Circulating levels of amyloid-beta (1-40) peptide associate with cardiometabolic traits and risk for metabolic dysfunction-associated steatotic liver disease

Kateryna Sopova (Mannheim)1, D. Delialis (Athens)2, E. Aivalioti (Athens)2, S. Athanasopoulos (Athens)2, G. Georgiopoulos (Athens)2, K. Stamatelopoulos (Athens)2, K. Stellos (Mannheim)1

1Universität Heidelberg Abteilung für Herz-Kreislauf-Forschung Mannheim, Deutschland; 2Alexandra Hospital Department of Clinical Therapeutics Athens, Griechenland


Background and Aims: The ageing-associated amyloid-beta 1-40 peptide (Αbeta40) has recently emerged as a blood-based biomarker of cardiovascular disease (CVD). Its levels predict future cardiovascular death and major adverse cardiovascular events in patients with established cardiovascular disease (CVD) including patients with coronary artery disease or heart failure. The clinical value of Abeta40 in patients with metabolic syndrome who do not concomitantly have clinically overt CVD or other end-organ damage remains poorly understood.  At the present study we investigated the clinical value of plasma Αbeta40 in patients with pre- or established metabolic syndrome who are at risk for metabolic dysfunction-associated steatotic liver disease (MASLD).

Methods: Αbeta40 was measured in plasma by enzyme-linked immunosorbent assay and cardiometabolic traits (waist circumference, blood pressure, fasting triglycerides, fasting HDL cholesterol, and fasting glucose) were determined in a mixed population (n=888) of patients with established (n=243) and pre- or without metabolic syndrome (n=645) who did not have clinical signs of established cardiometabolic disease (heart failure, coronary artery disease, MASLD, chronic kidney disease). The endpoint of the study was the association of Abeta40 with cardiometabolic indices and risk (BARD score) for metabolic dysfunction-associated steatotic liver disease (MASLD). Odds ratio (OR) was calculated by ordinal regression analysis for the increasing incidence of metabolic syndrome components per increasing Abeta40 (1-SD) after adjustment for age, sex, smoking status and hyperlipidemia

Results: Abeta40 levels are associated with the presence of metabolic syndrome (OR per 1-SD increase: 1.009, 95% CI: 1.003-1.015, P=0.003) and with higher odds for increasing incidence of metabolic syndrome components (prediabetes, low HDL-C levels, high triglyceride levels, increased waist circumference and high-risk for MASLD) after adjustment for sex, age, smoking status, hypertension and dyslipidemia. Increased Abeta40 plasma levels were associated with decreased HDL-C levels (OR: 1.004, 95% CI:1.000-1.009, P=0.049) and increased triglyceride levels (OR: 1.007, 95%CI: 1.001-1.012, P=0.033) after adjustment for traditional cardiovascular risk factors (age, sex, smoking status, hypertension and hyperlipidemia). Among the total population (n=888), we identified n=473 subjects with increased MASLD risk if any of the following was present: hepatic steatosis index≥36 or fatty liver index≥60 or Fib-4 index≥2.67 or NAFLD score≥0.675. Among patients with high-risk for MASLD, patients with increased BARD score had significantly higher Abeta40 levels (median Abeta40 concentration in patients with BARD score≥2 vs. patients with BARD score<2: 54.9 pg/ml (IQR=38.25) vs. 41.9 pg/m (IQR=30.35), P=0.012). Increased Abeta40 levels were associated with increased odds for AST/ALT≥0.8 ratio (OR:1.017, 95% CI: 1.006-1.028, P=0.003) and increased odds for BARD score≥2 (OR: 1.009 95% CI: 1.001-1.019, P=0.043) after adjustment for age, sex, smoking status, hypertension and hyperlipidemia.

Conclusion: Our findings suggest that Abeta40 peptide is associated with cardiometabolic traits and risk for MASLD. Whether Abeta40 may emerge as an early cardiometabolic prognostic biomarker, future longitudinal studies are warranted to determine the prognostic value of Abeta40 for the development of cardiometabolic diseases in patients with metabolic syndrome.

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