Relation of forward and backward traveling pressure waves with subclinical carotid artery wall remodeling and central pulse pressure

Central pulse pressure (PP) is the sum of forward and backward traveling pressure waves that have been associated with cardiovascular disease (CVD) risk. However, previous studies have reported differential findings regarding the importance of the forward versus the backward wave for CVD risk. Therefore, we sought to determine the degree to which the forward and backward pressure waves are associated with subclinical carotid artery wall remodeling and central PP in healthy adults. Using applanation tonometry, carotid pressure waveforms were acquired in 308 healthy individuals (aged 45 +/- 17 years, range 19-80 years, 61% women), from which the time integral of the forward (Pf(TI)) and backward (Pb-TI) pressure waves were derived via pressure-only wave separation analysis. Common carotid artery intima-media thickness (cIMT), a biomarker of subclinical CVD risk, was derived via B-mode ultrasonography measured similar to 2 cm from the carotid bulb. Both Pf(TI) (r = 0.31, P < 0.001) and Pb-TI (r = 0.40, P < 0.001) were correlated with cIMT. However, further analysis revealed that Pb-TI mediated the relation between Pf(TI) and cIMT (proportion mediated = 156%, P < 0.001). The association between Pb-TI and cIMT remained after adjusting for age, sex, body mass index, blood glucose, low-density lipoprotein cholesterol, heart rate, brachial systolic pressure, and aortic stiffness (B = 0.02, 95% confidence interval = 0.01, 2.77, P < 0.001). Both Pf(TI) (r = -0.58, P < 0.001) and Pb-TI (r = -0.50, P < 0.001) were correlated with central PP, however, Pf(TI) fully mediated the association between Pb-TI and central PP (proportion mediated = 124%, P < 0.001). Although Pf(TI) is correlated with higher central PP, it is Pb-TI that is directly associated with carotid artery wall remodeling. NEW & NOTEWORTHY The present study contributes to the growing body of evidence highlighting the physiological and clinical insight provided by the pulsatile hemodynamic components of central artery pulse pressure. The notable findings of this study are: 1) The reflected (backward) pressure wave is associated with carotid intima-media thickness independent of traditional cardiovascular risk factors, including systolic blood pressure and aortic stiffness. 2) The incident (forward) pressure wave, and not the reflected pressure wave, is associated with greater central pulse pressure.