Coffee intake, cardiovascular disease and all-cause mortality: observational and Mendelian randomization analyses in 95 000-223 000 individuals
Coffee intake, cardiovascular disease and all-cause mortality: observational and Mendelian randomization analyses in 95 000-223 000 individuals
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DOI：
10.1093/ije/dyw325
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发表时间：
2016-12-01
影响因子：
7.7
通讯作者：
Nordestgaard, Borge Gronne
中科院分区：
文献类型：
--
作者：
Nordestgaard, Ask Tybjaerg;Nordestgaard, Borge Gronne
背景资料：在荟萃分析中，咖啡与心血管疾病风险和全因死亡率的适度降低有关;然而，尚不清楚这些是否是因果关系。我们首先测试了咖啡摄入量是否与心血管疾病和全因死亡率相关;其次，先前与咖啡因摄入量相关的遗传变异是否与咖啡摄入量相关;第三，遗传变异是否与心血管疾病和全因死亡率相关。首先，我们使用多变量调整后的考克斯比例风险回归模型与限制性三次样条检查观察协会在95 366白色丹麦人。其次，我们根据AHR（rs 4410790; rs6968865）和CYP 1A 1/2基因（rs 2470893; rs 2472297; rs 2472299）附近的五种遗传变异估计平均咖啡摄入量。第三，我们使用性别和年龄调整的考克斯比例风险回归模型，以检查112509名丹麦人的心血管疾病和全因死亡率的遗传关联。最后，我们使用性别和年龄调整的逻辑回归模型来研究缺血性心脏病的遗传相关性，包括总共223414名个体的C4D和C4D联合体。我们应用类似的分析与血浆胆固醇水平相关的ApoE基因型，作为阳性control.Results：在观察分析中，我们观察到咖啡摄入量和心血管疾病和全因死亡率之间的U形关联;在中等咖啡摄入量的个体中观察到的风险最低。咖啡因摄入等位基因得分（rs 4410790 + rs 2470893）与高42%的咖啡摄入量相关。每个咖啡因摄入等位基因的风险比为1.02（95%可信区间：1.00-1.03）缺血性心脏病，1.02（0.99-1.02）缺血性卒中，1.02（1.00-1.03），心血管疾病死亡率为1.02（0.99-1.06），全因死亡率为1.01（0.99-1.03）。包括国际联盟，缺血性心脏病的咖啡因摄入等位基因的优势比为1.00（0.98-1.02）对于rs 4410790，1.01（0.99-1.03），rs 2470893为1.02（1.00-1.04），rs 2472297为1.02（1.00-1.04），rs 2472299为1.03（0.99-1.06）。相反，ApoE基因型引起的胆固醇水平降低5%，缺血性心脏病的相应比值比为0.93（0.89-0.97）。结论：观察发现，咖啡摄入量与心血管疾病风险和全因死亡率呈U形降低相关;然而，遗传性咖啡因摄入量与心血管疾病风险或全因死亡率无关。
Background: Coffee has been associated with modestly lower risk of cardiovascular disease and all-cause mortality in meta-analyses; however, it is unclear whether these are causal associations. We tested first whether coffee intake is associated with cardiovascular disease and all-cause mortality observationally; second, whether genetic variations previously associated with caffeine intake are associated with coffee intake; and third, whether the genetic variations are associated with cardiovascular disease and all-cause mortality.Methods: First, we used multivariable adjusted Cox proportional hazard regression models evaluated with restricted cubic splines to examine observational associations in 95 366 White Danes. Second, we estimated mean coffee intake according to five genetic variations near the AHR (rs4410790; rs6968865) and CYP1A1/2 genes (rs2470893; rs2472297; rs2472299). Third, we used sex-and age adjusted Cox proportional hazard regression models to examine genetic associations with cardiovascular disease and all-cause mortality in 112 509 Danes. Finally, we used sex and age-adjusted logistic regression models to examine genetic associations with ischaemic heart disease including the Cardiogram and C4D consortia in a total of up to 223 414 individuals. We applied similar analyses to ApoE genotypes associated with plasma cholesterol levels, as a positive control.Results: In observational analyses, we observed U-shaped associations between coffee intake and cardiovascular disease and all-cause mortality; lowest risks were observed in individuals with medium coffee intake. Caffeine intake allele score (rs4410790 + rs2470893) was associated with a 42% higher coffee intake. Hazard ratios per caffeine intake allele were 1.02 (95% confidence interval: 1.00-1.03) for ischaemic heart disease, 1.02 (0.99-1.02) for ischaemic stroke, 1.02 (1.00-1.03) for ischaemic vascular disease, 1.02 (0.99-1.06) for cardiovascular mortality and 1.01 (0.99-1.03) for all-cause mortality. Including international consortia, odds ratios per caffeine intake allele for ischaemic heart disease were 1.00 (0.98-1.02) for rs4410790, 1.01 (0.99-1.03) for rs6968865, 1.02 (1.00-1.04) for rs2470893, 1.02 (1.00-1.04) for rs2472297 and 1.03 (0.99-1.06) for rs2472299. Conversely, 5% lower cholesterol level caused by ApoE genotype had a corresponding odds ratio for ischaemic heart disease of 0.93 (0.89-0.97).Conclusions: Observationally, coffee intake was associated with U-shaped lower risk of cardiovascular disease and all-cause mortality; however, genetically caffeine intake was not associated with risk of cardiovascular disease or all-cause mortality.