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Published online March 16, 2007
Diabetes 56:1718-1726, 2007
DOI: 10.2337/db07-0078
© 2007 by the American Diabetes Association
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Prevalence and Prognostic Impact of Subclinical Cardiovascular Disease in Individuals With the Metabolic Syndrome and Diabetes

Erik Ingelsson1, Lisa M. Sullivan2, Joanne M. Murabito1,3, Caroline S. Fox1,4, Emelia J. Benjamin1,5,6, Joseph F. Polak7, James B. Meigs8, Michelle J. Keyes1,9, Christopher J. O'Donnell1,10,11, Thomas J. Wang1,10, Ralph B. D'Agostino, Sr.1,9, Philip A. Wolf1,12, and Ramachandran S. Vasan1,5,6

1 National Heart, Lung, and Blood Institute's Framingham Study, Framingham, Massachusetts
2 Department of Biostatistics, Boston University, Boston, Massachusetts
3 Section of General Internal Medicine, Boston University School of Medicine, Boston, Massachusetts
4 Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
5 Department of Preventive Medicine, Boston University School of Medicine, Boston, Massachusetts
6 Cardiology Section, Boston University School of Medicine, Boston, Massachusetts
7 New England Medical Center, Tuft's University, Boston, Massachusetts
8 General Medicine Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
9 Department of Mathematics and Statistics, Boston University, Boston, Massachusetts
10 Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
11 National Heart, Lung, and Blood Institute, Center for Population Studies, Bethesda, Maryland
12 Departments of Neurology and Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, Massachusetts

Address correspondence and reprint requests to Ramachandran S. Vasan, MD, FACC, Framingham Heart Study, 73 Mount Wayte Ave., Suite 2, Framingham, MA 01702-5803. E-mail: vasan{at}bu.edu

Abbreviations: CVD, cardiovascular disease; IMT, intima-media thickness; LVH, left ventricular hypertrophy; MetS, metabolic syndrome

Data are limited regarding prevalence and prognostic significance of subclinical cardiovascular disease (CVD) in individuals with metabolic syndrome (MetS). We investigated prevalence of subclinical CVD in 1,945 Framingham Offspring Study participants (mean age 58 years; 59% women) using electrocardiography, echocardiography, carotid ultrasound, ankle-brachial blood pressure, and urinary albumin excretion. We prospectively evaluated the incidence of CVD associated with MetS and diabetes according to presence versus absence of subclinical disease. Cross-sectionally, 51% of 581 participants with MetS had subclinical disease in at least one test, a frequency higher than individuals without MetS (multivariable-adjusted odds ratio 2.06 [95% CI 1.67–2.55]; P < 0.0001). On follow-up (mean 7.2 years), 139 individuals developed overt CVD, including 59 with MetS (10.2%). Overall, MetS was associated with increased CVD risk (multivariable-adjusted hazards ratio [HR] 1.61 [95% CI 1.12–2.33]). Participants with MetS and subclinical disease experienced increased risk of overt CVD (2.67 [1.62–4.41] compared with those without MetS, diabetes, or subclinical disease), whereas the association of MetS with CVD risk was attenuated in absence of subclinical disease (HR 1.59 [95% CI 0.87–2.90]). A similar attenuation of CVD risk in absence of subclinical disease was observed also for diabetes. Subclinical disease was a significant predictor of overt CVD in participants without MetS or diabetes (1.93 [1.15–3.24]). In our community-based sample, individuals with MetS have a high prevalence of subclinical atherosclerosis that likely contributes to the increased risk of overt CVD associated with the condition.


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