New York University School of Medicine, NY, USA.
Am Heart J. 2011 May;161(5):972-8. doi: 10.1016/j.ahj.2011.01.017.
Subjects with peripheral artery disease (PAD) are at increased risk of cardiovascular morbidity and mortality, perhaps in part, related to increased levels of inflammation, platelet activity, and lipids. We therefore sought to investigate the relationship between PAD and levels of inflammatory, platelet, and lipid biomarkers and the treatment effect of darapladib, a novel lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) inhibitor.
This is a post hoc analysis of the 959 patients with coronary disease or their risk equivalent receiving atorvastatin who were randomized to receive darapladib or placebo to examine the effects of an Lp-PLA(2) inhibitor on the biomarkers of cardiovascular risk. We conducted an exploratory analysis evaluating the levels of biomarkers in subjects with PAD (n = 172) compared with those without PAD (n = 787).
After adjustment for age, sex, smoking, body mass index, and diabetes, subjects with PAD had greater levels of matrix metalloproteinase-9 (between group comparisons 22%, 95% confidence interval [10-31], P < .01), myeloperoxidase (12% [2-20], P = .01), interleukin-6 (13% [4-21], P = .01), adiponectin (17% [7-26], P < .01), intercellular adhesion molecule-1 (7% [2-11], P < .01), osteoprotegrin (6% [1-10], P = .02), CD40 ligand (15% [1-28], P = .04), high-sensitivity C-reactive protein (17% [1-31], P = .04), and triglycerides (11% [0.2-21], P = .05). No significant difference was detected for Lp-PLA(2) activity, P-selectin, urinary 11-dehydrothroboxane B2, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol between subjects with and without PAD. Darapladib produced highly significant inhibition of Lp-PLA(2) activity when compared with placebo at weeks 4 and 12 (P < .01) in patients with and without PAD.
Subjects with PAD had elevated levels of matrix metalloproteinase-9, myeloperoxidase, interleukin-6, adiponectin, intercellular adhesion molecule-1, osteoprotegrin, CD40 ligand, high-sensitivity C-reactive protein, and triglycerides compared with those without PAD. Darapladib, a novel Lp-PLA(2) inhibitor, was equally effective in reducing Lp-PLA(2) activity levels in subjects with and without PAD.
外周动脉疾病（PAD）患者发生心血管发病率和死亡率的风险增加，这可能部分与炎症、血小板活性和脂质水平升高有关。因此，我们旨在研究 PAD 与炎症、血小板和脂质生物标志物水平之间的关系，并研究新型脂蛋白相关磷脂酶 A2（Lp-PLA2）抑制剂 darapladib 的治疗效果。
这是一项对 959 名接受阿托伐他汀治疗的冠心病或有其风险等同患者的事后分析，这些患者随机接受 darapladib 或安慰剂治疗，以研究 Lp-PLA2 抑制剂对心血管风险生物标志物的影响。我们进行了一项探索性分析，评估了有 PAD（n=172）和无 PAD（n=787）患者的生物标志物水平。
在校正年龄、性别、吸烟、体重指数和糖尿病后，PAD 患者的基质金属蛋白酶-9（组间比较 22%，95%置信区间 [10-31]，P<.01）、髓过氧化物酶（12% [2-20]，P=0.01）、白细胞介素-6（13% [4-21]，P=0.01）、脂联素（17% [7-26]，P<.01）、细胞间黏附分子-1（7% [2-11]，P<.01）、骨保护素（6% [1-10]，P=0.02）、CD40 配体（15% [1-28]，P=0.04）、高敏 C 反应蛋白（17% [1-31]，P=0.04）和三酰甘油（11% [0.2-21]，P=0.05）水平更高。PAD 患者与无 PAD 患者之间，脂蛋白相关磷脂酶 A2（Lp-PLA2）活性、P-选择素、尿 11-脱氢血栓烷 B2、低密度脂蛋白胆固醇和高密度脂蛋白胆固醇无显著差异。与安慰剂相比，PAD 患者和无 PAD 患者在第 4 周和第 12 周时，darapladib 对 Lp-PLA2 活性的抑制作用具有高度统计学意义（P<.01）。
与无 PAD 患者相比，PAD 患者的基质金属蛋白酶-9、髓过氧化物酶、白细胞介素-6、脂联素、细胞间黏附分子-1、骨保护素、CD40 配体、高敏 C 反应蛋白和三酰甘油水平更高。新型 Lp-PLA2 抑制剂 darapladib 同样有效降低有和无 PAD 患者的 Lp-PLA2 活性水平。
