Estimation of an Age-specific Reference Interval for Pulse Wave Velocity: a Meta-analysis

Objective: To estimate an age-specific reference interval for carotid-femoral pulse wave velocity (PWV), an index of aortic stiffness, and to determine the predictive values of the reference range for detecting those at moderate and high risk of cardiovascular disease (CVD).

Design And Methods: We searched MEDLINE using PubMed from 1995 to 2005 for all studies in which Carotid-Femoral PWV was measured using a Complior (Colson, Paris, France) apparatus in Caucasian non-pregnant adults. Twenty-five studies were included, covering 30 groups of subjects; these groups were classified a priori into low (normal), moderate, and high CVD risk categories, with 2008, 5979, and 180 (total 8167) subjects, respectively. Individual-level data were simulated for each group, and an age-specific reference interval was calculated by using fractional polynomial functions.

Results: We plotted an age-adjusted normal curve for PWV with 2.5, 5, 50, 90, 95, and 97.5 centile limits. Applying this reference interval to the moderate- and high-risk groups using simulations yielded sensitivities of 34.3 [95% confidence interval (CI) 33.2-35.3] and 57.2 (95% CI 55.2-59.3), respectively, specificities of 95.3 (95% CI 94.8-95.8) and 95.3 (95% CI 94.4-96.2), respectively, and positive likelihood ratios of 7.3 and 12.2, respectively.

Conclusion: We constructed an age-adjusted reference curve for PWV. Using the 95th centile of this curve as a threshold (e.g. 10.94, 11.86, and 13.18 m/s for 20, 40, and 60 years old) shows construct validity, as it appears to identify medium and high CVD risk groups reasonably accurately. This reference range needs to be tested using other datasets.