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

Abstract

Central pulse pressure (PP) is the sum of a forward and backward traveling pressure waves which have been associated with cardiovascular disease (CVD) risk. However, previous studies have reported differential findings regarding 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 (PfTI) and backward (PbTI) 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 ~2 cm from the carotid bulb. Both PfTI (r=0.31, P<0.001) and PbTI (r=0.40, P<0.001) were correlated with cIMT. However, further analysis revealed that PbTI mediated the relation between PfTI and cIMT (proportion mediated=156%, P<0.001). The association between PbTI 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 PfTI (r=-0.58, P<0.001) and PbTI (r=-0.50, P<0.001) were correlated with central PP, however, PfTI fully mediated the association between PbTI and central PP (proportion mediated=124%, P<0.001). Although PfTI is correlated with higher central PP, it is PbTI that is directly associated with carotid artery wall remodeling.