Effect of long-term homocysteine reduction with B vitamins on arterial wall inflammation assessed by fluorodeoxyglucose positron emission tomography: a randomised double-blind, placebo-controlled trial.
BACKGROUND
Homocysteine may promote atherosclerosis by exacerbating inflammatory processes within the arterial wall. B-vitamin supplements reduce total plasma homocysteine concentrations (tHcy), but it is not known whether the treatment also reduces arterial wall inflammation. We used (18)F-fluorodeoxygluose positron emission tomography ((18)F-FDG PET) to investigate whether long-term homocysteine-lowering treatment alters arterial wall inflammation in patients with a history of ischemic stroke.


METHODS
30 stroke patients were randomly assigned to B-vitamin therapy (folic acid 2 mg, vitamin B(6) 25 mg and vitamin B(12) 0.5 mg) or placebo in a double-blind clinical trial. After a mean treatment period of 4.0 +/- 0.7 years, all subjects had tHcy, carotid intima-medial thickness (CIMT) and flow-mediated dilation (FMD) of the brachial artery measured and underwent an (18)F-FDG PET scan. Standardised uptake values (SUV) were measured at six sites in the carotid, femoral and aortic arteries. Areas of locally increased tracer uptake in the arterial wall ('hot spots') were also identified and counted.


RESULTS
Long-term B-vitamin treatment significantly reduced tHcy compared with placebo (8.4 micromol/l, 95% confidence interval, CI, 7.2-9.6 vs. 11.6 micromol/l, 95% CI 10.0-13.4, p = 0.002). The treatment did not affect mean arterial SUV (2.0 +/- 0.3 vitamins vs. 2.1 +/- 0.3 placebo, p = 0.65) or the number of hot spots (n = 1.1 +/- 1.0 vitamins vs. n = 1.2 +/- 1.0 placebo, p = 0.65). There was no significant correlation between mean arterial SUV and CIMT or FMD.


CONCLUSIONS
These results suggest that a long-term Hcy reduction with B vitamins does not affect arterial wall inflammation assessed by (18)F-FDG PET.
Potter
Kathleen
K
School of Medicine and Pharmacology, University of Western Australia, W.A., Australia. pottek04@cyllene.uwa.edu.au
Lenzo
Nat
N
Eikelboom
John W
JW
Arnolda
Leonard F
LF
Beer
Christopher
C
Hankey
Graeme J
GJ
D000368:Aged; D000369:Aged, 80 and over; D001011:Aorta / Q000000981:diagnostic imaging; D001167:Arteritis / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000209:etiology*; D050197:Atherosclerosis / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000209:etiology*; D001916:Brachial Artery / Q000503:physiopathology; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D003430:Cross-Sectional Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005263:Femoral Artery / Q000000981:diagnostic imaging; D019788:Fluorodeoxyglucose F18; D005492:Folic Acid / Q000627:therapeutic use; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D020521:Stroke / Q000000981:diagnostic imaging / Q000209:etiology / Q000517:prevention & control; D013997:Time Factors; D016896:Treatment Outcome; D014463:Ultrasonography; D014664:Vasodilation; D014805:Vitamin B 12 / Q000627:therapeutic use; D025101:Vitamin B 6 / Q000627:therapeutic use; D014803:Vitamin B Complex / Q000627:therapeutic use*
D004338:Drug Combinations; D019275:Radiopharmaceuticals; D006710:Homocysteine; D019788:Fluorodeoxyglucose F18; D014803:Vitamin B Complex; D025101:Vitamin B 6; D005492:Folic Acid; D014805:Vitamin B 12