Wang J, Ruotsalainen S, Moilanen L, et al. The metabolic syndrome predicts cardiovascular mortality: a 13-year follow-up study in elderly non-diabetic Finns

Department of Medicine, University of Kuopio, Kuopio University Hospital, PO Box 1777, FI-70211 Kuopio, Finland.
European Heart Journal (Impact Factor: 15.2). 05/2007; 28(7):857-64. DOI: 10.1093/eurheartj/ehl524
Source: PubMed


The metabolic syndrome (MetS) is defined as a clustering of cardiovascular risk factors characterized by insulin resistance. We investigated the relationship of the MetS and its single components, defined by all six different criteria, with coronary heart disease (CHD), cardiovascular disease (CVD), and all-cause mortality in a prospective population-based study.
The MetS was defined according to the World Health Organization (WHO), the European Group for the Study of Insulin Resistance (EGIR), the National Cholesterol Education Program (NCEP), the American College of Endocrinology (ACE), the International Diabetes Federation (IDF), and the American Heart Association (updated NCEP) criteria. We investgated the relationship of the MetS defined by aforementioned six criteria with CHD, CVD, and all-cause mortality with Cox regression analyses in a non-diabetic Finnish population of 1025 subjects, aged 65-74 years, during the 13-year follow-up. The MetS defined by all aforementioned criteria was associated with a statistically significant risk for CVD mortality when adjusted for all confounding variables (Hazards Ratios, HRs from 1.31 to 1.51). The MetS defined by the WHO, ACE, and IDF criteria was associated with an increased risk of CHD mortality (HRs from 1.42 to 1.58). There was no association between the MetS by any criteria and all-cause mortality. Of the single components of the MetS, the following predicted CVD mortality in multivariable models: impaired fasting glucose by the WHO, NCEP, and ACE criteria (HR 1.34) and by the IDF and updated NCEP criteria (HR 1.29); impaired glucose tolerance by the WHO and ACE criteria (HR 1.55); low HDL cholesterol by the EGIR criteria (HR 1.50) and by the NCEP, IDF, and updated NCEP criteria (HR 1.29); and microalbuminuria according to the WHO definition (HR 1.86).
The MetS defined by all six current criteria predicts CVD mortality in elderly subjects. However, of the single components of the MetS, IFG, IGT, low HDL cholesterol, and microalbuminuria predicted CVD mortality with equal or higher HRs when compared with the different definitions of the MetS. Therefore, our study suggests that the MetS is a marker of CVD risk, but not above and beyond the risk associated with its individual components.

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Available from: Markku Laakso, Dec 27, 2013
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    • "Nevertheless, the association between MS phenotype and mortality has not been consistently confirmed in people over 65 years. Some studies reported a significant association of MS with total [5e7] or CVD mortality [5] [8] [9] also in older cohorts, while others found no association [10e13]. On the whole, it appears that MS phenotype becomes a weaker predictor of CVD/total mortality in late life, and this concept is supported by studies comparing mortality risk in middle-age versus elderly individuals [12] [14]. "
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    ABSTRACT: Background: Although metabolic syndrome (MS) is a typical condition of middle-aged/older person, the association between MS and mortality risk has not been confirmed in people over 65 years. We hypothesized that while in the elderly MS phenotype might lose its value in predicting mortality risk, the two core factors of MS, i.e. insulin resistance (IR) and low grade systemic inflammation (LGSI) would not. Methods: 1011 community-dwelling older individuals (InCHIANTI study) were included. MS phenotype was defined by NCEP-ATP-III criteria. IR was calculated by HOMA; high-sensitivity C reactive protein was measured by ELISA. Subjects were divided into four groups based on presence/absence of IR (HOMA ≥ 2.27) and LGSI (hs-CRP ≥ 3 g/L): Group 1: no IR/LGSI (reference); Group 2: LGSI only; Group 3: IR only; Group 4: IR + LGSI. Hazard Ratios (HR) for 9-years cardiovascular (CVD) and total mortality, according to IR/LGSI groups, were estimated in subjects with (n.311) and without MS by Cox model. Results: 31.8% of subjects with MS phenotype had no IR, 45.3% had no LGSI; moreover, 51% of subjects with both IR and LGSI didn't display the MS phenotype. MS phenotype was not associated with CVD (HR: 1.29; 95%C.I.:0.92-1.81) or total (HR: 1.07; 95%C.I.:0.86-1.34) mortality risk, whereas the presence of IR plus LGSI was associated with increased CVD (no MS: HR 2.07, 95%CI: 1.12-3.72; MS: HR 9.88, 95%CI: 2.18-4), and overall (no MS: HR 1.72, 95%CI: 1.001-3.17; MS: HR 1.51, 95%CI: 1.02-2.28) mortality risk. The presence of IR (HR: 6.90, 95%CI: 1.45-32) or LGSI (HR 7.56, 95%CI: 1.63-35) was associated with CVD mortality, only among individuals with MS phenotype. Conclusions: Among community-dwelling older individuals, IR and LGSI, but not MS phenotype, was associated with 9-years overall and CVD mortality risk. Since a reduced "overlap" between MS phenotype and its physiopathological core (IR and LGSI) might be present with aging, we suggest that the definition of MS might be more holistic in advanced age, and probably comprise the measurement of IR and LGSI.
    Full-text · Article · Jun 2014 · Atherosclerosis
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    • "However, it is still debatable whether the CAD risk associated with MS is above and beyond the risk associated with its individual components [9,10]. Previous studies have reported that the number of markers of MS, or the MS score, is more useful than a binary definition of MS to predict severity of CAD [11,12]. "
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    ABSTRACT: It is a matter of debate whether metabolic syndrome (MS) improves cardiovascular risk prediction beyond the risk associated with its individual components. The present study examined the association of MS score with high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), resistin, adiponectin, and angiographic coronary artery disease (CAD) severity according to the presence of DM. In addition, the predictive value of various clinical and biochemical parameters were analyzed, including the MS score for angiographic CAD. The study enrolled 363 consecutive patients (196 men, 62 +/- 11 years of age) who underwent coronary angiography for evaluation of chest pain. Blood samples were taken prior to elective coronary angiography. MS was defined by the National Cholesterol Education Program criteria, with MS score defined as the numbers of MS components. CAD was defined as > 50% luminal diameter stenosis of at least one major epicardial coronary artery. CAD severity was assessed using the Gensini score. Of the 363 patients studied, 174 (48%) had CAD and 178 (49%) were diagnosed with MS. When the patients were divided into 4 subgroups according to MS score (0--1, 2, 3, 4--5), IL-6 levels and the CAD severity as assessed by the Gensini score increased as MS scores increased. In contrast, adiponectin levels decreased significantly as MS scores increased. When subjects were divided into two groups according to the presence of DM, the relationships between MS score and IL-6, adiponectin, and Gensini score were maintained only in patients without DM. Age, smoking, DM, MS score, and adiponectin independently predicted angiographic CAD in the whole population. However, age is the only predictor for angiographic CAD in patients with DM. In the presence of DM, neither adipokines nor MS score predicted angiographic CAD. However, in non-diabetic patients, IL-6 and adiponectin showed progressive changes according to MS score, and MS score was an independent predictor of CAD in patients without DM.
    Full-text · Article · Oct 2013 · Cardiovascular Diabetology
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    • "Also, a considerable proportion of studies investigated subjects with MetS and overt hyperglycemia reported that increased CVD risk was linked to the presence of fasting hyperglycemia [2]. However, few published studies indicated MetS as an independent contributor to CVD outcomes in the absence of type 2 diabetes [14] [15] [16]. "
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    ABSTRACT: Background: The applicability of different definitions of metabolic syndrome (MetS) in predicting cardiovascular diseases (CVD) remains questionable. The aim of this study was to compare predictive ability of different definitions of MetS for CVD in non-diabetic subjects. Methods: In this community-based study, 5198 non-diabetic subjects aged ≥ 30 years (mean age 45.6 years, 45% men) free of CVD at baseline were followed for a median of 9.3 years to assess risk for CVD. We assessed the predictability of definitions of the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III), the International Diabetes Federation (IDF), the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI), and the joint interim statement (JIS) on development of CVD. Hazard ratios (HRs) were calculated using Cox proportional-hazards models. The receiver operating characteristic (ROC) curve was also used to compare discriminative power of these MetS definitions in predicting CVD events. Results: Compared to other definitions, the JIS identified more participants (41.8%) having MetS. First CVD events occurred in 311 subjects. After adjustment for potential confounders, the HRs of the NCEP-ATP III, AHA/NHLBI, IDF and JIS definitions for incident CVD were 1.55 (1.21-2.00), 1.73 (1.35-2.20), 1.54 (1.22-1.94) and 1.70 (1.34-2.17), respectively. All definitions showed higher HRs for females in comparison to males (P<0.05). ROC analysis showed no significant difference in the discriminative power of different MetS definitions in predicting CVD events (P>0.05). Conclusions: In the current study, compared to each other none of the definitions showed a superior discriminative power in predicting CVD; although, all definitions were more predictive in females than in males.
    Full-text · Article · Oct 2012 · International journal of cardiology
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