Bone hormone levels signal heart disease severity in ATTR-CM: Study
Blood levels of FGF23 may complement markers of heart damage
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Higher blood levels of fibroblast growth factor 23 (FGF23) — a bone-derived hormone — are associated with higher levels of established markers of heart damage and more advanced disease in people with transthyretin amyloid cardiomyopathy (ATTR-CM), according to a new study from Austria.
Because FGF23 levels were found to be an independent predictor of ATTR-CM severity, the hormone may complement established markers of heart damage in assessing ATTR-CM prognosis, particularly for confirming advanced disease, the researchers said. Specifically, FGF23 could potentially serve as a biomarker alongside markers such as NT-proBNP and troponin T, the team noted.
“This is the first study to demonstrate a significant association between FGF23 and established markers of cardiac [heart] injury and disease staging in ATTR-CM, supporting FGF23 as a potential complementary biomarker for risk stratification,” the researchers wrote.
The study, “Fibroblast growth factor 23 is associated with cardiac disease severity in transthyretin amyloid cardiomyopathy,” was published in the journal Scientific Reports by a team from the Medical University of Vienna.
In ATTR-CM, toxic clumps of a faulty version of the protein transthyretin (TTR) accumulate mainly in the heart, but can also affect other organs, including the kidneys. The disease may be caused by mutations in the gene that encodes TTR — then called hereditary ATTR-CM — or it can develop with age in the absence of mutations, which is known as wild-type ATTR-CM.
NT-proBNP and troponin-T are established biomarkers of heart damage used for the diagnosis and prognosis of ATTR-CM. However, they usually require additional insights from other biomarkers to assess disease severity and a patient’s risk of adverse events.
Patients divided into groups based on blood levels of bone hormone
FGF23 is emerging as a potential biomarker of cardiovascular diseases, but its role in ATTR-CM is poorly understood, according to scientists.
To fill this knowledge gap, the research team analyzed data from 114 adults, ranging in age from 71 to 86, with a confirmed diagnosis of ATTR-CM. Among them, 103 had the wild-type and 11 had the hereditary form.
The participants, who were recruited at a single Austrian hospital, were divided into three groups according to their blood FCF23 levels: the low-level group (18.5-81.3 picograms [pg]/mL), the intermediate-level group (81.3-103 pg/mL), and the high-level group (103.4 pg/mL or higher).
When comparing blood levels of NT-proBNP and troponin T across these three groups, the team found that levels of both markers increased significantly from the low FGF23 group to the high FGF23 group.
Further statistical analyses confirmed that higher FGF23 levels were significantly associated with higher blood levels of NT-proBNP and troponin T, reflecting greater heart damage.
The researchers then looked at potential links between FGF23 levels and estimated glomerular filtration rate (eGFR), a blood test to measure kidney function, in which higher values indicate better function.
The team found a reduction in eGFR as FGF23 levels increased, per the study.
“This downward trend was statistically significant … indicating that higher FGF23 levels may correlate with impaired renal function in patients with ATTR-CM,” the team wrote.
There was also a positive association between FGF23 levels and the National Amyloidosis Centre (NAC) staging system, commonly used to assess ATTR-CM severity and prognosis based on NT-proBNP and eGFR levels. There are three stages (I, II, and III); the higher the stage, the worse the prognosis.
Specifically, FGF23 levels were lowest in patients classified as NAC stage I, and increased pronouncedly in those with NAC stage II. The levels were high and remained so in those with NAC stage III.
“This pattern indicates that FGF23 levels parallel the severity of functional impairment in ATTR-CM and may serve as a marker of disease progression,” the researchers wrote.
Analysis confirms FGF23 as predictor of heart disease severity
Additional analyses identified FGF23 as an independent predictor of ATTR-CM severity, with elevated blood levels of the protein significantly associated with a greater chance of advanced NAC stage.
Similar associations were seen for NT-proBNP and troponin T in relation to NAC stage, “underscoring the combined predictive value of these biomarkers for staging ATTR-CM severity,” the team wrote.
The clinical utility of biomarkers for distinguishing people with NAC stage I, or early-stage disease, from those with NAC stage III, or advanced disease, was assessed using a statistical method called the area under the curve (AUC). Values range from zero to one, with higher values indicating better discriminative potential.
NT-proBNP demonstrated the highest accuracy for discriminating people with advanced ATTR-CM from those with early-stage disease (AUC of 0.874). Next was troponin T (AUC of 0.825), followed by FGF23 (AUC of 0.727).
At the optimal cutoff value of 114.95 pg/mL, FGF23 levels showed high specificity (89.2%), meaning the biomarker could correctly rule out patients without advanced disease in about 89% of the cases. However, the test’s sensitivity was low, at 47.5%, meaning FGF23 correctly identified fewer than half (48%) of patients with advanced disease.
Tests based on optimal cutoff values of NT-proBNP and troponin T had higher sensitivities (82.5% and 75%, respectively) but lower specificities (77% and 79.7%). This meant that these were better than FGF23 at correctly identifying advanced ATTR-CM patients, but inferior at correctly ruling out patients with early-stage disease and therefore, avoiding false positives.
“While these findings suggest that FGF23 correlates with disease burden …. FGF23 warrants further investigation as a potential adjunct biomarker,” the researchers wrote. Future studies, following patients over a long period, “are needed to determine its added value over NT-proBNP and eGFR alone in the clinical management of [ATTR-CM] patients.”
Caroline Johnson
Very important information. Thank you.
Jane Cline
I am 94 years. My main problem is shortness of breath and neuropathy in my feet and hands.