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European Heart Journal Advance Access originally published online on January 31, 2007
European Heart Journal 2007 28(4):484-491; doi:10.1093/eurheartj/ehl470
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© The European Society of Cardiology 2007. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Both vitamin B6 and total homocysteine plasma levels predict long-term atherothrombotic events in healthy subjects

Diego Vanuzzo1, Lorenza Pilotto1, Rossana Lombardi2, Guido Lazzerini3, Marisa Carluccio3, Silvia Diviacco4, Franco Quadrifoglio4, Giorgia Danek1, Dario Gregori6,7, Paolo Fioretti6, Marco Cattaneo2,5 and Raffaele De Caterina3,8,*

1 Cardiovascular Prevention Center, ASS 4 and Agenzia Regionale della Sanità del Friuli-Venezia Giulia, Udine, Italy
2 A. Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Internal Medicine, IRCCS Ospedale Maggiore, University of Milano, Milano, Italy
3 C.N.R. Institute of Clinical Physiology, Pisa, Italy
4 Department of Biomedical Sciences and Technologies, University of Udine, Udine, Italy
5 Unit of Hematology and Thrombosis, Ospedale San Paolo-DMCO University of Milan, Milan, Italy
6 IRCAB Foundation, Udine, Italy
7 Department of Public Health and Microbiology, University of Torino, Torino, Italy
8 Department of Cardiology, ‘G. d'Annunzio’ University, Chieti, C/o Ospedale S. Camillo de Lellis, Via Forlanini, 50-66100 Chieti, Italy

Received 7 April 2006; revised 13 November 2006; accepted 21 December 2006; online publish-ahead-of-print 31 January 2007.

* Corresponding author. Tel: +39 0871 41512; fax: +39 0871 553 461. E-mail address: rdecater{at}unich.it

Aims The contribution of homocysteine and group B vitamins in determining cardiovascular risk is debated. We assessed the predictive value of total homocysteine (tHcy), vitamin B12, folate, and vitamin B6 on the long-term occurrence of coronary and cerebral atherothrombotic events in a nested case–control study.

Methods and results Within a cohort of 1021 healthy subjects (490 men and 531 women) recruited in 1987, 66 first-ever coronary and 43 first-ever cerebrovascular events were recorded at a 12-year follow-up (cases, n = 109). A total of 109 control subjects (remaining free from events) were matched with cases according to age, sex, smoking, hypertension, dyslipidaemia, and body mass index. Serum samples obtained in 1987 at baseline were used to measure tHcy, folate, and vitamins B12 and B6, as well as C-reactive protein plasma concentrations. We found a significant graded association between tHcy levels and the risk of coronary and cerebrovascular events [odds ratio (OR) for uppermost vs. lowermost quartile = 1.34, 95% CI 1.01–1.76)]. Folate and vitamin B12 did not significantly differ between cases and controls, but were negatively (P < 0.01) correlated with tHcy. Vitamin B6 did not correlate with tHcy levels, but differed significantly between cases and controls: for subjects in the uppermost quartile vs. the lowermost quartile of vitamin B6, OR = 0.69 (95% CI 0.49–0.98). For subjects in the lowermost quartile of vitamin B6 and the uppermost quartile of tHcy, OR = 17.50 (95% CI 1.97, 155.59). Cases and controls were not different as to C-reactive protein.

Conclusion tHcy and plasma vitamin B6 are long-term independent risk factors for coronary and cerebrovascular events.

Key Words: Vitamin B6 • Homocysteine • Coronary heart disease • Cerebrovascular disease • Atherothrombosis


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