目的:补体系统,特别是替代补体途径,可能导致血管损伤和心血管疾病(CVD)的发展。我们调查了因子D的关联,替代途径激活中的限速蛋白酶,心血管不良结局。
方法:在2947名参与者中(50.6%为男性,59.9±8.2岁,26.5%2型糖尿病[T2D],过度采样)我们测量了低度炎症的标志物(LGI,综合评分,在SD中)和,内皮功能障碍(ED,综合评分,inSD),颈动脉内中膜厚度(cIMT,μm),踝肱指数(ABI),CVD(是/否)和因子D的血浆浓度(以SD计)。关联使用多元线性和逻辑回归进行估计,适应人口统计,生活方式,和饮食因素。
结果:因子D(每SD)与LGI显着相关(0.171SD[0.137;0.205]),ED(0.158SD[0.123;0.194])和CVD(OR1.15[1.04;1.27]),但与cIMT(-6.62μm[-13.51;0.27])或ABI(-0.003[-0.007;0.001])无关。交互作用分析表明,非糖尿病患者中因子D与ED的相关性更强(0.237SD[0.189;0.285]比T2D(0.095SD[0.034;0.157]),P交互作用<0.05。这些结果在很大程度上通过对C3和C3a的额外分析得到证实。相比之下,因子D与非糖尿病患者的cIMT呈负相关(-13.37μm[-21.84;-4.90]),但不在T2D(4.49[-7.91;16.89])中,P交互作用<0.05。
结论:血浆因子D与LGI独立相关,ED,和普遍的CVD,但没有ABI或cIMT。因此,CVD中更高的血浆因子D浓度可能潜在地诱导补体激活,反过来,可能通过可能涉及炎症和内皮功能障碍的过程导致疾病的进一步进展,但与动脉粥样硬化或动脉损伤没有直接关系。观察到,在没有糖尿病的参与者中,与ED较差但cIMT较小相关的因素D值得进一步调查。
The complement system, particularly the alternative complement pathway, may contribute to vascular damage and development of cardiovascular disease (CVD). We investigated the association of factor D, the rate-limiting protease in alternative pathway activation, with adverse cardiovascular outcomes.
In 2947 participants (50.6% men, 59.9 ± 8.2 years, 26.5% type 2 diabetes [T2D], oversampled) we measured markers of low-grade inflammation (LGI, composite score, in SD) and, endothelial dysfunction (ED, composite score, in SD), carotid intima-media thickness (cIMT, μm), ankle-brachial index (ABI), CVD (yes/no) and plasma concentrations of factor D (in SD). Associations were estimated using multiple linear and logistic regression, adjusting for demographic, lifestyle, and dietary factors.
Factor D (per SD) significantly associated with LGI (0.171 SD [0.137; 0.205]), ED (0.158 SD [0.123; 0.194]) and CVD (OR 1.15 [1.04; 1.27]) but not significantly with cIMT (-6.62 μm [-13.51; 0.27]) or ABI (-0.003 [-0.007; 0.001]). Interaction analyses show that factor D more strongly associated with ED in non-diabetes (0.237 SD [0.189; 0.285] than in T2D (0.095 SD [0.034; 0.157]), pinteraction <0.05. These results were largely corroborated by additional analyses with C3 and C3a. In contrast, factor D inversely associated with cIMT in non-diabetes (-13.37 μm [-21.84; -4.90]), but not in T2D (4.49 [-7.91; 16.89]), pinteraction <0.05.
Plasma factor D is independently associated with LGI, ED, and prevalent CVD but not with ABI or cIMT. Hence, greater plasma factor D concentration in CVD may potentially induce complement activation which, in turn, might contribute to further disease progression via a process that may involve inflammation and endothelial dysfunction but was not directly related to atherosclerosis or arterial injury. The observation that, in participants without diabetes, factor D associated with worse ED but smaller cIMT warrants further investigation.