑制 ADMA 水平随时间的升高。基线 ADMA 水平升高与 c-IMT 增加相关，与他汀类药物的分配无关。瑞舒伐他汀对 c-IMT 的有利影响似乎独立于精氨酸途径。
