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Obesity and the heart
Obesity and heart failure are a global epidemic associated with increased cardiovascular risk and significant healthcare costs.1 2 Epidemiological evidence suggests that obese patients are 30% more likely to develop heart failure3 and each incremental body mass index (BMI) rise of 1 kg/m2 can increase the risk of heart failure by 5% for men and by 7% for women.4 Moreover, heart weight and body weight have a linear relationship,5 and long-term obesity is associated with left ventricular hypertrophy and dilatation, which may result in cardiac failure. It remains difficult to distinguish whether symptoms of poor exercise tolerance, dyspnoea and peripheral oedema are secondary to obesity alone or ‘obesity cardiomyopathy’. On echocardiography left ventricular dilatation is present in 8–40% of obese individuals, and increased left ventricular wall mass exists in up to 87% of obese patients.6
Traditional haemodynamic model and its limitations
Obesity results in increased numbers of adipocytes, leading to an expanded circulating volume thereby raising metabolic demands.7 The subsequent increase of left ventricular stroke volume induces a persistent rise in cardiac output, which in turn results in systemic hypertension. In obese individuals, it was therefore proposed that the left ventricular stroke workload is higher owing to an increased preload and stroke volume so that left ventricular dilatation occurs, causing a rise in wall stress and increasing myocardial mass to compensate. Eccentric hypertrophy follows (figure 1) with subsequent left ventricular systolic and diastolic dysfunction (the latter being more significantly affected).6
The problems with this traditional haemodynamic hypothesis are: (i) the sequence of change in myocardial pathology which does not correlate with the extent of obesity; (ii) the fact that use of two-dimensional echocardiographic imaging is complicated by excessive fat-limiting acoustic windows; (iii) there is no consideration of the metabolic changes (both local and systemic) associated with heart failure; (iv) the volumetric changes in the circulation and cardiac adaption were not fully demonstrable; (v) it does not take into account the differentiation between eccentric, concentric and ventricular dilatation geometries and (vi) the model does not accommodate the obesity paradox where an increased BMI may provide prognostic benefits in the elderly.
Local and systemic metabolic effects of obesity on cardiac remodelling
At a local level, both epicardial fat and ventricular fatty infiltration are present in approximately 3% of severely obese individuals (BMI>40 kg/m2)8 and this can be associated with ventricular dysfunction. The excess ventricular adipocytes may result in myocardial steatosis acting as direct cardiotoxins.9 Epicardial fat also contributes to cardiac dysfunction, because unlike skeletal muscle, the myocardium has no fascial compartments to separate muscular and fatty layers which share the same local blood supply. Therefore epicardial fat can contribute to the metabolic dialogue between fat and muscle. The biochemical characteristics of epicardial fat reflect a tendency toward increased lipolysis and low mitochondrial oxidative capacity reinforced by the pro-atherogenic modulation of adipokines (decreased adiponectin and increased resistin) and inflammatory factors, which can contribute to adverse ventricular remodelling.10
The systemic metabolic profile of obesity is associated with impaired glucose metabolism or even frank diabetes and hypertension, leading to the status of ‘complicated obesity’ associated with disordered cardiac structure, which may be followed by cardiomyopathy.4 11 Identifying the relative contribution of obesity, diabetes, impaired glucose metabolism and hypertension on cardiac geometry and remodelling can thus be complex as these pathologies usually coexist within the same individuals. As a result, many patients with complicated obesity present with concentric hypertrophy (figure 1).
Integrating haemodynamics and metabolism: an alternative model
Rider et al12 in this issue of Heart (see page 203) deal with many of the limitations of previous studies on obesity and cardiac geometry. They applied their extensive expertise in cardiovascular magnetic resonance (CMR) to achieve clear and consistent measures of ventricular mass and volumes in 88 non-diabetic normotensive female subjects over a range of BMIs from normal weight to overweight, obese and morbidly obese.
They demonstrated that a subtle increase in BMI from normal to overweight results in eccentric cardiac hypertrophy without the expected volume-dependent change to myocardial dilatation (figure 1). This geometry is consistent even in mild obesity and only tends toward dilatation in morbid obesity. The authors suggest that the early hypertrophic changes of the heart are secondary to obesity-associated hyperleptinaemia and the subsequent cardiac dilatation seen in morbid obesity is probably volume-induced. The multifaceted metabolic role of increased leptin levels in obesity has been increasingly recognised, and the data from this study are consistent with in vitro experiments suggesting that leptin causes cardiac hypertrophy.13 This hypothesis lends itself to further testing as the 20–30% weight loss achieved with metabolic surgery decreases leptin significantly.14 Moreover, metabolic surgery demonstrated improved glycaemic control, reduced epicardial fat thickness and beneficial reverse modelling through reduction in wall thickness and ventricular mass.14 Rider et al12 therefore contribute to our understanding as the majority of previous studies only used two-dimensional echocardiography to quantify cardiac geometry. The role of male gender on ventricular remodelling and subsequent heart failure, however, still needs to be examined.4
Future research can benefit by correlating these geometric findings with cardiac function to derive further mechanistic insights. These can clarify whether the initial effects of obesity are associated with diastolic dysfunction in the context of disordered metabolism and whether subsequent volume overload eventually progresses to systolic dysfunction. Furthermore, the obesity paradox remains an unanswered entity in these obese patients, as despite the prevalence of cardiac geometric abnormalities a lower mortality is seen than in normal weight patients.15 Elucidating this geometry–mortality paradox in obese patients therefore remains a crucial question to be answered. Identifying the precise mechanisms of obesity-induced cardiac remodelling can facilitate the prediction of patients at higher risk of cardiac failure and can also provide new treatments in the management of obesity-associated heart disease.
Linked articles 185009.
Funding We are grateful for support from the Wellcome Trust and the NIHR Biomedical Research Centre Funding Scheme.
Competing interests None.
Provenance and peer review Commissioned; not externally peer reviewed.
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