Gil Brown
Oct. 11, 1996
65 yo AAM s/p MI at unknown time in past, with NIDDM, normal LDL, low HDL, non-smoker, +
family history,
h/o HTN. Should I give this patient supplemental folate in efforts to reduce CAD risk
factors?
I. Coronary heart disease death occurred 1.6 x's more frequently in persons with folate
less than 3.0 ng/ml than persons with folate of 26.0 ng/ml.
II. Finding is independent of cholesterol, age, tobacco, diabetes, diastolic blood
pressure, Vit A, C, or E levels.
III.Currently acknowledged side effects of administering folate are masking Vit B'2
deficiency, interference with anticonvulsant therapy and cost.
Retrospective cohort study with 15 year follow-up of 5056 enrollees of Nutrition Canada
Survey (men and women
aged 35-79). Exclusion criteria: pregnancy, native Indian, Inuit, missing data,
pre-existing heart disease.
Serum Folate Age < 65 (at study beginning) |
||||
(ng/ml) |
Deaths |
person-yrs |
Risk ratio |
95% CI |
>/=6.0 |
7 |
10,539 |
1.00 |
-------- |
4.0-/<6.0 |
12 |
12,156 |
1.49 |
0.58-3.8 |
3.0-<4.0 |
10 |
9,747 |
1.55 |
0.6-4.17 |
<3.0 |
11 |
10,614 |
1.56 |
0.69-4.71 |
| Serum Folate Age>/=65 (at study beginning) | ||||
(ng/ml) |
Deaths |
person-yrs |
Risk ratio |
95% CI |
| >/=6.0 | 28 | 3888 | 1.00 | -------- |
| 4.0-<6.0 | 31 | 4416 | .97 | 0.61-1.70 |
| 3.0-<4.0 | 25 | 3241 | 1.07 | 0.64-1.90 |
| <3.0 | 41 | 3560 | 1.60 | 1.03-2.71 |
I. Weaknesses of Study:
A. Serum folate effects may be confounded by other unmeasured parameters or attributes of individual that may parallel folate concentration, is intracellular folate, carotenoids, minerals, or lifestyle of patient.
B. What type of folate is being measured?- tetrahydrofolate vs dihydrofolate?
C. Family history not considered in data stratification.
D. Significant differences exist only between lowest and highest quartile
E. Population not reflective of US population, re: race (South African blacks do not respond to same extent as South African whites with respect to decreased homocysteine in response to folate supplementation)
II. Strengths of study:
A. Very diverse population examined with multiple parameters examined and consistent trends throughout(sex, cholesterol, tobacco, etc).
B. Examined primary prevention only-secondary prevention may offer larger 'n' and thus increase power for detecting trends in CAD prevention.
C. Results are consistent with multiple previous studies demonstrating similar associations, either between folate or homocysteine and CAD/peripheral vascular disease/stroke.
D. Results are consistent with biochemical model for hyperhomocysteinemia as risk for CAD.
III. Why I should treat:
A. Relatively benign intervention with potentially life-saving benefit.
B. Other likely benefits from folate supplementation include reduced risks for cervical cancer and neural tube defects in pregnancy, and rectal cancer.
IV. Why I should not treat:
A. No randomized controlled trial demonstrating efficacy.
B. Potential side effects of folate: mask vitamin B12deficiency, reduces phenytoin levels and cost.
C. Long term effects of folate supplementation unknown.
V. What will I do?
A. Check vitamin B12 folate and homocysteine levels and if abnormal, will start folate with or without vitamin B12 supplementation.
REFERENCES:
1. Morrison, HI, et al. Serum folate and risk of fatal coronary heart disease. JAMA. 275(24),
1893-1896, 1996,
June 26.
2. Ubbink, J., et al. Effective homocysteine metabolism may protect South African blacks
against coronary heart
disease. American J. of Clin. Nutr. 62(4):802-808, 1995, Oct.