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The increase in pulse pressure (PP) that occurs with advancing age is predominantly due to reduced arterial distensibility leading to decreased aortic compliance, particularly in the elderly, in whom high blood pressure mainly manifests as isolated systolic hypertension. Since age-related changes in stroke volume are minimal compared with changes in PP, PP is often considered a surrogate measure of arterial stiffness. However, since PP is determined by both cardiac and arterial function, a more precise and reliable means of assessment of arterial stiffness is arterial pulse wave velocity (PWV), a parameter that is only dependent on arterial properties. Arterial stiffness as measured by PWV has been found to be a powerful pressure-related indicator for cardiovascular morbidity and mortality. We analyzed PP and PWV in men and women of various age groups in healthy volunteers as well as cardiac patients with different types of diseases. The findings identified several striking sex-specific differences which demand consideration in guidelines for diagnostic procedures, for epidemiological analysis, and in evaluation of therapeutic interventions.

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BackgroundThe hemodynamic basis for increased pulse pressure (PP) with aging remains controversial. The classic paradigm attributes a predominant role to increased pulse wave velocity (PWV) and premature wave reflections (WRs). A controversial new paradigm proposes increased forward pressure wave amplitude (FWA), attributed to proximal aortic characteristic impedance (Zc), as the predominant factor, with minor contributions from WRs. Based on theoretical considerations, we hypothesized that (rectified) WRs drive the increase in FWA, and that the forward pressure wave does not depend solely on the interaction between flow and Zc (QZc product).Methods and ResultsWe performed 3 substudies: (1) open‐chest anesthetized dog experiments (n=5); (2) asymmetric T‐tube model‐based study; and (3) human study in a diverse clinical population (n=193). Animal experiments demonstrated that FWA corresponds to peak QZc only when WRs are minimal. As WRs increased, FWA was systematically greater than QZc and peaked well after peak flow, analogous to late‐systolic peaking of pressure attributable to WRs. T‐tube modeling confirmed that increased/premature WRs resulted in increased FWA. Magnitude and timing of WRs explained 80.8% and 74.3% of the variability in the difference between FWA and peak QZc in dog and human substudies, respectively.ConclusionsOnly in cases of minimal reflections does FWA primarily reveal the interaction between peak aortic flow and proximal aortic diameter/stiffness. FWA is strongly dependent on rectified reflections. If interpreted out of context with the hemodynamic principles of its derivation, the FWA paradigm inappropriately amplifies the role of the proximal aorta in elevation of FWA and PP.

BackgroundDespite pronounced increases in central pulse wave velocity (PWV) with aging, reflected wave transit time (RWTT), traditionally defined as the timing of the inflection point (TINF) in the central pressure waveform, does not appreciably decrease, leading to the controversial proposition of a “distal‐shift” of reflection sites. TINF, however, is exceptionally prone to measurement error and is also affected by ejection pattern and not only by wave reflection. We assessed whether RWTT, assessed by advanced pressure‐flow analysis, demonstrates the expected decline with aging.Methods and ResultsWe studied a sample of unselected adults without cardiovascular disease (n=48; median age 48 years) and a clinical population of older adults with suspected/established cardiovascular disease (n=164; 61 years). We measured central pressure and flow with carotid tonometry and phase‐contrast MRI, respectively. We assessed RWTT using wave‐separation analysis (RWTTWSA) and partially distributed tube‐load (TL) modeling (RWTTTL). Consistent with previous reports, TINF did not appreciably decrease with age despite pronounced increases in PWV in both populations. However, aging was associated with pronounced decreases in RWTTWSA (general population −15.0 ms/decade, P<0.001; clinical population −9.07 ms/decade, P=0.003) and RWTTTL (general −15.8 ms/decade, P<0.001; clinical −11.8 ms/decade, P<0.001). There was no evidence of an increased effective reflecting distance by either method. TINF was shown to reliably represent RWTT only under highly unrealistic assumptions about input impedance.Conclusions RWTT declines with age in parallel with increased PWV, with earlier effects of wave reflections and without a distal shift in reflecting sites. These findings have important implications for our understanding of the role of wave reflections with aging.

The role that the pattern of vessel wall growth plays in determining pressure-lumen area (P-A) and pressure-compliance curves was examined. A P-A vessel model was developed that encompasses the complete range of pressure, including negative values, and accounts for size given the fixed length, nonlinear elastic wall properties, constant wall area, and collapse. Data were obtained from excised canine carotid and femoral arteries, jugular veins, and elastic tubing. The mean error of estimate was 8 mmHg for all vessels studied and 2 mmHg for blood vessels. The P-A model was employed to examine two patterns of arterial wall thickening, outward growth and remodeling (constant wall area), under the assumption of constant wall properties. The model predicted that only outward wall growth resets compliance such that it increases at a given arterial pressure, explaining previously contradictory data. In addition, it was found that outward wall growth increases the lumen area between normal and high pressures. Remodeling resulted in lumen narrowing and a decrease in compliance for positive pressures.

Ejection Fraction (EF) has attained the recognition as indicator of global ventricular performance. Remarkably, precise historical origins promoting the apparent importance of EF are scant. During early utilization EF has been declared a gold standard for the evaluation of the heart as a pump. In contrast, during the last two decades, clinicians have developed a measure of doubt in the universal applicability of EF. This reluctance lead to the introduction of a new and prevalent syndrome in which heart failure (HF) is diagnosed as having a preserved EF (pEF). We examine the existing criticism regarding EF, and describe a novel avenue to characterize ventricular function within the unifying framework of cardiac input–output volume regulation. This approach relates end-systolic volume (ESV) to end-diastolic volume (EDV), and derives for a subgroup matching pEF criteria a distinct pattern in the ESV–EDV domain. In patients with pEF (n = 34), a clear difference (P < 0.0004) in the slope of the regression line for ESV versus EDV was demonstrated compared to control patients with EF < 50% (n = 29). These findings are confirmed by analysis of data presented in two independent publications. The volume regulation approach proposed employs primary end-point determinants (such as ESV and EDV) rather than derived quantities (e.g., the ratio EF or its differential parameter, that is, stroke volume) and confirms a distinct advantage over the classical Starling curve. Application of the ESV-EDV-construct provides the basis and clarifies why some patients present as HFpEF, while others have reduced EF.