Circulating Vitamin E Levels and Risk of Coronary Artery Disease and Myocardial Infarction: A Mendelian Randomization Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Data Sources
2.1.1. Vitamin E Levels
2.1.2. Coronary Artery Disease and Its Risk Factors
2.2. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Clarke, M.W.; Burnett, J.R.; Croft, K.D. Vitamin E in human health and disease. Crit. Rev. Clin. Lab. Sci. 2008, 45, 417–450. [Google Scholar] [CrossRef] [PubMed]
- Navab, M.; Ananthramaiah, G.M.; Reddy, S.T.; Van Lenten, B.J.; Ansell, B.J.; Fonarow, G.C.; Vahabzadeh, K.; Hama, S.; Hough, G.; Kamranpour, N.; et al. The oxidation hypothesis of atherogenesis: The role of oxidized phospholipids and HDL. J. Lipid. Res. 2004, 45, 993–1007. [Google Scholar] [CrossRef] [PubMed]
- Harrison, D.; Griendling, K.K.; Landmesser, U.; Hornig, B.; Drexler, H. Role of oxidative stress in atherosclerosis. Am. J. Cardiol. 2003, 91, 7A–11A. [Google Scholar] [CrossRef]
- Rimm, E.B.; Stampfer, M.J.; Ascherio, A.; Giovannucci, E.; Colditz, G.A.; Willett, W.C. Vitamin E consumption and the risk of coronary heart disease in men. N. Engl. J. Med. 1993, 328, 1450–1456. [Google Scholar] [CrossRef] [PubMed]
- Kushi, L.H.; Folsom, A.R.; Prineas, R.J.; Mink, P.J.; Wu, Y.; Bostick, R.M. Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women. N. Engl. J. Med. 1996, 334, 1156–1162. [Google Scholar] [CrossRef] [PubMed]
- Stampfer, M.J.; Hennekens, C.H.; Manson, J.E.; Colditz, G.A.; Rosner, B.; Willett, W.C. Vitamin E consumption and the risk of coronary disease in women. N. Engl. J. Med. 1993, 328, 1444–1449. [Google Scholar] [CrossRef] [PubMed]
- Lee, C.H.; Chan, R.S.M.; Wan, H.Y.L.; Woo, Y.C.; Cheung, C.Y.Y.; Fong, C.H.Y.; Cheung, B.M.Y.; Lam, T.H.; Janus, E.; Woo, J.; et al. Dietary Intake of Anti-Oxidant Vitamins A, C, and E Is Inversely Associated with Adverse Cardiovascular Outcomes in Chinese-A 22-Years Population-Based Prospective Study. Nutrients 2018, 10, 1664. [Google Scholar] [CrossRef]
- De Oliveira Otto, M.C.; Alonso, A.; Lee, D.H.; Delclos, G.L.; Bertoni, A.G.; Jiang, R.; Lima, J.A.; Symanski, E.; Jacobs, D.R., Jr.; Nettleton, J.A. Dietary intakes of zinc and heme iron from red meat, but not from other sources, are associated with greater risk of metabolic syndrome and cardiovascular disease. J. Nutr. 2012, 142, 526–533. [Google Scholar] [CrossRef] [PubMed]
- Goyal, A.; Terry, M.B.; Siegel, A.B. Serum antioxidant nutrients, vitamin A, and mortality in U.S. Adults. Cancer epidemiology, biomarkers & prevention: A publication of the American Association for Cancer Research. Cancer Epidemiol. Biomark. Prev. 2013, 22, 2202–2211. [Google Scholar] [CrossRef]
- Hense, H.W.; Stender, M.; Bors, W.; Keil, U. Lack of an association between serum vitamin E and myocardial infarction in a population with high vitamin E levels. Atherosclerosis 1993, 103, 21–28. [Google Scholar] [CrossRef]
- Karppi, J.; Laukkanen, J.A.; Makikallio, T.H.; Kurl, S. Low serum lycopene and beta-carotene increase risk of acute myocardial infarction in men. Eur. J. Public Health 2012, 22, 835–840. [Google Scholar] [CrossRef] [PubMed]
- Nagao, M.; Moriyama, Y.; Yamagishi, K.; Iso, H.; Tamakoshi, A.; Group, J.S. Relation of serum alpha- and gamma-tocopherol levels to cardiovascular disease-related mortality among Japanese men and women. J. Epidemiol. 2012, 22, 402–410. [Google Scholar] [CrossRef] [PubMed]
- Wright, M.E.; Lawson, K.A.; Weinstein, S.J.; Pietinen, P.; Taylor, P.R.; Virtamo, J.; Albanes, D. Higher baseline serum concentrations of vitamin E are associated with lower total and cause-specific mortality in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Am. J. Clin. Nutr. 2006, 84, 1200–1207. [Google Scholar] [CrossRef] [PubMed]
- Mezzetti, A.; Zuliani, G.; Romano, F.; Costantini, F.; Pierdomenico, S.D.; Cuccurullo, F.; Fellin, R.; Associazione Medica, S. Vitamin E and lipid peroxide plasma levels predict the risk of cardiovascular events in a group of healthy very old people. J. Am. Geriatr. Soc. 2001, 49, 533–537. [Google Scholar] [CrossRef] [PubMed]
- Lee, I.M.; Cook, N.R.; Gaziano, J.M.; Gordon, D.; Ridker, P.M.; Manson, J.E.; Hennekens, C.H.; Buring, J.E. Vitamin E in the primary prevention of cardiovascular disease and cancer: The Women’s Health Study: A randomized controlled trial. Jama 2005, 294, 56–65. [Google Scholar] [CrossRef] [PubMed]
- Tognoni, G.; Avanzini, F.; Pangrazzi, J.; Roncaglioni, M.C.; Bertele, V.; de Gaetano, G.; Caimi, V.; Tombesi, M.; Colombo, F.; Barlera, S.; et al. Low-dose aspirin and vitamin E in people at cardiovascular risk: A randomised trial in general practice. Lancet 2001, 357, 89–95. [Google Scholar]
- Hercberg, S.; Galan, P.; Preziosi, P.; Bertrais, S.; Mennen, L.; Malvy, D.; Roussel, A.M.; Favier, A.; Briancon, S. The SU.VI.MAX Study: A randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch. Intern. Med. 2004, 164, 2335–2342. [Google Scholar] [CrossRef]
- Sesso, H.D.; Buring, J.E.; Christen, W.G.; Kurth, T.; Belanger, C.; MacFadyen, J.; Bubes, V.; Manson, J.E.; Glynn, R.J.; Gaziano, J.M. Vitamins E and C in the prevention of cardiovascular disease in men: The Physicians’ Health Study II randomized controlled trial. Jama 2008, 300, 2123–2133. [Google Scholar] [CrossRef]
- Vivekananthan, D.P.; Penn, M.S.; Sapp, S.K.; Hsu, A.; Topol, E.J. Use of antioxidant vitamins for the prevention of cardiovascular disease: Meta-analysis of randomised trials. Lancet 2003, 361, 2017–2023. [Google Scholar] [CrossRef]
- Myung, S.K.; Ju, W.; Cho, B.; Oh, S.W.; Park, S.M.; Koo, B.K.; Park, B.J. Efficacy of vitamin and antioxidant supplements in prevention of cardiovascular disease: Systematic review and meta-analysis of randomised controlled trials. BMJ 2013, 346, f10. [Google Scholar] [CrossRef]
- Lonn, E.; Bosch, J.; Yusuf, S.; Sheridan, P.; Pogue, J.; Arnold, J.M.; Ross, C.; Arnold, A.; Sleight, P.; Probstfield, J.; et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: A randomized controlled trial. Jama 2005, 293, 1338–1347. [Google Scholar] [CrossRef] [PubMed]
- Marchioli, R.; Levantesi, G.; Macchia, A.; Marfisi, R.M.; Nicolosi, G.L.; Tavazzi, L.; Tognoni, G.; Valagussa, F.; Investigators, G.I.-P. Vitamin E increases the risk of developing heart failure after myocardial infarction: Results from the GISSI-Prevenzione trial. J. Cardiovasc. Med. 2006, 7, 347–350. [Google Scholar] [CrossRef] [PubMed]
- Bjelakovic, G.; Nikolova, D.; Gluud, C. Meta-regression analyses, meta-analyses, and trial sequential analyses of the effects of supplementation with beta-carotene, vitamin A, and vitamin E singly or in different combinations on all-cause mortality: Do we have evidence for lack of harm? PLoS ONE 2013, 8, e74558. [Google Scholar] [CrossRef] [PubMed]
- Bjelakovic, G.; Nikolova, D.; Gluud, L.L.; Simonetti, R.G.; Gluud, C. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: Systematic review and meta-analysis. Jama 2007, 297, 842–857. [Google Scholar] [CrossRef] [PubMed]
- Miller, E.R.; Pastor-Barriuso, R.; Dalal, D.; Riemersma, R.A.; Appel, L.J.; Guallar, E. Meta-analysis: High-dosage vitamin E supplementation may increase all-cause mortality. Ann. Intern. Med. 2005, 142, 37–46. [Google Scholar] [CrossRef] [PubMed]
- Davies, N.M.; Holmes, M.V.; Davey Smith, G. Reading Mendelian randomisation studies: A guide, glossary, and checklist for clinicians. BMJ 2018, 362, k601. [Google Scholar] [CrossRef]
- Major, J.M.; Yu, K.; Wheeler, W.; Zhang, H.; Cornelis, M.C.; Wright, M.E.; Yeager, M.; Snyder, K.; Weinstein, S.J.; Mondul, A.; et al. Genome-wide association study identifies common variants associated with circulating vitamin E levels. Hum. Mol. Genet. 2011, 20, 3876–3883. [Google Scholar] [CrossRef]
- Schunkert, H.; Konig, I.R.; Kathiresan, S.; Reilly, M.P.; Assimes, T.L.; Holm, H.; Preuss, M.; Stewart, A.F.; Barbalic, M.; Gieger, C.; et al. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat. Genet. 2011, 43, 333–338. [Google Scholar] [CrossRef]
- Nikpay, M.; Goel, A.; Won, H.H.; Hall, L.M.; Willenborg, C.; Kanoni, S.; Saleheen, D.; Kyriakou, T.; Nelson, C.P.; Hopewell, J.C.; et al. A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease. Nat. Genet. 2015, 47, 1121–1130. [Google Scholar] [CrossRef]
- Morris, A.P.; Voight, B.F.; Teslovich, T.M.; Ferreira, T.; Segre, A.V.; Steinthorsdottir, V.; Strawbridge, R.J.; Khan, H.; Grallert, H.; Mahajan, A.; et al. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat. Genet. 2012, 44, 981–990. [Google Scholar] [CrossRef]
- DIAbetes Genetics Replication and Meta-analysis (DIAGRAM) Consortium. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility. Nat. Genet. 2014, 46, 234–244. [Google Scholar] [CrossRef] [PubMed]
- Willer, C.J.; Schmidt, E.M.; Sengupta, S.; Peloso, G.M.; Gustafsson, S.; Kanoni, S.; Ganna, A.; Chen, J.; Buchkovich, M.L.; Mora, S.; et al. Discovery and refinement of loci associated with lipid levels. Nat. Genet. 2013, 45, 1274–1283. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dupuis, J.; Langenberg, C.; Prokopenko, I.; Saxena, R.; Soranzo, N.; Jackson, A.U.; Wheeler, E.; Glazer, N.L.; Bouatia-Naji, N.; Gloyn, A.L.; et al. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat. Genet. 2010, 42, 105–116. [Google Scholar] [CrossRef] [PubMed]
- Xu, L.; Lin, S.L.; Schooling, C.M. A Mendelian randomization study of the effect of calcium on coronary artery disease, myocardial infarction and their risk factors. Sci. Rep. 2017, 7, 42691. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xu, L.; Hao, Y.T. Effect of handgrip on coronary artery disease and myocardial infarction: A Mendelian randomization study. Sci. Rep. 2017, 7, 954. [Google Scholar] [CrossRef]
- Burgess, S.; Scott, R.A.; Timpson, N.J.; Davey Smith, G.; Thompson, S.G.; Consortium, E.-I. Using published data in Mendelian randomization: A blueprint for efficient identification of causal risk factors. Eur. J. Epidemiol. 2015, 30, 543–552. [Google Scholar] [CrossRef]
- Eidelman, R.S.; Hollar, D.; Hebert, P.R.; Lamas, G.A.; Hennekens, C.H. Randomized trials of vitamin E in the treatment and prevention of cardiovascular disease. Arch. Intern. Med. 2004, 164, 1552–1556. [Google Scholar] [CrossRef]
- Virtamo, J.; Rapola, J.M.; Ripatti, S.; Heinonen, O.P.; Taylor, P.R.; Albanes, D.; Huttunen, J.K. Effect of vitamin E and beta carotene on the incidence of primary nonfatal myocardial infarction and fatal coronary heart disease. Arch. Intern. Med. 1998, 158, 668–675. [Google Scholar] [CrossRef]
- Heart Outcomes Prevention Evaluation Study, I.; Yusuf, S.; Dagenais, G.; Pogue, J.; Bosch, J.; Sleight, P. Vitamin E supplementation and cardiovascular events in high-risk patients. N. Engl. J. Med. 2000, 342, 154–160. [Google Scholar] [CrossRef]
- Boaz, M.; Smetana, S.; Weinstein, T.; Matas, Z.; Gafter, U.; Iaina, A.; Knecht, A.; Weissgarten, Y.; Brunner, D.; Fainaru, M.; et al. Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): Randomised placebo-controlled trial. Lancet 2000, 356, 1213–1218. [Google Scholar] [CrossRef]
- Stephens, N.G.; Parsons, A.; Schofield, P.M.; Kelly, F.; Cheeseman, K.; Mitchinson, M.J. Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet 1996, 347, 781–786. [Google Scholar] [CrossRef]
- Schurks, M.; Glynn, R.J.; Rist, P.M.; Tzourio, C.; Kurth, T. Effects of vitamin E on stroke subtypes: Meta-analysis of randomised controlled trials. BMJ 2010, 341, c5702. [Google Scholar] [CrossRef] [PubMed]
- Ference, B.A.; Julius, S.; Mahajan, N.; Levy, P.D.; Williams, K.A., Sr.; Flack, J.M. Clinical effect of naturally random allocation to lower systolic blood pressure beginning before the development of hypertension. Hypertension 2014, 63, 1182–1188. [Google Scholar] [CrossRef] [PubMed]
- Bowry, V.W.; Ingold, K.U.; Stocker, R. Vitamin E in human low-density lipoprotein. When and how this antioxidant becomes a pro-oxidant. Biochem. J. 1992, 288, 341–344. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jiang, Q.; Christen, S.; Shigenaga, M.K.; Ames, B.N. gamma-tocopherol, the major form of vitamin E in the US diet, deserves more attention. Am. J. Clin. Nutr. 2001, 74, 714–722. [Google Scholar] [CrossRef] [PubMed]
- Lawlor, D.A. Commentary: Two-sample Mendelian randomization: Opportunities and challenges. Int. J. Epidemiol. 2016, 45, 908–915. [Google Scholar] [CrossRef] [PubMed]
SNP | Chromosome | Nearby Gene | Effect Allele b | Other Allele | Effect (Beta) c | SE | p-Value | EAF |
---|---|---|---|---|---|---|---|---|
rs11057830 | 12 | SCARB1 | A | G | 0.03 | 0.01 | 8.2 × 10−9 | 0.15 |
rs2108622 | 19 | CYP4F2 | T | C | 0.03 | 0.01 | 1.4 × 10−10 | 0.21 |
rs964184 | 11 | BUD13/ZNF259/APOA5 | G | C | 0.04 | 0.01 | 7.8 × 10−12 | 0.15 |
Consortia | OR | 95% CI | p-Value | IVW (Fixed or Random Effect Model) | Heterogeneity | ||
---|---|---|---|---|---|---|---|
I2 | p-Value | ||||||
Coronary artery disease | CARDIoGRAMplusC4D (n = 60,801 cases and 123,504 controls) | 1.05 | 1.032 to 1.057 | <0.001 | Fixed | 0 | 0.98 |
Myocardial infarction | CARDIoGRAMplusC4D (n = 43,676 cases and 128,199 controls) | 1.04 | 1.03 to 1.058 | <0.001 | Fixed | 0 | 0.54 |
Type 2 diabetes | DIAGRAM (n = 12,171 cases and 56,862 controls) | 1.00 | 0.977 to 1.027 | 0.89 | Fixed | 47% | 0.15 |
Beta | 95% CI | p-value | |||||
LDL-C, SD (1 SD = 38.7 mg/dL) | Global Lipids Genetics Consortium (n = 188,577) | 0.021 | 0.016 to 0.027 | <0.001 | Random | 99% | <0.001 |
HDL-C, SD (1 SD = 15.5 mg/dL) | Global Lipids Genetics Consortium (n = 188,577) | −0.019 | −0.024 to −0.014 | <0.001 | Random | 98% | <0.001 |
TC, SD (1 SD = 41.8 mg/dL) | Global Lipids Genetics Consortium (n = 188,577) | 0.026 | 0.021 to 0.031 | <0.001 | Random | 99% | <0.001 |
TG, SD (1 SD = 90.7 mg/dL) | Global Lipids Genetics Consortium (n = 188,577) | 0.043 | 0.038 to 0.048 | <0.001 | Random | 99% | <0.001 |
Fasting glucose, mmol/L | Meta-Analyses of Glucose and Insulin-related traits Consortium (n = 46,186) | 0.003 | −0.003 to 0.008 | 0.98 | Fixed | 0 | 0.38 |
OR | 95% CI | p-Value | |
Coronary artery disease | 1.04 | 1.028–1.059 | <0.001 |
Myocardial infarction | 1.04 | 1.027–1.06 | <0.001 |
Type 2 diabetes | 0.98 | 0.95–1.015 | 0.31 |
Beta | 95% CI | p-Value | |
LDL-C, SD (1 SD = 38.7 mg/dL) | 0.011 | 0.005–0.016 | <0.001 |
HDL-C, SD (1 SD = 15.5 mg/dL) | −0.004 | −0.009–0.002 | 0.20 |
TC, SD (1 SD = 41.8 mg/dL) | 0.01 | 0.004–0.016 | 0.001 |
TG, SD (1 SD = 90.7 mg/dL) | 0.009 | 0.003–0.014 | 0.002 |
Fasting glucose, mmol/L | 0.001 | −0.006–0.007 | 0.85 |
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Wang, T.; Xu, L. Circulating Vitamin E Levels and Risk of Coronary Artery Disease and Myocardial Infarction: A Mendelian Randomization Study. Nutrients 2019, 11, 2153. https://doi.org/10.3390/nu11092153
Wang T, Xu L. Circulating Vitamin E Levels and Risk of Coronary Artery Disease and Myocardial Infarction: A Mendelian Randomization Study. Nutrients. 2019; 11(9):2153. https://doi.org/10.3390/nu11092153
Chicago/Turabian StyleWang, Tao, and Lin Xu. 2019. "Circulating Vitamin E Levels and Risk of Coronary Artery Disease and Myocardial Infarction: A Mendelian Randomization Study" Nutrients 11, no. 9: 2153. https://doi.org/10.3390/nu11092153
APA StyleWang, T., & Xu, L. (2019). Circulating Vitamin E Levels and Risk of Coronary Artery Disease and Myocardial Infarction: A Mendelian Randomization Study. Nutrients, 11(9), 2153. https://doi.org/10.3390/nu11092153