Overweight is defined as a body mass index (BMI) of ≥25kg/m², while obesity is defined as a BMI ≥30 kg/m². Obesity is associated with the development of heart failure (HF), coronary heart disease, sudden cardiac death, and atrial fibrillation (AFib).^2,3,4

How does obesity affect the CV system?

Obesity accelerates the onset of CVD, leading to a shorter lifespan and increased lifetime CVD burden compared to individuals with normal weight. It harms the CV system both directly and indirectly, influencing risk factors and sleep disorders linked to obesity.^4p1,5p2

The impact of obesity on the CV system is multifaceted. Excessive adipose tissue functions as an endocrine organ, releasing adipokines like leptin and interleukin 6, which regulate energy balance and insulin sensitivity.⁴

However, overproduction of adipokines in obesity creates an imbalance, fostering insulin resistance, metabolic syndrome, and inflammation, evidenced by high C-reactive protein levels.⁴

This inflammation contributes to endothelial damage, vascular hypertrophy, and increased CVD risk. Additionally, obesity leads to left ventricular hypertrophy (LVH) due to increased plasma renin, aldosterone activity, and insulin levels. The resulting left ventricular dilation and eccentric LVH increase the risk of HF, AFib, and ventricular arrhythmias.⁴

To reduce the impact of obesity-associated CVD risk, international obesity management guidelines universally recommend multicomponent lifestyle interventions, including diet, physical activity, and behaviour change support for six to 12 months.⁶

While lifestyle modifications remain the primary treatment for obesity, anti-obesity medications (AOMs) offer supplemental options. Pharmacotherapy is recommended for individuals with a BMI of ≥30 kg/m² or ≥27 kg/m² with at least one weight-related comorbidity, such as CVD, type 2 diabetes (T2DM), hypertension, or dyslipidaemia. It is also suitable for those who cannot achieve significant weight loss through lifestyle changes alone.⁷

Do AOMs increase the risk of CVD?

Over the past 20 years, numerous anti-obesity medications (AOMs) have been withdrawn due to CV safety concerns. Phentermine, approved in 1959, however has been associated with a reduction in low-density lipoprotein (LDL) cholesterol and an increase in high-density lipoprotein (HDL)^8p6,8p12 cholesterol and remains widely used worldwide.⁸

In South Africa, a 2016 study revealed that phentermine was the most prescribed AOM, accounting for 92.44% of prescriptions, followed by orlistat, phendimetrazine, D-norpseudoephedrine, and diethylpropion.⁹

In South Africa, phentermine is approved as a short-term adjunct to a comprehensive weight reduction programme that includes exercise, dietary changes, and behaviour modification for obese patients with a BMI of ≥30kg/m² who have not achieved satisfactory results with lifestyle changes alone. It may also be prescribed to those with a lower BMI if other risk factors are present.¹⁰

For adults with a BMI ≥35 kg/m² who have failed non-surgical methods, bariatric surgery may be an option. Guidelines also advocate for managing obesity as a chronic disease with multidisciplinary teams.⁶

Phentermine is contraindicated in patients with pulmonary artery hypertension, arterial hypertension, cerebrovascular disease, cardiac disease including arrhythmias, and advanced arteriosclerosis. It is also contraindicated in individuals with known hypersensitivity to phentermine or sympathomimetic drugs, hyperthyroidism, agitated states, or a history of psychiatric disorders, including anorexia nervosa and depression.¹⁰

Additionally, it should not be used by those with glaucoma, a history of drug or alcohol abuse or dependence, obstructive uropathy, poorly controlled epilepsy, or those undergoing concomitant treatment with monoamine oxidase inhibitors or within 14 days following their administration.¹⁰

How does weight-loss benefit CV health?

Weight loss offers significant benefits across various health parameters, particularly in managing CVD, T2DM, hypertension, cholesterol levels, glycaemic control, and insulin resistance.¹¹

Weight loss interventions have shown a promising impact on reducing the incidence of CVD. Studies indicate a mean weight reduction of about 2.2kg, with evidence suggesting that weight loss can lead to a lower incidence of CVD over time.¹¹

At one year, the predicted reduction in CVD incidence is ~20.2 per 1000 person-months, increasing to 39.3 per 1000 person-months at five years. This benefit is sustained despite some weight regain.¹¹

Weight loss interventions are associated with lower incidence rates of T2DM. The mean weight difference of 4.1kg between intervention and control groups leads to a reduction in diabetes incidence. Over time, this advantage persists, with a predicted lower incidence of ~62 per 1000 person-months one year after weight loss, maintaining a similar reduction at five years.¹¹

While data on hypertension incidence is limited, evidence suggests that weight loss can reduce hypertension rates. The reduction in hypertension incidence is about 67 per 1000 person-months, and although data on long-term remission is sparse, weight loss is beneficial.¹¹

Weight loss results in improvements in cholesterol levels. The average reduction in total cholesterol/HDL ratio is about 1.2. The benefit is sustained over five years, with weight regain impacting this advantage minimally.¹¹

Weight loss improves glycaemic control, with reductions in HbA1c levels. The modeled estimate suggests a decrease in glycemic control by ~0.26 units at one- and five-years post weight-loss. Weight-loss also decreases insulin resistance. The reduction in insulin resistance is notable, with a sustained benefit over three years.¹¹

Cardiology is entering a new era in the fight against obesity

According to Sattar et al, cardiology is entering a new era in the fight against obesity. With many patients at risk of or living with CVD also struggling with overweight and obesity, and often facing multiple weight-related comorbidities, evidence-based weight loss treatments that address major adverse CV events and other weight-related outcomes hold transformative potential.¹²

This should encourage cardiologists to integrate weight-related interventions earlier in the disease course, aiming to prevent or delay the onset of adverse CVD and enhance patients’ quality of life.¹²

If obesity is not managed effectively, rates of multimorbidity, stroke, and HF could rise, potentially undoing the progress made over the past few decades. It is imperative for the cardiology community to collaborate with other medical fields to address the public health challenge of obesity and reduce both CV and non-CV complications associated with excess adiposity in this new era.¹²

References

1. World Health Organization. World Obesity Day 2022 – Accelerating action to stop obesity. Updated 2022. [Internet]. Available from: https://www.who.int/news/item/04-03-2022-world-obesity-day-2022-accelerating-action-to-stop-obesity#:~:text=More%20than%201%20billion%20people,they%20are%20overweight%20or%20obese
2. Boachie M. Obesity costs South Africa billions. We did the sums. 2022. [Internet]. Available from: https://www.wits.ac.za/news/latest-news/opinion/2022/2022-09/obesity-costs-south-africa-billions-we-did-the-sums.html
3. Goetjes E, Pavlova M, Hongoro C, Groot W. Socioeconomic Inequalities and Obesity in South Africa-A Decomposition Analysis. Int J Environ Res Public Health, 2021.
4. Ashraf MJ, Baweja P. Obesity: the 'huge' problem in cardiovascular diseases. Mo Med, 2013.
5. Khan SS, Ning H, Wilkins JT, et al. Association of Body Mass Index With Lifetime Risk of Cardiovascular Disease and Compression of Morbidity. JAMA Cardiol, 2018.
6. Gaskin CJ, Cooper K, Stephens LD, et al. Clinical practice guidelines for the management of overweight and obesity published internationally: A scoping review. Obes Rev, 2024.
7. Alobaida M, Alrumayh A, Oguntade AS, et al. Cardiovascular Safety and Superiority of Anti-Obesity Medications. Diabetes Metab Syndr Obes, 2021.
8. Bramante CT, Raatz S, Bomberg EM, et al. Cardiovascular Risks and Benefits of Medications Used for Weight Loss. Front Endocrinology, 2020.
9. Trutera I. Dispensing patterns of prescription-only anti-obesity preparations in South Africa Ilse Trutera. South African Journal of Clinical Nutrition, 2016.
10. Professional Information. Duromine. Updated 2020. [Internet]. Available at: https://inovapharma.co.za/wp-content/uploads/2022/01/Duromine-PI.pdf
11. Hartmann-Boyce J, Theodoulou A, Oke JL, et al. Long-Term Effect of Weight Regain Following Behavioral Weight Management Programs on Cardiometabolic Disease Incidence and Risk: Systematic Review and Meta-Analysis. Circulation, 2023. 
12. Sattar N, Neeland J, McGuire DK. Obesity and Cardiovascular Disease: A New Dawn. Circulation, 2024.