Atherosclerosis 145 (1999) 221 – 224
Rapid communication
Prevalence of mild fasting hyperhomocysteinemia in renal transplant
versus coronary artery disease patients after fortification of cereal
grain flour with folic acid
Andrew G. Bostom
a,b,
*, Reginald Y. Gohh
c
, Gintaras Liaugaudas
a
, Andrew J. Beaulieu
c
,
Haewook Han
b
, Paul F. Jacques
b
, Lance Dworkin
c
, Irwin H. Rosenberg
b
, Jacob Selhub
b
a
Diision of General Internal Medicine, Memorial Hospital of Rhode Island, 111 Brewster Street, Pawtucket, RI 02860, USA
b
Tufts Jean Mayer USDA Human Nutrition Research Center on Aging, Boston, MA, USA
c
Diision of Renal Diseases, Rhode Island Hospital, Proidence, RI, USA
Received 19 November 1998; received in revised form 23 December 1998; accepted 11 January 1999
Abstract
Cereal grain flour products fortified with 140 g folic acid per 100 g flour became widely available in southeast New England
by July 1997. We hypothesized that improved folate status secondary to this fortification policy would have a much more limited
impact on the prevalence of mild fasting hyperhomocysteinemia in renal transplant versus coronary artery disease patients.
Between October 1997 and October 1998, fasting plasma total homocysteine (tHcy), folate and vitamin B12 levels were determined
in a total of 86 renal transplant patients with stable allograft function, and 175 coronary artery disease patients whose serum
creatinine was (1.4 mg/dl). All subjects lived in the Providence, RI, metropolitan area, and were either non-users of any
supplements containing folic acid, vitamins B6 or B12, or had refrained from using such supplements for 6 weeks. Geometric
mean fasting tHcy levels were 88.0% higher (15.6 vs. 8.3 mol/l; P 0.001), and the prevalence of fasting tHcy levels 12 M
(69.8% vs. 10.9%, P 0.001) was markedly increased in the renal transplant patients, despite a much younger mean age and a
relative preponderance of women. In the era of folic acid fortified flour, hyperhomocysteinemia is much more common in stable
renal transplant versus coronary artery disease patients. As a result, renal transplant patients are a preferable high risk target
population for controlled trials evaluating the tenable hypothesis that lowering total homocysteine levels will reduce cardiovascu-
lar disease outcomes. © 1999 Elsevier Science Ireland Ltd. All rights reserved.
Keywords: Arteriosclerosis; Folate; Homocysteine; Renal disease
1. Introduction
Mild hyperhomocysteinemia may increase the risk
for both recurrent cardiovascular disease in patients
with established coronary artery disease [1] and de novo
cardiovascular disease in stable renal transplant pa-
tients [2]. Folate status is a determinant of mild hyper-
homocysteinemia in general populations [3], coronary
artery disease patients [4] and renal transplant patients
[5]. Cereal grain flour products fortified with 140 g
folic acid per 100 g flour began appearing voluntarily in
the USA after March 1996 [6]. The availability of such
products was widespread in southeast New England by
July 1997 (J. Watson, Watson Foods, New Haven, CT,
personal communication), and mandated throughout
the USA by 1 January 1998 [7].
Given that renal disease renders individuals some-
what refractory to the effect of low dose folic acid
* Corresponding author. Tel.: +1-401-729-2859; fax: +1-401-729-
2950.
E-mail address: abostom@loa.com (A.G. Bostom)
0021-9150/99/$ - see front matter © 1999 Elsevier Science Ireland Ltd. All rights reserved.
PII:S0021-9150(99)00023-4