Lm. Taylor et al., Prospective blinded study of the relationship between plasma homocysteine and progression of symptomatic peripheral arterial disease, J VASC SURG, 29(1), 1999, pp. 8-19
Citations number
34
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Purpose: An elevated plasma homocysteine level is an established risk facto
r for atherosclerotic coronary heart disease (CHD), cerebro vascular diseas
e (CVD), and lower extremity occlusive disease (LED). An elevated plasma ho
mocysteine level can be reduced by therapy with folate and vitamins B6 and
B12. An accurate evaluation of the role of vitamin therapy requires knowled
ge of the influence of plasma homocysteine levels on the progression of CHD
, CVD, and LED.
Methods: The Homocysteine and Progression of Atherosclerosis Study is a bli
nded prospective study of the influence of homocysteine and of other athero
sclerotic risk factors on the progression of disease in patients with sympt
omatic CVD, LED, or both. This study is set in a university hospital vascul
ar surgery clinic and the General Clinical Research Center. Consecutive pat
ients with stable symptomatic CVD or LED underwent baseline clinical, labor
atory, and vascular laboratory testing for homocysteine and other risk fact
ors and were examined every 6 months. The primary endpoints were ankle brac
hial pressure index, duplex scan-determined carotid stenosis, and death. Th
e secondary endpoints were the clinical progressions of CHD, LED, and CVD.
The hypothesis that was tested was whether the progression of symptomatic C
VD or LED was more frequent or more rapid in patients with elevated plasma
homocysteine levels.
Results: After a mean follow-up period of 37 months (range, 1 to 78 months)
for deaths from all causes (>14 mu mol/L; elevated, 18.6%; normal, 9.4%; P
=.022), deaths from cardiovascular disease (elevated, 12.5%; normal, 6.3%;
P=.05) and the clinical progression of CHD (highest 20% of homocysteine lev
els, 80%; lowest 20% of homocysteine levels, 39%; P =.007) were significant
ly more frequent or more rapid by life-table analysis when the homocysteine
levels were elevated. Multivariate Cox proportional hazards regression mod
el showed a significant independent and increasing relationship between the
plasma homocysteine levels and the time to death (relative risk for highes
t one third of homocysteine values, 1.6; 95% confidence interval [CI], 1.04
to 2.56; P =.029; and relative risk for highest one fifth of homocysteine
values, 3.13; 95% CI, 1.69 to 6.64; P =.0001). After an adjustment for age,
smoking, hypertension, diabetes, cholesterol, and the vascular laboratory
progression of CVD or LED, each 1.0 mu mol/L increase in the plasma homocys
teine levels resulted in a 3.6% increase (95% CI, 0.0% to 6.6%; P =.06) in
the risk of death (all causes) at 3 years and a 5.6% increase (95% CI, 2.2%
to 8.5%; P =.003) in the risk of death from cardiovascular disease.
Conclusion: We conclude that elevated plasma homocysteine levels are associ
ated significantly with death, with death from cardiovascular disease, and
with the progression of CHD in patients with symptomatic CVD or LED. These
results strongly mandate clinical trials of homocysteine-lowering vitamin t
herapy in such patients.