The number of people with obesity — having excessive fat deposits and a body mass index (BMI) greater than 30 — continues to increase around the world. Now, more than 16% of all adults worldwide are living with the condition. In the United States, the National Institutes of Health reports that 42.4% (2 in 5) of all adults have obesity.
Heart failure — where the heart does not circulate blood efficiently — is more common in people with obesity than those of a healthy weight. One study found that obesity doubled the risk of heart failure; another that obesity is a factor that causes both heart failure and death from heart failure.
Heart failure with preserved ejection fraction (HFpEF) — a condition where the heart pumps normally, but does not fill properly because the heart muscle stiffens — accounts for around half of all cases of heart failure, and is more common in people with obesity than other types of heart failure.
Now, a study has found that losing weight can help reverse the effects of HFpEF and improve the contraction ability of heart muscle cells.
In the study, published in Science, researchers found that in people with severe obesity and HFpEF, those who lost more than 2kg/m2 of BMI with GLP-1 agonist treatment saw improvements in heart muscle contraction.
The researchers analyzed heart muscle cells (myocytes) taken by biopsy from 80 patients with obesity and HFpEF. They divided them into 2 groups — group 1 was cells from patients with a lower BMI (30 people), and group 2 was those from patients with more severe obesity (50 people).
As well as having substantially higher BMIs, people in group 2 had a greater incidence of other co-morbidities, including insulin resistance and sleep apnea.
Heart muscle cells from patients with HFpEF and severe obesity had a greatly reduced ability to increase force, which affects the ability of the muscle to contract. Cells from those with less severe obesity and HFpEF, and those without heart failure were more able to increase force.
The researchers found that cells from those with HFpEF and severe obesity showed similar changes to cells from people in end-stage heart failure, who were awaiting heart transplants.
The key change researchers discovered was in a protein, troponin-I, that is vital for contraction and relaxation of muscle in people with severe obesity and HFpEF. People who were more obese had greater phosphorylation of troponin-I, which the researchers showed weakened the force of the muscle cells.
David Kass, MD, the Abraham and Virginia Weiss Professor of Cardiology at the Johns Hopkins University School of Medicine, and corresponding author on the study, said that no drugs that might reverse this change had yet been approved by the FDA:
“There have been some efforts along this line, and some drugs worked quite well in cells — even human heart HFpEF cells — but failed in clinical testing where the drug appeared to have no effects at all. More work is needed, both academic and from industry around finding such drugs,” he told Medical News Today.
So why does obesity increase risk of heart failure, particularly HFpEF? Naveed Sattar, Professor of Cardiometabolic Medicine at the University of Glasgow, UK, explained to MNT:
“Obesity impacts blood volume, blood pressure, and so the pressures the heart has to work against. It also impacts how much tissue needs to be perfused [provided with blood] and it impacts kidney and inflammation pathways and some aspects of heart function in the left atrium, so that all the collective effects of obesity can lead to signs and symptoms of heart failure even if the main pump — the left ventricle — remains in good order in HFpEF.”
Kass explained how the prevalence of HFpEF has changed:
“When HFpEF was mostly found in older individuals who had poorly controlled chronic high blood pressures and ventricular hypertrophy that formed in response to this, obesity was much less common. Over the past 20 years, we have treated these comorbidities better, while obesity and severe obesity are increasing in prevalence substantially.”
But he reassured that, although the epidemiological association between severe obesity and HFpEF is well established, only around 5% of people with severe obesity in the United States have HFpEF.
Heart function is not the only thing affected by obesity. A study presented last week at the American Physiology Summit in Minneapolis highlighted that, in older adults, obesity adversely affects lung function. The results of the study have yet to be published in a peer-reviewed scientific journal.
In their study, researchers reported that not only did those with obesity have significantly lower lung capacity, which limits the amount of air that can be inhaled, but they also were unable to fully empty their lungs when exhaling. These issues can cause chronic shortness of breath, wheezing and inefficient breathing, symptoms that are also seen in people with HFpEF.
In the heart study, a subset of 16 patients, with a mean BMI of 39, undertook a 1.5 year course of weight-loss therapy, using GLP-1 receptor agonists (GLP-1RAs), injectable treatments used to treat both obesity and type 2 diabetes.
Their muscle cells regained contraction abilities and, in those who lost 10% or more of their body weight, their cells recovered to almost normal peak muscle cell force.
Kass suggested why this might have happened: “One possibility [is] that the change in the muscle protein — troponin I — that we highlight in [our study], that increased in tandem with BMI in the HFpEF patients, was reversed in those that lost weight.”
“We also show that in HFpEF patients, the capacity of of the heart muscle to contract to calcium declined in direct relation to the BMI increase; so we are in a way then reversing that same association — lower BMI [led to] greater calcium-tension response,” he added.
However, he cautioned that: “Much still needs to be done to confirm the exact biological changes that occur with the GLP1-RA treatments that are involved.”
Cheng-Han Chen, MD, board certified interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, CA, concurred:
“Recent research does suggest that GLP-1 receptor agonists may have direct effects on the health and function of heart muscle cells. However, more research is necessary to determine whether these direct effects are responsible for the beneficial effects of GLP-1 RAs, rather than their effects on weight loss.”
“It’s become clear that large scale weight loss is already something many heart failure experts wish for their patients living with obesity with HFpEF, given such meaningful symptom and functional benefits, never mind the potentially many other comorbidity benefits. We now view obesity as a major target in HFpEF management.”
— Prof. Naveed Sattar
