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

Abstract

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.

Keywords: All-cause mortality; Arterial stiffness; Cardiovascular disease; Hypertensive end-organ damage; Prevention; Pulse wave velocity; Reference values; Risk factors.

Central Illustration

Pathophysiological and clinical correlates of arterial stiffness and trajectories of pulse wave velocity by age and sex. Arterial stiffness represents a sensitive marker of vascular ageing reflecting diverse vascular pathologies (top left). Arterial stiffening increases central blood pressure and pulse pressure, predisposing to cardiac disease by increasing afterload and decreasing coronary perfusion and damaging the microcirculation of the low vascular resistance organs kidney and brain (top right). Pulse wave velocity (PWV) is a validated non-invasive measure of arterial stiffness and powerfully predicts both CVD and all-cause mortality. Here we provide age- and sex-specific regional and global (bottom part of figure) distributions and reference values for brachial-ankle and carotid-femoral PWV to facilitate routine clinical use of PWV. This figure includes content from Servier Medical Art by Servier, licensed under a Creative Commons Attribution 3.0 unported license.

Fig. 1

Global age- and sex-dependent distributions of baPWV and cfPWV. For both baPWV and cfPWV, levels and variability increased with age. Males showed a faster increase than females in baPWV after age 20, but sex differences vanished at higher ages. For cfPWV, males featured higher values beginning in adolescence, and the sex difference remained constant throughout the remaining lifespan. This analysis is based on n = 178,073 individual data points and participants from 45 studies conducted in 24 countries.

Fig. 2

Trajectories of PWV over the lifespan by country and world region. Individual lines represent individual countries and line colours, world regions. Age trajectories of baPWV were relatively uniform within Asia and Europe individually whereas inter-country differences were more pronounced for cfPWV trajectories. This analysis is based on data from n = 509,743 participants of 167 studies conducted in 34 countries.

Fig. 3

Age-standardised PWV by country and world region. Countries are ordered according to average PWV. baPWV was uniformly lower in European as compared to Asian countries. There was a wide range of cfPWV averages between countries within the same region. Poland, Russia, Iceland, France, and China featured the highest cfPWV. Estimates for the “Total” sex group include PWV summary data extracted from the literature without reporting of PWV by sex and may therefore differ from pooled estimates of included data in men and in women.

Fig. 5

Sexdifferences in PWV by country. Age-standardized PWV values in males (x axis) vs. in females (y axis) are shown by country. Males featured higher baPWV and cfPWV in most countries and sex differences were more uniform between countries for baPWV than for cfPWV. Variability in PWV due to sex was less than variability due to country. Diagonal lines indicate identical PWV in males and females. Algeria is not shown because no data on cfPWV in Algerian females was available.

Fig. 4

a:World map ofbaPWV by country. For Indonesia, data from fewer than 1000 participants were available. b: World map of cfPWV by country. For the following countries, data from fewer than 1000 participants were available: Algeria, Angola, Canada, Hungary, Iceland, Lithuania, North Macedonia, Poland, Russia, and Spain.