Homocysteine-lowering treatment with folic acid plus vitamin B6 lowers urinary albumin excretion but not plasma markers of endothelial function or C-reactive protein: further analysis of secondary end-points of a randomized clinical trial.
BACKGROUND
Hyperhomocysteinaemia is an independent risk factor for atherosclerosis and is thought to induce its effects through causing endothelial dysfunction. We studied the effect of homocysteine-lowering treatment with folic acid plus vitamin B6 on urinary and plasma markers of endothelial function, and on plasma C-reactive protein, a marker of chronic inflammation.


METHODS
We performed a placebo-controlled 2-year trial among 158 healthy siblings of patients with premature atherosclerotic disease to determine the effect of daily folic acid (5 mg) plus vitamin B6 (250 mg) treatment as compared with placebo medication (n = 80) on markers of endothelial function (urinary albumin-to-creatinine ratio and plasma concentrations of soluble E-selectin, soluble vascular cell adhesion molecule-1, von Willebrand factor, tissue-type plasminogen activator and plasminogen activator inhibitor-1) and inflammation (C-reactive protein). Outcome variables were assessed at baseline and after 1 and 2 years of treatment.


RESULTS
Fasting homocysteine concentrations ( micromol L-1) at baseline and after treatment were 14.7 +/- 8.2 and 7.4 +/- 1.9 in the vitamin and 14.7 +/- 8.8 and 12.0 +/- 5.4 for the placebo group, respectively. Vitamin treatment was associated with a decreased urinary albumin-to-creatinine ratio at follow up [regression coefficient (beta) -0.20 mg mmol-1 (CI: -0.43-0.03); P = 0.09]. After adjustment for age, sex, baseline concentrations of postmethionine total homocysteine plus the baseline albumin-to-creatinine ratio, the beta was -0.23 mg mmol-1 (CI: -0.43 to -0.02; P = 0.03), which amounts to a decrease of approximately 20%. There was no apparent effect of vitamin treatment on the other markers.


CONCLUSIONS
Homocysteine-lowering vitamin treatment in healthy siblings of patients with premature atherosclerotic disease is associated with a decreased urinary albumin-to-creatinine ratio, but not with other markers of endothelial dysfunction, or in plasma C-reactive protein. The clinical significance of these findings remains to be determined.
Vermeulen
E G J
EG
Department of Vascular Surgery, Vrije Universiteit Medical Center, Amsterdam, The Netherlands. egj.vermeulen@gelre.nl
Rauwerda
J A
JA
van den Berg
M
M
de Jong
S C
SC
Schalkwijk
C
C
Twisk
J W R
JW
Stehouwer
C D A
CD
D000328:Adult; D000419:Albuminuria / Q000652:urine*; D001161:Arteriosclerosis / Q000209:etiology; D015415:Biomarkers; D002097:C-Reactive Protein / Q000378:metabolism*; D004727:Endothelium / Q000187:drug effects*; D005492:Folic Acid / Q000627:therapeutic use*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications / Q000517:prevention & control*; D008875:Middle Aged; D025101:Vitamin B 6 / Q000627:therapeutic use*
D015415:Biomarkers; D025101:Vitamin B 6; D002097:C-Reactive Protein; D005492:Folic Acid