TY - JOUR
T1 - Classical Pathway of Complement Activation: Longitudinal Associations of C1q and C1-INH With Cardiovascular Outcomes: The CODAM Study (Cohort on Diabetes and Atherosclerosis Maastricht)Brief Report
AU - Hertle, Elisabeth
AU - Arts, Ilja C. W.
AU - van der Kallen, Carla J. H.
AU - Feskens, Edith J. M.
AU - Schalkwijk, Casper G.
AU - Stehouwer, Coen D. A.
AU - van Greevenbroek, Marleen M. J.
PY - 2018/5/1
Y1 - 2018/5/1
N2 - Objective The classical complement pathway has been assigned both protective and pathological effects in cardiovascular disease (CVD), but human data are lacking. We determined the associations of the pattern recognition factor C1q and the regulator C1-INH (C1-inhibitor) with incident CVD, carotid intima-media thickness, endothelial dysfunction, and low-grade inflammation. Approach and Results Baseline concentrations of C1q and C1-INH were measured in the CODAM study (Cohort on Diabetes and Atherosclerosis Maastricht; n=574; 61% men; age, 607 years). The 7-year incidence of CVD in participants free of CVD at baseline was evaluated using logistic regression analyses (n=342; 73 cases). The lowest incidence of CVD was observed in the middle tertile of C1q (T-low compared with T-middle: odds ratio, 2.38 [95% confidence interval, 1.14-4.95]; T-high compared with T-middle: odds ratio, 1.96 [95% confidence interval, 0.94-4.07]). C1-INH was not associated with CVD. During the 7-year follow-up period, C1q and C1-INH were not, or inconsistently, associated with carotid intima-media thickness or with biomarker scores reflecting endothelial dysfunction and low-grade inflammation. Conclusions Our results suggest a nonlinear association between C1q and incident CVD. This supports the concept that early steps in classical pathway activation may have both protective and pathological effects on human CVD.
AB - Objective The classical complement pathway has been assigned both protective and pathological effects in cardiovascular disease (CVD), but human data are lacking. We determined the associations of the pattern recognition factor C1q and the regulator C1-INH (C1-inhibitor) with incident CVD, carotid intima-media thickness, endothelial dysfunction, and low-grade inflammation. Approach and Results Baseline concentrations of C1q and C1-INH were measured in the CODAM study (Cohort on Diabetes and Atherosclerosis Maastricht; n=574; 61% men; age, 607 years). The 7-year incidence of CVD in participants free of CVD at baseline was evaluated using logistic regression analyses (n=342; 73 cases). The lowest incidence of CVD was observed in the middle tertile of C1q (T-low compared with T-middle: odds ratio, 2.38 [95% confidence interval, 1.14-4.95]; T-high compared with T-middle: odds ratio, 1.96 [95% confidence interval, 0.94-4.07]). C1-INH was not associated with CVD. During the 7-year follow-up period, C1q and C1-INH were not, or inconsistently, associated with carotid intima-media thickness or with biomarker scores reflecting endothelial dysfunction and low-grade inflammation. Conclusions Our results suggest a nonlinear association between C1q and incident CVD. This supports the concept that early steps in classical pathway activation may have both protective and pathological effects on human CVD.
KW - cardiovascular diseases
KW - carotid intima-media thickness
KW - follow-up studies
KW - humans
KW - incidence
KW - SYSTEMIC-LUPUS-ERYTHEMATOSUS
KW - C1Q-ADIPONECTIN/TOTAL ADIPONECTIN RATIO
KW - JAPANESE TYPE-2 DIABETICS
KW - INSULIN-RESISTANCE
KW - SERUM
KW - MBL
KW - EVENTS
KW - RISK
U2 - 10.1161/ATVBAHA.118.310806
DO - 10.1161/ATVBAHA.118.310806
M3 - Article
C2 - 29567681
SN - 1079-5642
VL - 38
SP - 1242
EP - 1244
JO - Arteriosclerosis Thrombosis and Vascular Biology
JF - Arteriosclerosis Thrombosis and Vascular Biology
IS - 5
ER -