Cardiovascular-kidney-metabolic (CKM) syndrome stage is associated with impaired cardiac structure/function and increased symptom burden in patients with MASLD
A Stanchev, F S D Filip Soeskov Davidovski, C A E Caroline Espersen, M O R Mohammed Ramadan, P U N Puria Nabilou, S S W Signe Skovgaard Wiese, M A D Maria Dons, O L A Oliver Arendschneider, A N J Anne Marie Reimer Jensen, M A L Mats C. Hoejbjerg Lassen, M P W Mikkel Parsberg Werge, E R B Elias Rashu Badu, M I T Mira Thing, L L G Lise Lotte Gluud, T B S Tor Biering-SoerensenAbstract
Background
Metabolic dysfunction associated steatotic liver disease (MASLD) is closely linked with cardiometabolic risk, but how cardiometabolic burden translates into early cardiac dysfunction in MASLD remains incompletely characterized. We evaluated whether higher cardiovascular-kidney-metabolic (CKM) syndrome stage was associated with impaired echocardiographic function and greater symptom burden in MASLD.
Purpose
To examine the association between CKM stages (1-3) in patients with MASLD and cardiac structure and function, with a particular focus on the prevalence of systolic dysfunction assessed by left ventricular (LV) global longitudinal strain (GLS), diastolic indices, and left atrial (LA) strain, and the burden of self-reported symptoms and functional limitations.
Methods
This cross-sectional study included adults with MASLD confirmed by vibration-controlled transient elastography (controlled attenuation parameter >280 dB/m) who underwent comprehensive echocardiography according to a pre-defined research protocol. Participants were classified according to the American Heart Association’s CKM syndrome staging framework, where stage 1 reflects adiposity, stage 2 metabolic risk factors and/or chronic kidney disease, and stage 3 subclinical cardiovascular disease defined by cardiac dysfunction on echocardiography. Analyses were restricted to CKM stages 1-3 to capture progressive cardiometabolic burden, while excluding established clinical cardiovascular disease (CKM stage 4). Clinical characteristics and echocardiographic measures of cardiac structure, systolic and diastolic function, and atrial function were compared across CKM stages using trend tests. Self-reported symptoms and functional limitations were summarized by CKM stage.
Results
We included 470 MASLD patients (mean age 60 years; 51% female), distributed across CKM stages 1 (n=113), 2 (n=257), and 3 (n=100) (Table 1). Higher CKM stage was associated with cardiac remodeling, including higher left ventricular mass index (67 to 79 g/m², p-trend<0.001). Subclinical systolic function was worse, reflected by lower absolute LV GLS (18.46 to 15.24, p-trend<0.001), alongside a more adverse diastolic profile with higher E/e′ (6.6 to 8.4, p-trend<0.001). Left atrial function declined in parallel, with lower peak atrial longitudinal strain (42 to 36, p-trend<0.001) and left atrial conduit strain (21 to 15, p-trend<0.001).
Higher CKM stage was associated with higher symptom burden, with higher prevalence of NYHA class ≥ II (35% to 52%, p-trend=0.017), peripheral oedema (6% to 20%, p-trend=0.008), and greater impact on hobbies/leisure (20% to 39%, p-trend=0.003). Other symptoms and functional limitations generally increased with CKM stage (Figure 1).
Conclusion
In MASLD, higher CKM stage (1-3) was associated with worse cardiac structure and function including lower LV GLS, a more adverse diastolic profile, and reduced LA strain and with greater symptom burden.