TY - JOUR
T1 - C-reactive protein and all-cause mortality--the Copenhagen City Heart Study
AU - Zacho, Jeppe
AU - Tybjærg-Hansen, Anne
AU - Nordestgaard, Børge G
PY - 2010/7/1
Y1 - 2010/7/1
N2 - Aims We tested whether elevated levels of C-reactive protein is robustly and causally associated with all-cause mortality. Methods and results We studied 10 388 white persons from the general population. During 16 years 3124 persons died. We measured baseline high-sensitivity C-reactive protein and fibrinogen levels and genotyped for four C-reactive protein polymorphisms and two apolipoprotein E polymorphisms. Levels of C-reactive protein >3 mg/L vs. <1 mg/L associated with a multi-factorially adjusted two-fold increased risk of all-cause mortality. Stratifying C-reactive protein into tertiles, quintiles, or octiles resulted in step-by-step increased risk of all-cause mortality, even after fibrinogen adjustment. Finally, genetically elevated C-reactive protein levels associated with a causal hazard ratio of 0.94 (95 CI: 0.64-1.39) for all-cause mortality per doubling of C-reactive protein levels on instrumental variable analysis, for which the corresponding hazard ratio on Cox regression for a doubling in measured plasma C-reactive protein levels was 1.25 (1.21-1.29). As a positive control, a doubling in genetically elevated cholesterol levels via apolipoprotein E associated with a hazard ratio of 6.3 (1.8-22) for all-cause mortality. Conclusion A single C-reactive protein measurement robustly associates with increased risk of all-cause mortality; however, this does not appear to be a causal association. Therefore, elevated C-reactive protein levels more likely are a marker of hidden, potentially fatal inflammatory disease. Published on behalf of the European Society of Cardiology. All rights reserved.
AB - Aims We tested whether elevated levels of C-reactive protein is robustly and causally associated with all-cause mortality. Methods and results We studied 10 388 white persons from the general population. During 16 years 3124 persons died. We measured baseline high-sensitivity C-reactive protein and fibrinogen levels and genotyped for four C-reactive protein polymorphisms and two apolipoprotein E polymorphisms. Levels of C-reactive protein >3 mg/L vs. <1 mg/L associated with a multi-factorially adjusted two-fold increased risk of all-cause mortality. Stratifying C-reactive protein into tertiles, quintiles, or octiles resulted in step-by-step increased risk of all-cause mortality, even after fibrinogen adjustment. Finally, genetically elevated C-reactive protein levels associated with a causal hazard ratio of 0.94 (95 CI: 0.64-1.39) for all-cause mortality per doubling of C-reactive protein levels on instrumental variable analysis, for which the corresponding hazard ratio on Cox regression for a doubling in measured plasma C-reactive protein levels was 1.25 (1.21-1.29). As a positive control, a doubling in genetically elevated cholesterol levels via apolipoprotein E associated with a hazard ratio of 6.3 (1.8-22) for all-cause mortality. Conclusion A single C-reactive protein measurement robustly associates with increased risk of all-cause mortality; however, this does not appear to be a causal association. Therefore, elevated C-reactive protein levels more likely are a marker of hidden, potentially fatal inflammatory disease. Published on behalf of the European Society of Cardiology. All rights reserved.
U2 - http://dx.doi.org/10.1093/eurheartj/ehq103
DO - http://dx.doi.org/10.1093/eurheartj/ehq103
M3 - Journal article
SN - 0195-668X
VL - 31
SP - 1624
EP - 1632
JO - European Heart Journal
JF - European Heart Journal
IS - 13
ER -