Obesity, a disease that deserves clinical awareness

This editorial refers to ‘Rethinking weight loss treatments as cardiovascular medicine in obesity: a comprehensive review’, by D. Tuccinardi et al., https://doi.org/10.1093/eurjpc/zwae171. Obesity is a chronic relapsing and progressive disease that plays a role in the progression of cardiovascular disease (CVD), such as atrial fibrillation, coronary artery disease, and heart failure, as it often co-occurs with other common cardiometabolic risk factors such as dyslipidaemia, pre-diabetes, type 2 diabetes, hypertension, and obstructive sleep apnoea syndrome.1,2 The European Society of Cardiology guidelines for the prevention of CVD in clinical practice recommend appropriate treatment in people who are overweight or with obesity to improve their cardiometabolic disease risk profile. Unfortunately, cardiologists’ clinical awareness of the need for treatment of obesity is often overlooked.2 The obesity–CVD relationship is deeply complex. This interesting review by Tuccinardi et al. takes from the epidemiology to the pathophysiology, consequences, and treatment of obesity and delves into most of the cardiometabolic-related comorbidities. This review explores the concept of the obesity paradox, highlighting the limitations of using the body mass index (BMI) as the only indicator of obesity, as it cannot discriminate between visceral and subcutaneous adipose tissue or distinguish body lean mass from fat mass. In addition, this index may not be valid for all ethnic groups for the classification. Antonopoulos et al.3 have shown that when other anthropometric indices are used to define obesity, such as waist circumference or waist to height ratio, this obesity paradox is no longer observed as adiposity depends not only on regional fat distribution but also on adipose tissue adaptations to excess caloric intake and the type of fat expansion. Indeed, subjects with central obesity have been shown to have a higher risk of cardiovascular mortality than those with the same BMI but without central adiposity.1 Furthermore, obesity is recognized as an heterogeneous disease, in which individuals with similar BMI could have different metabolic and cardiovascular risk profiles.1 For the diagnosis of obesities, the use of additional indices should be encouraged. To quantify body composition and to stratify cardiometabolic risk, non-anthropomorphic measures based on ultrasonography, bioelectrical impedance analysis, dual X-ray absorptiometry, computed tomography (CT), and magnetic resonance imaging can also be used.1 A crucial strategy to treat obesity and cardiometabolic diseases involves promoting a combined lifestyle approach of balanced nutrition and regular physical activity.4 A recent systematic review and meta-analysis showed that exercise training has a positive impact on cardiometabolic health in adults who are overweight or with obesity.5 In these individuals, blood pressure, insulin resistance, and intrahepatic fat decreased significantly after the exercise programme.5 Even light physical activity, like a walk, is associated with a reduction in all-cause and cardiovascular mortality with an improvement in the quality of life.6 In a meta-analysis of 17 studies with nearly 227 000 participants that evaluated the health effects of physical activity as expressed by the number of steps, an increase of 1000 steps was shown to correlate with a significant reduction in all-cause mortality by 15%, and similarly, an increase of 500 steps correlated with a reduction in cardiovascular mortality risk by 7%.6 For this reason, moderate modulation of energy expenditure and preservation of lean mass prevented by resistance exercise, possibly in combination with effective appetite-reducing compounds, are a prerequisite for a healthy, significant, and lasting weight loss.7 Moreover, lifestyle interventions, particularly physical activity behaviour or the combined changes in diet and physical activity, showed a reduction of visceral adipose tissue depot and ectopic fat, independent of weight loss.1 Current evidence clearly shows that resistance training is a safe, effective, and important part of an overall physical training programme to reduce the risk of CVD.8 Unfortunately, participation rates in resistance training are lower than in aerobic training despite the fact that these programmes need not take a long time to be effective: they require only 30–60 min/week, about 10 min/day.8 To promote resistance training, it is important to proactively address the obstacles to this form of training, such as equipment availability, perceived complexity, and issues related to the safety and effectiveness of strength training.8 Nevertheless, given the many benefits of exercise on important aspects of cardiometabolic health, treatment of patients who are overweight or with obesity should focus more on personalized exercise recommendations.5 In contrast, a sedentary lifestyle is significantly associated with an increased risk of mortality from any cause, from cardiovascular to oncological diseases, with a greater risk of type 2 diabetes.6 Although the causes of obesity are complex and individual choices are critical to health, this condition is largely driven by environmental factors, which undermine the self-regulatory ability that people have to make responsible decisions about personal diet and physical activity.9 Increasingly around the world, the environment hinders healthy living with incessant and unavoidable marketing of unhealthy foods and sugary drinks, lack of places to exercise, and junk food sold at school or at work.9 Therefore, it is difficult for individuals to make the healthy choices that contrast the obesogenic environment and enable them to have a good quality of life.9 Pharmacological strategies for the treatment of obesity have shown an important effect on weight loss and visceral adiposity reduction, improving cardiometabolic risk factors.10 Interestingly, epicardial adipose tissue (EAT) has been identified as a modifiable cardiometabolic risk factor.11 Epicardial adipose tissue is a distinct metabolically active visceral fat depot located between the myocardium and the visceral layer of the pericardium which has been suggested to play a role in the progression and the development of major causes of morbidity and mortality, such as coronary artery disease, atrial fibrillation, and heart failure.11 Epicardial adipose tissue can be clinically measured with cardiac imaging techniques such as echocardiography, CT, and magnetic resonance imaging, which can help to predict and stratify cardiovascular risk.11 Moreover, advances in coronary CT angiography (CCTA) allow measurement of EAT that intimately overlays the coronary arteries, known as pericoronary adipose tissue (PCAT).12 Routine CCTA enables the evaluation of EAT and PCAT attenuation, which is a measure of density expressed in Hounsfield unit (HU), which ranges between −30 and −190 HU, where a lower negative means higher density.13 Radiographic fat density is determined by adipocyte hypertrophy, hyperplasia, and fibrosis which oppositely influence fat CT attenuation; hypertrophic and hyperplastic fat depots usually have low density.13 Given its rapid metabolism, clinical measurability, and modifiability, EAT represents a therapeutic target for innovative drugs, such as glucagon-like peptide 1 receptor agonists (GLP-1RAs) and sodium–glucose co-transporter 2 inhibitors, which exert a positive cardiometabolic activity.11,14 Recently, it has been shown that glucose-dependent insulinotropic polypeptide receptors (GIPRs) and glucagon-like receptors (GCGRs), as well as GLP-1 receptors, are present at the mRNA and protein level in human EAT, particularly in macrophages and partly in adipocytes.15 These G-protein-coupled receptors, therefore, could be potential targets for pleiotropic therapies used in the treatment of obesity, such as GLP-1R agonists, GIPR/GLP-1R dual agonists, and GLP-1R/GIPR/GCGR triagonists, which produce beneficial cardiometabolic outcomes far beyond their effects on glucose and body weight.15 In addition to drug therapy,14 healthy diet and physical exercise are shown to have a positive effect on EAT volume reduction.16 In particular, supervised exercise programme (from 2 to 16 weeks, ≥ 3 sessions per week) reduced EAT in patients who are overweight or with obesity, regardless of the method of EAT assessment or duration of intervention.16 This supports the implementation of supervised exercise programmes, especially endurance training, in individuals with an unfavourable cardiometabolic profile.16 This study was partially supported by Ricerca Corrente funding from the Italian Ministry of Health to IRCCS Policlinico San Donato. No new data were generated or analysed in support of this research.