Obesity is an independent risk factor for heart failure, said Dr. Carolyn Lam during the opening presentation of the European Society of Cardiology (ESC) 2024 Congress.
Lam, a professor, at SingHealth Duke-NUS Cardiovascular Sciences Academic Clinical Programme, was one of several experts speaking at a session on obesity in heart failure on the first day of ESC Congress, which is taking place in London between the 30th of August and 2 September.
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“A link between obesity and heart failure has been established and it is stronger in comparison to the link of obesity to other cardiovascular diseases,” Lam added. She highlighted that obesity is more strongly related to the risk of heart failure with preserved ejection fraction (HFpEF) than heart failure with reduced ejection fraction (HFrEF). Additionally, increased visceral adiposity is associated with a higher risk of heart failure. During her presentation, she mentioned that “this association between increasing adiposity and HFpEF is stronger in women as opposed to men”.
In her speech, Lam also explained the obesity paradox; although obesity is a risk factor for developing this condition, in patients who already have heart failure, a high body mass index (BMI) protects them from worse outcomes. However, that is not the case when considering central adiposity and not BMI. If central adiposity is measured by waist circumference, an increase in fat distribution around the abdomen correlates with a higher risk of hospitalisation due to heart failure.
In the Phase III PARAGON-HF trial (NCT01920711) data, which Lam presented, almost half of the patients with HFpEF were obese with a BMI > 30kg/m2, while almost all (96%) of patients in the trial had central adiposity by waist-to-height ratio (WHR> or = 0.5).
The next speaker, Dr. Mikhail Kosiborod, cardiologist at Saint Luke’s Mid America Heart Institute, emphasised the importance of understanding the systemic and local effects of obesity on heart failure and the need for further studies to comprehend the relationship between visceral adiposity and heart failure. Specifically, Kosiborod focused on different treatment strategies, such as lifestyle interventions, bariatric surgery and medications for the prevention of obesity to reduce the risk of heart failure and relevant clinical trial results.
Referencing the Look AHEAD trial results, he stated that “as the amount of adiposity goes down, the risk of heart failure is decreased as well”. However, even if lifestyle interventions lead to weight loss, this impact did not result in a reduction of the cumulative incidence of heart failure risk in long-term, randomised controlled studies.
In comparison, observational data looking at bariatric surgery as a treatment strategy is very compelling, suggesting a 62% reduction in the incidence of heart failure in this patient population. Still, there is a bias due to the observational nature of this data and a need to fill in the gap of randomised clinical trial data looking at the effects of bariatric surgery in heart failure.
Kosiborod also referenced the recently published results of the Phase III SELECT trial (NCT03574597), in which incretins appeared to be a promising medication for heart failure prevention. In that study, semaglutide consistently reduced the composite heart failure events and cardiovascular death— the trial’s primary endpoint—and showed benefits in both participants with and without heart failure, which Kosiborod highlighted could be a heart failure prevention signal. At the end of his presentation, Kosiborod, mentioned the newly-published Phase III FLOW trial (NCT03819153) results that were presented at the conference earlier today (30 August). In the study, patients treated with semaglutide also saw a reduction in the risk of combined heart failure events or cardiovascular death over a median follow-up period of 40 months.
STEP HFpEF trial results
Dr. Mark Petrie, professor/Honorary Consultant (Cardiovascular & Metabolic Health), at University of Glasgow, presented the results of the STEP HFpEF trial in which semaglutide showed major benefits in health status and weight loss as well as a reduction in CRP, inflammation and heart failure events. Petrie noted that the STEP-HFpEF trial is “the springboard for large randomised controlled clinical trials in heart failure”.
He added that the STEP-HFpEF study represents a major milestone because weight loss was previously thought to lead to worse outcomes in heart failure and glucagon-like receptor agonists (GLP-1RAs) that increase heart rate were considered dangerous for such patients. Lastly, in his closing statements, Petrie mentioned the unpublished SUMMIT trial results which looked at the effect of tirzepatide in 731 patients with HFpEF. The trial’s primary outcomes of cardiovascular death, oral diuretic intensification or heart failure event and Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) were positive and secondary endpoints such as 6-minute walk, CRP levels and body weight were improved.
Overall, all speakers underlined the importance of understanding the systemic and local effects of obesity to develop effective interventions for heart failure and emphasised the gap in data from large, sophisticated, randomised clinical trials in the indication.
However, based on available clinical trial data, the experts’ consensus was that treating obesity might be key for the prevention of heart failure and obesity medications such as incretins may be valuable tools for that.
