Management of Obesity in Cardiovascular Practice: JACC Focus Seminar

Abstract

Obesity contributes to reduced life expectancy because of its link with type 2 diabetes and cardiovascular disease. Yet, targeting this poorly diagnosed, ill-defined, and underaddressed modifiable risk factor remains a challenge. In this review, we emphasize that the tendency among health care professionals to amalgam all forms of obesity altogether as a single entity may contribute to such difficulties and discrepancies. Obesity is a heterogeneous condition both in terms of causes and health consequences. Attention should be given to 2 prevalent subgroups of individuals: 1) patients who are overweight or moderately obese with excess visceral adipose tissue; and 2) patients with severe obesity, the latter group having distinct additional health issues related to their large body fat mass. The challenge of tackling high-cardiovascular-risk forms of obesity through a combination of personalized clinical approaches and population-based solutions is compounded by the current obesogenic environment and economy.

Keywords: cardiovascular disease; ectopic fat deposition; massive obesity; type 2 diabetes; visceral obesity.

Conflict of interest statement

Funding Support and Author Disclosures Dr Després is the Scientific Director of the International Chair on Cardiometabolic Risk supported by the Fondation de l’Université Laval. Research from Dr Després discussed in this paper has been and is currently supported by the Canadian Institutes of Health Research (Foundation grant: FDN-167278) as well as by the Fondation of the Québec Heart and Lung Institute. Dr Carpentier holds the Canada Research Chair in Molecular Imaging of Diabetes; and has received funding for consulting from Eli Lilly, HLS Therapeutics, Janssen, Novartis Pharmaceuticals Canada, and Novo Nordisk Canada. Dr Tchernof has received research funding from Johnson & Johnson Medical Companies, Medtronic, and Bodynov for studies unrelated to this work; and has received consulting fees from Bausch Health and Novo Nordisk. Dr Neeland has received a grant from National Institutes of Health/NIDDK (K23 DK106520); has received speaking and consultancy fees from Boehringer Ingelheim, Merck, and AMRA Medical; and has received a grant from Novo Nordisk. Dr Poirier has received honoraria for CME/consultant/expert events from Abbott, Amgen, AstraZeneca, Bayer, Bausch Health, Boehringer Ingelheim, Eli Lilly, HLS Therapeutics, Janssen, Merck, Novartis, Novo Nordisk, Sanofi, and Servier.

Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1:. Sedentary 49-year-old Man with Visceral Obesity.

Despite being nonobese, this individual developed coronary heart disease. BMI: body mass index

Figure 2:. Sedentary 41-year-old Woman with Severe Obesity.

This patient has symptoms of heart failure. BMI: body mass index

Figure 3:. Prevalence of Obesity in the U.S. in 2011 and 2019.

Data are derived from the Behavioral Risk Factor Surveillance System which used reported weight and height. Obesity is defined by a body mass index of ≥30 kg/m2. From reference .

Figure 4:. Cardiovascular and Systemic Effects of Obesities.

In addition to cardiovascular outcomes, high-risk forms of obesities are associated with various combinations of abnormalities causing prejudice to patients’ health and quality of life. ***Commonly seen with severe obesity COVID-19: coronavirus disease 2019, HDL: high-density lipoprotein, HFpEF: heart failure with preserved ejection fraction, HFrEF: heart failure with reduced ejection fraction, LDL: low-density lipoprotein

Figure 5:. Management of Obesities throughout the Spectrum of Disease Progression.

Lifestyle changes are recommended in all obesities. Medical treatment of cardiovascular disease (CVD) risk factors is also indicated, except perhaps in very advanced renal and/or heart failure where statin therapy is not recommended. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are indicated in patients with type 2 diabetes (T2D) in the presence of CVD in all obesities. SGLT2 inhibitors are also indicated in patients with heart and/or kidney failure. Glucagon-like protein-1 receptor agonists (GLP1-RA) are indicated in patients with T2D with CVD. Liraglutide is indicated for treatment of obesity. Weight loss drugs/bariatric surgery should be considered in high-risk patients with severe obesity.

Figure 6:. Weight Loss Induced by SGLT2 Inhibitors and GLP1-RA and MACE/Mortality.

Relationship between reported difference in average body weight loss (BWL, in kg) between the active treatment vs. placebo and relative risk reduction (RRR) of 3-point major adverse cardiovascular events (MACE) (left panel) or total mortality (right panel) from major adverse cardiovascular outcome trials with sodium-glucose cotransporter 2 (SGLT2) inhibitors or glucagon-like peptide-1 receptor agonists (GLP1-RA) in patients with type 2 diabetes (T2D). CKD: chronic kidney disease; CVD: cardiovascular disease; HF: heart failure. * Difference in average weight loss estimated from data reported in a graph. † P <0.05 between the active vs. placebo treatment groups.

Figure 7:. Steps in the Clinical Management of Obesities.

Initial assessment of the form of obesity (visceral vs. severe) is key in the determination of the therapeutic approach. Whereas lifestyle changes inducing limited weight loss could nevertheless positively impact ectopic fat and related cardiometabolic risk in patients with visceral obesity, more severe forms of obesity may require additional diagnostic tools and management approaches as a function of disease progression. LVH: left ventricular hypertrophy; MRI: magnetic resonance imaging.

Figure 8:. Clinical Approaches and Public Health Solutions to tackle Obesities.

As high-risk forms of obesity result from the complex interactions of biological, behavioral, psycho-social and environmental factors, the current obesity epidemic will not be curbed until an integrated set of population-based solutions and clinical approaches are put in place, going beyond body weight/weight loss as the single assessment/management outcome. AT: adipose tissue, CVD: cardiovascular disease; PA: physical activity.

Central Illustration:. Key Factors Involved in Visceral Obesity and Related Cardiometabolic Risk.

Subcutaneous adipose tissue plays an important role in the storage of excess calories resulting from a positive energy imbalance. When facing caloric surplus, functional subcutaneous adipose tissue expands to allow the storage of excess energy, a process that also limits accumulation of fat in intra-abdominal adipose depots (visceral adipose tissue). In the presence of dysfunctional subcutaneous adipose tissue, the resulting lipid spillover must then be stored in visceral adipose tissue as well as in normally lean tissues (heart, liver, skeletal muscle, kidney, pancreas), a process referred to as ectopic fat deposition.