title: Effect of folic acid fortification of food on homocysteine-related mortality.
abstract: OBJECTIVE
  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 micromol/L (P <0.001), and the proportion of patients with high homocysteine levels (>15 micromol/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 micromol/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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cardiovascular Department, LDS Hospital, and University of Utah, Salt Lake City, Utah 84143, USA.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Anderson
authors.forename: Kurt R
authors.initials: KR
authors.lastname: Jensen
authors.forename: John F
authors.initials: JF
authors.lastname: Carlquist
authors.forename: Tami L
authors.initials: TL
authors.lastname: Bair
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Horne
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Muhlestein
mesh_terms: D000368:Aged; D003327:Coronary Disease / Q000097:blood / Q000401:mortality*; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D005527:Food, Fortified; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D012307:Risk Factors
chemical_list: D006710:Homocysteine; D005492:Folic Acid