Systolic Blood Pressure and Longitudinal Progression of Arterial Stiffness: A Quantitative Meta-Analysis

Abstract

Background Arterial stiffness predicts the risk of cardiovascular events and all-cause mortality and is associated with age and hypertension. However, the magnitude of the relationship between blood pressure (BP) and progression of arterial stiffness is unclear, limiting our understanding of how arterial stiffness mediates clinical effects of hypertension and planning of clinical trials. Methods and Results Medline and EMBASE were searched for prospective studies reporting linear models between baseline BP and progression of arterial stiffness, with and without adjustment for demographic characteristics and baseline stiffness. Standardized and unstandardized β coefficients for pulse wave velocity were combined by fixed and random effects meta-analysis, weighted by the inverse variance. Of 566 fully reviewed articles from 30, 524 titles, 22 populations from 21 reports were included. In 9 cohorts, there were consistent, adjusted associations between baseline systolic BP and progression of arterial stiffness (11 781 patients; standardized β=0.041; 95% CI, 0.026-0.055; P<0.001; P value for heterogeneity=0.70), equivalent to a 1.14-m/s increase in standard carotid-femoral pulse wave velocity per decade per 20-mm Hg systolic BP, independent of age. Unstandardized, adjusted associations were similar (1762 patients; β=0.0047; 95% CI, 0.004-0.006; P<0.001; P value for heterogeneity=0.64), equivalent to a 0.94-m/s increase per decade per 20-mm Hg systolic BP. In limited studies, standardized associations between mean BP and arterial stiffness progression were not significant and heterogeneous (913 patients; β=0.039; 95% CI, -0.008 to 0.086; P=0.11; P value for heterogeneity=0.03). Conclusions Baseline systolic BP was associated with a clinically important progression of arterial stiffness, independent of age, providing a reference for the potential effect of arterial stiffness in mediating changes in clinical outcomes associated with hypertension and providing a reference value to aid clinical trial design.

Keywords: arterial stiffness; hypertension; longitudinal cohort study; meta‐analysis; systematic review.

Figure 1. Forest plot of the effect of baseline systolic blood pressure on annual progression of arterial stiffness by meta‐analysis of standardized β regression coefficients from analyses adjusted for demographic variables.

Effects were analyzed by both fixed and random effects meta‐analysis weighted by the inverse variance. CIhigh indicates CI upper limit; CIlow, CI lower limit; I‐sq, I² statistic; N, number of subjects; P‐Het, P value for heterogeneity; and StdBeta, standardized regression coefficient.

Figure 2. Forest plot of the effect of baseline systolic blood pressure on annual progression of arterial stiffness by meta‐analysis of standardized β regression coefficients from analyses adjusted for demographic variables and stratified by age.

A, Mean age >50 years old. B, Mean age <50 years old. C, Including studies reporting effects on progression of carotid‐femoral pulse wave velocity (cfPWV). D, Including studies reporting effects on brachial‐ankle pulse wave velocity (baPWV). Effects were analyzed by both fixed and random effects meta‐analysis weighted by the inverse variance. CIhigh indicates CI upper limit; CIlow, CI lower limit; I‐sq, I² statistic; N, number of subjects; P‐Het, P value for heterogeneity; and StdBeta, standardized regression coefficient.

Figure 3. Forest plot of the effect of baseline systolic blood pressure on annual progression of arterial stiffness by meta‐analysis of unstandardized β regression coefficients from analyses adjusted for demographic variables.

Effects were analyzed by both fixed and random effects meta‐analysis weighted by the inverse variance. CIhigh indicates CI upper limit; CIlow, CI lower limit; I‐sq, I² statistic; N, number of subjects; P‐Het, P value for heterogeneity; and RawBeta, unstandardized regression coefficient.

Figure 4. Forest plot of the effect of baseline mean blood pressure on annual progression of arterial stiffness by meta‐analysis of standardized β regression coefficients from analyses adjusted for demographic variables.

Effects were analyzed by both fixed and random effects meta‐analysis weighted by the inverse variance. A, Includes all studies according to original inclusion criteria. B, Excludes interventional studies with a reported reduction in pulse wave velocity during follow‐up. CIhigh indicates CI upper limit; CIlow, CI lower limit; I‐sq, I² statistic; N, number of subjects; P‐Het, P value for heterogeneity; and StdBeta, standardized regression coefficient.

Figure 5. Forest plot of the effect of baseline diastolic blood pressure on annual progression of arterial stiffness by meta‐analysis of standardized β regression coefficients from analyses not adjusted for demographic variables.

Effects were analyzed by both fixed and random effects meta‐analysis weighted by the inverse variance. CIhigh indicates CI upper limit; CIlow, CI lower limit; I‐sq, I² statistic; N, number of subjects; P‐Het, P value for heterogeneity; and StdBeta, standardized regression coefficient.