Romero-Corral A, Montori VM, Somers VK, et al. Association of bodyweight with total mortality and with cardiovascular events in coronary artery disease: A systematic review of cohort studies

Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, Mayo Foundation, Rochester, MN 55905, USA.
The Lancet (Impact Factor: 45.22). 08/2006; 368(9536):666-78. DOI: 10.1016/S0140-6736(06)69251-9
Source: PubMed


Studies of the association between obesity, and total mortality and cardiovascular events in patients with coronary artery disease (CAD) have shown contradictory results. We undertook a systematic review to determine the extent and nature of this association.
We selected cohort studies that provided risk estimates for total mortality, with or without cardiovascular events, on the basis of bodyweight or obesity measures in patients with CAD, and with at least 6 months' follow-up. CAD was defined as history of percutaneous coronary intervention, coronary artery bypass graft, or myocardial infarction. We obtained risk estimates for five predetermined bodyweight groups: low, normal weight (reference), overweight, obese, and severely obese.
We found 40 studies with 250,152 patients that had a mean follow-up of 3.8 years. Patients with a low body-mass index (BMI) (ie, <20) had an increased relative risk (RR) for total mortality (RR=1.37 [95% CI 1.32-1.43), and cardiovascular mortality (1.45 [1.16-1.81]), overweight (BMI 25-29.9) had the lowest risk for total mortality (0.87 [0.81-0.94]) and cardiovascular mortality (0.88 [0.75-1.02]) compared with those for people with a normal BMI. Obese patients (BMI 30-35) had no increased risk for total mortality (0.93 [0.85-1.03]) or cardiovascular mortality (0.97 [0.82-1.15]). Patients with severe obesity (> or =35) did not have increased total mortality (1.10 [0.87-1.41]) but they had the highest risk for cardiovascular mortality (1.88 [1.05-3.34]).
The better outcomes for cardiovascular and total mortality seen in the overweight and mildly obese groups could not be explained by adjustment for confounding factors. These findings could be explained by the lack of discriminatory power of BMI to differentiate between body fat and lean mass.

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    • "However, BMI has only 50% sensitivity to detect excess adiposity [36] and it is not able to differentiate between an elevated body fat content and preserved or increased lean mass, especially in individuals with a BMI < 30 kg/ m 2 . This may explain better cardiovascular outcomes seen in overweight and mildly obese [37] and increased risk of mortality in normal weight subjects with central obesity [38]. Several studies have shown that measures assessing abdominal fat mass may be more closely related to cardiovascular morbidity and mortality than measures of general obesity [39e41]. "
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    ABSTRACT: Objective: Increased aortic stiffness may be one of the mechanisms by which obesity increases cardiovascular risk independently of traditional risk factors. While body mass index (BMI) is generally used to define excess adiposity, several studies have suggested that measures of central obesity may be better predictors of cardiovascular risk. However, data comparing the association between several measures of central and general obesity with aortic stiffness in the general population are inconclusive. Methods: In 1031 individuals (age 53 ± 13 years, 45% men) without manifest cardiovascular disease randomly selected from population, we tested the association between parameters of central obesity (waist circumference - WC, waist-to-hip-ratio - WHR, waist-to-height ratio - WHtR) and general obesity (BMI) with carotid-femoral pulse wave velocity (cfPWV). Results: In univariate analysis, WC and WHtR were more strongly associated with cfPWV than BMI in both genders, while WHR showed a stronger association with cfPWV only in women. WHtR was more closely associated with cfPVW than WHR. This difference between obesity measures remained after multivariate adjustment. When the fully adjusted hierarchical regression was used, among central obesity measures, WHtR had the largest additive value on top of BMI, while there was no additive value of BMI on top of WHtR. Conclusion: Central obesity parameters are more closely associated with aortic stiffness than BMI. Of central adiposity measures, WHtR has the strongest association with aortic stiffness beyond body mass index and cardiovascular risk factors. Our results suggest that WHtR may be the best anthropometric measure of excess adiposity in the general population.
    Atherosclerosis 06/2014; 235(2):625-631. DOI:10.1016/j.atherosclerosis.2014.05.958 · 3.99 Impact Factor
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    • "It is important to bear in mind that obese subjects are defined solely by BMI without considering other metabolic parameters such as circulating cholesterol and triglycerides. In rodents, a study by Thim et al reported no differences in infract size between lean and DIO rat hearts following MI [36]. Our findings are by and large consistent with their report. "
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    ABSTRACT: Fibroblast growth factor 21 (FGF21) is a hepatic metabolic regulator with pleotropic actions. Its plasma concentrations are increased in obesity and diabetes; states associated with an increased incidence of cardiovascular disease. We therefore investigated the direct effect of FGF21 on cardio-protection in obese and lean hearts in response to ischemia. FGF21, FGF21-receptor 1 (FGFR1) and beta-Klotho (βKlotho) were expressed in rodent, human hearts and primary rat cardiomyocytes. Cardiac FGF21 was expressed and secreted (real time RT-PCR/western blot and ELISA) in an autocrine-paracrine manner, in response to obesity and hypoxia, involving FGFR1-βKlotho components. Cardiac-FGF21 expression and secretion were increased in response to global ischemia. In contrast βKlotho was reduced in obese hearts. In isolated adult rat cardiomyocytes, FGF21 activated PI3K/Akt (phosphatidylinositol 3-kinase/Akt), ERK1/2(extracellular signal-regulated kinase) and AMPK (AMP-activated protein kinase) pathways. In Langendorff perfused rat [adult male wild-type wistar] hearts, FGF21 administration induced significant cardio-protection and restoration of function following global ischemia. Inhibition of PI3K/Akt, AMPK, ERK1/2 and ROR-α (retinoic-acid receptor alpha) pathway led to significant decrease of FGF21 induced cardio-protection and restoration of cardiac function in response to global ischemia. More importantly, this cardio-protective response induced by FGF21 was reduced in obesity, although the cardiac expression profiles and circulating FGF21 levels were increased. In an ex vivo Langendorff system, we show that FGF21 induced cardiac protection and restoration of cardiac function involving autocrine-paracrine pathways, with reduced effect in obesity. Collectively, our findings provide novel insights into FGF21-induced cardiac effects in obesity and ischemia.
    PLoS ONE 02/2014; 9(2):e87102. DOI:10.1371/journal.pone.0087102 · 3.23 Impact Factor
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    • "Given its complexity of interaction and arguable robustness of BMI in defining obesity, it is not surprising that evidences of ability of obesity to be a risk factor and a poor prognosticator are inconsistent among studies. There have been multiple studies describing “obesity paradox,” a protective effect of obesity, with various clinical surrogates and outcomes in different populations of CAD including asymptomatic population [5, 7], myocardial infarction [8–10], and patients treated with revascularization [11, 12]. However, in patients with acute chest pain undergoing coronary artery calcification (CAC) evaluation, there have been sparse studies. "
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    ABSTRACT: Obesity paradox has been described in various populations of coronary artery disease, mainly asymptomatic subjects. However, relationship between obesity and coronary artery calcification detected by cardiac CT in symptomatic patients has rarely been demonstrated. This study seeks to investigate whether the paradoxical relationship between obesity and coronary artery calcification exists in patients with acute chest pain. A final cohort of 1030 chest pain patients presenting at our emergency department who underwent coronary evaluation by multidetector cardiac CT were examined. With absent-to-mild coronary calcification (CAC score < 100) as a referent, multivariable analysis showed that presence of obesity (OR 0.564; 95% CI 0.395, 0.806; P 0.002), body mass index (OR 0.945; 95% CI 0.920, 0.971; P < 0.001), body weight (OR 0.987; 95% CI 0.979, 0.995; P 0.001), and body surface area (OR 0.582; 95% CI 0.369, 0.920; P 0.020) were inversely associated with moderate-to-severe coronary calcification (CAC score ≥ 100). This study extends the concept of obesity paradox to symptomatic patients undergoing coronary artery calcium score assessment. However, biological explanation(s) of this paradox remains unanswered.
    01/2014; 2014:634717. DOI:10.1155/2014/634717
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