Department of Internal Medicine, Maastricht University Medical Centre and CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands.
Endocrine. 2018 Dec;62(3):617-627. doi: 10.1007/s12020-018-1712-3. Epub 2018 Aug 21.
We investigated the associations of components of the alternative (C3, C3a, Bb, factor D [FD], factor H [FH], properdin) and the classical complement pathway (C4, C1q, C1-inhibitor [C1-INH]) with prevalent and incident metabolic syndrome in a cohort with a moderately increased risk of cardiometabolic disease.
The study cohort was comprised of 574 participants (61% men, age 59.6 ± 7.0 years) at baseline and 489 participants after 7-year follow-up. Multiple logistic regression analyses were done to investigate the associations of concentrations of baseline plasma complement (standardized values) with prevalent and incident (in those without metabolic syndrome at baseline, n = 189) metabolic syndrome.
C3 (odds ratio (OR) = 1.48 [95% confidence interval: 1.02; 2.14]) and C4 (OR = 1.95 [1.32; 2.88]), but none of the other complement components were associated with incident metabolic syndrome (n = 40 cases). Notably, in the cross-sectional analyses, we did observe higher levels of C3a (OR = 1.25 [1.03; 1.52]), FH (OR = 2.93 [2.24; 3.83]), and properdin (OR = 1.88 [1.50; 2.34]), in addition to C3 (OR = 3.60 [2.73; 4.75]) and C4 (OR = 1.39 [1.13; 1.69]), in those with the metabolic syndrome compared to those without, while no association was observed for FD, Bb, C1q, or C1-INH.
In the cross-sectional analyses, the effects sizes (standardized regression coefficients) for C3 and C4 were similar to those of (some of) the regulators and activators, yet only C3 and C4 were associated with incident disease. These findings suggest a role for C3 and C4, but not their regulators or activated products, in the development of the metabolic syndrome.
我们研究了替代（C3、C3a、Bb、因子 D [FD]、因子 H [FH]、备解素）和经典补体途径（C4、C1q、C1 抑制剂 [C1-INH]）各成分与心血管代谢疾病风险中等升高的队列中现患和新发代谢综合征的相关性。
研究队列由 574 名参与者（61%为男性，年龄 59.6±7.0 岁）组成，基线时有 489 名参与者在 7 年随访后入组。采用多元逻辑回归分析，研究基线时血浆补体浓度（标准化值）与现患和新发（在基线时无代谢综合征的参与者中，n=189）代谢综合征的相关性。
C3（比值比 [OR] = 1.48 [95%置信区间：1.02；2.14]）和 C4（OR = 1.95 [1.32；2.88]），但其他补体成分均与新发代谢综合征无关（n=40 例）。值得注意的是，在横断面分析中，我们观察到 C3a（OR = 1.25 [1.03；1.52]）、FH（OR = 2.93 [2.24；3.83]）和备解素（OR = 1.88 [1.50；2.34]）水平升高，除 C3（OR = 3.60 [2.73；4.75]）和 C4（OR = 1.39 [1.13；1.69]）外，在代谢综合征患者中，而 FD、Bb、C1q 或 C1-INH 与代谢综合征无关。
在横断面分析中，C3 和 C4 的效应大小（标准化回归系数）与调节剂和激活剂中的一些相似，但只有 C3 和 C4 与疾病发生相关。这些发现表明 C3 和 C4，而不是它们的调节剂或激活产物，在代谢综合征的发展中起作用。
