Highlights
- •Higher RBC folate concentrations were significantly associated with an elevated risk of CHD.
- •The association was independent of traditional CHD risk factors.
- •The positive RBC folate–CHD relationship is more apparent in male than female.
Abstract
Background and aim
Folate is involved in a number of metabolic pathways. Red blood cell (RBC) folate
is a well-established indicator of folate intake. However, studies focused on the
association between RBC folate and coronary heart disease (CHD) are limited. The aim
of the current study was to investigate the effect of RBC folate concentrations on
the presence of CHD in a nationally representative sample of American adults.
Methods and results
In the 1999–2012 National Health and Nutrition Examination Survey (NHANES), 22,499
subjects aged 30–74 years with RBC folate concentrations, CHD status and responses
to co-variates questions were included; 822 (3.65%) participants were identified as
having CHD. Bio-Rad Quanta Phase II radioassay and microbiological assay were used
to measure RBC folate concentrations. Firstly, we treated RBC folate as a categorical
variable, based on RBC folate tertiles, and used logistic regression analysis to display
the RBC folate and CHD relationship. Secondly, we explored associations using a combination
of restricted cubic spline and logistic regression models, stratified by sex. After
adjusting for several well-established traditional CHD risk factors, RBC folate was
positively related to CHD presence in the total population and the association was
more pronounced among males than females. A J-shaped pattern was observed in RBC folate
concentrations for females.
Conclusion
Elevated RBC folate concentrations were associated with higher CHD risk. Further investigation
is needed to test the association in large-scale follow-up studies.
Keywords
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References
- Folate and DNA methylation: a review of molecular mechanisms and the evidence for folate's role.Adv Nutr. 2012; 3: 21-38
- FAD/folate-dependent tRNA methyltransferase: flavin as a new methyl-transfer agent.J Am Chem Soc. 2012; 134: 19739-19745
- Folate and methylation status in relation to phosphorylated tau protein(181P) and beta-amyloid(1-42) in cerebrospinal fluid.Clin Chem. 2007; 53: 1129-1136
- Comparison of standardised dietary folate intake across ten countries participating in the European Prospective Investigation into Cancer and Nutrition.Br J Nutr. 2012; 108: 552-569
- Use of high doses of folic acid supplements in pregnant women in Spain: an INMA cohort study.BMJ Open. 2015; 5: e009202
- Food standards: amendment of standards of identity for enriched grain products to require addition of folic acid.Fed Regist. 1996; 61: 8781-8797
- Impact of voluntary fortification and supplement use on dietary intakes and biomarker status of folate and vitamin B-12 in Irish adults.Am J Clin Nutr. 2015; 101: 1163-1172
- Biomarkers of folate status in NHANES: a roundtable summary.Am J Clin Nutr. 2011; 94: 303S-312S
- Quantifying options for reducing coronary heart disease mortality by 2020.Circulation. 2013; 127: 2477-2484
- Regional variation in coronary heart disease mortality trends in Portugal, 1981–2012.Int J Cardiol. 2016; 224: 279-285
- Coronary heart disease mortality, cardiovascular disease mortality and all-cause mortality attributable to dietary intake over 20 years in Brazil.Int J Cardiol. 2016; 217: 64-68
- Short-term exposure to ambient air pollution and coronary heart disease mortality in 8 Chinese cities.Int J Cardiol. 2015; 197: 265-270
- The beneficial effect of folate-enriched egg on the folate and homocysteine levels in rats fed a folate- and choline-deficient diet.J Food Sci. 2012; 77: H268-H272
- Multimarker prediction of coronary heart disease risk: the Women's Health Initiative.J Am Coll Cardiol. 2010; 55: 2080-2091
- Serum folate and risk of fatal coronary heart disease.JAMA. 1996; 275: 1893-1896
- Serum homocysteine and folate but not vitamin B12 are predictors of CHD mortality in older adults.Eur J Prev Cardiol. 2012; 19: 1420-1429
- Coronary heart disease mortality, plasma homocysteine, and B-vitamins: a prospective study.Atherosclerosis. 2003; 166: 369-377
- Serum folate and homocysteine and the incidence of acute coronary events: the Kuopio Ischaemic Heart Disease Risk Factor Study.Am J Clin Nutr. 2004; 80: 317-323
- Serum folate and risk for coronary heart disease: results from a cohort of US adults.Ann Epidemiol. 1998; 8: 490-496
- Folate and vitamin B-12 and risk of fatal cardiovascular disease: cohort study from Busselton, Western Australia.BMJ. 2003; 326: 131
- Serum vitamins, carotenoids, and angina pectoris: findings from the National Health and Nutrition Examination Survey III.Ann Epidemiol. 2000; 10: 106-116
- High red blood cell folate is associated with an increased risk of death among adults with diabetes, a 15-year follow-up of a national cohort.Nutr Metab Cardiovasc Dis. 2015; 25: 997-1006
National Health and Examination Survey. https://www.cdc.gov/nchs/nhanes/index.htm [accessed 28.06.17.].
- Prediction of coronary heart disease using risk factor categories.Circulation. 1998; 97: 1837-1847
- Regression modeling strategies: with applications to linear models, logistic regression, and survival analysis.2nd ed. Springer, New York2015
- Urinary sodium and potassium excretion and risk of cardiovascular events.JAMA. 2011; 306: 2229-2238
- Conclusions of a WHO Technical Consultation on folate and vitamin B12 deficiencies.Food Nutr Bull. 2008; 29: S238-S244
- Estimation of trends in serum and RBC folate in the U.S. population from pre- to postfortification using assay-adjusted data from the NHANES 1988-2010.J Nutr. 2012; 142: 886-893
- Folate and vitamin B-12 biomarkers in NHANES: history of their measurement and use.Am J Clin Nutr. 2011; 94: 322S-331S
- Food fortification with folic acid: has the other shoe dropped?.Nutr Rev. 2007; 65: 512-515
- Examination of circulating folate levels as a reflection of folate intakes among older adult supplement users and nonusers in the National Health and Nutrition Examination Survey 2003–2004.J Acad Nutr Diet. 2012; 112: 285-290
- Too much folate: a risk factor for cancer and cardiovascular disease?.Curr Opin Clin Nutr Metab Care. 2009; 12: 30-36
- Homocysteine determinants and the evidence to what extent homocysteine determines the risk of coronary heart disease.Pharmacol Rev. 2002; 54: 599-618
- Intake of folate, vitamin B6 and vitamin B12 and the risk of CHD: the Japan Public Health Center-Based Prospective Study Cohort I.J Am Coll Nutr. 2008; 27: 127-136
Article info
Publication history
Published online: July 24, 2017
Accepted:
July 17,
2017
Received in revised form:
June 28,
2017
Received:
June 1,
2017
Handling Editor: F. GallettiIdentification
Copyright
© 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
