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Coffee intake, cardiovascular disease and all-cause mortality: observational and Mendelian randomization analyses in 95 000-223 000 individuals.
Int J Epidemiol 2016; 45(6):1938-1952IJ

Abstract

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.

Authors+Show Affiliations

Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Frederiksberg, Denmark.

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28031317

Citation

Nordestgaard, Ask Tybjærg, and Børge Grønne Nordestgaard. "Coffee Intake, Cardiovascular Disease and All-cause Mortality: Observational and Mendelian Randomization Analyses in 95 000-223 000 Individuals." International Journal of Epidemiology, vol. 45, no. 6, 2016, pp. 1938-1952.
Nordestgaard AT, Nordestgaard BG. Coffee intake, cardiovascular disease and all-cause mortality: observational and Mendelian randomization analyses in 95 000-223 000 individuals. Int J Epidemiol. 2016;45(6):1938-1952.
Nordestgaard, A. T., & Nordestgaard, B. G. (2016). Coffee intake, cardiovascular disease and all-cause mortality: observational and Mendelian randomization analyses in 95 000-223 000 individuals. International Journal of Epidemiology, 45(6), pp. 1938-1952. doi:10.1093/ije/dyw325.
Nordestgaard AT, Nordestgaard BG. Coffee Intake, Cardiovascular Disease and All-cause Mortality: Observational and Mendelian Randomization Analyses in 95 000-223 000 Individuals. Int J Epidemiol. 2016 12 1;45(6):1938-1952. PubMed PMID: 28031317.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Coffee intake, cardiovascular disease and all-cause mortality: observational and Mendelian randomization analyses in 95 000-223 000 individuals. AU - Nordestgaard,Ask Tybjærg, AU - Nordestgaard,Børge Grønne, PY - 2016/10/17/accepted PY - 2016/12/30/pubmed PY - 2018/2/13/medline PY - 2016/12/30/entrez KW - Genetics KW - death KW - ischaemic heart disease KW - lifestyle KW - nutrition KW - stroke SP - 1938 EP - 1952 JF - International journal of epidemiology JO - Int J Epidemiol VL - 45 IS - 6 N2 - 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. SN - 1464-3685 UR - https://www.unboundmedicine.com/medline/citation/28031317/Coffee_intake_cardiovascular_disease_and_all_cause_mortality:_observational_and_Mendelian_randomization_analyses_in_95_000_223_000_individuals_ L2 - https://academic.oup.com/ije/article-lookup/doi/10.1093/ije/dyw325 DB - PRIME DP - Unbound Medicine ER -