AUTHOR=Lechner Katharina , Kia Sylvia , von Korn Pia , Dinges Sophia M. , Mueller Stephan , Tjønna Arnt-Erik , Wisløff Ulrik , Van Craenenbroeck Emeline M. , Pieske Burkert , Adams Volker , Pressler Axel , Landmesser Ulf , Halle Martin , Kränkel Nicolle 

TITLE=Cardiometabolic and immune response to exercise training in patients with metabolic syndrome: retrospective analysis of two randomized clinical trials

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=11

YEAR=2024

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2024.1329633

DOI=10.3389/fcvm.2024.1329633

ISSN=2297-055X

ABSTRACT=<sec><title>Background</title><p>Metabolic syndrome (MetS) is defined by the presence of central obesity plus ≥two metabolic/cardiovascular risk factors (RF), with inflammation being a major disease-driving mechanism. Structured endurance exercise training (ET) may positively affect these traits, as well as cardiorespiratory fitness (V̇O<sub>2</sub>peak).</p></sec><sec><title>Aims</title><p>We explore individual ET-mediated improvements of MetS-associated RF in relation to improvements in V̇O<sub>2</sub>peak and inflammatory profile.</p></sec><sec><title>Methods</title><p>MetS patients from two randomized controlled trials, ExMET (<italic>n</italic> = 24) and OptimEx (<italic>n</italic> = 34), had performed 4- or 3-months supervised ET programs according to the respective trial protocol. V̇O<sub>2</sub>peak, MetS-defining RFs (both RCTs), broad blood leukocyte profile, cytokines and plasma proteins (ExMET only) were assessed at baseline and follow-up. Intra-individual changes in RFs were analysed for both trials separately using non-parametric approaches. Associations between changes in each RF over the exercise period (<italic>n</italic>-fold of baseline values) were correlated using a non-parametrical approach (Spearman). RF clustering was explored by uniform manifold approximation and projection (UMAP) and changes in RF depending on other RF or exercise parameters were explored by recursive partitioning.</p></sec><sec><title>Results</title><p>Four months of ET reduced circulating leukocyte counts (63.5% of baseline, <italic>P</italic> = 8.0e-6), especially effector subtypes. ET response of MetS-associated RFs differed depending on patients’ individual RF constellation, but was not associated with individual change in V̇O<sub>2</sub>peak. Blood pressure lowering depended on cumulative exercise duration (ExMET: ≥102 min per week; OptimEx-MetS: ≥38 min per session) and baseline triglyceride levels (ExMET: &lt;150 mg/dl; OptimEx-MetS: &lt;174.8 mg/dl). Neuropilin-1 plasma levels were inversely associated with fasting plasma triglycerides (<italic>R</italic>: −0.4, <italic>P</italic> = 0.004) and changes of both parameters during the ET phase were inversely correlated (<italic>R</italic>: −0.7, <italic>P</italic> = 0.0001).</p></sec><sec><title>Conclusions</title><p>ET significantly lowered effector leukocyte blood counts. The improvement of MetS-associated cardiovascular RFs depended on individual basal RF profile and exercise duration but was not associated with exercise-mediated increase in V̇O<sub>2</sub>peak. Neuropilin-1 may be linked to exercise-mediated triglyceride lowering.</p></sec>