Global distributions of age- and sex-related arterial stiffness: systematic review and meta-analysis of 167 studies with 509,743 participants

Background: Arterial stiffening is central to the vascular ageing process and a powerful predictor and cause of diverse vascular pathologies and mortality. We investigated age and sex trajectories, regional differences, and global reference values of arterial stiffness as assessed by pulse wave velocity (PWV).

Methods: Measurements of brachial-ankle or carotid-femoral PWV (baPWV or cfPWV) in generally healthy participants published in three electronic databases between database inception and August 24th, 2020 were included, either as individual participant-level or summary data received from collaborators (n = 248,196) or by extraction from published reports (n = 274,629). Quality was appraised using the Joanna Briggs Instrument. Variation in PWV was estimated using mixed-effects meta-regression and Generalized Additive Models for Location, Scale, and Shape.

Findings: The search yielded 8920 studies, and 167 studies with 509,743 participants from 34 countries were included. PWV depended on age, sex, and country. Global age-standardised means were 12.5 m/s (95% confidence interval: 12.1-12.8 m/s) for baPWV and 7.45 m/s (95% CI: 7.11-7.79 m/s) for cfPWV. Males had higher global levels than females of 0.77 m/s for baPWV (95% CI: 0.75-0.78 m/s) and 0.35 m/s for cfPWV (95% CI: 0.33-0.37 m/s), but sex differences in baPWV diminished with advancing age. Compared to Europe, baPWV was substantially higher in the Asian region (+1.83 m/s, P = 0.0014), whereas cfPWV was higher in the African region (+0.41 m/s, P < 0.0001) and differed more by country (highest in Poland, Russia, Iceland, France, and China; lowest in Spain, Belgium, Canada, Finland, and Argentina). High vs. other country income was associated with lower baPWV (-0.55 m/s, P = 0.048) and cfPWV (-0.41 m/s, P < 0.0001).

Interpretation: China and other Asian countries featured high PWV, which by known associations with central blood pressure and pulse pressure may partly explain higher Asian risk for intracerebral haemorrhage and small vessel stroke. Reference values provided may facilitate use of PWV as a marker of vascular ageing, for prediction of vascular risk and death, and for designing future therapeutic interventions.

Funding: This study was supported by the excellence initiative VASCage funded by the Austrian Research Promotion Agency, by the National Science Foundation of China, and the Science and Technology Planning Project of Hunan Province. Detailed funding information is provided as part of the Acknowledgments after the main text.