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(Circulation. 2008;118:2687-2693.)
© 2008 American Heart Association, Inc.

Heart Disease in Asia

Elevated Heat Shock Protein 60 Levels Are Associated With Higher Risk of Coronary Heart Disease in Chinese

Xiaomin Zhang, MD, PhD; Mei'an He, MD, PhD; Longxian Cheng, MD, PhD; Ying Chen, MD; Li Zhou, MD; Hesong Zeng, MD, PhD; A. Graham Pockley, PhD; Frank B. Hu, MD, PhD; Tangchun Wu, MD, PhD

From the Institute of Occupational Medicine and the Ministry of Education Key Lab of Environment and Health, School of Public Health (X.Z., M.H., L.Z., T.W.); Department of Cardiology, Union Hospital (L.C., Y.C.), and Department of Cardiology, Tongji Hospital (H.Z.), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; School of Medicine and Biomedical Sciences, University of Sheffield (A.G.P.), Sheffield, United Kingdom; and Departments of Nutrition and Epidemiology, Harvard School of Public Health (F.B.H.), Boston, Mass.

Correspondence to Tangchun Wu, Institute of Occupational Medicine, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd, Wuhan, Hubei 430030, China. E-mail wut{at}mails.tjmu.edu.cn or Frank B. Hu, Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA 02115. E-mail Frank.hu@channing.harvard.edu

Background— Although heat shock protein 60 (Hsp60) is implicated in the pathogenesis of atherosclerosis, its role in coronary heart disease (CHD) is uncertain. This study explored the influence of circulating Hsp60 on CHD in a large case-control study, as well as the impact of acute myocardial infarction on Hsp60 levels in a prospective study.

Methods and Results— Plasma Hsp60 and anti-Hsp60 antibody levels were determined by immunoassay. In the case-control study (1003 patients with CHD, 1003 matched control subjects), Hsp60 levels were higher in patients with CHD and were related to CHD (OR comparing extreme quartiles=4.14, P<0.0001). This association remained after adjustment for traditional risk factors (P for trend <0.0001). Individuals having high levels of Hsp60 (greater than the median of 160.24 ng/mL) and anti-Hsp60 antibody (greater than the median of 38.42 U/mL) were at a greater risk of CHD than those with low levels (OR 2.30, P<0.0001). Stronger additive effects (OR 14.04, P<0.0001) were apparent at higher Hsp60 and anti-Hsp60 antibody levels (>1000 ng/mL and greater than the median of 38.42 U/mL, respectively). The simultaneous presence of high Hsp60 and anti-Hsp60 antibody levels, current smoking, hypertension, and diabetes were cumulatively associated with CHD. Individuals who had any 4 or more of these 5 factors had an OR of 38.61 for CHD (P<0.0001) compared with individuals who had none of these factors. For the prospective study, blood was drawn from 20 patients immediately after admission for acute myocardial infarction and 2, 3, and 7 days thereafter. Hsp60 levels were significantly higher on the day of and the day after arrival than 7 days after an acute myocardial infarction (P=0.011 and P=0.026, respectively).

Conclusions— Elevated Hsp60 levels are associated with an increased risk for CHD, and Hsp60 and anti-Hsp60 antibody levels combine to increase this risk. In addition, acute myocardial infarction induces Hsp60 release.

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