Stroes E, de Bruin T, de Valk H, Erkelens W, Banga J D, van Rijn H, Koomans H, Rabelink T
Department of Nephrology and Hypertension, University Hospital Utrecht, The Netherlands.
Cardiovasc Res. 1997 Dec;36(3):445-52. doi: 10.1016/s0008-6363(97)00199-5.
Patients with familial combined hyperlipidemia (FCH) have an increased cardiovascular mortality despite only moderate elevations of LDL-cholesterol. Since endothelial NO release is intimately involved in the anti-atherosclerotic effects of the endothelium, we studied the effect of short-term lipid-lowering therapy on NO-mediated vasodilatation in patients with FCH. In view of only moderate LDL elevations, we evaluated whether alterations in other lipid fractions upon therapy correlated to changes in NO-mediated vasodilatation.
NO activity was assessed by serotonin-induced, nitric oxide-mediated increase in forearm blood flow (FBF). Measurements were performed 2 weeks off and 4 weeks on lipid-lowering therapy in 12 FCH patients using forearm venous occlusion plethysmography. Control experiments were performed in 12 healthy subjects.
Serotonin-induced vasodilatation was impaired in FCH patients (FBF (unit ml/100 ml forearm tissue/min) from 3.0 (0.3) to 4.8 (0.4)) compared to controls (FBF from 2.9 (0.3) to 6.5 (0.6); p < 0.05 vs. FCH). FBF response to serotonin improved significantly upon lipid-lowering therapy (from 3.0 (0.3) to 5.7 (0.5); p < 0.05 treated vs. untreated). The level of improvement in endothelial function was significantly correlated to the absolute reduction of intermediate density lipoproteins upon lipid-lowering therapy (r = -0.64; p < 0.05), whereas it did not correlate to changes in VLDL- or LDL-cholesterol, nor to Lp(a).
Patients with familial combined hyperlipidemia have impaired NO-mediated vasodilatation, that responds rapidly to lipid lowering medication, and may be related to changes in intermediate density lipoproteins.
家族性混合型高脂血症（FCH）患者尽管低密度脂蛋白胆固醇仅中度升高，但心血管死亡率却有所增加。由于内皮一氧化氮释放与内皮的抗动脉粥样硬化作用密切相关，我们研究了短期降脂治疗对FCH患者一氧化氮介导的血管舒张的影响。鉴于低密度脂蛋白仅中度升高，我们评估了治疗后其他脂质成分的变化是否与一氧化氮介导的血管舒张变化相关。
通过血清素诱导的、一氧化氮介导的前臂血流量（FBF）增加来评估一氧化氮活性。使用前臂静脉阻塞体积描记法，对12例FCH患者在降脂治疗停药2周和治疗4周时进行测量。在12名健康受试者中进行对照实验。
与对照组相比，FCH患者血清素诱导的血管舒张受损（FCH患者的FBF（单位为ml/100 ml前臂组织/分钟）从3.0（0.3）降至4.8（0.4）），而对照组的FBF从2.9（0.3）升至6.5（0.6）；与FCH组相比，p<0.05）。降脂治疗后，FBF对血清素的反应显著改善（从3.0（0.3）升至5.7（0.5）；治疗组与未治疗组相比，p<0.05）。内皮功能的改善水平与降脂治疗后中密度脂蛋白的绝对降低显著相关（r=-0.64；p<0.05），而与极低密度脂蛋白或低密度脂蛋白胆固醇的变化以及脂蛋白（a）均无相关性。
家族性混合型高脂血症患者一氧化氮介导的血管舒张受损，对降脂药物反应迅速，且可能与中密度脂蛋白的变化有关。
