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From the Vitamin Bioavailability Laboratory (A.G.B., M.R.N., P.F.J., J.S., I.H.R.), Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts New England Medical Center, Boston, Mass; the Division of Renal Diseases (D.S., L.D.), Rhode Island Hospital, Providence, RI; and the Department of Nutrition (P.V.), Agricultural University, Wageningen, Netherlands.
Abstract There is an excess prevalence of
hyperhomocysteinemia in dialysis-dependent end-stage renal disease
(ESRD) patients. Cross-sectional studies of the relationship between
elevated total homocysteine (tHcy) levels and prevalent
cardiovascular disease (CVD) in this patient population
suffer from severe methodologic limitations. No prospective
investigations examining the association between tHcy levels and the
subsequent development of arteriosclerotic CVD
outcomes among maintenance dialysis patients have been
reported. To assess whether elevated plasma tHcy is an independent risk
factor for incident CVD in dialysis-dependent ESRD patients, we studied
73 maintenance peritoneal dialysis or hemodialysis patients who
received a baseline examination between March and December 1994, with
follow-up through April 1, 1996. We determined the incidence of
nonfatal and fatal CVD events, which included all validated
coronary heart disease, cerebrovascular disease, and abdominal
aortic/lower-extremity arterial disease outcomes. After a
median follow-up of 17.0 months, 16 individuals experienced at least
one arteriosclerotic CVD event. Cox
proportional-hazards regression analyses, unadjusted and
individually adjusted for creatinine, albumin, and
total cholesterol levels, total/HDL cholesterol
ratio, dialysis adequacy/residual renal function, baseline CVD, and the
established CVD risk factors (ie, age, sex, smoking, hypertension,
diabetes/glucose intolerance, and dyslipidemia) revealed
that tHcy levels in the upper quartile (
27.0 µmol/L) versus
the lower three quartiles (<27.0 µmol/L) were associated with
relative risk estimates (hazards ratios, with 95% confidence intervals
for the occurrence of (pooled) nonfatal and fatal CVD ranging from 3.0
to 4.4; 95% confidence intervals (1.1-8.1) to (1.6-12.2). We conclude
that the markedly elevated fasting tHcy levels found in
dialysis-dependent ESRD patients may contribute independently to their
excess incidence of fatal and nonfatal CVD outcomes.
Key Words: hyperhomocysteinemia end-stage renal disease arteriosclerosis longitudinal study
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