Increased Heart Failure Risk in Normal-Weight People With Metabolic Syndrome Compared With Metabolically Healthy Obese Individuals

First Department of Cardiology, Athens University Medical School, Hippokration Hospital, Athens, Greece.
Journal of the American College of Cardiology (Impact Factor: 16.5). 09/2011; 58(13):1343-50. DOI: 10.1016/j.jacc.2011.04.047
Source: PubMed


The purpose of this study was to assess whether the metabolically healthy obese phenotype is associated with lower heart failure (HF) risk compared with normal-weight individuals with metabolic syndrome (MetS).
Obesity and MetS often coexist and are associated with increased HF risk. It is controversial whether obese individuals with normal insulin sensitivity have decreased HF risk.
A total of 550 individuals without diabetes or baseline macrovascular complications were studied during a median follow-up of 6 years. Participants were classified by presence (n = 271) or absence (n = 279) of MetS and by body mass index (body mass index: <25 kg/m(2) = normal weight, n = 177; 25 to 29.9 kg/m(2) = overweight, n = 234; ≥ 30 kg/m(2) = obese, n = 139). MetS was diagnosed with the National Cholesterol Education Program Adult Treatment Panel III criteria. Left ventricular functional capacity, myocardial structure, and performance were assessed echocardiographically.
Body mass index was not associated with increased HF risk. The presence of MetS conferred a 2.5-fold higher HF risk (hazard ratio [HR]: 2.5, 95% confidence interval [CI]: 1.68 to 3.40). Overweight and obese individuals without MetS had the lowest 6-year HF risk (HR: 1.12, 95% CI: 0.35 to 1.33 [corrected] and HR: 0.41, 95% CI: 0.10 to 1.31, respectively) compared with normal-weight individuals with MetS (HR: 2.33, 95% CI: 1.25 to 4.36, p < 0.001). From the individual components of MetS, impaired fasting glucose (HR: 1.09, 95% CI: 1.06 to 1.10), high BP (HR: 2.36, 95% CI: 1.03 to 5.43), low high-density lipoprotein cholesterol (HR: 1.88, 95% CI: 1.29 to -2.77), and central obesity (HR: 2.22, 95% CI: 1.02 to 1.05) were all associated with increased HF risk. Factors commonly associated with MetS such as insulin resistance and inflammation (high-sensitivity C-reactive protein and microalbuminuria) were also independently associated with HF incidence.
In contrast to normal weight insulin-resistant individuals, metabolically healthy obese individuals show decreased HF risk in a 6-year follow-up study.

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Available from: Nicholas Tentolouris, Mar 10, 2014
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    • "Three studies included measures of inflammation (either C-Reactive protein [CRP] or white blood cell [WBC] count) in the definition of MHO [11,15,17]. Two studies defined “metabolically healthy” as absence of metabolic syndrome (MetS) based on the NCEP ATP III definition of MetS without any modification [18,19]. Five studies defined “metabolically healthy” as absence of MetS with study specific modifications to the MetS criteria [11,12,16,20,21]. "
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    ABSTRACT: A subgroup has emerged within the obese that do not display the typical metabolic disorders associated with obesity and are hypothesized to have lower risk of complications. The purpose of this review was to analyze the literature which has examined the burden of cardiovascular disease (CVD) and all-cause mortality in the metabolically healthy obese (MHO) population. Pubmed, Cochrane Library, and Web of Science were searched from their inception until December 2012. Studies were included which clearly defined the MHO group (using either insulin sensitivity and/or components of metabolic syndrome AND obesity) and its association with either all cause mortality, CVD mortality, incident CVD, and/or1 subclinical CVD. A total of 20 studies were identified; 15 cohort and 5 cross-sectional. Eight studies used the NCEP Adult Treatment Panel III definition of metabolic syndrome to define "metabolically healthy", while another nine used insulin resistance. Seven studies assessed all-cause mortality, seven assessed CVD mortality, and nine assessed incident CVD. MHO was found to be significantly associated with all-cause mortality in two studies (30%), CVD mortality in one study(14%), and incident CVD in three studies (33%). Of the six studies which examined subclinical disease, four (67%) showed significantly higher mean common carotid artery intima media thickness (CCA-IMT), coronary artery calcium (CAC), or other subclinical CVD markers in the MHO as compared to their MHNW counterparts. MHO is an important, emerging phenotype with a CVD risk between healthy, normal weight and unhealthy, obese individuals. Successful work towards a universally accepted definition of MHO would improve (and simplify) future studies and aid inter-study comparisons. Usefulness of a definition inclusive of insulin sensitivity and stricter criteria for metabolic syndrome components as well as the potential addition of markers of fatty liver and inflammation should be explored. Clinicians should be hesitant to reassure patients that the metabolically benign phenotype is safe, as increased risk cardiovascular disease and death have been shown.
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    • "Previous studies of the mechanism of the association between increased BMI, diastolic dysfunction and the risk of heart failure have had difficulty separating the effects of BMI from the effects of the metabolic syndrome, impaired insulin sensitivity and cardiac hypertrophy [8,39,40], and some studies suggested that the metabolic syndrome, and not increased BMI per se, is associated with increased risk of heart failure [41,42]. We previously reported that PCWP was increased in men with diabetes and the metabolic syndrome [21], but we found that neither diabetes nor the metabolic syndrome was associated with alteration in capillary length density [21]. "
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    • "It was shown that resistance to insulin-stimulated glucose uptake, especially in adipose tissue, liver, and muscle brings about type 2 diabetes, one of the most common chronic diseases [4] [5]. Insulin resistance also interferes with lipid metabolism leading to atherosclerosis, hypertension, and cardiovascular disease (CVD) [6]. "
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