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ORIGINAL CONTRIBUTION

The Metabolic Syndrome and Total and Cardiovascular Disease Mortality in Middle-aged Men
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
HE METABOLIC SYNDROME , A concurrence of disturbed glucose and insulin metabolism, overweight andabdominal fat distribution, mild dyslipidemia, and hypertension, is most important because of its association with subsequent development of type 2 diabetes mellitus and cardiovascular disease (CVD).1,2 The syndrome is characterized by insulin resistance and is also known as the insulin resistance syndrome. The pathogenesis of the syndrome has multiple origins, but obesity and sedentary lifestylecoupled with diet and still largely unknown genetic factors clearly interact to produce the syndrome.1-3 Despite abundant research on the subject, definitions of the metabolic syndrome and the various cutoffs for its components have varied widely.1,2 To aid in the research and clinical application of the metabolic syndrome, the World Health Organization (WHO) consultation for the classification ofdiabetes and its complications4 and the National Cholesterol Education Program (NCEP) expert panel5 have recently published definitions.

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 cardiovasculardisease (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 FactorStudy, 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 CholesterolEducation 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 11.4year 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...