Renal insufficiency, vitamin B12 status, and population attributable risk for mild hyperhomocysteinemia among coronary artery disease patients in the era of folic acid-fortified cereal grain flour

Abstract

Fortification of enriched cereal grain flour products with folic acid has drastically reduced the prevalence of deficient plasma folate status, a major determinant of plasma total homocysteine (tHcy) levels. We hypothesized that even more liberally defined "suboptimal" plasma folate status might no longer contribute importantly to the population attributable risk (PAR) for mild hyperhomocysteinemia, a putative atherothrombotic risk factor. We determined fasting plasma tHcy, folate, vitamin B12, and pyridoxal 5′-phosphate levels, along with serum creatinine and albumin levels, in 267 consecutive patients (aged 61±9 [mean±SD] years, 76.4% men and 26.6% women) with stable coronary artery disease (CAD) who were nonusers of vitamin supplements or had abstained from supplement use for at least 6 weeks before examination. Subjects were evaluated a minimum of 3 months after the implementation of flour fortification was largely completed. Relative risk estimates for the calculation of PAR were derived from a multivariable-adjusted logistic regression model with ≥12 μmol/L tHcy as the dependent variable and with age, sex, pyridoxal 5′-phosphate (continuous), albumin (continuous), <5 ng/mL folate, <250 pg/mL vitamin B12, and ≥1.3 mg/dL creatinine as the independent variables. The prevalence of ≥12 μmol/L plasma tHcy was 11.2% (30 of 267 patients). PAR estimates (percentage) for ≥12 μmol/L tHcy were as follows: <5 ng/mL folate (<1%), <250 pg/mL vitamin B12 (24.5%), and ≥1.3 mg/dL creatinine (37.5%). In the era of folic acid-fortified cereal grain flour, renal insufficiency and suboptimal vitamin B12 status (but not folate status) contribute importantly to the PAR for mild hyperhomocysteinemia among patients with stable CAD.