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(Circulation. 1999;100:1169-1174.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Association of Serum Antibodies to Heat-Shock Protein 65 With Carotid Atherosclerosis
Clinical Significance Determined in a Follow-Up Study
From the Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck (Q.X., M.M., G.W.) and the Clinics for Neurology (S.K., J.W.) and Cardiology (B.M), Institute for General and Experimental Pathology (G.W.), University of Innsbruck, Medical School, Innsbruck, Austria, and the Department of Internal Medicine, Hospital of Bruneck, Italy (G.E., F.O.).
Correspondence to Dr Qingbo Xu, Institute for Biomedical Aging Research, Austrian Academy of Sciences, Rennweg 10, A-6020 Innsbruck, Austria. E-mail qingbo.xu{at}oeaw.ac.at
Background—Previous work has proved that increased titers of antibodies against heat-shock protein (hsp) 65 are associated with atherosclerotic lesions independently of other established risk factors. The present follow-up study was designed to further scrutinize the association of hsp antibodies and atherosclerosis and evaluate the possible predictive value of these antibodies for the development and/or progression of lesions in the same population.
Methods and Results—A total of 750 subjects 45 to 74 years old were recruited, and the rate of participation was 93.6%; 58 subjects died between 1990 and 1995. All participants were subjected to determination of serum antibodies against hsp65 and sonography to assess carotid atherosclerotic lesions and evaluate other risk factors, ie, age, sex, body mass index, blood cholesterol, apolipoprotein B, apolipoprotein A, triglycerides, lipoprotein(a), fibrinogen, leukocyte number, antithrombin III, ESR, ferritin, hypertension, smoking, and diabetes mellitus. Our data show that hsp65 antibody titers in the population emerged as highly consistent over a 5-year observation period (r=0.78, P<0.0001). Titers were significantly elevated in subjects with progressive carotid atherosclerosis and correlated with intima/media thickness. Multiple linear regression analysis documented these associations to be independent of age, sex, and other risk factors. Subanalyses revealed a preferential association of hsp65 antibody titers with advanced lesions (odds ratio, 1.42; 95% CI, 1.02 to 1.98; P=0.039). Other risk factors neither confounded nor modified this association. Finally, hsp65 antibody titers significantly predicted the 5-year mortality (hazard ratio, 1.52; 95% CI, 1.14 to 2.03; P<0.001).
Conclusions—These findings indicate a sustained existence of anti-hsp65 antibodies in subjects with severe atherosclerosis, which is predictive for mortality.
Key Words: atherosclerosis • antibodies • immunology • follow-up studies
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|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
P. Libby and P. M. Ridker Novel Inflammatory Markers of Coronary Risk : Theory Versus Practice Circulation, September 14, 1999; 100(11): 1148 - 1150. [Full Text] [PDF]
|
|