(Commonwealth Union)_ Heart failure is a complex clinical syndrome characterised by the inability of the heart to pump blood effectively, resulting in inadequate blood flow to meet the body’s metabolic demands. This condition affects millions of people worldwide and is associated with significant morbidity and mortality. The pathophysiology of heart failure is multifactorial, involving genetic, hemodynamic, neurohormonal and metabolic factors. Proteins play a crucial role in the development and progression of heart failure, with various proteins involved in different aspects of the disease.
Proteins play a significant role in living organisms and in recent years scientists have used more advanced techniques to delve into further details of the various types of proteins and their effect on certain activities. Researchers at UT Southwestern Medical Center conducted an analysis of blood samples from thousands of participants, uncovering 18 proteins linked to heart failure frailty, a condition frequently arising in older age. Their study, published in JAMA Cardiology, could pave the way for new methods to simultaneously predict risk, implement preventive measures, or treat these co-occurring conditions.
“Our findings support shared biological pathways underlying both heart failure and frailty, suggesting interventions to prevent or treat one outcome may help decrease the burden of the other,” explained the study leader Amil Shah, M.D., M.P.H., Professor of Internal Medicine in the Division of Cardiology and in the Peter O’Donnell Jr. School of Public Health at UT Southwestern.
As the global population continues to age, the occurrence and rate of heart failure and frailty are also on the rise, particularly in individuals in their 70s and older. Heart failure is defined by the heart’s inability to meet the body’s demands, while frailty manifests as a general decline in physical function, often marked by unintended weight loss, persistent fatigue and reduced physical activity. Up to 50% of individuals with heart failure may experience frailty and those who are frail face a higher likelihood of developing heart failure.
While inflammation has been linked to both of these complex disorders, it has remained unclear whether heart failure and frailty share common molecular pathways.
To investigate this, Dr. Shah and his colleagues utilized data from the Atherosclerosis Risk in Communities (ARIC) study, an ongoing longitudinal research project that began in the late 1980s across locations in North Carolina, Mississippi, Minnesota and Maryland. Initially aimed at examining factors affecting atherosclerosis risk in participants over multiple visits, ARIC has broadened its focus over the past 40 years to include assessments of frailty during study visits five, six, and seven from 2011 to 2019.
The researchers utilized medical records to identify hospitalisations due to heart failure among 10,630 ARIC participants who had previously provided blood samples. They analyzed and contrasted nearly 5,000 proteins in the blood samples of those who had heart failure with those who did not, identifying 83 proteins linked to heart failure occurring in both middle and later life. When they examined proteins in participants who developed frailty later in life (by the sixth visit), they reduced the list to 18 proteins that appeared associated with both heart failure and frailty. These same 18 proteins were also found to be linked to both conditions in 3,189 participants of another study, the Cardiovascular Health Study.
Researchers pointed out that unsurprisingly, many of these proteins are known to play roles in inflammation. However, some are also involved in fibrosis (the thickening and scarring of tissue), lipid metabolism and cell death. A separate genetic analysis indicated that five of these proteins might be causative factors for both conditions.
Dr. Shah stated that future research will expand on these findings by investigating the mechanisms through which the proteins may either contribute to or result from heart failure frailty. A deeper understanding of these 18 proteins could eventually enable researchers to develop drugs that simultaneously prevent or treat both conditions. The proteins may play a key role to prevent or treat heart failure frailty. The biological pathways of these may also prove crucial.
Other UTSW contributors to this study included first author Diego Ramonfaur, M.D., M.Sc., M.P.H., Research Associate, and Victoria Lamberson, Ph.D., Data Scientist II.
