The link between obesity and cardiovascular changes leading to increased CVD morbidity and mortality is well established (both myocardial infarction and ischemic stroke), mediated by metabolic and vascular pathophysiological traits as well as other mechanisms. Even though it has been shown in in some, but not all, epidemiological studies that weight reduction is associated with decreased CVD risk, so far the results of studies on the effects of weight-reducing drugs, with the aim of reducing cardiovascular morbidity and mortality, have been disappointing [
24]. One potential explanation for this is that the CVD risk associated with obesity is not causally related to overweight but instead to some other factor which is increased in parallel, for example insulin resistance or chronic inflammation. So, whereas it is clear that obese patients are at increased risk of hypertension, CVD, and heart failure, identification of new drug-modifiable biological pathways causally related to both obesity and CVD still remains challenging. Recently, the GLP-1 agonists have revealed a lot of attention due to their favorable effect in reducing cardiovascular risk in high-risk diabetes patients [
25,
26]. Existing on the market to date for the treatment of obesity is the GLP-1 agonist liraglutide, but other similar drugs are also being tested, for example semaglutide. Its efficacy is comparable with other available agents and greater than that seen with orlistat or lorcaserin, but slightly less than weight loss seen with phentermine/topiramate combination treatment. However, liraglutide offers the unique benefit of improved glycemic control in addition to weight loss. Although it has been shown that liraglutide, apart from lowering weight and blood glucose in subjects with diabetes at high cardiovascular risk, also reduces mortality and CVD risk [
26], additional studies are needed to determine its long-term efficacy and safety profile in non-diabetic obese patients [
27].
Even if drug treatment still is under development to address obesity and its complication, the role of bariatric surgery is better established for long-term benefits, also for improving cardiac structure and function [
28]. Such surgical interventions could also be considered for MHO subjects to relieve from symptoms of musculoskeletal and joint pain, or for improving self-esteem and reduce psycho-social stigma.