P. Verhoef et al., PLASMA TOTAL HOMOCYSTEINE, VITAMIN-B, AND RISK OF CORONARY ATHEROSCLEROSIS, Arteriosclerosis, thrombosis, and vascular biology, 17(5), 1997, pp. 989-995
Epidemiological research has shown that elevated plasma total homocyst
eine (tHcy) is a risk factor for atherosclerotic disease. In the prese
nt case-control study, we investigated whether fasting or postmethioni
ne-loading tHcy was a stronger predictor of risk of severe coronary at
herosclerosis. Furthermore, we studied levels of B vitamins, which are
involved in homocysteine metabolism. Subjects were recruited from men
and women, aged 25 to 65 years, who underwent coronary angiography be
tween June 1992 and June 1994 in a hospital in Rotterdam, The Netherla
nds. Cases (n=131) were defined as those with greater than or equal to
90% occlusion in one and greater than or equal to 40% occlusion in a
second coronary artery, while control subjects (n=88) had less than or
equal to 50% occlusion in only one coronary vessel. In addition, a po
pulation-based control group free from clinical cardiovascular disease
(n=101) was studied. Coronary patients were studied at least 2.5 mont
hs after angiography or other acute illness, such as myocardial infarc
tion. After adjusting for age and sex differences between the groups,
cases had 9% (P=.01) higher geometric mean fasting and 7% (P=.04) high
er geometric mean postload tHcy than the combined control groups. Desp
ite higher levels of tHcy for cases, their geometric mean levels of re
d cell folate and pyridoxal 5'-phosphate were higher than for control
subjects, whereas plasma vitamin B-12 was only slightly lower in cases
. The frequency distribution of tHcy values in cases was slightly shif
ted toward the right, across the entire range, compared with the distr
ibution in the combined control group. This was somewhat more obvious
for fasting than postload tHcy levels. The odds ratio (OR) for severe
coronary atherosclerosis (case status) for each 1 SD increase in fasti
ng tHcy (5 mu mol/L) was 1.3 (95% confidence interval [CI], 1.0-1.6),
similar to the OR for each 1 SD increase (12 mu mol/L) in postmethioni
ne-loading tHcy (1.3 [95 CI, 1.0-1.7]), after adjustment for sex, age,
and other potential confounders. Furthermore, there was a significant
linear trend of increasing fasting tHcy with increasing number of occ
luded arteries (P=.01), correcting for sex, age, and other potential c
onfounders. Our data show a positive association between plasma tHcy a
nd risk of severe coronary atherosclerosis, of similar strength for fa
sting and postload tHcy levels. The data suggest that the association
exists over a wide range of tHcy levels, without a clear cutoff point
below which there is no increased risk.