Jonkers Iris J, Mohrschladt Martina F, Westendorp Rudi G, van der Laarse Arnoud, Smelt Augustinus H
Department of General Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Am J Med. 2002 Mar;112(4):275-80. doi: 10.1016/s0002-9343(01)01123-8.
To determine whether hypertriglyceridemia is associated with systemic inflammation, which may contribute to the increased cardiovascular risk in patients who have hypertriglyceridemia. In addition, we investigated whether fibrates reverse this inflammatory state.
Serum lipid levels, body mass index, insulin resistance, and inflammatory parameters were compared between 18 patients who had severe hypertriglyceridemia without cardiovascular disease and 20 normolipidemic controls. We measured the ex vivo production capacity of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 after whole-blood stimulation with lipopolysaccharide, as well as circulating levels of C-reactive protein and fibrinogen. A randomized controlled trial was conducted to determine whether bezafibrate (400 mg administered daily for 6 weeks) affected these parameters in hypertriglyceridemic patients.
When compared with normolipidemic controls, hypertriglyceridemic patients had significantly lower high-density lipoprotein (HDL) cholesterol and higher triglyceride levels, body mass index, and insulin resistance. In addition, hypertriglyceridemic patients had a significantly higher production capacity of TNF-alpha (mean difference, 11 700 pg/mL; 95% confidence interval [CI]: 7800 to 15,700 pg/mL]) and IL-6 (mean difference, 20,400 pg/mL; 95% CI: 7800 to 32,900 pg/mL), and higher levels of C-reactive protein (mean difference, 0.8 mg/L; 95% CI: 0.1 to 2.4 mg/L) and fibrinogen (mean difference, 0.8 g/dL; 95% CI: 0.3 to 1.3 g/dL). Bezafibrate therapy significantly increased HDL cholesterol levels, reduced triglyceride and insulin resistance levels, and reduced production capacity of TNF-alpha and IL-6, as well as levels of C-reactive protein and fibrinogen.
Systemic inflammation is present in patients who have the clinical phenotype that is associated with severe hypertriglyceridemia, and may contribute to the increased risk of cardiovascular disease in these patients. Bezafibrate has anti-inflammatory effects in these patients.
确定高甘油三酯血症是否与全身炎症相关，而全身炎症可能导致高甘油三酯血症患者心血管风险增加。此外，我们研究了贝特类药物是否能逆转这种炎症状态。
比较了18例无心血管疾病的严重高甘油三酯血症患者和20例血脂正常的对照者的血脂水平、体重指数、胰岛素抵抗和炎症参数。我们测定了用脂多糖刺激全血后肿瘤坏死因子（TNF）-α和白细胞介素（IL）-6的体外产生能力，以及C反应蛋白和纤维蛋白原的循环水平。进行了一项随机对照试验，以确定苯扎贝特（每日服用400mg，共6周）是否会影响高甘油三酯血症患者的这些参数。
与血脂正常的对照者相比，高甘油三酯血症患者的高密度脂蛋白（HDL）胆固醇显著降低，甘油三酯水平、体重指数和胰岛素抵抗更高。此外，高甘油三酯血症患者的TNF-α产生能力显著更高（平均差异为11700pg/mL；95%置信区间[CI]：7800至15700pg/mL）和IL-6（平均差异为20400pg/mL；95%CI：7800至32900pg/mL），C反应蛋白水平更高（平均差异为0.8mg/L；95%CI：0.1至2.4mg/L）和纤维蛋白原（平均差异为0.8g/dL；95%CI：0.3至1.3g/dL）。苯扎贝特治疗显著提高了HDL胆固醇水平，降低了甘油三酯和胰岛素抵抗水平，降低了TNF-α和IL-6的产生能力，以及C反应蛋白和纤维蛋白原水平。
具有与严重高甘油三酯血症相关临床表型的患者存在全身炎症，这可能导致这些患者心血管疾病风险增加。苯扎贝特对这些患者具有抗炎作用。
