ABSTRACT
COVID-19-associated vascular disease complications are primarily associated with endothelial dysfunction; however, the consequences of disease on vascular structure and function, particularly in the long term (>7 weeks post-infection), remain unexplored. Individual pre- and post-infection changes in arterial stiffness as well as central and systemic hemodynamic parameters were measured in patients diagnosed with mild COVID-19. As part of in-laboratory observational studies, baseline measurements were taken up to two years before, whereas the post-infection measurements were made 2-3 months after the onset of COVID-19. We used the same measurement protocol throughout the study as well as linear and mixed-effects regression models to analyze the data. Patients (N = 32) were predominantly healthy and young (mean age ± SD: 36.6 ± 12.6). We found that various parameters of arterial stiffness and central hemodynamics-cfPWV, AIx@HR75, and cDBP as well as DBP and MAP-responded to a mild COVID-19 disease. The magnitude of these responses was dependent on the time since the onset of COVID-19 as well as age (pregression_models ≤ 0.013). In fact, mixed-effects models predicted a clinically significant progression of vascular impairment within the period of 2-3 months following infection (change in cfPWV by +1.4 m/s, +15% in AIx@HR75, approximately +8 mmHg in DBP, cDBP, and MAP). The results point toward the existence of a widespread and long-lasting pathological process in the vasculature following mild COVID-19 disease, with heterogeneous individual responses, some of which may be triggered by an autoimmune response to COVID-19.
ABSTRACT
Pulse wave velocity (PWV), a direct measure of arterial stiffness, is a promising biomarker of cardiovascular risk and a cardiovascular surrogate outcome. The resolution for detecting its smallest clinically significant change is dependent on the expected reproducibility, but there is currently no consensus on this. We estimated the PWV reproducibility in a range of intra-subject values that were observed over a 2 week period in a broad range of participants and under clinically relevant experimental conditions (two observers, morning/afternoon sessions, and number of visits) using SphygmoCor and Arteriograph devices. Each participant was recorded 12 times with each device over three visits, one week apart, and two morning and two afternoon recordings were taken per visit. The factors affecting reproducibility and the discrepancies between the consecutive PWV measurements for each device were also examined using multilevel mixed-effect models. We show that current PWV estimation guidance recommending 2 + 1 measurements is suboptimal because the PWV range was outside of the 1 m/s threshold for most of the participants, which is proposed as a minimal clinically important difference. The best reproducibility was yielded with median of four measurements and a 1.1 m/s threshold. Although PWV reproducibility and repeatability are frequently used interchangeably in studies, we demonstrated that despite their relative measures of variability (e.g., coefficient of variation) being comparable, their ranges revealed a clinically significant difference between them. We also found that different physiological variables were predictors of the discrepancy between the consecutive measurements made by the two devices, which is likely due to their distinct modes of operation. The evidence base for PWV reproducibility is limited, and more research is needed to deepen our understanding of the variation in arterial stiffness over time, as well as fluctuations within a population group and in an intervention setting.
ABSTRACT
Background: Large longitudinal studies with repeated pulse wave velocity (PWV) measurements, a direct measure of arterial stiffness, are required to realize the full potential of arterial stiffness in clinical practice. To facilitate such studies it is important to increase the power of a study by reducing within-subject variability of PWV, and to ease the use of a PWV device in clinical settings by minimizing PWV measurement difficulties. Methods: We systematically investigated experimental setting and meteorological conditions, as well as physiological factors and participant characteristics, to determine whether and to what extent they affected: between- and within-subjects variability of PWV recordings, and measurement difficulties of a particular device. We conducted a 2-week longitudinal block-randomized cross-over study with two blinded observers and two commonly used devices: applanation tonometry SphygmoCor CvMS and oscillometric Arteriograph to assess carotid-femoral (cfPWV) or aortic (PWVao) PWV, respectively. Our sample had uniform and wide-spread distribution of age, blood pressures, hypertensive status and BMI. Each participant (N = 35) was recorded 12 times over 3 visiting days, 7 days apart. On each day, recordings were made twice in the morning (7-10 a.m.) and afternoon (16-18 p.m.). Data were analyzed using multilevel mixed-effects models, separately for each device. Results: In addition to age and mean arterial pressure (MAP) that strongly affected both cfPWV and PWVao, other significant factors appeared to indicate a measurement approach. cfPWV as a more direct measure of arterial stiffness was additionally affected by hypertension status, outdoor temperature, interaction of MAP with outdoor temperature and the order of visit, with MAP within-subject variability contributing on average 0.27 m/s to difference in repeated measurements at 5°C and 0.004 m/s at 25°C. PWVao measurements derived at a single brachial site were more dependent on age than cfPWV and also depended on personal characteristics such as height and sex, and heart rate; with within-subject MAP variability adding on average 0.23 m/s to the difference in repeated measures. We also found that female sex significantly increased, and recording in afternoon vs. morning significantly decreased measurement difficulties of both devices. Conclusion: We identified factors affecting PWV recordings and measurement-difficulties and propose how to improve PWV measuring protocols.
