Review Demonstrates Potential Role of Sarcopenic Obesity in HFpEF

November 4, 2020
Maggie L. Shaw

Sarcopenic obesity is a condition in which obesity is accompanied by loss of muscle mass and function; the condition is common among older adults with heart failure with preserved ejection fraction (HFpEF).

Sarcopenic obesity (SO) is a condition in which obesity is accompanied by loss of muscle mass and function. The condition is common among older adults with heart failure with preserved ejection fraction (HFpEF), as “aging and obesity are hallmarks of HFpEF,” noted the authors of a recent review in Frontiers in Endocrinology.

Close to half of Americans who have heart failure have HFpEF, which is characterized by a left ventricular ejection fraction above 50%. There are no FDA-approved therapies to treat the condition, and it remains “one of the greatest unmet needs in cardiovascular medicine,” the study authors wrote.

They examined the current knowledge surrounding HFpEF-related SO, with the ultimate goal being insight into contributing physiological mechanisms and outcomes, because SO has been linked to worsened outcomes in cardiovascular health, hospitalization, quality of life (QOL), and mortality.

Age, the authors noted, is “the largest risk factor for cardiovascular disease,” so older patients face an increased risk of heart failure. This coupled with a high prevalence of both overweight and obesity among patients with HFpEF, as well as common comorbidities of type 2 diabetes and chronic kidney disease, points to the emergence of obesity as a distinct phenotype of HFpEF.

They also point to potential contributions from inflammation and endocrine changed related to myopenia (or muscle wasting) that when coupled with a sedentary lifestyle are more likely to lead to cardiac diastolic dysfunction. Intertwined with this are data showing increased ventricular filling pressures and abnormal right and left cardiac structure in patients with HFpEF and obesity.

In addition, exercise intolerance, the authors highlight, is “the most commonly reported clinical symptom” of SO, and obesity tied to regional distribution of adipose tissue (or fat) is a central contributing factor to the symptom in individuals with HFpEF. Previous research, they note, also links diastolic dysfunction to limited exercise capacity and a drop in cardiorespiratory fitness (ie, maximal oxygen uptake) to obesity.

Additional factors that delineate the potential role of SO in HFpEF are skeletal muscle mitochondrial dysfunction and its effect on myocyte function and viability, as well as iron deficiency that can lead to lean mass abnormalities.

“SO is prevalent in patients with HFpEF and has noteworthy adverse consequences on end point outcomes, health-related outcomes, and patient-reported QoL,” the authors concluded. “Although the multifaceted pathophysiology of HFpEF-related SO is not yet fully understood, inflammation, oxidative stress, hormonal imbalances, iron deficiency, and sedentary lifestyle appear to contribute to this condition.”

They suggested several areas for future study among individuals living with comorbid HFpEF and SO, “citing an urgent need for lifestyle, pharmaceutical, or nutraceutical approaches”:

  1. Potential role of SO in cardiac dysfunction, as driven by “synergistic crosstalk” between reduced lean mass and excess obesity (or adiposity)
  2. Influence of concomitant sarcopenia and obesity on clinical outcomes
  3. Effects of adipose tissue on skeletal muscle
  4. Sources of excessive reactive species generation, specifically for targeted treatment against oxidative stress
  5. Impact of high-intensity resistance training as it influences body composition
  6. Contributions of nutrition interventions (eg, the Mediterranean and DASH diets) toward lowering sarcopenia
  7. Dietary patterns, protein supplementation, caloric restrictions, and bariatric surgery as therapeutic interventions
  8. Outcomes from combining pharmacological or nutraceutical therapies and exercise training
  9. How obesity and HFpEF affect clinical outcomes
  10. Improving QOL as the primary endpoint

Reference

Kirk DL, Bohmke N, Billingsley HE, Carbone S. Sarcopenic obesity in heart failure with preserved ejection fraction. Front Endocrinol (Lausanne). Published online September 30, 2020. doi:10.3389/fendo.2020.558271