Zhang Yan, Zhu Cheng-Gang, Guo Yuan-Lin, Li Sha, Xu Rui-Xia, Dong Qian, Li Jian-Jun
Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Heart Lung Circ. 2016 Jun;25(6):558-67. doi: 10.1016/j.hlc.2016.01.001. Epub 2016 Jan 19.
It has been proposed that plasma fibrinogen is associated with lipid levels and increased cardiovascular risk. However, the interrelationship has not been well-elucidated. We hypothesise that lipids may be potential mediators.
We enrolled 4748 consecutive subjects scheduled for coronary angiography in this study. The severity of coronary atherosclerosis was assessed by Gensini score (GS). By principle component analysis, a multi-marker lipid index was extracted weighting the coefficients of six atherogenic lipid parameters: total cholesterol (TC), low-density lipoprotein-cholesterol, non-high-density lipoprotein-cholesterol (non-HDL-C), apolipoprotein (apo) B, apoB/apoA1, and TC/HDL-C ratio. Moreover, using mediation analysis, the relationship between fibrinogen and lipids with high GS was evaluated.
Fibrinogen was positively associated with GS after adjustment (β=0.100, p<0.001). We stratified our analyses by statin use status and found that subjects in the upper fibrinogen tertiles had higher levels of atherogenic lipid parameters irrespective of statin status (p<0.001, all). Significantly, we observed a synergistic effect of fibrinogen and concurrent elevated lipid index for high GS. The adjusted odds ratios were greater in participants who had high fibrinogen levels and also high lipid index compared to those with low lipid index [on statin: 1.725(1.258-2.364) vs. 1.261(0.962-1.652); not on statin: 2.197(1.450-3.328) vs. 1.166(0.417-3.258)]. Specifically, mediation analysis indicated that around 24% of the effect of fibrinogen on high GS was mediated by lipid index, which was attenuated to 13% by statin status.
The increased risk of fibrinogen on coronary atherosclerosis appeared to be enhanced by the high atherogenic lipid levels, which mediated around 24% of this effect.
有观点认为血浆纤维蛋白原与血脂水平及心血管疾病风险增加有关。然而，它们之间的相互关系尚未得到充分阐明。我们推测血脂可能是潜在的介导因素。
本研究纳入了4748例连续接受冠状动脉造影的受试者。采用Gensini评分（GS）评估冠状动脉粥样硬化的严重程度。通过主成分分析，提取了一个多标志物血脂指数，对六个致动脉粥样硬化血脂参数的系数进行加权：总胆固醇（TC）、低密度脂蛋白胆固醇、非高密度脂蛋白胆固醇（非HDL-C）、载脂蛋白（apo）B、apoB/apoA1以及TC/HDL-C比值。此外，采用中介分析评估纤维蛋白原与血脂和高GS之间的关系。
校正后纤维蛋白原与GS呈正相关（β=0.100，p<0.001）。我们根据他汀类药物使用情况对分析进行分层，发现无论他汀类药物使用情况如何，纤维蛋白原三分位数较高的受试者具有更高水平的致动脉粥样硬化血脂参数（p<0.001，均为）。值得注意的是，我们观察到纤维蛋白原与同时升高的血脂指数对高GS具有协同作用。与低血脂指数的参与者相比，纤维蛋白原水平高且血脂指数也高的参与者校正后的比值比更大[使用他汀类药物：1.725（1.258 - 2.364）对1.261（0.962 - 1.652）；未使用他汀类药物：2.（1.450 - 3.328）对1.166（0.417 - 3.258）]）。具体而言，中介分析表明，纤维蛋白原对高GS的影响约24%由血脂指数介导，他汀类药物使用情况使其减弱至13%。
纤维蛋白原对冠状动脉粥样硬化风险增加的影响似乎因高致动脉粥样硬化血脂水平而增强，后者介导了约24%的这种影响。
