C-reactive protein and all-cause mortality--the Copenhagen City Heart Study

Area of Science:

• Biomedical research
• Epidemiology
• Genetics

Background:

• High-sensitivity C-reactive protein (hs-CRP) is a marker of inflammation.
• Elevated hs-CRP levels are linked to increased risk of cardiovascular disease and mortality.
• The causal relationship between hs-CRP and all-cause mortality requires further investigation.

Purpose of the Study:

• To determine if elevated C-reactive protein (CRP) levels are robustly and causally associated with all-cause mortality.
• To investigate the association between hs-CRP, fibrinogen, and mortality risk.
• To differentiate between observational associations and causal links using genetic data.

Main Methods:

• Studied 10,388 individuals from the general population over 16 years.
• Measured baseline hs-CRP and fibrinogen levels.
• Genotyped for CRP and apolipoprotein E polymorphisms.
• Utilized instrumental variable analysis to assess causality.

Main Results:

• High hs-CRP levels (>3 mg/L) were associated with a two-fold increased risk of all-cause mortality.
• A dose-response relationship was observed between hs-CRP levels and mortality risk, even after fibrinogen adjustment.
• Instrumental variable analysis indicated no causal association between genetically elevated CRP and all-cause mortality (hazard ratio: 0.94).

Conclusions:

• While hs-CRP measurements robustly associate with increased all-cause mortality risk, the association appears non-causal.
• Elevated hs-CRP may serve as a marker for underlying, potentially fatal inflammatory diseases.
• Further research is needed to elucidate the specific inflammatory conditions indicated by elevated CRP.