Blood biomarkers and atrial remodeling in patients at risk of atrial fibrillation

Two very different groups of people share a quiet vulnerability to the same heart rhythm disorder. Endurance athletes whose hearts have spent years adapting to relentless volume loads, and patients with arterial hypertension whose atria have been stretched by chronic pressure overload, both develop structural changes in the left atrium that can set the stage for atrial fibrillation. A new cross-sectional study published in Frontiers in Molecular Medicine has now mapped how a comprehensive panel of blood biomarkers relates to the imaging signatures of atrial remodeling in these two populations, and the results point to galectin-3 as a potential molecular companion to the echocardiographic assessment of atrial health in hypertensive patients.

The research team, led by investigators from Hospital Clinic de Barcelona, Klinicki bolnicki centar Zagreb, IDIBAPS and ICREA, analyzed 511 subjects: 286 endurance athletes training more than three hours per week for at least five years, and 225 patients with established systemic arterial hypertension treated with at least one antihypertensive drug for at least three years. Each participant underwent a detailed cardiovascular risk assessment, followed by two-dimensional and three-dimensional echocardiography with speckle-tracking strain analysis, and a peripheral venous blood sample drawn during the same clinical visit. The imaging protocol followed society recommendations for chamber quantification, and three-dimensional left atrial volumes were analyzed in 84 percent of the cohort using dedicated quantification software.

The biomarker panel was deliberately broad, spanning three biological domains relevant to atrial pathology. Markers of myocardial damage included brain natriuretic peptide, troponin I, oncostatin M, heart-type fatty acid-binding protein and placenta growth factor. Vascular endothelial dysfunction was assessed through endothelial cell-specific molecule 1, also known as endocan-1. Fibrosis was probed with matrix metalloproteinases 1, 2 and 9, the chemokines CXCL6 and CXCL16, and galectin-3, a beta-galactoside-binding lectin that mediates profibrotic pathways. The investigators then fitted univariable and multivariable linear regression models, using stepwise backward selection, to determine which patient characteristics and echocardiographic measures of left ventricular and left atrial size and function predicted each biomarker level.

The first striking finding concerns what did not differ between the groups. Markers of myocardial damage, including BNP and troponin I, occupied a narrow range of values in this relatively healthy cohort, reflecting the low prevalence of heart failure and acute myocardial injury among the participants. Oncostatin M and heart-type fatty acid-binding protein showed wider distributions but no statistically significant difference between athletes and hypertensive patients. Placenta growth factor, although similarly narrow in range, was significantly lower in athletes than in hypertensive patients, while endocan-1, the endothelial dysfunction marker, was significantly higher in the athlete group.

In contrast, the fibrosis biomarkers told a more consistent story. CXCL6, CXCL16, MMP-1, MMP-9 and galectin-3 were all uniformly elevated in the hypertensive cohort compared with the endurance athletes. Median galectin-3 levels, for instance, stood at 7.5 nanograms per milliliter in hypertensive patients versus 6.8 in athletes, a statistically significant difference. Median MMP-9 concentrations were also markedly higher in the hypertension group. These elevations align with the known biology of pressure-overload atrial remodeling, in which chronic stretch activates fibroblasts and drives extracellular matrix turnover in the atrial wall.

The regression analysis revealed that biomarker levels are far from pure readouts of atrial pathology. Age, gender, body mass index, body surface area and renal function all exerted significant influence on circulating concentrations. Only heart-type fatty acid-binding protein showed a weak correlation with impaired renal function, and the estimated glomerular filtration rate, although statistically lower in hypertensive patients, was not clinically different between groups. The authors caution that biomarker levels are shaped by renal clearance, hepatic metabolism, inflammation and other systemic factors unrelated to atrial remodeling, which complicates any direct comparison between patient groups.

Within the hypertensive cohort, several specific associations emerged. Dyslipidemia predicted BNP and troponin levels. Oncostatin M related to smoking status, left ventricular dimensions and left atrial active emptying fraction. Placenta growth factor associated with body mass index. MMP-1 levels were predicted by body surface area, left ventricular longitudinal function and left atrial active emptying fraction, while MMP-9 related to blood pressure, body surface area and left atrial contractile function. CXCL6 associated with gender and left atrial maximal volume. Notably, patients on ACE inhibitors showed slightly lower CXCL16 levels, whereas biomarker levels did not differ based on angiotensin II receptor blocker use.

In the athlete cohort, the picture was different. Troponin levels related to left ventricular ejection fraction, average mitral annular velocity and left atrial active emptying fraction. Placenta growth factor associated with left ventricular mass index and left atrial active emptying fraction. MMP-2 levels were predicted by weekly training volume measured in metabolic equivalent minutes. Endocan-1 related to body mass index, basal septal thickness and left atrial maximal volume. Galectin-3, in athletes, associated only with body mass index rather than any atrial functional measure.

The headline result concerns galectin-3 in hypertension. In the multivariable regression model, galectin-3 was independently associated with left atrial reservoir strain, with a Pearson correlation of minus 0.286 and a standardized beta of minus 0.254 at a p-value of 0.007. Crucially, this association was not confounded by patient characteristics such as gender, body mass index or body surface area that would otherwise complicate interpretation. Left atrial reservoir strain, measured by speckle-tracking echocardiography, captures the atrium’s ability to expand during ventricular systole and is considered a sensitive marker of atrial cardiopathy. The finding suggests that in hypertensive patients, circulating galectin-3 may serve as a molecular counterpart to this imaging parameter.

The authors are careful about the limits of their work. Fibrosis biomarkers are not cardiac-specific but reflect systemic collagen turnover, and because the left atrium has relatively low tissue mass, even significant atrial fibrosis may only marginally affect total circulating concentrations. Larger organs such as the liver correlate better with blood biomarkers due to their greater organ mass. Moreover, circulating biomarkers reflect active fibrogenesis and fibrolysis, whereas imaging captures both long-term structural remodeling and acute changes in loading conditions. The study lacked a matched control group, and underlying age and sex differences between the two cohorts limit direct comparison, although the authors argue these differences reflect real-world population characteristics and should not bias within-group analyses. Corrections for multiple comparisons were not performed, increasing the risk of false positive findings.

Overall, the weak correlation between circulating and imaging biomarkers underscores their complementary rather than interchangeable nature. The modest relationship between galectin-3 and left atrial reservoir strain highlights the limitations of using galectin-3 alone as a strong predictor of atrial fibrosis and remodeling. The authors suggest that prospective follow-up of this cohort, identifying individuals who develop atrial fibrillation, could confirm whether biomarker levels serve as an additional complementary screening marker of atrial cardiopathy and arrhythmia risk. Until then, galectin-3 stands as a promising but unproven molecular companion to the echocardiographic evaluation of atrial health in hypertension, with clinical follow-up needed to relate these findings to outcomes.

Subject of Research: Blood biomarkers of left atrial remodeling in people at risk of atrial fibrillation

Article Title: Blood biomarkers and atrial remodeling in patients at risk of atrial fibrillation

Article References: Loncaric, F., Forado Benatar, I., Mimbrero Guillamon, M., Nunno, L., Jimenez-Arjona, R., Tirapu, L., Montserrat, S., Sanchis, L., Doltra, A., Bijnens, B., & Sitges, M. (2026). Blood biomarkers and atrial remodeling in patients at risk of atrial fibrillation. Frontiers in Molecular Medicine, 6, Article 1801523. https://doi.org/10.3389/fmmed.2026.1801523

Image Credits: AI Generated

DOI: 10.3389/fmmed.2026.1801523

Keywords: atrial fibrillation, left atrial remodeling, galectin-3, biomarkers, arterial hypertension, endurance athletes, echocardiography, speckle-tracking strain, fibrosis, cardiology, molecular medicine, preventive cardiology