Longitudinal Adipokine and Lipid Profiles in Fabry Disease

<b>Background/Objectives:</b> Fabry disease (FD) is a lysosomal storage disorder characterized by progressive renal and cardiac involvement and an increased burden of cardiovascular and cerebrovascular events. While cardiac magnetic resonance imaging (CMR) has significantly advanced structural assessment, circulating biomarkers reflecting disease-related cardiac manifestations remain incompletely understood. We therefore investigated adiponectin and leptin, two adipokines involved in inflammatory, metabolic, and fibrotic pathways, in relation to cardiac involvement and analyzed long-term lipid trajectories in FD. <b>Methods:</b> This longitudinal observational study included 49 patients with FD with 149 study visits. Circulating adiponectin, leptin, NT-proBNP, and conventional lipid parameters were assessed longitudinally and stratified by FD-specific therapy status and sex. Multivariable linear regression was performed to evaluate independent associations with log-transformed NT-proBNP values. <b>Results:</b> Adiponectin was positively associated with NT-proBNP, reflecting cardiac involvement, independent of age, sex, BMI, and eGFR (<i>p</i> < 0.001). Higher adiponectin levels were observed in patients with left ventricular hypertrophy or low T1 and those with fibrosis, detected by CMR (<i>p</i> = 0.009 and <i>p</i> < 0.001, respectively). This association was mainly seen in patients receiving FD-specific therapy, raising the question of whether this reflects underlying organ involvement or treatment effects. Leptin demonstrated weaker, inverse associations. Adiponectin, leptin, Triglycerides, total cholesterol, and HDL- and LDL-cholesterol levels remained stable over long-term follow-up, irrespective of FD-specific therapy or sex. <b>Conclusions:</b> In FD, adiponectin appears to be associated with cardiac involvement, and conventional lipid parameters remained unchanged over time. These findings suggest that alterations in adipokines, rather than progressive dyslipidemia, may reflect disease-related cardiac manifestations.