Liuba Petru, Aburawi Elhadi H, Pesonen Erkki, Andersson Sture, Truedsson Lennart, Ylä-Herttuala Seppo, Holmberg Lars
Paediatric Cardiology, Lund University Hospital, Lund, Sweden.
Ann Med. 2007;39(5):392-9. doi: 10.1080/07853890701390111.
Several clinical studies have suggested possible increase in cardiovascular risk during and in the first weeks after an acute inflammatory disease. Using influenza vaccine as inflammatory stimulus, we investigated whether arterial endothelial dysfunction could persist beyond the inflammatory state, and whether amplified oxidative modification of low-density lipoprotein (LDL) accompanies this vascular disturbance.
The brachial artery responses to hyperemia (flow-mediated dilatation (FMD), and to sublingual glyceryl trinitrate (GTN), and the carotid intima-media thickness were assessed by external ultrasound in eight healthy male volunteers (age 17-30 y) before, and 2 and 14 days after intramuscular administration of influenza vaccine. Plasma levels of high-sensitivity C-reactive protein (CRP), fibrinogen, cyclic guanosine monophosphate (cGMP), and antibodies against oxidized LDL (oxLDL) were measured at each time point. Data are means+/-standard errors of the mean (SEM).
Influenza vaccination caused a slight elevation in CRP (from 0.5+/-0.1 at baseline, to 2+/-0.6 mg/L, P = 0.01) and fibrinogen (from 2.3+/-0.1 to 2.7+/-0.1 g/L, P = 0.01) at 2 days, which completely resolved at 14 days (CRP: 0.6+/-0.2 mg/L, P = 0.9, and fibrinogen: 2.3+/-0.1 g/L, P = 0.8 versus baseline). OxLDL antibody levels rose significantly at 2 days (from 1+/-0.1 at baseline to 2+/-0.4, P = 0.04), and remained elevated at 14 days (1.7+/-0.3, P = 0.1 versus baseline). FMD of the brachial artery decreased at 2 days (from 8.3+/-1.2% at baseline, to 5.4+/-1%, P = 0.05) with a further decrease at 14 days (4.9+/-0.8%, P = 0.03 versus baseline). The dilatory responses to GTN and the carotid IMT remained unchanged throughout the study period (P>0.5).
Abnormalities in arterial function and LDL oxidation may persist for at least 2 weeks after a slight inflammatory reaction induced by influenza vaccination. These could explain in part the earlier reported increase in cardiovascular risk during the first weeks after an acute inflammatory disorder.
多项临床研究表明，在急性炎症性疾病期间及之后的最初几周内，心血管风险可能会增加。我们以流感疫苗作为炎症刺激物，研究动脉内皮功能障碍是否会在炎症状态消退后持续存在，以及低密度脂蛋白（LDL）氧化修饰增强是否伴随这种血管紊乱。
在8名健康男性志愿者（年龄17 - 30岁）肌肉注射流感疫苗前、注射后2天和14天，通过外部超声评估肱动脉对充血（血流介导的扩张（FMD））以及舌下含服硝酸甘油（GTN）的反应，以及颈动脉内膜中层厚度。在每个时间点测量血浆中高敏C反应蛋白（CRP）、纤维蛋白原、环磷酸鸟苷（cGMP）以及抗氧化型LDL（oxLDL）抗体的水平。数据为平均值±平均标准误差（SEM）。
流感疫苗接种后2天，CRP（从基线时的0.5±0.1升高至2±0.6 mg/L，P = 0.01）和纤维蛋白原（从2.3±0.1升高至2.7±0.1 g/L，P = 0.01）略有升高，在14天时完全恢复正常（CRP：0.6±0.2 mg/L，P = 0.9；纤维蛋白原：2.3±0.1 g/L，与基线相比P = 0.8）。oxLDL抗体水平在2天时显著升高（从基线时的1±0.1升高至2±0.4，P = 0.04），并在14天时仍保持升高（1.7±0.3，与基线相比P = 0.1）。肱动脉FMD在2天时降低（从基线时的8.3±1.2%降至5.4±1%，P = 0.05），在14天时进一步降低（4.9±0.8%，与基线相比P = 0.03）。在整个研究期间，对GTN的扩张反应和颈动脉IMT保持不变（P>0.5）。
流感疫苗接种引发的轻微炎症反应后，动脉功能异常和LDL氧化可能至少持续2周。这可能部分解释了先前报道的急性炎症性疾病后最初几周内心血管风险增加的现象。
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