Contributions of elevated C-reactive protein (CRP), hyperglycaemia, and type 2 diabetes to cardiovascular risk in the general population: observational and Mendelian randomization studies
Authors' conclusion
Elevated concentrations of plasma CRP and glucose are predictors of IHD and CVD death in the general population. We found no genetic association between CRP and glucose, or vice versa, suggesting that lowering glucose pharmacologically does not have a direct effect on low-grade inflammation.
Study context
- Population
- General population: Copenhagen General Population Study and Copenhagen City Heart Study
- Participants
- 112,815 participants
- Exposure
- Higher vs lower plasma CRP and glucose; T2D and CRP ≥2 mg/L vs neither
- Outcome
- Risk of ischemic heart disease (IHD) and CVD death
Methodological detailsbidirectional one-sample Mendelian randomization (MR), bidirectional two-sample MR with summary level data (CHARGE and MAGIC)
- Bidirectional one-sample MR
- Bidirectional two-sample MR with summary level data (CHARGE and MAGIC)
Main finding
As reported in the abstract
- Ischemic heart disease (IHD), 20% highest CRP: HR
- 1.50 (1.38, 1.62) (95% CI)
- Cardiovascular disease (CVD) death, 20% highest CRP: HR
- 2.44 (1.93, 3.10) (95% CI)
- IHD, elevated plasma glucose: HR
- 1.10 (1.02, 1.18)
- CVD death, elevated plasma glucose: HR
- 1.22 (1.01, 1.49)
- Higher cumulative incidence of IHD with both T2D and CRP ≥2 mg/L vs neither
- 365%
- Higher cumulative incidence of CVD death with both T2D and CRP ≥2 mg/L vs neither
- 592%
Observational data: associations, not effects.
Further findings
Association of plasma CRP and glucose
- Observational β-coefficient
- 0.02 (0.02, 0.03), p = 3 × 10- 20
- One-sample MR, CRP on glucose
- −0.04 (−0.12, 0.32)
- Two-sample MR, CRP on glucose
- - 0.03 (−0.13, 0.06)
- One-sample MR, glucose on CRP
- −0.01 (−0.08, 0.07)
- Two-sample MR, glucose on CRP
- - 0.00 (−0.14, 0.13)
- MR did not support a causal effect in either direction
Original publication
Contributions of elevated CRP, hyperglycaemia, and type 2 diabetes to cardiovascular risk in the general population: observational and Mendelian randomization studies. Cardiovasc Diabetol. Published 10 May 2024. doi:10.
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