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Milk intake is not associated with ischaemic heart disease in observational or Mendelian randomization analyses in 98,529 Danish adults.
Int J Epidemiol 2015; 44(2):587-603IJ

Abstract

BACKGROUND

Observationally, reports on the association between milk intake and risk of ischaemic heart disease (IHD) and myocardial infarction (MI) have produced conflicting results; and no previous large-scale study using the lactase persistent/non-persistent LCT-13910 C/T genotype as a largely unconfounded proxy for milk intake free of reverse causation has been conducted. We tested the hypothesis that milk intake observationally and genetically through the LCT-13910 C/T genotype is associated with risk of IHD and MI in a Mendelian randomization design.

METHODS

We included 98,529 White individuals of Danish descent, aged 20-100 years, from three studies of the general population. Information on IHD (N = 10,372) and MI (N = 4188) were obtained from national Danish registries. First, we investigated observational associations between milk intake and incident IHD and MI. Second, we confirmed the association between the rs4988235 genetic variant LCT-13910 C/T, associated with lactase persistence/non-persistence, and milk intake. Finally, we tested whether LCT-13910 C/T genotype was associated with risk of IHD and MI as well as with cardiovascular risk factors.

RESULTS

During a mean follow-up time of 5.4 years, the observational hazard ratio for a 1 glass/week higher milk intake was 1.00 [95% confidence interval (CI): 1.00,1.01] for both IHD and MI. Median milk intake was 3 glasses/week (interquartile range: 0-7) in lactase CC non-persistent individuals compared with 5 glasses/week (0-10) in lactase TC/TT persistent individuals (P = 3*10(-60)). In the dominant genetic model comparing lactase TC/TT persistent individuals with lactase CC non-persistent individuals, the odds ratio was 1.00 (0.92,1.09) for IHD and 0.96 (0.84,1.09) for MI. Finally, in the dominant genetic model genotype was not associated convincingly with plasma levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides or glucose, nor with blood pressure.

CONCLUSION

Milk intake was not associated with risk of IHD or MI, observationally or genetically.

Authors+Show Affiliations

Department of Clinical Biochemistry, Naestved Hospital, 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, Denmark, Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark, Department of Research, Nykoebing Falster Hospital, Nykoebing Falster, Denmark and Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA, USA Department of Clinical Biochemistry, Naestved Hospital, 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, Denmark, Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark, Department of Research, Nykoebing Falster Hospital, Nykoebing Falster, Denmark and Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA, USA.Department of Clinical Biochemistry, Naestved Hospital, 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, Denmark, Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark, Department of Research, Nykoebing Falster Hospital, Nykoebing Falster, Denmark and Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA, USA Department of Clinical Biochemistry, Naestved Hospital, 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, Denmark, Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark, Department of Research, Nykoebing Falster Hospital, Nykoebing Falster, Denmark and Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA, USA Department of Clinical Biochemistry, Naestved Hospital, 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, Denmark, Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark, Department of Research, Nykoebing Falster Hospital, Nykoebing Falster, Denmark and Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA, USA.Department of Clinical Biochemistry, Naestved Hospital, 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, Denmark, Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark, Department of Research, Nykoebing Falster Hospital, Nykoebing Falster, Denmark and Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA, USA Department of Clinical Biochemistry, Naestved Hospital, 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, Denmark, Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark, Department of Research, Nykoebing Falster Hospital, Nykoebing Falster, Denmark and Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA, USA.Department of Clinical Biochemistry, Naestved Hospital, 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, Denmark, Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark, Department of Research, Nykoebing Falster Hospital, Nykoebing Falster, Denmark and Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA, USA Department of Clinical Biochemistry, Naestved Hospital, 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, Denmark, Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark, Department of Research, Nykoebing Falster Hospital, Nykoebing Falster, Denmark and Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA, USA Department of Clinical Biochemistry, Naestved Hospital, 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, Denmark, Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark, Department of Research, Nykoebing Falster Hospital, Nykoebing Falster, Denmark and Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA, USA christina@ellervik.dk.

Pub Type(s)

Journal Article
Observational Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26085675

Citation

Bergholdt, Helle K M., et al. "Milk Intake Is Not Associated With Ischaemic Heart Disease in Observational or Mendelian Randomization Analyses in 98,529 Danish Adults." International Journal of Epidemiology, vol. 44, no. 2, 2015, pp. 587-603.
Bergholdt HK, Nordestgaard BG, Varbo A, et al. Milk intake is not associated with ischaemic heart disease in observational or Mendelian randomization analyses in 98,529 Danish adults. Int J Epidemiol. 2015;44(2):587-603.
Bergholdt, H. K., Nordestgaard, B. G., Varbo, A., & Ellervik, C. (2015). Milk intake is not associated with ischaemic heart disease in observational or Mendelian randomization analyses in 98,529 Danish adults. International Journal of Epidemiology, 44(2), pp. 587-603. doi:10.1093/ije/dyv109.
Bergholdt HK, et al. Milk Intake Is Not Associated With Ischaemic Heart Disease in Observational or Mendelian Randomization Analyses in 98,529 Danish Adults. Int J Epidemiol. 2015;44(2):587-603. PubMed PMID: 26085675.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Milk intake is not associated with ischaemic heart disease in observational or Mendelian randomization analyses in 98,529 Danish adults. AU - Bergholdt,Helle K M, AU - Nordestgaard,Børge G, AU - Varbo,Anette, AU - Ellervik,Christina, PY - 2015/6/19/entrez PY - 2015/6/19/pubmed PY - 2016/3/16/medline KW - Mendelian randomization analysis KW - ischaemic heart disease KW - lactase persistence KW - milk KW - myocardial infarction SP - 587 EP - 603 JF - International journal of epidemiology JO - Int J Epidemiol VL - 44 IS - 2 N2 - BACKGROUND: Observationally, reports on the association between milk intake and risk of ischaemic heart disease (IHD) and myocardial infarction (MI) have produced conflicting results; and no previous large-scale study using the lactase persistent/non-persistent LCT-13910 C/T genotype as a largely unconfounded proxy for milk intake free of reverse causation has been conducted. We tested the hypothesis that milk intake observationally and genetically through the LCT-13910 C/T genotype is associated with risk of IHD and MI in a Mendelian randomization design. METHODS: We included 98,529 White individuals of Danish descent, aged 20-100 years, from three studies of the general population. Information on IHD (N = 10,372) and MI (N = 4188) were obtained from national Danish registries. First, we investigated observational associations between milk intake and incident IHD and MI. Second, we confirmed the association between the rs4988235 genetic variant LCT-13910 C/T, associated with lactase persistence/non-persistence, and milk intake. Finally, we tested whether LCT-13910 C/T genotype was associated with risk of IHD and MI as well as with cardiovascular risk factors. RESULTS: During a mean follow-up time of 5.4 years, the observational hazard ratio for a 1 glass/week higher milk intake was 1.00 [95% confidence interval (CI): 1.00,1.01] for both IHD and MI. Median milk intake was 3 glasses/week (interquartile range: 0-7) in lactase CC non-persistent individuals compared with 5 glasses/week (0-10) in lactase TC/TT persistent individuals (P = 3*10(-60)). In the dominant genetic model comparing lactase TC/TT persistent individuals with lactase CC non-persistent individuals, the odds ratio was 1.00 (0.92,1.09) for IHD and 0.96 (0.84,1.09) for MI. Finally, in the dominant genetic model genotype was not associated convincingly with plasma levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides or glucose, nor with blood pressure. CONCLUSION: Milk intake was not associated with risk of IHD or MI, observationally or genetically. SN - 1464-3685 UR - https://www.unboundmedicine.com/medline/citation/26085675/Milk_intake_is_not_associated_with_ischaemic_heart_disease_in_observational_or_Mendelian_randomization_analyses_in_98529_Danish_adults_ L2 - https://academic.oup.com/ije/article-lookup/doi/10.1093/ije/dyv109 DB - PRIME DP - Unbound Medicine ER -