Interleukin-6 is independently associated with subclinical left atrial pressure elevation in patients with MASLD and preserved systolic function

Background

Heart Failure with Preserved Ejection Fraction (HFpEF) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) belong to a group of cardio-hepatic-inflammatory diseases that share common pathophysiological mechanisms. They present as a bidirectional interaction with the low-grade inflammatory pathway as an important mechanism still not completely elucidated.

Purpose

This study reports pilot results from a single-center cross-sectional observational study designed to investigate the association between IL-6 and elevated left atrial pressure (LAP) in patients with MASLD.

Methods

Asymptomatic patients with MASLD were recruited. Exclusion criteria were alcoholic liver disease, chronic viral hepatitis, ejection fraction less than 50%, aortic or mitral valve disease more than mild, or previous use of anthracyclines. After written informed consent was obtained, patients underwent transthoracic echocardiography (TTE), transient hepatic elastography, and laboratory testing. Elevated LAP was defined according to the 2025 update of the American Society of Echocardiography guidelines on diastolic function. The study is registered at the Local Ethics Committee under the number: 7.172.537. SPSS V31.0.0.0 was used.

The primary endpoint was to assess the association between Interleukin-6 (IL-6) levels and elevated LAP in patients with MASLD and preserved systolic function. The secondary endpoints included evaluation of other risk factors for the same dependent outcome.

Results

Of 91 patients evaluated, 3 were excluded because of incident HCV-positive serology. Among the remaining patients, 70.5% (n=62) were female. Mean age was 62.8 (±9.7). Median body mass index (BMI) was 31.2 (IQR 28.01 – 36.21), glycated hemoglobin 6.8% (IQR 6% – 8.2%), NT-proBNP 65.7 pg/mL (IQR 37.3 – 165.30), C-reactive protein 2 mg/dL (IQR 0.9 – 5.5), IL-6 was 2.47 pg/mL (IQR 1.42-3.62). Median liver stiffness (LS) was 6.7 kPa (IQR 4.6 – 14.2). 23.9% (n=21) of the patients had elevated LAP on TTE.

On univariate analysis evaluating age, BMI, C-reactive protein, AST, ALT, platelets, glycated hemoglobin, LS, and IL-6, only LS and IL-6 were associated with elevated LAP. IL-6 levels were significantly higher in patients with elevated LAP compared to those without (3.73 [2.47–6.82] vs 1.83 [1.36–3.15] pg/mL; p<0.001) and demonstrated good discriminative performance (AUC 0.78; 95% CI 0.67–0.90; p<0.001). In multivariate logistic regression including BMI and IL-6, only IL-6 remained independently associated with elevated LAP (OR 1.40; 95% CI 1.06–1.85; p=0.017).

Conclusion

IL-6 levels were independently associated with elevated left atrial pressure in asymptomatic patients with MASLD and preserved systolic function. This association remained significant after adjustment for BMI. These findings suggest that systemic inflammation may play a key role in early hemodynamic alterations preceding clinical HFpEF in patients with MASLD.BoxPlot Fig1ROC fig 2