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June 26, 1996, Vol 275, No. 24 >
ARTICLE | June 26, 1996

Serum Folate and Risk of Fatal Coronary Heart Disease FREE

Howard I. Morrison, PhD; Douglas Schaubel; Marie Desmeules, MSc; Donald T. Wigle, MD, PhD
[+] Author Affiliations

Reprints: Howard Morrison, PhD, Cancer Bureau, Laboratory Centre for Disease Control Building, Tunney's Pasture, Ottawa, Ontario, Canada K1A 0L2.


JAMA. 1996;275(24):1893-1896. doi:10.1001/jama.1996.03530480035037
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References

Objective.  —To assess the relationship between serum folate level and the risk of fatal coronary heart disease (CHD) among men and women.

Design.  —Retrospective cohort study with serum folate levels measured from September 1970 to December 1972, with follow-up through 1985.

Setting.  —Participants in the Nutrition Canada Survey.

Participants.  —A total of 5056 Canadian men and women aged 35 to 79 years with no history of self-reported CHD.

Main Outcome Measure.  —Fifteen-year CHD mortality.

Results.  —A total of 165 CHD deaths were observed. We found a statistically significant association between serum folate level and risk of fatal CHD, with rate ratios for individuals in the lowest serum folate level category (<6.8 nmol/L [3 ng/mL]) compared with the highest category (>13.6 nmol/L [6 ng/mL]) of 1.69 (95% confidence interval, 1.10-2.61).

Conclusions.  —These data indicate that low serum folate levels are associated with an increased risk of fatal CHD.(JAMA. 1996;275:1893-1896)

REFERENCES

1 +
Semenciw R, Morrison H, Mao Y, Johansen H, Davies JW, Wigle D.  Major risk factors for cardiovascular disease mortality in adults: results from the Nutrition Canada Survey. Int J Epidemiol . 1988;;17:317-324.
2 +
Kannel B.  An overview of the risk factors for cardiovascular disease.  In: Kaplan N, Stamler J, eds. Prevention of Coronary Heart Disease . Philadelphia, Pa: WB Saunders Co; 1983;:1-19.
3 +
Martin M, Browner WS, Wentworth D, Hulley SB, Kuller LH.  Serum cholesterol, blood pressure, and mortality: implications from a cohort of 361662 men. Lancet . 1986;;2:923-926.
4 +
Pancharuniti N, Lewis CA, Sauberlich HE, et al.  Plasma homocysteine, folate, and vitamin B-12 concentrations and risk for early onset coronary artery disease. Am J Clin Nutr . 1994;;59:940-948.
5 +
Selhub J, Jacques PF, Bostom AG, et al.  Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis. N Engl J Med . 1995;;332:286-291.
6 +
Stampfer MJ, Malinow MR.  Can lowering homocysteine levels reduce cardiovascular risk? N Engl J Med . 1995;;332:328-329.
7 +
Ueland PM, Refsum H, Brattström L.  Plasma homocysteine and cardiovascular disease.  In: Francis RB Jr, ed. Atherosclerotic Cardiovascular Disease, Hemostasis, and Endothelial Function . New York, NY: Marcel Dekker Inc; 1992;:183-236.
8 +
Kang S, Wong PW, Malinow MR.  Hyperhomocysteinemia as a risk factor for occlusive vascular disease. Annu Rev Nutr . 1992;;12:279-298.
9 +
Gaby SK, Bendich A.  Folic acid . In: Gaby SK, Bendich A, Singh VN, et al, eds. Vitamin Intake and Health: A Scientific Review . New York, NY: Marcel Dekker Inc; 1991;.
10 +
Kang SS, Wong PW, Norusis M.  Homocysteinemia due to folate deficiency. Metabolism . 1987;;36: 458-462.
11 +
Department of National Health and Welfare. Nutrition Canada National Survey . Ottawa, Ontario: Information Canada; 1973;. Catalog No. H58-36/1973.
12 +
Johansen H, Semenciw R, Morrison HI, et al.  Important risk factors for adult mortality: a ten year follow-up of the Nutrition Canada Survey cohort. Can Med Assoc J . 1987;;136:823-828.
13 +
Watt BK, Merrill AL. Composition of Foods . Washington, DC: Agricultural Research Service, US Dept of Agriculture; 1963;. Agricultural Handbook No. 8.
14 +
Department of National Health and Welfare. Nutrition Canada Food Consumption Patterns Report . Ottawa, Ontario: Information Canada; 1973;. Catalog No. H58-36/1973.
15 +
Howe G, Lindsay J.  A generalized iterative record linkage computer system for use in medical follow-up studies. Comput Biomed Res . 1981;;14: 327-340.
16 +
National Center for Health Statistics. International Classification of Diseases, Adapted for Use in the United States . 8th rev. Washington, DC: US Dept of Health, Education, and Welfare, Public Health Service; 1967;.
17 +
Shannon HS, Jamieson E, Walsh C, Julian JA, Fair ME, Buffet A.  Comparison of individual follow-up and computerized linkage using the Canadian Mortality Data Base. Can J Public Health . 1989;; 80:54-57.
18 +
Aronow WS, Ahn C, Schonenfeld M, Gutstein H.  Extracranial carotid arterial disease: a prognostic factor for atherothrombotic brain infarction and cerebral transient ischemic attack. N Y State J Med . 1992;;92:424-425.
19 +
O'Leary DH, Polak JF, Kronmal RA, et al.  Distribution and correlates of sonographically detected carotid artery disease in the Cardiovascular Health Study. Stroke . 1992;;23:1752-1760.
20 +
Salonen JT, Salonen R.  Ultrasonographically assessed carotid morphology and the risk of coronary heart disease. Arterioscler Thromb . 1991;;11: 1245-1249.
21 +
Aronow WS, Schonenfeld MR.  Forty-five month follow-up of extracranial carotid arterial disease for new coronary events in elderly patients. Coron Artery Dis . 1992;;3:249-251.
22 +
Mojonnier L, Hall Y.  The National Diet Heart Study—assessment of dietary adherence. J Am Diet Assoc . 1968;;52:288-292.
23 +
MRC Vitamin Study Research Group.  Prevention of neural tube defects: results from the Medical Research Council Vitamin Study. Lancet . 1991;;338: 131-137.
24 +
Butterworth CE Jr, Hatch KD, Macaluso M, et al.  Folate deficiency and cervical dysplasia. JAMA . 1992;;267:528-533.
25 +
Freudenheim JL, Graham S, Marshall JR, Haughey BP, Cholewinski S, Wilkinson G.  Folate intake and carcinogenesis of the colon and rectum. Int J Epidemiol . 1991;;20:368-374.
26 +
Block G.  Micronutrients and cancer: time for action? J Natl Cancer Inst . 1993;;85:846-848.
27 +
Romano PS, Waitzman NJ, Scheffler RM, Pi RD.  Folic acid fortification of grain: an economic analysis. Am J Public Health . 1995;;85:667-676.
28 +
Chanarin I.  Adverse effects of increased dietary folate: relation to measures to reduce the incidence of neural tube defects. Clin Invest Med . 1994;;17:253-255.
29 +
Bayless EM, Crowley JM, Preece JM, et al.  Influence of folic acid on blood phenytoin levels. Lancet . 1971;;1:62-64.
30 +
National Research Council. Recommended Dietary Allowances , 10th ed. Washington, DC: National Academy Press; 1989;.
31 +
Subar AF, Block G, James LD.  Folate intake and food sources in the US population. Am J Clin Nutr . 1989;;50:508-516.
32 +
Sauberlich HE, Dretsch MJ, Skala JH, Johnson HL, Taylor PC.  Folate requirement and metabolism in nonpregnant women. Am J Clin Nutr . 1987;; 46:1016-1028.
33 +
Foulke J. Folic acid to fortify U.S. food products to prevent birth defects. Food and Drug Administration press release, February 29, 1996.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Semenciw R, Morrison H, Mao Y, Johansen H, Davies JW, Wigle D.  Major risk factors for cardiovascular disease mortality in adults: results from the Nutrition Canada Survey. Int J Epidemiol . 1988;;17:317-324.
2 +
Kannel B.  An overview of the risk factors for cardiovascular disease.  In: Kaplan N, Stamler J, eds. Prevention of Coronary Heart Disease . Philadelphia, Pa: WB Saunders Co; 1983;:1-19.
3 +
Martin M, Browner WS, Wentworth D, Hulley SB, Kuller LH.  Serum cholesterol, blood pressure, and mortality: implications from a cohort of 361662 men. Lancet . 1986;;2:923-926.
4 +
Pancharuniti N, Lewis CA, Sauberlich HE, et al.  Plasma homocysteine, folate, and vitamin B-12 concentrations and risk for early onset coronary artery disease. Am J Clin Nutr . 1994;;59:940-948.
5 +
Selhub J, Jacques PF, Bostom AG, et al.  Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis. N Engl J Med . 1995;;332:286-291.
6 +
Stampfer MJ, Malinow MR.  Can lowering homocysteine levels reduce cardiovascular risk? N Engl J Med . 1995;;332:328-329.
7 +
Ueland PM, Refsum H, Brattström L.  Plasma homocysteine and cardiovascular disease.  In: Francis RB Jr, ed. Atherosclerotic Cardiovascular Disease, Hemostasis, and Endothelial Function . New York, NY: Marcel Dekker Inc; 1992;:183-236.
8 +
Kang S, Wong PW, Malinow MR.  Hyperhomocysteinemia as a risk factor for occlusive vascular disease. Annu Rev Nutr . 1992;;12:279-298.
9 +
Gaby SK, Bendich A.  Folic acid . In: Gaby SK, Bendich A, Singh VN, et al, eds. Vitamin Intake and Health: A Scientific Review . New York, NY: Marcel Dekker Inc; 1991;.
10 +
Kang SS, Wong PW, Norusis M.  Homocysteinemia due to folate deficiency. Metabolism . 1987;;36: 458-462.
11 +
Department of National Health and Welfare. Nutrition Canada National Survey . Ottawa, Ontario: Information Canada; 1973;. Catalog No. H58-36/1973.
12 +
Johansen H, Semenciw R, Morrison HI, et al.  Important risk factors for adult mortality: a ten year follow-up of the Nutrition Canada Survey cohort. Can Med Assoc J . 1987;;136:823-828.
13 +
Watt BK, Merrill AL. Composition of Foods . Washington, DC: Agricultural Research Service, US Dept of Agriculture; 1963;. Agricultural Handbook No. 8.
14 +
Department of National Health and Welfare. Nutrition Canada Food Consumption Patterns Report . Ottawa, Ontario: Information Canada; 1973;. Catalog No. H58-36/1973.
15 +
Howe G, Lindsay J.  A generalized iterative record linkage computer system for use in medical follow-up studies. Comput Biomed Res . 1981;;14: 327-340.
16 +
National Center for Health Statistics. International Classification of Diseases, Adapted for Use in the United States . 8th rev. Washington, DC: US Dept of Health, Education, and Welfare, Public Health Service; 1967;.
17 +
Shannon HS, Jamieson E, Walsh C, Julian JA, Fair ME, Buffet A.  Comparison of individual follow-up and computerized linkage using the Canadian Mortality Data Base. Can J Public Health . 1989;; 80:54-57.
18 +
Aronow WS, Ahn C, Schonenfeld M, Gutstein H.  Extracranial carotid arterial disease: a prognostic factor for atherothrombotic brain infarction and cerebral transient ischemic attack. N Y State J Med . 1992;;92:424-425.
19 +
O'Leary DH, Polak JF, Kronmal RA, et al.  Distribution and correlates of sonographically detected carotid artery disease in the Cardiovascular Health Study. Stroke . 1992;;23:1752-1760.
20 +
Salonen JT, Salonen R.  Ultrasonographically assessed carotid morphology and the risk of coronary heart disease. Arterioscler Thromb . 1991;;11: 1245-1249.
21 +
Aronow WS, Schonenfeld MR.  Forty-five month follow-up of extracranial carotid arterial disease for new coronary events in elderly patients. Coron Artery Dis . 1992;;3:249-251.
22 +
Mojonnier L, Hall Y.  The National Diet Heart Study—assessment of dietary adherence. J Am Diet Assoc . 1968;;52:288-292.
23 +
MRC Vitamin Study Research Group.  Prevention of neural tube defects: results from the Medical Research Council Vitamin Study. Lancet . 1991;;338: 131-137.
24 +
Butterworth CE Jr, Hatch KD, Macaluso M, et al.  Folate deficiency and cervical dysplasia. JAMA . 1992;;267:528-533.
25 +
Freudenheim JL, Graham S, Marshall JR, Haughey BP, Cholewinski S, Wilkinson G.  Folate intake and carcinogenesis of the colon and rectum. Int J Epidemiol . 1991;;20:368-374.
26 +
Block G.  Micronutrients and cancer: time for action? J Natl Cancer Inst . 1993;;85:846-848.
27 +
Romano PS, Waitzman NJ, Scheffler RM, Pi RD.  Folic acid fortification of grain: an economic analysis. Am J Public Health . 1995;;85:667-676.
28 +
Chanarin I.  Adverse effects of increased dietary folate: relation to measures to reduce the incidence of neural tube defects. Clin Invest Med . 1994;;17:253-255.
29 +
Bayless EM, Crowley JM, Preece JM, et al.  Influence of folic acid on blood phenytoin levels. Lancet . 1971;;1:62-64.
30 +
National Research Council. Recommended Dietary Allowances , 10th ed. Washington, DC: National Academy Press; 1989;.
31 +
Subar AF, Block G, James LD.  Folate intake and food sources in the US population. Am J Clin Nutr . 1989;;50:508-516.
32 +
Sauberlich HE, Dretsch MJ, Skala JH, Johnson HL, Taylor PC.  Folate requirement and metabolism in nonpregnant women. Am J Clin Nutr . 1987;; 46:1016-1028.
33 +
Foulke J. Folic acid to fortify U.S. food products to prevent birth defects. Food and Drug Administration press release, February 29, 1996.

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