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on February 3, 2003

Circulation. 2003
Published online before print February 3, 2003, doi: 10.1161/01.CIR.0000050626.25057.51
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Submitted on August 2, 2002
Revised on November 5, 2002
Accepted on November 6, 2002

Six-Year Effect of Combined Vitamin C and E Supplementation on Atherosclerotic Progression. The Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) Study

Riitta M. Salonen MD, PhD, Kristiina Nyyssönen PhD, Jari Kaikkonen PhD, Elina Porkkala-Sarataho PhD, Sari Voutilainen PhD, RD, Tiina H. Rissanen MScPH, RD, Tomi-Pekka Tuomainen MD, Veli-Pekka Valkonen MD, Ulla Ristonmaa MSc, Hanna-Maaria Lakka MD, PhD, Meri Vanharanta PhD, MPH, Jukka T. Salonen MD, PhD*, and Henrik E. Poulsen MD, PhD

From the Research Institute of Public Health (R.M.S., K.N., E.P.-S., S.V., T.H.R., T.-P.T., V.-P.V., H.-M.L., M.V., J.T.S.) and Department of Public Health and General Practice (T.H.R., H.-M.L., J.T.S.), University of Kuopio, Finland; Oy Jurilab Ltd (J.K., U.R.), Kuopio, Finland; Inner Savo Health Centre (J.T.S.), Suonenjoki, Finland; and Department of Clinical Pharmacology (H.E.P.), Rigshospitalet, University of Copenhagen, Denmark.

* To whom correspondence should be addressed. E-mail: jukka.salonen{at}uku.fi.

Background--Self-selected supplementation of vitamin E has been associated with reduced coronary events and atherosclerotic progression, but the evidence from clinical trials is controversial. In the first 3 years of the ASAP trial, the supplementation with 136 IU of vitamin E plus 250 mg of slow-release vitamin C twice daily slowed down the progression of carotid atherosclerosis in men but not women. This article examines the 6-year effect of supplementation on common carotid artery (CCA) intima-media thickness (IMT).

Methods and Results--The subjects were 520 smoking and nonsmoking men and postmenopausal women aged 45 to 69 years with serum cholesterol >=5.0 mmol/L (193 mg/dL), 440 (84.6%) of whom completed the study. Atherosclerotic progression was assessed ultrasonographically. In covariance analysis in both sexes, supplementation reduced the main study outcome, the slope of mean CCA-IMT, by 26% (95% CI, 5 to 46, P=0.014), in men by 33% (95% CI, 4 to 62, P=0.024) and in women by 14% (not significant). In both sexes combined, the average annual increase of the mean CCA-IMT was 0.014 mm in the unsupplemented and 0.010 mm in the supplemented group (25% treatment effect, 95% CI, 2 to 49, P=0.034). In men, this treatment effect was 37% (95 CI, 4 to 69, P=0.028). The effect was larger in subjects with either low baseline plasma vitamin C levels or CCA plaques. Vitamin E had no effect on HDL cholesterol.

Conclusions--These data replicate our 3-year findings confirming that the supplementation with combination of vitamin E and slow-release vitamin C slows down atherosclerotic progression in hypercholesterolemic persons.


Key words: arteriosclerosis • trials • ultrasonics • antioxidants • lipids


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