The Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
Am Heart J. 2013 Apr;165(4):609-14. doi: 10.1016/j.ahj.2013.01.006. Epub 2013 Feb 16.
Although rosiglitazone favorably affects myriad intermediate markers of atherosclerosis, it appears to increase myocardial infarction (MI) risk. We analyzed the effects of rosiglitazone on a panel of 8 novel circulating biomarkers, 4 of which are independently associated with atherosclerosis: lymphotoxin β receptor, peptidoglycan recognition protein 1, chemokine ligand 23, and soluble receptor for advanced glycation end products (sRAGE) as well as on high-sensitivity C-reactive protein (hs-CRP).
Blood samples were analyzed at baseline and after 6 months of study treatment from subjects with type 2 diabetes with or at high risk for coronary artery disease in a randomized trial comparing rosiglitazone versus placebo.
Data from 111 subjects (rosiglitazone 55, placebo 56) were analyzed. Mean age was 56 years, 41% were women, and 66% were nonwhite. Compared with baseline values, rosiglitazone adversely affected levels of lymphotoxin β receptor (1.7 vs 2.4 ng/mL, P = .002), peptidoglycan recognition protein 1 (29.0 vs 30.1 ng/mL, P = .01), and chemokine ligand 23 (0.76 vs 0.84 ng/mL, P = .02) and favorably affected levels of sRAGE (inversely associated with atherosclerosis, 1.1 vs 1.4 ng/mL, P = .003) and hs-CRP (0.42 vs 0.31 ng/mL, P = .02); no changes were observed with rosiglitazone in the other biomarkers. In the placebo group, change was observed only for sRAGE (1.0 vs 1.1 ng/mL, P = .046).
Rosiglitazone adversely affected 3 novel biomarkers and favorably affected a fourth previously associated with atherosclerosis while improving hs-CRP, as has previously been shown. Whether these complex effects on circulating inflammatory biomarkers contribute to the signal of increased MI risk with rosiglitazone and whether pioglitazone has similar effects warrant further investigation.
虽然罗格列酮有利于影响动脉粥样硬化的众多中间标志物，但它似乎会增加心肌梗死（MI）的风险。我们分析了罗格列酮对一组 8 种新型循环生物标志物的影响，其中 4 种与动脉粥样硬化独立相关：淋巴毒素β受体、肽聚糖识别蛋白 1、趋化因子配体 23 和可溶性晚期糖基化终产物受体（sRAGE）以及高敏 C 反应蛋白（hs-CRP）。
在一项比较罗格列酮与安慰剂的随机试验中，从患有 2 型糖尿病或有冠心病高风险的受试者中采集血液样本，在基线和研究治疗 6 个月后进行分析。
对 111 名受试者（罗格列酮 55 名，安慰剂 56 名）的数据进行了分析。平均年龄为 56 岁，41%为女性，66%为非白人。与基线值相比，罗格列酮对淋巴毒素β受体（1.7 对 2.4 ng/mL，P =.002）、肽聚糖识别蛋白 1（29.0 对 30.1 ng/mL，P =.01）和趋化因子配体 23（0.76 对 0.84 ng/mL，P =.02）的水平产生不利影响，而对 sRAGE（与动脉粥样硬化呈负相关，1.1 对 1.4 ng/mL，P =.003）和 hs-CRP（0.42 对 0.31 ng/mL，P =.02）的水平产生有利影响；罗格列酮对其他生物标志物没有变化。在安慰剂组中，仅 sRAGE 发生变化（1.0 对 1.1 ng/mL，P =.046）。
罗格列酮对 3 种新型生物标志物产生不利影响，对第 4 种先前与动脉粥样硬化相关的生物标志物产生有利影响，同时改善 hs-CRP，如先前所示。这些对循环炎症生物标志物的复杂影响是否导致罗格列酮增加心肌梗死风险的信号，以及吡格列酮是否有类似影响，需要进一步研究。
