Study identifies 18 proteins associated with heart failure and frailty

Analysis of blood samples from thousands of study participants led by researchers at UT Southwestern Medical Center identified 18 proteins associated with both heart failure and frailty, two common conditions that occur later in life. JAMA Cardiologywhich could lead to new strategies to jointly predict risk, implement preventive approaches, or treat these conditions, which often occur together.

“Our findings support common biological pathways underlying heart failure and frailty and suggest that interventions to prevent or treat one outcome may help reduce the burden of the other,” said study leader Amir Shah, MD, professor of medicine in the departments of cardiology and the Peter O’Donnell Jr. School of Public Health at UT Southwestern.

As the world’s population ages, so too does the prevalence and incidence of heart failure and frailty, diseases that tend to develop after the seventh decade of life. Heart failure is characterised by the heart’s inability to keep up with the body’s demands. Symptoms of frailty are a general decline in physical function, often marked by unintentional weight loss, physical fatigue and reduced physical activity. Up to half of people with heart failure will be frail, and frail people are at increased risk of heart failure.

Inflammation is thought to be involved in both of these multi-organ diseases, but whether heart failure and frailty share molecular pathways was unclear.

To answer this question, Dr. Shah and colleagues from around the country drew on data from the Atherosclerosis Risk in Communities (ARIC) study, a longitudinal study that began in the late 1980s at sites in North Carolina, Mississippi, Minnesota, and Maryland and continues to this day. Initially designed to examine factors influencing atherosclerosis risk in study participants over a series of visits, ARIC has expanded its scope over the past 40 years to include assessments of frailty at the fifth, sixth, and seventh study visits from 2011 to 2019.

The researchers used medical records to search for hospitalizations for heart failure among the 10,630 ARIC participants who had provided blood samples during the study’s early stages. They then compared nearly 5,000 proteins in the blood samples from participants who had experienced heart failure with those who had not, and found 83 proteins that appeared to be associated with heart failure occurring in both middle age and old age.

After searching for proteins in participants who developed frailty later in life (up to the sixth visit), the researchers narrowed the list to 18 proteins that appeared to be associated with both heart failure and frailty. The same 18 proteins were also associated with both diseases among 3,189 participants in a separate study, the Cardiovascular Health Study.

Not surprisingly, some of these proteins have known roles in inflammation, but others appear to be involved in fibrosis (tissue thickening and scarring), lipid metabolism, and cell death. A separate genetic analysis suggested that five of the proteins may be responsible for both conditions.

Shah said future studies will build on these findings by looking more closely at the mechanisms by which these proteins contribute to or cause heart failure and frailty. Understanding more about the 18 proteins may ultimately enable researchers to develop drugs to prevent or treat both conditions simultaneously, he added.

Other UTSW researchers who contributed to the study include lead author Diego Ramonfaur, MD, MS, MPH, research associate, and Victoria Lamberson, PhD, data scientist II.