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Cardiovascular Diabetology

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Open Access 01-12-2024 | Type 2 Diabetes | Research

Contributions of elevated CRP, hyperglycaemia, and type 2 diabetes to cardiovascular risk in the general population: observational and Mendelian randomization studies

Authors: Monica G Rolver, Frida Emanuelsson, Børge G Nordestgaard, Marianne Benn

Published in: Cardiovascular Diabetology | Issue 1/2024

Abstract

Objective

To investigate the contributions of low-grade inflammation measured by C-reactive protein (CRP), hyperglycaemia, and type 2 diabetes to risk of ischemic heart disease (IHD) and cardiovascular disease (CVD) death in the general population, and whether hyperglycaemia and high CRP are causally related.

Research design and methods

Observational and bidirectional, one-sample Mendelian randomization (MR) analyses in 112,815 individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study, and bidirectional, two-sample MR with summary level data from two publicly available consortia, CHARGE and MAGIC.

Results

Observationally, higher plasma CRP was associated with stepwise higher risk of IHD and CVD death, with hazard ratios and 95% confidence intervals (95%CI) of 1.50 (1.38, 1.62) and 2.44 (1.93, 3.10) in individuals with the 20% highest CRP concentrations. The corresponding hazard ratios for elevated plasma glucose were 1.10 (1.02, 1.18) and 1.22 (1.01, 1.49), respectively. Cumulative incidences of IHD and CVD death were 365% and 592% higher, respectively, in individuals with both type 2 diabetes and plasma CRP ≥ 2 mg/L compared to individuals without either. Plasma CRP and glucose were observationally associated (β-coefficient: 0.02 (0.02, 0.03), p = 3 × 10^− 20); however, one- and two-sample MR did not support a causal effect of CRP on glucose (−0.04 (−0.12, 0.32) and − 0.03 (−0.13, 0.06)), nor of glucose on CRP (−0.01 (−0.08, 0.07) and − 0.00 (−0.14, 0.13)).

Conclusions

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.

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Title: Contributions of elevated CRP, hyperglycaemia, and type 2 diabetes to cardiovascular risk in the general population: observational and Mendelian randomization studies
Authors: Monica G Rolver
Frida Emanuelsson
Børge G Nordestgaard
Marianne Benn
Publication date: 01-12-2024
Publisher: BioMed Central
Keywords: Type 2 Diabetes
Hyperglycemia
Published in: Cardiovascular Diabetology / Issue 1/2024
Electronic ISSN: 1475-2840
DOI: https://doi.org/10.1186/s12933-024-02207-0

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