Atrial fibrillation (AF) remains one of the commonest causes of arrhythmia or disturbance of the heart rhythm. It affects around 1.6 million people in the United Kingdom and is often the underlying cause for a stroke. According to the British Heart Foundation, this is an important study as it can help detect AF early and predict the risk of stroke in thousands of individuals. People with atrial fibrillation are much more likely to develop blood clots and suffer from strokes. To avoid strokes it is important for them to take anticoagulant drugs to prevent blood clotting. However, atrial fibrillation is often only diagnosed after a patient has suffered a stroke. Therefore it is important that patients at risk are screened so that they can begin taking anticoagulants to prevent potentially life-threatening complications. At present EKG remains the only method to detect AF. Blood biomarkers have the potential to support community screening programs for AF.
Several candidate biomarkers for detection of AF have been proposed, such as N-terminal pro-hormone of brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) reflecting atrial strain, C-reactive protein reflecting inflammation, galectin-3 correlating with cardiac fibrosis, or cystatin or glomerular filtration rate as a marker of chronic kidney disease. Brain natriuretic peptide, the best-studied marker, is similarly elevated both in patients with prevalent AF and in cohorts analysed for incident AF. So far, most analyses identifying biomarkers in patients with AF have been hypothesis-driven and involved measurement of a single or a small selection of blood biomarkers. These markers also compete with other cardiovascular markers related to prognosis or diagnosis of other cardiac conditions (e.g. heart failure and coronary events) or death.
According to the researchers at the University of Birmingham, there are three clinical risk factors and two biomarkers that have an association with AF. The team looked at 638 hospital patients between 2014 and 2016. The blood samples from these patients were analyzed for 40 cardiovascular biomarkers and the patients were assessed for seven clinical risk factors: age, sex, hypertension, heart failure, history of stroke or TIA, kidney function and body mass index (BMI). All participants underwent an ECG. They pinpointed that older, males with a high Body Mass Index or BMI were at the greatest risk of strokes. Of all the biomarkers, two seemed most relevant for strokes. These were brain natriuretic peptide (BNP) and fibroblast growth factor-23 (FGF-23). BNP is a hormone that is secreted by the heart and FGF-23 is a protein that takes part in phosphate regulation.
If the levels of these markers are elevated, a person can be considered to be at risk. According to lead author of the study, the biomarkers they have identified have the potential to be used in a blood test in community settings such as in GP practices to simplify patient selection for EKG screening. Therefore, a simple assessment of age, sex, BMI, BNP and FGF-23 can identify patients with AF, for example to enrich populations undergoing ECG screening. Brain natriuretic peptide and FGF-23 may also be useful to stratify patients with AF. Professor Metin Avkiran, associate medical director at the BHF, stated: “Atrial fibrillation increases the risk of stroke, a serious condition that causes over 36,000 deaths in the UK each year, but is often detected too late. This research has used sophisticated statistical and machine learning methods to analyse patient data and provides encouraging evidence that a combination of easy-to-measure indices may be used to predict atrial fibrillation.
Three simple clinical risk factors (age, sex, and BMI) and two biomarkers (BNP and FGF-23) may identify patients with AF. FGF-23 is a phosphate and calcium-regulating hormone primarily secreted by osteocytes and osteoblasts. As FGF-23 promotes myocardial remodelling and cardiac hypertrophy, it can cause or enhance hypertrophy-related ectopic activity and automaticity, leading to AF. FGF-23 is also associated with endothelial dysfunction. It is possible that all of the mechanisms discussed contribute in some part to the development of AF in patients with elevated FGF-23. The study may pave the way towards better detection of people with AF and their targeted treatment with blood-thinning medicines for the prevention of stroke and its devastating consequences. Further research from the team is warranted to elucidate FGF-23 dependent mechanisms of atrial fibrillation.
- edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Chua W, Purmah Y et al. Eur Heart J. 2019 Jan 7.
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Lind L, Sundström J et al. Heart 2017; 103(5):377.
Pello AM et al. J Cardiol. 2015; 66(1):22-27.
Seiler S et al. Eur Heart J. 2011; 32(21):2688.
Dott. Gianfrancesco Cormaci
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