Aya Kadota, M.D., Department of Health Science and Department of Internal Medicine, Shiga University of Medical Science, Otsu, Japan

Prevention of cardiovascular disease (CVD) is a worldwide major healthcare burden since it impairs our activities of daily living and quality of life. The World Health Organization (WHO) states that individual risk factors for CVD convey great CVD risk. Furthermore, even though each one of these risk factors alone is not serious, the risk becomes more “powerful” when they are combined [1]. Metabolic syndrome is the concept of clustering metabolic risk factors comprising insulin resistance, abdominal fat distribution, dyslipidemia, hypertension, and so on [2-5]. Several academic societies established their own diagnostic criteria for metabolic syndrome. The National Cholesterol Education Program (NCEP) considers that each metabolic factor has the same importance [6], whereas the WHO requires impaired glucose tolerance among its criteria to diagnose metabolic syndrome [7]. Finally, the International Diabetes Federation (IDF) and the Japanese guidelines require central obesity defined by waist circumference to diagnose metabolic syndrome [8,9].

Thus, whether a relationship between metabolic risk factor clustering and CVD mortality differs according to obesity or impaired glucose tolerance, which are both required for a diagnosis of metabolic syndrome, should be determined. We recently investigated the association between metabolic risk factor clustering and CVD mortality stratified according to obesity or impaired glucose tolerance in a population-based cohort study (NIPPON DATA90) in the Japanese general population [10]. In this prospective population-based cohort study, metabolic factor clustering, i.e. high blood pressure, high blood glucose, high triglycerides, low high-density lipoprotein cholesterol, and obesity assessed by body mass index (BMI), was positively associated with CVD mortality as was the case in previous studies [11-16]. The risk increase in participants with both high blood glucose and two or more metabolic factors was significantly higher (HR = 3.67, CI, 1.49-9.03) than that in those with neither high blood glucose nor metabolic risk factors. However, the risk increase was only modest in participants without high blood glucose even if they had ≧ 2 other metabolic risk factors (HR = 1.99, CI, 0.93-4.28). On the other hand, the risk in non-obese participants with more metabolic factors was also increased and metabolic risk factor clustering was related to CVD mortality irrespective of obesity (BMI ≧ 25kg/m2).

Our results suggest that glucose tolerance plays an important role in CVD mortality. There are also many studies reporting the HR of metabolic syndrome on CVD mortalities [11-16]. Ford et al. summarized that the HR of metabolic syndrome using the definition of WHO is higher than that using the definition of NCEP [17]. This is consistent with our results although we used non-fasting blood samples. Although increased waist circumference is an important risk factor and supposedly indicates visceral fat accurately [18], individuals with multiple risk factors and an increased risk of CVD have normal waist circumference [19-20]. The prevalence of non-obese participants with multiple metabolic risk factors was high and their CVD risk was also high in our results. Thus, metabolic factors should be carefully considered and appropriately managed even among individuals with a BMI below 25. We believe our results give an important message for the prevention of CVD, especially in non-Western populations with a relatively low prevalence of obesity.

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Please address correspondence to:
Aya Kadota, M.D.
Department of Health Science
Shiga University of Medical Science
Seta Tsukinowa-cho Otsu, Shiga 520-2192, Japan
Tel: +81-77-548-2191
Fax: +81-77-543-9732
E-mail: ayakd[at]belle.shiga-med.ac.jp