Clinical study
Effect of folic acid fortification of food on homocysteine-related mortality

https://doi.org/10.1016/j.amjmed.2003.10.024Get rights and content

Abstract

Background

In 1998, the Food and Drug Administration mandated the fortification of food products with folic acid. The effect of this rule on mortality associated with homocysteine levels in patients with coronary artery disease is unknown.

Methods

We studied 2481 consecutive patients with coronary artery disease who underwent coronary angiography between 1994 and 1999, and who had baseline homocysteine measurements and at least 2 years of follow-up. Patients were divided into prefortification (1994 to 1997, n = 1595) and postfortification (1998 to 1999, n = 886) groups, as well as classified based on baseline homocysteine levels (normal to low, intermediate, and high). Homocysteine levels were measured by fluorescence polarization immunoassay. Mortality was determined by telephone survey or from a national Social Security database or hospital records.

Results

After implementation of the fortification rule, median homocysteine levels declined from 13.8 to 12.3 μmol/L (P <0.001), and the proportion of patients with high homocysteine levels (>15 μmol/L) decreased from 41% (n = 650) to 28% (n = 249) (P <0.001). Overall, homocysteine was a modest risk factor for mortality (adjusted relative risk [RR] = 1.03 per μmol/L; 95% confidence interval [CI]: 1.01 to 1.05; P = 0.006). There was no significant interaction between fortification status and homocysteine category with mortality (P for interaction = 0.85). Two-year mortality was reduced minimally (7.8% [n = 124] to 7.2% [n = 64]; RR = 0.93; 95% CI: 0.68 to 1.27; P = 0.63; adjusted RR = 0.97; 95% CI: 0.68 to 1.40), but was consistent with the expectation of a modest reduction in homocysteine levels.

Conclusion

Homocysteine is an independent, graded risk factor for mortality. Homocysteine levels decreased modestly after the fortification of food with folic acid, but the effects on mortality were minor and likely attributable to other factors, indicating the need for more aggressive measures to reduce homocysteine-associated cardiovascular risk.

Section snippets

Study sample

The study sample consisted of 2481 patients selected from the cardiac catheterization laboratory registry of the Intermountain Heart Collaborative Study (13). Patients had to have undergone angiography, have one or more ≥70% stenotic lesions, and have provided written consent to a blood draw at the time of angiography for use in confidential research studies approved by the LDS Hospital Institutional Review Board. Each patient had a minimum of 2 years of clinical follow-up. (The study sample

Results

Patients in the pre- and postfortification groups generally had similar characteristics (Table 1). The mean (± SD) age was 65 ± 11 years, and 77% were men. However, the postfortification cohort more often had a history of hypertension and hyperlipidemia, and a positive family history of coronary artery disease, but a slightly smaller proportion had three-vessel coronary disease. Patients enrolled after the 1998 mandate were also more likely to undergo percutaneous coronary intervention, but

Discussion

We found that after implementation of an FDA-mandated rule requiring fortification of food products with folic acid, there was a redistribution within homocysteine risk categories in a cohort of nearly 2500 patients with coronary artery disease. This was associated with a modest overall reduction in median homocysteine levels in the postfortification cohort. Generally, the relation of homocysteine to mortality risk was unchanged by fortification, although an improving survival trend was

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  • Cited by (0)

    This study was supported by a grant from the Deseret Foundation, Salt Lake City, Utah, and an in-kind grant from Abbott Diagnostics, Abbott Park, Illinois.

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