Abstract Background Patients with stroke are at greater risk of developing cardiovascular complications. Purpose We addressed endothelial glycocalyx, arterial stiffness, left atrial and ventricular function in patients with lacunar, atherosclerotic, cardioembolic and stroke of undetermined source (ESUS). Methods We recruited 194 patients (aged 58.8± 10.8 years old) with acute cerebral stroke (47 lacunar, 50 atherosclerotic,48 ESUS and 49 cardioembolic) and 50 controls with similar risk factors and 40 controls with similar profile regarding common risk factors (diabetes, hypertension, hyperlipidemia, coronary artery disease, smoking; p>0.05 for all comparisons). We measured: (1) perfused boundary region (PBR) of the sublingual microvessels (diameter range 5–25 μm), a marker inversely related with glycocalyx thickness, (2) pulse wave velocity carotid-to-femoral (PWV), central systolic blood pressure (cSBP), and central diastolic blood pressure (cDBP), (3) Left atrial (LA) strain using speckle-tracking imaging, (4) left ventricular global longitudinal strain and (5) left ventricular myocardial work index (GWI), constructive work (GCW), wasted work (GWW) and work efficiency (GWE), (6) ventriculoarterial coupling, expressed by the ratio PWV/GLS. Results Compared with controls, patients with stroke had higher PWV (11.98±3.21 vs 9.61±1.28 m/sec, p=0.001), PBR (2.20±0.31 vs 1.94±0.20, p=0.019) and central SBP (137.41±24.83 vs 121.15±17.46 mmHg, p=0.018), while LV ventricular (-16.44±4.70 vs -20.89±2.45%, p=0.001) and atrial deformation (26.81±9.32 vs 37.05±5.08%, p<0.001) were more impaired in patients with stroke (p < 0.05). Patients with ESUS had more impaired LA reservoir strain and contraction strain compared to the other 2 stroke types (ESUS 22.9±8.72%, -13.90±4.96%, Lacunar 29.71±10.52%, -16.11±6.10%, atherosclerotic 26.78±10.14%, -13.74±5.65%, p<0.05). Also, patients with ESUS demonstrated better PBR compared to the lacunar and atherosclerotic types (ESUS 2.10±0.27 μm, Lacunar 2.26±0.29 μm, atherosclerotic 2.19±0.29μm, p<0.05). Patients with atherosclerotic stroke had higher PWV compared with other stroke types (Atherosclerotic: 13.59±3.87 m/sec, Lacunar: 11.41±2.35 m/sec, Cardioembolic: 10.66±3.28 m/sec, ESUS: 11.72±2.67 m/sec). Also, patients with atherosclerotic stroke demonstrated the worst PWV/GLS ratio (Atherosclerotic: -0.97±0.35, Lacunar: -0.69±0.25, Cardioembolic: -0.76±0.21, ESUS: -0.70±0.28). Patients with cardioembolic stroke showed similar trend with ESUS, as far LA strain is considered. Conclusion Patients with stroke have impaired atrial strain, endothelial glycocalyx and arterial stiffness, compared with controls. Arterial stiffness and ventriculoarterial coupling are more affected in atherosclerotic strokes. LA strain is more impaired in the ESUS and cardioembolic stroke albeit that endocalyx, though abnormal,is less impaired in these stroke types.