- 作者：Marianne Benn ; MD ; PhD ; DMSc鈦?/sup> ; &dagger ; ; &Dagger ; ; Anne Tybjæ ; rg-Hansen ; MD ; DMSc&dagger ; ; &Dagger ; ; § ; ; 鈭?/sup> ; Mark I. McCarthy ; MD¶ ; ; # ; 鈦庘亷 ; Gorm B. Jensen ; MD ; DMSc&Dagger ; ; § ; ; Peer Grande ; MD ; DMSc&Dagger ; ; § ; ; Bø ; rge G. Nordestgaard ; MD ; DMSc鈦?/sup> ; &dagger ; ; &Dagger ; ; 鈭?/sup> ; Boerge.Nordestgaard@regionh.dk
- 关键词：cardiovascular disease ; diabetes mellitus ; epidemiology ; nonfasting ; plasma glucose ; post-prandial
- 刊名：Journal of the American College of Cardiology
- 出版年：2012
- 期刊代码：201_07351097
- 类别：med
- 出版时间：19-26 June, 2012
- 卷：59
- 期：25
- 页码：2356-2365
- 文件大小：2021 K
Objectives
The purpose of this study was to test whether elevated nonfasting glucose levels associate with and cause ischemic heart disease (IHD) and myocardial infarction (MI).Background
Elevated fasting plasma glucose levels associate with increased risk of IHD, but whether this is also true for nonfasting levels and whether this is a causal relationship is unknown.
Methods
Using a Mendelian randomization approach, we studied 80,522 persons from Copenhagen, Denmark. Of those, IHD developed in 14,155, and MI developed in 6,257. Subjects were genotyped for variants in GCK (rs4607517), G6PC2 (rs560887), ADCY5 (rs11708067), DGKB (rs2191349), and ADRA2A (rs10885122) associated with elevated fasting glucose levels in genome-wide association studies.
Results
Risk of IHD and MI increased stepwise with increasing nonfasting glucose levels. The hazard ratio for IHD in subjects with nonfasting glucose levels 鈮?1 mmol/l (鈮?98 mg/dl) versus <5 mmol/l (<90 mg/dl) was 6.9 (95%confidence interval [CI]: 4.2 to 11.2) adjusted for age and sex, and 2.3 (95%CI: 1.3 to 4.2) adjusted multifactorially; corresponding values for MI were 9.2 (95%CI: 4.6 to 18.2) and 4.8 (95%CI: 2.1 to 11.2). Increasing number of glucose-increasing alleles was associated with increasing nonfasting glucose levels and with increased risk of IHD and MI. The estimated causal odds ratio for IHD and MI by instrumental variable analysis for a 1-mmol/l (18-mg/dl) increase in nonfasting glucose levels due to genotypes combined were 1.25 (95%CI: 1.03 to 1.52) and 1.69 (95%CI: 1.28 to 2.23), and the corresponding observed hazard ratio for IHD and MI by Cox regression was 1.18 (95%CI: 1.15 to 1.22) and 1.09 (95%CI: 1.07 to 1.11), respectively.
Conclusions
Like common nonfasting glucose elevation, plasma glucose-increasing polymorphisms associate with increased risk of IHD and MI. These data are compatible with a causal association.