Published Online
on July 14, 2003

A more recent version of this article appeared on July 29, 2003

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Submitted on November 19, 2002
Revised on April 29, 2003
Accepted on May 2, 2003

Relationship of Metabolic Syndrome and Fibrinolytic Dysfunction to Cardiovascular Disease

Sonia S. Anand MD, PhD^*, Qilong Yi MSc, Hertzel Gerstein MD, Eva Lonn MD, Ruby Jacobs RN, Vlad Vuksan PhD, Koon Teo MBBS, Bonnie Davis RN, Patty Montague MSc, Salim Yusuf DPhil, and for the Study of Health Assessment and Risk in Ethnic groups (SHARE) and Study of Health Assessment and Risk Evaluation in Aboriginal Peoples (SHARE-AP) Investigators

From the Department of Medicine, McMaster University (S.S.A., H.G., E.L., K.T., P.M., S.Y.), Hamilton, Canada; Population Health Research Institute, Hamilton Health Sciences and McMaster University (S.S.A., Q.Y., H.G., E.L., K.T., P.M., S.Y.), Hamilton, Canada; Six Nations Health Services (R.J., B.D.), Ohsweken, Canada; and University of Toronto (V.V.), Toronto, Canada.

Background--The clustering of impaired glucose metabolism, elevated triglycerides, low HDL cholesterol, and abdominal obesity is known as the metabolic syndrome. Individuals with this syndrome suffer an excess of cardiovascular disease (CVD) for reasons that are unclear.

Methods and Results--We randomly sampled 1276 adults of South Asian, Chinese, European, and Native Indian ancestry from 4 communities in Canada. Participants provided fasting blood samples for glucose, lipids, and fibrinolytic measurements; had an oral glucose tolerance test; and underwent a B-mode carotid ultrasound examination. CVD was determined by history and ECG. The prevalence of the metabolic syndrome was 25.8% (95% CI, 23.5 to 28.2) and varied substantially by ethnic group: 41.6% among Native Indians, 25.9% among South Asians, and 22.0% among Europeans, compared with 11.0% among the Chinese (overall, P=0.0001). People with the metabolic syndrome had more atherosclerosis (maximum intimal medial thickness, 0.78±0.18 versus 0.74±0.18 mm; P=0.0005), CVD (17.2% versus 7.0%; P=0.0001), and elevated plasminogen activator inhibitor-1 (24.2 versus 14.6 U/mL; P=0.001) compared with levels among people without the metabolic syndrome. For the same amount of atherosclerosis, people with the metabolic syndrome had a greater prevalence of CVD, even among nondiabetic individuals. This difference in CVD prevalence among the groups was attenuated after adjustment for plasminogen activator inhibitor-1 levels, suggesting that fibrinolytic dysfunction mediates the increased risk of CVD in individuals with the metabolic syndrome.

Conclusion--CVD among people with the metabolic syndrome is explained by their excess of atherosclerosis and impaired fibrinolysis. Interventions to prevent atherosclerosis progression and improve fibrinolytic function require evaluation in this high-risk group.

Key words: diabetes mellitus • atherosclerosis • fibrinolysis • epidemiology

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