Published Online
on November 11, 2002

A more recent version of this article appeared on November 26, 2002

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Submitted on May 15, 2002
Revised on September 10, 2002
Accepted on September 11, 2002

Relationship of Anti-60 kDa Heat Shock Protein and Anti-Cholesterol Antibodies to Cardiovascular Events

Amarilla Veres MD, George Füst MD, DSc, Marek Smieja MD, MSc, FRCPC, Matthew McQueen MBChB, PhD, FRCPC, Anna Horváth MD, Qilong Yi PhD, Adrienn Bíró , Janice Pogue MSc, László Romics MD, DCs, István Karádi MD, DSc, Mahavir Singh PhD, Judy Gnarpe PhD, Zoltán Prohászka MD, PhD, Salim Yusuf DPhil, FRCP^*, and for the Heart Outcomes Prevention Evaluation (HOPE) Study Investigators

From the Third Department of Internal Medicine (A.V., G.F., A.H., A.B., L.R., I.K., Z.P.), Faculty of Medicine, Semmelweis University, Budapest, Hungary; Research Group of Metabolism, Genetics and Immunology (G.F., L.R., Z.P.), Hungarian Academy of Sciences, Budapest, Hungary; Department of Pathology and Molecular Medicine (M. Smieja, M.M.), McMaster University, Hamilton, Ontario, Canada; Population Health Research Institute (M. Smieja, M.M., Q.Y., J.P., S.Y.), Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada; Lionex Ltd (M. Singh), Braunschweig, Germany; Department of Microbiology and Immunology (J.G.), University of Alberta, Edmonton, Alberta, Canada; and Department of Medicine (M. Smieja, M.M., S.Y.), McMaster University, Hamilton, Ontario, Canada.

^* To whom correspondence should be addressed. E-mail: yusufs{at}mcmaster.ca.

Background—Several recent studies have indicated an association between key inflammatory mediators and atherosclerotic diseases. We evaluated whether high levels of antibodies against heat shock proteins and cholesterol (ACHA) predicted cardiovascular (CV) events.

Methods and Results—We used blood samples from the Heart Outcomes Prevention Evaluation (HOPE) study to conduct a nested case-control study of 386 cases with CV events and 386 age- and sex-matched HOPE study controls without events. We explored the relationship between anti-hsp antibodies, ACHA, and subsequent outcomes (incident myocardial infarction, stroke, or CV death) during a mean follow-up of 4.5 years using conditional logistic regression. High levels of anti-hsp65 antibodies (90th percentile) predicted CV events (OR, 2.1; 95% CI, 1.2 to 3.9, P=0.01). Anti-hsp60 antibodies did not predict any event type, whereas incident stroke developed significantly less frequently in patients with high ACHA levels. Anti-hsp antibodies and ACHA did not correlate with inflammatory (fibrinogen, C-reactive protein, interleukin-6, intracellular adhesion molecule-1) or infectious markers (C pneumoniae or cytomegalovirus antibodies). Anti-hsp65 antibodies (90th percentile) and fibrinogen (highest tertile) had a strong joint effect: patients with high concentrations of both had more CV events (OR, 5.5; 95% CI, 1.8 to 17.5, P=0.004) than patients with low levels of both. A similar joint effect (OR, 2.7; 95% CI, 1.3 to 5.7, P=0.01) was found for high levels of anti-hsp65 and presence of cytomegalovirus antibodies.

Conclusions—Serum antibodies to hsp65 were associated with subsequent CV events in this study of high-risk patients, independent of conventional cardiovascular risk factors and other inflammatory markers.

Key words: antibodies • atherosclerosis • cardiovascular diseases • inflammation • prognosis

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