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Vitamin D and cause-specific vascular disease and mortality: a Mendelian randomisation study involving 99,012 Chinese and 106,911 European adults.
BMC Med. 2019 08 30; 17(1):160.BM

Abstract

BACKGROUND

Randomised control trials and genetic analyses have demonstrated that vitamin D or 25-hydroxyvitamin D (25[OH]D) levels may not play a causal role in the development of cardiovascular disease. However, it is unclear if 25(OH)D is causally associated with cause-specific vascular disease and lipids. Therefore, we examined the causal association of 25(OH)D with myocardial infarction, stroke, ischaemic heart disease, ischaemic stroke, subarachnoid haemorrhage, intracerebral haemorrhage, and lipid levels among both Chinese and Europeans.

METHODS

We used a Mendelian randomisation (MR) design in the China Kadoorie Biobank, the Copenhagen City Heart Study, and the Copenhagen General Population Study. The 25(OH)D-related genetic variants in the CYP2R1 and DCHR7 genes were genotyped in 99,012 Chinese adults and 106,911 Danish adults.

RESULTS

In Chinese adults, plasma 25(OH)D levels were not significantly associated with cause-specific vascular disease or mortality, with the exception of intracerebral haemorrhage (HR, 1.09 [95% CI, 1.01,1.18] per 25 nmol/L higher plasma 25(OH)D). In Europeans, plasma 25(OH)D levels were inversely associated with all types of vascular diseases and mortality. However, MR analysis did not demonstrate causal associations of genetically increased 25(OH)D levels with cause-specific vascular diseases, or mortality in both Chinese and European adults. In addition, each 25 nmol/L higher 25(OH)D was observationally associated with lower total cholesterol and low-density lipoprotein cholesterol levels, but higher high-density lipoprotein cholesterol levels. Likewise, MR analysis showed that 25(OH)D levels were not causally associated with lipids in both Chinese and European adults after Bonferroni correction.

CONCLUSIONS

We found no evidence to support that genetically increased 25(OH)D was associated with a lower risk of ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and lipid levels in both Chinese and European adults. These results suggest that the inverse associations of vitamin D with vascular disease could be the result of confounding.

Authors+Show Affiliations

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China. Key Laboratory of Molecular Cardiovascular Sciences (Peking University), Ministry of Education, Beijing, China.Department of Clinical Biochemistry and Copenhagen General Population Study, Copenhagen University Hospital, Herlev and Gentofte Hospital Copenhagen, Copenhagen, Denmark.Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.Chinese Academy of Medical Sciences, Beijing, China.Chinese Academy of Medical Sciences, Beijing, China.Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.NCDs Prevention and Control Department, Liuzhou Center for Disease Control and Prevention, Liuzhou, China.Qingdao Center for Disease Control and Prevention, Qingdao, China.China National Center for Food Safety Risk Assessment, Beijing, China.Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.Department of Clinical Biochemistry and Copenhagen General Population Study, Copenhagen University Hospital, Herlev and Gentofte Hospital Copenhagen, Copenhagen, Denmark. The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Copenhagen, Denmark. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.Department of Clinical Biochemistry and Copenhagen General Population Study, Copenhagen University Hospital, Herlev and Gentofte Hospital Copenhagen, Copenhagen, Denmark. The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Copenhagen, Denmark. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China. epi.lvjun@vip.163.com. Key Laboratory of Molecular Cardiovascular Sciences (Peking University), Ministry of Education, Beijing, China. epi.lvjun@vip.163.com. Peking University Institute of Environmental Medicine, Beijing, China. epi.lvjun@vip.163.com.Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China. lmlee@vip.163.com. Chinese Academy of Medical Sciences, Beijing, China. lmlee@vip.163.com.No affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

31466528

Citation

Huang, Tao, et al. "Vitamin D and Cause-specific Vascular Disease and Mortality: a Mendelian Randomisation Study Involving 99,012 Chinese and 106,911 European Adults." BMC Medicine, vol. 17, no. 1, 2019, p. 160.
Huang T, Afzal S, Yu C, et al. Vitamin D and cause-specific vascular disease and mortality: a Mendelian randomisation study involving 99,012 Chinese and 106,911 European adults. BMC Med. 2019;17(1):160.
Huang, T., Afzal, S., Yu, C., Guo, Y., Bian, Z., Yang, L., Millwood, I. Y., Walters, R. G., Chen, Y., Chen, N., Gao, R., Chen, J., Clarke, R., Chen, Z., Ellervik, C., Nordestgaard, B. G., Lv, J., & Li, L. (2019). Vitamin D and cause-specific vascular disease and mortality: a Mendelian randomisation study involving 99,012 Chinese and 106,911 European adults. BMC Medicine, 17(1), 160. https://doi.org/10.1186/s12916-019-1401-y
Huang T, et al. Vitamin D and Cause-specific Vascular Disease and Mortality: a Mendelian Randomisation Study Involving 99,012 Chinese and 106,911 European Adults. BMC Med. 2019 08 30;17(1):160. PubMed PMID: 31466528.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vitamin D and cause-specific vascular disease and mortality: a Mendelian randomisation study involving 99,012 Chinese and 106,911 European adults. AU - Huang,Tao, AU - Afzal,Shoaib, AU - Yu,Canqing, AU - Guo,Yu, AU - Bian,Zheng, AU - Yang,Ling, AU - Millwood,Iona Y, AU - Walters,Robin G, AU - Chen,Yiping, AU - Chen,Ningyu, AU - Gao,Ruqin, AU - Chen,Junshi, AU - Clarke,Robert, AU - Chen,Zhengming, AU - Ellervik,Christina, AU - Nordestgaard,Børge G, AU - Lv,Jun, AU - Li,Liming, AU - ,, Y1 - 2019/08/30/ PY - 2019/04/24/received PY - 2019/07/30/accepted PY - 2019/8/31/entrez PY - 2019/8/31/pubmed PY - 2020/1/7/medline KW - Cardiovascular diseases KW - Causal effect KW - Lipids KW - Mendelian randomisation KW - Vitamin D SP - 160 EP - 160 JF - BMC medicine JO - BMC Med VL - 17 IS - 1 N2 - BACKGROUND: Randomised control trials and genetic analyses have demonstrated that vitamin D or 25-hydroxyvitamin D (25[OH]D) levels may not play a causal role in the development of cardiovascular disease. However, it is unclear if 25(OH)D is causally associated with cause-specific vascular disease and lipids. Therefore, we examined the causal association of 25(OH)D with myocardial infarction, stroke, ischaemic heart disease, ischaemic stroke, subarachnoid haemorrhage, intracerebral haemorrhage, and lipid levels among both Chinese and Europeans. METHODS: We used a Mendelian randomisation (MR) design in the China Kadoorie Biobank, the Copenhagen City Heart Study, and the Copenhagen General Population Study. The 25(OH)D-related genetic variants in the CYP2R1 and DCHR7 genes were genotyped in 99,012 Chinese adults and 106,911 Danish adults. RESULTS: In Chinese adults, plasma 25(OH)D levels were not significantly associated with cause-specific vascular disease or mortality, with the exception of intracerebral haemorrhage (HR, 1.09 [95% CI, 1.01,1.18] per 25 nmol/L higher plasma 25(OH)D). In Europeans, plasma 25(OH)D levels were inversely associated with all types of vascular diseases and mortality. However, MR analysis did not demonstrate causal associations of genetically increased 25(OH)D levels with cause-specific vascular diseases, or mortality in both Chinese and European adults. In addition, each 25 nmol/L higher 25(OH)D was observationally associated with lower total cholesterol and low-density lipoprotein cholesterol levels, but higher high-density lipoprotein cholesterol levels. Likewise, MR analysis showed that 25(OH)D levels were not causally associated with lipids in both Chinese and European adults after Bonferroni correction. CONCLUSIONS: We found no evidence to support that genetically increased 25(OH)D was associated with a lower risk of ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and lipid levels in both Chinese and European adults. These results suggest that the inverse associations of vitamin D with vascular disease could be the result of confounding. SN - 1741-7015 UR - https://www.unboundmedicine.com/medline/citation/31466528/Vitamin_D_and_cause_specific_vascular_disease_and_mortality:_a_Mendelian_randomisation_study_involving_99012_Chinese_and_106911_European_adults_ L2 - https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-019-1401-y DB - PRIME DP - Unbound Medicine ER -