Abstract
The assessment of flow-mediated dilation (FMD) is widely used in clinical research to quantify endothelial function. FMD is calculated by subtracting the artery's baseline diameter from the peak diameter during hyperemia. However, there is no consensus on how to determine peak diameter. Many authors report FMD results based on values assessed at predefined time points. This may limit the accuracy and reproducibility of FMD. We hypothesised that FMD values using maximum dilatory peak time (MDP) would differ from those using predefined time points. Using individually determined MDP may lead to a lower number of subjects needed to show significance for a given difference in FMD.
FMD was measured in middle-aged subjects with and without diabetes mellitus type 2 (T2DM) by ultrasound (12-MHz transducer). In a subset of subjects, FMD was measured again 30 days later. All measurements were performed by certified research physicians and evaluated using appropriate software. FMD values were compared at 60 s and 90 s after start of hyperaemia and at MDP during hyperaemia.
FMD was measured in 100 healthy subjects and 72 subjects with T2DM (mean ± SD age 57±6 years, healthy: body mass index 26.2±3 kg/m2, blood pressure 127±10 /80±7 mmHg, DMT2: body mass index 29±3 kg/m2, blood pressure 135±11 / 86±5 mmHg, HbA1c 7.1±0.7%). FMD in healthy subjects was lower at predefined time points compared to MDP (least square mean difference (95% CI)) 60 s vs. MDP −1.14% (−1.72 to −0.56; p<0.0001) and 90 s vs. MDP −1.87% (−2.48 to −1.26; p<0.0001). Also in subjects with DMT2, FMD at predefined time points was lower compared to MDP (least square mean difference (95% CI)) 60 s vs. MDP −1.08% (−1.71 to −0.44; p<0.001) and 90 s vs. MDP −1.73% (−2.38 to −1.06; p<0.001). The intra-subject variability was lowest for MDP compared to 60 s and 90 s (15% vs. 36% and 51%, respectively). Assuming 80% power and alpha at 0.05, the individually determined peak requires 15 people to detect a 1% difference in FMD versus 26 subjects if determined at 60 s and 31 subjects if determined at 90 s.
This study demonstrated significantly higher FMD values and superior reproducibility of the individually determined maximum dilatory peak compared to peaks at predefined time points in healthy middle-aged people and patients with type 2 diabetes. This roughly halves the number of study participants needed to detect a 1% difference in FMD.