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Hanna-Maaria Lakka, MD, PhD; David E. Laaksonen, MD, MPH; Timo A. Lakka, MD, PhD; Leo K. Niskanen, MD, PhD; Esko Kumpusalo, MD, PhD; Jaakko Tuomilehto, MD, PhD; Jukka T. Salonen, MD, PhD

JAMA. 2002;288:2709-2716.

Context  The metabolic syndrome, a concurrence of disturbed glucose and insulin metabolism, overweight and abdominal fat distribution, mild dyslipidemia, and hypertension, is associated with subsequent development of type 2 diabetes mellitus and cardiovascular disease (CVD). Despite its high prevalence, little is known of the prospective association of the metabolic syndrome with cardiovascular and overall mortality.

Objective  To assess the association of the metabolic syndrome with cardiovascular and overall mortality using recently proposed definitions and factor analysis.

Design, Setting, and Participants  The Kuopio Ischaemic Heart Disease Risk Factor Study, a population-based, prospective cohort study of 1209 Finnish men aged 42 to 60 years at baseline (1984-1989) who were initially without CVD, cancer, or diabetes. Follow-up continued through December 1998.

Main Outcome Measures  Death due to coronary heart disease (CHD), CVD, and any cause among men with vs without the metabolic syndrome, using 4 definitions based on the National Cholesterol Education Program (NCEP) and the World Health Organization (WHO).

Results  The prevalence of the metabolic syndrome ranged from 8.8% to 14.3%, depending on the definition. There were 109 deaths during the approximately 11.4-year follow-up, of which 46 and 27 were due to CVD and CHD, respectively. Men with the metabolic syndrome as defined by the NCEP were 2.9 (95% confidence interval [CI], 1.2-7.2) to 4.2 (95% CI, 1.6-10.8) times more likely and, as defined by the WHO, 2.9 (95% CI, 1.2-6.8) to 3.3 (95% CI, 1.4-7.7) times more likely to die of CHD after adjustment for conventional cardiovascular risk factors. The metabolic syndrome as defined by the WHO was associated with 2.6 (95% CI, 1.4-5.1) to 3.0 (95% CI, 1.5-5.7) times higher CVD mortality and 1.9 (95% CI, 1.2-3.0) to 2.1 (95% CI, 1.3-3.3) times higher all-cause mortality. The NCEP definition less consistently predicted CVD and all-cause mortality. Factor analysis using 13 variables associated with metabolic or cardiovascular risk yielded a metabolic syndrome factor that explained 18% of total variance. Men with loadings on the metabolic factor in the highest quarter were 3.6 (95% CI, 1.7-7.9), 3.2 (95% CI, 1.7-5.8), and 2.3 (95% CI, 1.5-3.4) times more likely to die of CHD, CVD, and any cause, respectively.

Conclusions  Cardiovascular disease and all-cause mortality are increased in men with the metabolic syndrome, even in the absence of baseline CVD and diabetes. Early identification, treatment, and prevention of the metabolic syndrome present a major challenge for health care professionals facing an epidemic of overweight and sedentary lifestyle.

Author Affiliations: Research Institute of Public Health (Drs H.-M. Lakka, T. Lakka, and Salonen), Department of Public Health and General Practice (Drs H.-M. Lakka, Kumpusalo, and Salonen), and Department of Physiology (Dr Laaksonen), University of Kuopio, Finland; Pennington Biomedical Research Center, Louisiana State University, Baton Rouge (Drs H.-M. Lakka and T. Lakka); Department of Medicine, Kuopio University Hospital, Finland (Drs Laaksonen and Niskanen); Kuopio Research Institute of Exercise Medicine, Finland (Dr T. Lakka); Inner Savo Health Center, Suonenjoki, Finland (Dr Salonen); General Practice, Kuopio University Hospital, Finland (Dr Kumpusalo); Department of Public Health, University of Helsinki, Finland (Dr Tuomilehto); and Department of Epidemiology and Health Promotion, National Public Health Institute, Helsinki, Finland (Dr Tuomilehto).

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