Components of hemodynamic load and cardiovascular events: the Framingham Heart Study.

Blood pressure is a major risk factor for cardiovascular disease (CVD) that accounts for almost 8 million premature deaths per year worldwide.1, 2 Over the past decades, medications used to treat hypertension and prevent CVD events were designed to reduce mean arterial pressure (MAP). However, this MAP-focused approach may be suboptimal in light of the preponderance of predominant or isolated systolic hypertension, particularly among patients with persistently elevated blood pressure despite treatment.3-5 To assess residual CVD risk associated with persistently elevated blood pressure, investigators have evaluated novel measures of aortic stiffness and hemodynamic load, such as peripheral and central pulse pressure (PP) and aortic pulse wave velocity, which may be predictive of CVD progression and events.6-14 Indeed, we have shown previously that increased carotid-femoral pulse wave velocity (CFPWV) is associated with increased risk for CVD events.6 Yet, little is known about the relative and incremental contributions to CVD risk of the mean and various pulsatile components of blood pressure. PP plays an important role in the pathogenesis of hypertension, particularly after midlife, and higher PP is related to clinical events.11, 15-18 However, the components of PP that confer higher risk remain unclear. Some have argued that greater wave reflection, as indicated by augmentation index or augmented pressure, is associated with increased risk.7, 19-21 Yet, augmentation index and augmented pressure are composite measures that may be affected by forward and backward waves.22, 23 One must measure pressure and flow in order to separate forward and backward waves and compute the global reflection coefficient, which is the reference standard for assessing wave reflection.24, 25 Systolic blood pressure (SBP) has been proposed as a primary guide to prognosis and therapy; however, SBP provides an aggregate measure of the effects of mean and pulsatile pressure that may potentially overlook components of each. Therefore, knowledge of SBP alone does not establish whether an individual has an abnormality of mean or pulsatile load, which is a distinction that may have treatment implications. Moreover, an earlier Framingham study showed that blood pressure models combining SBP with diastolic blood pressure (DBP) or PP with MAP were superior to any of the four single blood pressure components (SBP, DBP, MAP or PP) considered alone at predicting CVD risk.26 To our knowledge, no prior community-based study has compared the relations to incident CVD of a comprehensive panel of individual mean and pulsatile components of blood pressure derived from an analysis of measured central aortic pressure and flow. We hypothesized that true central forward pressure wave amplitude (FWA), the primary hemodynamic correlate of variability in central and peripheral PP in younger and older individuals,27 would be an important predictor of CVD risk in models that adjusted for standard risk factors, including SBP.