Department of Clinical Biochemistry ( A.V., B.G.N.) and Copenhagen General Population Study (A.V., M.B., A.T.-H., B.G.N.), Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (A.V., M.B., A.T.-H., B.G.N.); Department of Clinical Biochemistry, Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark (M.B.); Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Denmark (A.T.-H., B.G.N.); and Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark (A.T.-H.).
Circulation. 2013 Sep 17;128(12):1298-309. doi: 10.1161/CIRCULATIONAHA.113.003008. Epub 2013 Aug 7.
Elevated nonfasting remnant cholesterol and low-density lipoprotein (LDL) cholesterol are causally associated with ischemic heart disease (IHD), but whether elevated nonfasting remnant cholesterol and LDL cholesterol both cause low-grade inflammation is currently unknown.
We studied 60 608 individuals from the Copenhagen General Population Study, the Copenhagen City Heart Study, and the Copenhagen Ischemic Heart Disease study, of whom 10 668 had IHD diagnosed between 1977 and 2011. We genotyped for variants affecting levels of nonfasting remnant cholesterol, LDL cholesterol, C-reactive protein by CRP alleles, and C-reactive protein by IL6R alleles. Using a multidirectional mendelian randomization design, we investigated possible causal associations between the lipoproteins and C-reactive protein and between the lipoproteins and IHD. A 1-mmol/L(39 mg/dL) higher level of nonfasting remnant cholesterol was associated observationally with a 37% (95% confidence interval, 35-39) higher C-reactive protein level and causally with a 28% (95% confidence interval, 10-48) higher level. For LDL cholesterol, a 1-mmol/L (39-mg/dL) higher level was associated observationally with a 7% (95% confidence interval, 6-7) higher C-reactive protein level, but we found no causal association. Likewise, higher levels of C-reactive protein did not associate causally with elevated nonfasting remnant cholesterol or LDL cholesterol. Finally, the causal risk ratio for IHD for a 1-mmol/L (39-mg/dL) higher level was 3.3 (95% confidence interval, 2.1-5.2) for nonfasting remnant cholesterol and 1.8 (95% confidence interval, 1.5-2.2) for LDL cholesterol. The causal associations for remnant cholesterol were present even in those without diabetes mellitus and obesity.
Elevated nonfasting remnant cholesterol is causally associated with low-grade inflammation and with IHD, whereas elevated LDL cholesterol is associated causally with IHD without inflammation.
非空腹残余胆固醇和低密度脂蛋白（LDL）胆固醇升高与缺血性心脏病（IHD）有因果关系，但升高的非空腹残余胆固醇和 LDL 胆固醇是否都会引起低度炎症目前尚不清楚。
我们研究了来自哥本哈根普通人群研究、哥本哈根心脏研究和哥本哈根缺血性心脏病研究的 60608 名个体，其中 10668 人在 1977 年至 2011 年间被诊断为 IHD。我们对影响非空腹残余胆固醇、LDL 胆固醇、C 反应蛋白（CRP）等位基因和 IL6R 等位基因的 CRP 水平以及 C 反应蛋白（CRP）的变体进行了基因分型。使用多向孟德尔随机化设计，我们研究了脂蛋白与 C 反应蛋白之间以及脂蛋白与 IHD 之间可能存在的因果关系。非空腹残余胆固醇水平每升高 1mmol/L（39mg/dL），C 反应蛋白水平就会升高 37%（95%置信区间，35-39），具有观察性和因果关系；而 LDL 胆固醇水平每升高 1mmol/L（39mg/dL），C 反应蛋白水平就会升高 7%（95%置信区间，6-7），但我们没有发现因果关系。同样，较高的 C 反应蛋白水平与升高的非空腹残余胆固醇或 LDL 胆固醇没有因果关系。最后，对于非空腹残余胆固醇，每升高 1mmol/L（39mg/dL），IHD 的因果风险比为 3.3（95%置信区间，2.1-5.2）；对于 LDL 胆固醇，该比值为 1.8（95%置信区间，1.5-2.2）。即使在没有糖尿病和肥胖症的人群中，残余胆固醇的因果关系仍然存在。
升高的非空腹残余胆固醇与低度炎症和 IHD 有因果关系，而升高的 LDL 胆固醇与 IHD 有因果关系，而与炎症无关。
