Multiparameter assessment of vasodilatory endothelial dysfunction in preclinical and severe cardiovascular risk...

Vasodilatory endothelial dysfunction (VED) is identified as a precursor to cardiovascular diseases (CVDs) and atherosclerosis. Therefore, early detection of VED is important to prevent the development of severe CVDs and prescribe lifestyle changes or make clinical interventions. Though Acetylcholine-induced coronary vasodilation test is the invasive gold standard to detect VED, specialized devices have provided alternative means of detecting VED non-invasively. With these, they have already detected presence of VED in patients who are already diagnosed with CVD or Diabetes Mellitus (DM). This study focused on early detection of VED in preclinical stages: individuals with pre-diabetes (PDM) and asymptomatic individuals with cardiovascular risk factors (ARF) along with individuals with DM, individuals with CVD with/without DM and healthy (control). Non-invasive physiological parameters were employed to assess VED in these five subject categories.

We developed a custom-made device to record non-invasive physiological parameters of digital body temperature, peripheral arterial tone, photo plethysmography and peripheral bio-impedance from the distal end of upper limbs. Multiple indices which represent unique features of these parameters were calculated considering both long-term and short-term variations. Using these, the performance of this device was validated against the flow-mediated dilation (FMD) procedure in a preliminary study with 10 volunteers (age range: 35 - 60 years): 5 healthy subjects (control) and 5 CVD patients with/without DM. Then the clinical study was conducted with 69 participants (age range: 35-60 years) with all the subject categories: healthy (n = 9), ARF (n = 15), PDM (n = 6), type-2 DM (n = 15), 24 CVD with/without DM (n = 24). CVD risk factors identified for the ARF category were physical inactivity, unhealthy diet, smoking, alcohol consumption, body mass index and family history of CVD. Participants with type-1 DM, liver cirrhosis, renal failure, thyroid disease, spinal cord injuries and finger deformities were excluded from the study.

In the preliminary study, an unpaired t-test and Bland Altman analysis were performed between FMD readings and indices derived from parameters measured from the custom-made device, to validate the device's performance. In the clinical study, the ANOVA analysis showed promising results (p < 0.05) in distinguishing long-term trend variations and short-term variations of VED-associated physiological parameters in test subjects diagnosed with CVD or DM along with preclinical stages (ARF and PDM) compared to the healthy (control).

We have demonstrated that monitoring VED-associated physiological parameters could potentially enable the early detection of cardiovascular disease (CVD) during its preclinical stages. Thereby, preventive measures or treatments can be initiated at early stages while preventing the severe development of CVDs.