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European Heart Journal Advance Access published online on February 17, 2009
European Heart Journal, doi:10.1093/eurheartj/ehp015
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org
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Pre-operative homocysteine levels and morbidity and mortality following cardiac surgery

Marco Ranucci1, Andrea Ballotta1, Alessandro Frigiola2, Alessandra Boncilli1, Simonetta Brozzi1, Elena Costa3 and Rajendra H. Mehta4,*

1 Department of Cardiothoracic—Vascular Anesthesia and Intensive Care, IRCCS Policlinico S.Donato, Milan, Italy
2 Department of Cardiac Surgery, IRCCS Policlinico S.Donato, Milan, Italy
3 Clinical Research Laboratory, IRCCS Policlinico S.Donato, Milan, Italy
4 Duke Clinical Research Institute, Box 17969, Durham, NC 27715, USA

Received 8 September 2008; revised 20 December 2008; accepted 5 January 2009.

* Corresponding author. Tel: +1 919 668 8971, Fax: +1 919 668 7059, Email: mehta007{at}dcri.duke.edu

Aims: Elevated homocysteinaemia is associated not only with an increased risk for cardiovascular disease but also for increased morbidity and mortality in patients with established coronary artery or cerebrovascular disease. Whether elevated homocysteine further increases the morbidity and mortality in patients undergoing cardiac surgery on cardiopulmonary bypass (CPB) (a prothrombotic state itself) remains less known.

Methods and results: Accordingly, we conducted a prospective observational study with pre-operative measurement of plasma homocysteine levels in 531 consecutive patients undergoing cardiac operations on CPB. The association of pre-operative plasma homocysteine levels with post-operative morbidity and hospital mortality was evaluated. Elevated homocysteine levels (>15 µmol/L) were observed in 209 patients (39.4%), and homocysteinaemia was associated with a higher mortality and perioperative morbidity (major morbidity, low cardiac output, acute renal failure, mesenteric infarction, and thrombo-embolic events). Even after accounting for the differences in baseline clinical features, EuroSCORE, and CPB time, pre-operative homocysteine levels remained independently associated with hospital mortality [odds ratio (OR) 1.06, 95% confidence interval (CI) 1.03–1.11], major morbidity (OR 1.04, 95% CI 1.01–1.07), low cardiac output (OR 1.04, 95% CI 1.02–1.08), mesenteric infarction (OR 1.06, 95% CI 1.01–1.11), and thrombo-embolic events (OR 1.09, 95% CI 1.04–1.13). This association of homocysteine with increased risk of morbidity and mortality was observed particularly in CABG patients.

Conclusion: Elevated pre-operative homocysteine level is independently associated with increased morbidity and mortality, particularly in patients undergoing CABG. Specific post-operative antithrombotic strategies may be advisable in hyperhomocysteinaemic patients.

Key Words: Homocysteine • Risk factors • Cardiac surgery • Outcomes


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