BACKGROUND: Arterial stiffness, as measured by arterial pulse wave velocity (PWV), is an established biomarker for cardiovascular risk and target-organ damage in individuals with hypertension. With the emergence of new devices for assessing PWV, it has become evident that some of these devices yield results that display significant discrepancies compared with previous devices. This discrepancy underscores the importance of comprehensive validation procedures and the need for international recommendations. METHODS: A stepwise approach utilizing the modified Delphi technique, with the involvement of key scientific societies dedicated to arterial stiffness research worldwide, was adopted to formulate, through a multidisciplinary vision, a shared approach to the validation of noninvasive arterial PWV measurement devices. RESULTS: A set of recommendations has been developed, which aim to provide guidance to clinicians, researchers, and device manufacturers regarding the validation of new PWV measurement devices. The intention behind these recommendations is to ensure that the validation process can be conducted in a rigorous and consistent manner and to promote standardization and harmonization among PWV devices, thereby facilitating their widespread adoption in clinical practice. CONCLUSIONS: It is hoped that these recommendations will encourage both users and developers of PWV measurement devices to critically evaluate and validate their technologies, ultimately leading to improved consistency and comparability of results. This, in turn, will enhance the clinical utility of PWV as a valuable tool for assessing arterial stiffness and informing cardiovascular risk stratification and management in individuals with hypertension.

Arterial stiffness index β and cardio-ankle vascular index (CAVI) are widely accepted to quantify the intrinsic exponent (β0) of the blood pressure (BP)-diameter relationship. CAVI and β assume an exponential relationship between pressure (P) and diameter (d). We aim to demonstrate that, under this assumption, β and CAVI as currently implemented are inherently BP-dependent and to provide corrected, BP-independent forms of CAVI and β. In P = Prefeβ0[(d/dref)-1], usually reference pressure (Pref) and reference diameter (dref) are substituted with DBP and diastolic diameter to accommodate measurements. Consequently, the resulting exponent is not equal to the pressure-independent β0. CAVI does not only suffer from this ‘reference pressure’ effect, but also from the linear approximation of (dP/dd). For example, assuming β0 = 7, an increase of SBP/DBP from 110/70 to 170/120 mmHg increased β by 8.1% and CAVI by 14.3%. We derived corrected forms of β and of CAVI (CAVI0) that indeed did not change with BP and represent the pressure-independent β0. To substantiate the BP effect on CAVI in a typical follow-up study, we realistically simulated patients (n = 161) before and following BP-lowering ‘treatment’ (assuming no follow-up change in intrinsic β0 and therefore in actual P–d relationship). Lowering BP from 160 ± 14/111 ± 11 to 120 ± 15/79 ± 11 mmHg (p < 0.001) resulted in a significant CAVI decrease (from 8.1 ± 2.0 to 7.7 ± 2.1, p = 0.008); CAVI0 did not change (9.8 ± 2.4 and 9.9 ± 2.6, p = 0.499). β and CAVI as currently implemented are inherently BP-dependent, potentially leading to erroneous conclusions in arterial stiffness trials. BP-independent forms are presented to readily overcome this problem.

Carotid-femoral pulse wave velocity (cfPWV) quantifies large artery stiffness, it is used in hemodynamic research and is considered a useful cardiovascular clinical marker. cfPWV is blood pressure (BP) dependent. Intrinsic heart rate (HR) dependency of cfPWV is unknown because increasing HR is commonly accompanied by increasing BP. This study aims to quantify cfPWV dependency on acute, sympathovagal-independent changes in HR, independent of BP. Individuals (n=52, age 40–93 years, 11 female) with in situ cardiac pacemakers or cardioverter defibrillators were paced at 60, 70, 80, 90, and 100 bpm. BP and cfPWV were measured at each HR. Both cfPWV (mean [95% CI], 0.31 [0.26–0.37] m/s per 10 bpm; P <0.001) and central aortic diastolic pressure (3.78 [3.40–4.17] mm Hg/10 bpm; P <0.001) increased with HR. The HR effect on cfPWV was isolated by correcting the BP effects by 3 different methods: (1) statistically, by a linear mixed model; (2) mathematically, using an exponential relationship between BP and cross-sectional lumen area; and (3) using measured BP dependency of cfPWV derived from changes in BP induced by orthostatic changes (seated and supine) in a subset of subjects (n=17). The BP-independent effects of HR on cfPWV were quantified as 0.20 [0.11–0.28] m/s per 10 bpm ( P <0.001, method 1), 0.16 [0.11–0.22] m/s per 10 bpm ( P <0.001, method 2), and 0.16 [0.11–0.21] m/s per 10 bpm ( P <0.001, method 3). With a mean HR dependency in the range of 0.16 to 0.20 m/s per 10 bpm, cfPWV may be considered to have minimal physiologically relevant changes for small changes in HR, but larger differences in HR must be considered as contributing to significant differences in cfPWV.

Automated ‘oscillometric’ blood pressure (BP) measuring devices (BPMDs) were developed in the 1970s to replace manual auscultatory BP measurement by mercury sphygmomanometer. Automated BPMDs that have passed accuracy testing versus a reference auscultatory sphygmomanometer using a scientifically accepted validation protocol are recommended for clinical use globally. Currently, there are many thousands of unique automated BPMDs manufactured by hundreds of companies, with each device using proprietary algorithms to estimate BP and using a method of operation that is largely unchanged since inception. Validated automated BPMDs provide similar BP values to those recorded using manual auscultation albeit with potential sources of error mostly associated with using empirical algorithms to derive BP from waveform pulsations. Much of the work to derive contemporary BP thresholds and treatment targets used to manage cardiovascular disease risk was obtained using automated BPMDs. While there is room for future refinement to improve accuracy for better individual risk stratification, validated BPMDs remain the recommended standard for office and out-of-office BP measurement to be used in hypertension diagnosis and management worldwide.

Arterial stiffness, as measured by aortic pulse wave velocity (PWV), is an independent marker of cardiovascular disease and events in both healthy and diseased populations. Although some cardiovascular risk factors, such as age and blood pressure, show a strong association with PWV, the association between heart rate (HR) and PWV is not firmly established. Furthermore, this association has not been investigated at different arterial blood pressures. To study effects of HR on aortic PWV at different mean arterial pressures (MAPs), adult (12 weeks; n=7), male, anesthetized Sprague-Dawley rats were randomly paced at HRs of between 300 and 450 bpm, at 50-bpm steps. At each pacing step, aortic PWV was measured across a physiological MAP range of 60 to 150 mmHg by infusing sodium nitroprusside and phenylephrine. When compared at the same MAP, increases in HR resulted in significant increases in PWV at all of the MAPs >80 mmHg (ANOVA, P <0.05), with the greatest significant change of 6.03±0.93% observed in the range 110 to 130 mmHg. The positive significant association between HR and PWV remained when PWV was adjusted for MAP (ANOVA, P <0.001). These results indicate that HR dependency of PWV is different at higher pressures than at lower pressures and that HR may be a confounding factor that should be taken into consideration when performing analysis based on PWV measurements.