Department of Clinical Biochemistry, Copenhagen University Hospital - Herlev Gentofte, Borgmester Ib Juuls Vej 1, Herlev, 2730, Denmark.
Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, Copenhagen, 2200, Denmark.
Cardiovasc Diabetol. 2024 May 10;23(1):165. doi: 10.1186/s12933-024-02207-0.
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.
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.
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); 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)).
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.
探讨 C 反应蛋白（CRP）所衡量的低度炎症、高血糖和 2 型糖尿病对普通人群中缺血性心脏病（IHD）和心血管疾病（CVD）死亡风险的影响，以及高血糖和高 CRP 是否存在因果关系。
在哥本哈根普通人群研究和哥本哈根城市心脏研究的 112815 名个体中进行观察性和双向、单一样本 Mendelian 随机分析，并利用两个公开的联盟 CHARGE 和 MAGIC 的汇总水平数据进行双向、两样本 Mendelian 随机分析。
观察性分析显示，较高的血浆 CRP 与 IHD 和 CVD 死亡的风险呈逐步升高相关，在 CRP 浓度最高的 20%个体中，危险比（HR）及其 95%置信区间（95%CI）分别为 1.50（1.38，1.62）和 2.44（1.93，3.10）。而升高的血浆葡萄糖的相应 HR 分别为 1.10（1.02，1.18）和 1.22（1.01，1.49）。与无任何一种情况的个体相比，同时患有 2 型糖尿病和 CRP≥2mg/L 的个体的 IHD 和 CVD 死亡累积发生率分别高出 365%和 592%。CRP 和葡萄糖在观察上呈正相关（β系数：0.02（0.02，0.03），p=3×10）；然而，单样本和两样本 Mendelian 随机分析均不支持 CRP 对葡萄糖的因果效应（-0.04（-0.12，0.32）和-0.03（-0.13，0.06）），也不支持葡萄糖对 CRP 的因果效应（-0.01（-0.08，0.07）和-0.00（-0.14，0.13））。
较高的血浆 CRP 和葡萄糖浓度是普通人群中 IHD 和 CVD 死亡的预测指标。我们未发现 CRP 和葡萄糖之间存在遗传关联，反之亦然，这表明通过药物降低血糖不会对低度炎症产生直接影响。
