Lack of association between plasma homocysteine and angiographic coronary artery disease in the era of fortification of cereal grain flour with folic acid
Introduction
Several studies have demonstrated an association between plasma homocysteine level (tHcy) and the presence and extent of coronary artery disease (CAD), as assessed by angiography [1], [2], [3], [4], [5], [6], [7], [8]. The association persisted after controlling for conventional risk factors for atherosclerosis, such as age, gender, dyslipidemia, hypertension, diabetes mellitus, and smoking [1], [2], [5]. All these studies were performed in populations whose flour products were not fortified with folic acid.
In March 1996 the United States Food and Drug Administration issued a regulation requiring that all flour products, including rice, pasta, cornmeal, etc. contain 140 μg of folic acid per 100 g [9]. The goal of this regulation was to increase folic acid intake in women of childbearing age in order to decrease the incidence of neural tube defects. The effective date of the legislation was January 1998, although many manufacturers implemented the supplementation even earlier [10]. A similar regulation had been issued in Canada in 1997 [11]. This policy resulted in approximately 50% reduction in the prevalence of hyperhomocysteinemia (defined as homocysteine >13 μmol/l) in the Framingham offspring population study [10].
The goal of the present study was to determine whether an association between tHcy and the presence and severity of angiographic CAD could be observed in a US population exposed to folic acid fortified flour, particularly after accounting for conventional and other emerging risk factors.
Section snippets
Patient population
The sample included 504 patients (>97% Caucasian), age 27–77, from the adult population undergoing coronary angiography at Mayo Clinic, Rochester, Minnesota. Consecutive consenting patients (18 or older) for whom the coronary angiography was clinically-indicated were included. Patients were excluded if they had diabetes mellitus or a >50 pack-year smoking history, because these are such powerful risk factors; they were also excluded if they had a history of organ transplantation, pregnancy,
Statistics
To assess whether hyperhomocysteinemia is associated with the presence of significant CAD, patients were divided in two groups: those with significant CAD (luminal stenosis ≥50% in at least one epicardial coronary artery) and without significant CAD (no luminal stenosis ≥50% in any epicardial artery). Continuous variables with symmetric distributions were summarized by mean±standard deviation (S.D.) and compared with the two-sample t-test. Variables with skewed distributions were summarized by
Patient characteristics
Mean age was 60.1±10.9 years and 38% were women. Significant CAD was present in 271 patients (54%): 85 (31%), 80 (30%), and 106 (39%) patients had one-, two-, and three-VD, respectively. Non-significant CAD was present in 233 patients: 122 (52%) had <10% luminal stenosis, and 111 (48%) had >10 and <50% luminal stenosis (Table 1). Patients with CAD were more likely to be older and male and to have a history of hyperlipidemia, hypertension, smoking, angina, and myocardial infarction (Table 1).
Homocysteine and CAD
Discussion
Our study demonstrates that in the era of fortification of flour with folic acid, there is no significant association between plasma homocysteine and angiographic CAD.
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