This Article Full Text Full Text (PDF) All Versions of this Article: 106/22/2775    most recent 01.CIR.0000038890.39298.8Dv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Veres, A. Search for Related Content PubMed PubMed Citation Articles by Veres, A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CHOLESTEROL Related Collections Risk Factors for Stroke Chronic ischemic heart disease

(Circulation. 2002;106:2775.)
© 2002 American Heart Association, Inc.

Clinical Investigation and Reports

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, 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.

Correspondence to Dr Salim Yusuf, Population Health Research Institute, Hamilton General Hospital, Hamilton, Ontario, Canada L8L 2X2. 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

This article has been cited by other articles:

				X. Zhang, M. He, L. Cheng, Y. Chen, L. Zhou, H. Zeng, A. G. Pockley, F. B. Hu, and T. Wu Elevated Heat Shock Protein 60 Levels Are Associated With Higher Risk of Coronary Heart Disease in Chinese Circulation, December 16, 2008; 118(25): 2687 - 2693. [Abstract] [Full Text] [PDF]

				A G Pockley and J Frostegard Heat shock proteins in cardiovascular disease and the prognostic value of heat shock protein related measurements Heart, September 1, 2005; 91(9): 1124 - 1126. [Abstract] [Full Text] [PDF]

				D H Birnie, L E Vickers, W S Hillis, J Norrie, and S M Cobbe Increased titres of anti-human heat shock protein 60 predict an adverse one year prognosis in patients with acute cardiac chest pain Heart, September 1, 2005; 91(9): 1148 - 1153. [Abstract] [Full Text] [PDF]

				M. Ghayour-Mobarhan, S. A New, D. J Lamb, B. J Starkey, C. Livingstone, T. Wang, N. Vaidya, and G. A Ferns Dietary antioxidants and fat are associated with plasma antibody titers to heat shock proteins 60, 65, and 70 in subjects with dyslipidemia Am. J. Clinical Nutrition, May 1, 2005; 81(5): 998 - 1004. [Abstract] [Full Text] [PDF]

				K. Uray, F. Hudecz, G. Fust, and Z. Prohaszka Comparative analysis of linear antibody epitopes on human and mycobacterial60-kDa heat shock proteins using samples of healthy blood donors Int. Immunol., October 1, 2003; 15(10): 1229 - 1236. [Abstract] [Full Text] [PDF]

				A. G. Pockley, A. Georgiades, T. Thulin, U. de Faire, and J. Frostegard Serum Heat Shock Protein 70 Levels Predict the Development of Atherosclerosis in Subjects With Established Hypertension Hypertension, September 1, 2003; 42(3): 235 - 238. [Abstract] [Full Text] [PDF]