Forward Pressure Wave Amplitude Research Articles

Association of Aortic Stiffness and Pressure Pulsatility With Noninvasive Estimates of Hepatic Steatosis and Fibrosis: The Framingham Heart Study.

Arterial stiffening may contribute to the pathogenesis of metabolic dysfunction-associated steatotic liver disease. We aimed to assess relations of vascular hemodynamic measures with measures of hepatic steatosis and fibrosis in the community. Our sample was drawn from the Framingham Offspring, New Offspring Spouse, Third Generation, Omni-1, and Omni-2 cohorts (N=3875; mean age, 56 years; 54% women). We used vibration-controlled transient elastography to assess controlled attenuation parameter and liver stiffness measurements as measures of liver steatosis and liver fibrosis, respectively. We assessed noninvasive vascular hemodynamics using arterial tonometry. We assessed cross-sectional relations of vascular hemodynamic measures with continuous and dichotomous measures of hepatic steatosis and fibrosis using multivariable linear and logistic regression. In multivariable models adjusting for cardiometabolic risk factors, higher carotid-femoral pulse wave velocity (estimated β per SD, 0.05 [95% CI, 0.01-0.09]; P=0.003), but not forward pressure wave amplitude and central pulse pressure, was associated with more liver steatosis (higher controlled attenuation parameter). Additionally, higher carotid-femoral pulse wave velocity (β=0.11 [95% CI, 0.07-0.15]; P<0.001), forward pressure wave amplitude (β=0.05 [95% CI, 0.01-0.09]; P=0.01), and central pulse pressure (β=0.05 [95% CI, 0.01-0.09]; P=0.01) were associated with more hepatic fibrosis (higher liver stiffness measurement). Associations were more prominent among men and among participants with obesity, diabetes, and metabolic syndrome (interaction P values, <0.001-0.04). Higher carotid-femoral pulse wave velocity, but not forward pressure wave amplitude and central pulse pressure, was associated with higher odds of hepatic steatosis (odds ratio, 1.16 [95% CI, 1.02-1.31]; P=0.02) and fibrosis (odds ratio, 1.40 [95% CI, 1.19-1.64]; P<0.001). Elevated aortic stiffness and pressure pulsatility may contribute to hepatic steatosis and fibrosis.

Association of Arterial Stiffness With Mid- to Long-Term Home Blood Pressure Variability in the Electronic Framingham Heart Study: Cohort Study.

Short-term blood pressure variability (BPV) is associated with arterial stiffness in patients with hypertension. Few studies have examined associations between arterial stiffness and digital home BPV over a mid- to long-term time span, irrespective of underlying hypertension. This study aims to investigate if arterial stiffness traits were associated with subsequent mid- to long-term home BPV in the electronic Framingham Heart Study (eFHS). We hypothesized that higher arterial stiffness was associated with higher home BPV over up to 1-year follow-up. At a Framingham Heart Study research examination (2016-2019), participants underwent arterial tonometry to acquire measures of arterial stiffness (carotid-femoral pulse wave velocity [CFPWV]; forward pressure wave amplitude [FWA]) and wave reflection (reflection coefficient [RC]). Participants who agreed to enroll in eFHS were provided with a digital blood pressure (BP) cuff to measure home BP weekly over up to 1-year follow-up. Participants with less than 3 weeks of BP readings were excluded. Linear regression models were used to examine associations of arterial measures with average real variability (ARV) of week-to-week home systolic (SBP) and diastolic (DBP) BP adjusting for important covariates. We obtained ARV as an average of the absolute differences of consecutive home BP measurements. ARV considers not only the dispersion of the BP readings around the mean but also the order of BP readings. In addition, ARV is more sensitive to measurement-to-measurement BPV compared with traditional BPV measures. Among 857 eFHS participants (mean age 54, SD 9 years; 508/857, 59% women; mean SBP/DBP 119/76 mm Hg; 405/857, 47% hypertension), 1 SD increment in FWA was associated with 0.16 (95% CI 0.09-0.23) SD increments in ARV of home SBP and 0.08 (95% CI 0.01-0.15) SD increments in ARV of home DBP; 1 SD increment in RC was associated with 0.14 (95% CI 0.07-0.22) SD increments in ARV of home SBP and 0.11 (95% CI 0.04-0.19) SD increments in ARV of home DBP. After adjusting for important covariates, there was no significant association between CFPWV and ARV of home SBP, and similarly, no significant association existed between CFPWV and ARV of home DBP (P>.05). In eFHS, higher FWA and RC were associated with higher mid- to long-term ARV of week-to-week home SBP and DBP over 1-year follow-up in individuals across the BP spectrum. Our findings suggest that higher aortic stiffness and wave reflection are associated with higher week-to-week variation of BP in a home-based setting over a mid- to long-term time span.

Abstract 14300: Arterial Stiffness is Associated With Intermediate-Term Home Blood Pressure Variability: The Electronic Framingham Heart Study

Introduction: Short-term blood pressure variability (BPV) is associated with arterial stiffness in patients with hypertension. Few studies examined associations between arterial stiffness and digital home BPV over an intermediate time span. Objective: We investigated if antecedent arterial stiffness was associated with home BPV among participants in the electronic Framingham Heart Study (eFHS). We hypothesize that higher arterial stiffness predicts higher intermediate-term home BPV over one-year follow-up. Methods: At an FHS research exam (2016-2019), participants underwent arterial tonometry to acquire mean arterial pressure (MAP) and measures of arterial stiffness (carotid femoral pulse wave velocity, CFPWV; forward pressure wave amplitude, FWA) and wave reflection (reflection coefficient, RC). Participants who agreed to enroll in eFHS were provided with a digital blood pressure (BP) cuff to measure home BP weekly. Participants with &lt; 3 weeks of BP readings were excluded. Linear regression models were used to examine associations of arterial measures with home average real variability (ARV) of systolic (SBP) and diastolic (DBP) BP adjusting for covariates. We obtained ARV as an average of the absolute differences of consecutive BP measurements. ARV considers not only the dispersion of the BP readings around the mean, but also the order of BP readings. We used p&lt;0.05 for significance. Results: Among 857 eFHS participants (mean age 54 years, 59% women, mean BP 119/76, 47% hypertension, mean ARV of DBP 5.50, mean ARV of SBP 8.61), higher FWA and RC were associated with higher ARV of SBP ( Table ). Higher CFPWV was associated with lower ARV of DBP ( Table ). Conclusion: In eFHS, higher FWA and RC were associated with higher intermediate-term home BPV of SBP while higher CFPWV was associated with blunted BPV of DBP. Our findings suggest that higher aortic stiffness and wave reflection may affect day-to-day modulation of blood pressure in a home-based setting.

Single vs Serial Assessments of Arterial Hemodynamics to Predict Thoracic Aortic Aneurysm Expansion

BackgroundThoracic aortic aneurysm (TAA) is a highly morbid disease. We have previously shown that baseline hemodynamic measures reflecting aortic function are associated with future TAA expansion. However, whether serial arterial hemodynamic assessment further improves TAA growth assessment remains unknown. Therefore, we aimed to compare single vs serial arterial hemodynamic assessments in the evaluation of future TAA growth. MethodsEighty-six unoperated participants with TAA underwent noninvasive arterial hemodynamic assessment using arterial tonometry and echocardiography at baseline and after 1 year. Aortic diameter was measured serially with the use of standard imaging modalities. Stepwise multivariable linear regression was used to assess associations of baseline and 1-year change (Δ) in arterial hemodynamic measures with TAA growth. ResultsMean age was 62.7 ± 11.0 years; 79% were male. Mean aneurysm growth was 0.48 ± 0.54 mm/year after a follow-up of 2.96 ± 1.03 years. Yearly changes in arterial hemodynamic measures ranged from −3.2% to +4.2%. Linear regression results showed that while baseline arterial hemodynamic measures were independently associated with aneurysm growth (carotid-femoral pulse wave velocity: β ± SE = 0.038 ± 0.013; aortic characteristic impedance: β ± SE = 0.002 ± 0.001; proximal aortic compliance: β ± SE = −0.011 ± 0.006; forward pressure wave amplitude: β ± SE 0.009 ± 0.002; reflected pressure wave amplitude: β ± SE = 0.017 ± 0.006; P < 0.05 for each), the 1-year Δ in these measures did not incrementally add to aneurysm growth assessment (P > 0.05 for each Δ). ConclusionsAlthough baseline measures of aortic function independently predict TAA expansion, 1-year changes in these measures do not improve this prediction. Thus, for TAA risk assessment purposes, a baseline assessment of aortic function may suffice, which simplifies its use for potential predictive algorithms.

Lower-body dynamic exercise reduces wave reflection in healthy young adults.

What is the central question of this study? There is a paradoxical reduction in augmentation index during lower-body dynamic (LBD) exercise in the face of an increase in central pressure. To determine causality, the amplitudes of forward and backward pressure waves were assessed separately using wave separation analysis. What is the main finding and its importance? Reflection magnitude decreased during LBD exercise in healthy young adults and was attributable to an increased forward pressure wave amplitude and decreased backward pressure wave amplitude. This vasoactive response might limit the adverse effects of wave reflection during LBD exercise, optimizing ventricular-arterial interactions. Acute lower-body dynamic (LBD) exercise decreases surrogate measures of wave reflection, such as the augmentation index. However, the augmentation index is influenced by the combined effects of wave reflection timing, magnitude and other confounding factors external to wave reflection, which make it difficult to discern the origin of changes in surrogate measures. The relative contributions of forward (Pf) and backward (Pb) pressure wave amplitudes to central pressure can be determined by wave separation analysis. Reflection magnitude (RM=Pb/Pf) and the timing of apparent wave reflection return can also be determined. We tested the hypothesis that acute LBD exercise decreases RM and reflected wave transit time (RWTT). Applanation tonometry was used to record radial artery pressure waveforms in 25 adults (24 ± 4 years of age) at baseline and during light-, moderate- and vigorous-intensity exercise. Wave separation analysis was conducted offline using a personalized physiological flow wave to determine Pf, Pb, RM and RWTT. The RM decreased during all intensities of exercise compared with baseline (all P<0.001; baseline, 43 ± 5%; light, 33 ± 6%; moderate, 23 ± 7%; vigorous, 17 ± 5%). The reduction in RM was attributable to the combined effect of increased Pf and decreased Pb during exercise. The RWTT decreased during all intensities of exercise compared with baseline (all P<0.04; baseline, 156 ± 17ms; light, 144 ± 15ms; moderate, 129 ± 16ms; vigorous, 121 ± 17ms). Lastly, in a stepwise multilinear regression, Pf, but not Pb and RWTT, contributed to increased central pulse pressure during LBD exercise. These data show that wave reflection decreased and that central pulse pressure is most influenced by Pf during LBD exercise.

Clinical Associations of Vascular Stiffness, Microvascular Dysfunction, and Prevalent Cardiovascular Disease in a Black Cohort: The Jackson Heart Study.

BackgroundMeasures of vascular dysfunction are related to adverse cardiovascular disease (CVD) outcomes in non‐Hispanic, White populations; however, data from Black individuals are limited. We aimed to investigate the associations between novel hemodynamic measures and prevalent CVD in a sample of Black individuals.Methods and ResultsAmong older Black participants of the Jackson Heart Study, we assessed noninvasive vascular hemodynamic measures using arterial tonometry and Doppler ultrasound. We assessed 5 measures of aortic stiffness and wave reflection (carotid‐femoral pulse wave velocity, pulse wave velocity ratio, forward pressure wave amplitude, central pulse pressure, and augmentation index), and 2 measures of microvascular function (baseline and hyperemic brachial flow velocity). Using multivariable logistic regression models, we examined the relations between vascular hemodynamic measures and prevalent CVD. In models adjusted for traditional CVD risk factors, higher carotid‐femoral pulse wave velocity (odds ratio [OR],1.25; 95% CI, 1.01–1.55; P=0.04), lower augmentation index (OR, 0.84; 95% CI, 0.70–0.99; P=0.05), and lower hyperemic brachial flow velocity (OR, 0.77; 95% CI, 0.65–0.90; P=0.001) were associated with higher odds of CVD. After further adjustment for hypertension treatment, lower augmentation index (OR, 0.84; 95% CI, 0.70–0.99; P=0.04) and hyperemic brachial flow velocity (OR, 0.79; 95% CI, 0.67–0.94; P=0.006), but not carotid‐femoral pulse wave velocity (OR, 1.23; 95% CI, 0.99–1.051; P=0.06), were associated with higher odds of CVD.ConclusionsIn a sample of older Black individuals, more severe microvascular damage and aortic stiffness were associated with prevalent CVD. Further research on hemodynamic mechanisms that contribute to cardiovascular risk among older Black individuals is merited.

Long- and short-term air pollution exposure and measures of arterial stiffness in the Framingham Heart Study

BackgroundStudies of air pollution exposure and arterial stiffness have reported inconsistent results and large studies employing the reference standard of arterial stiffness, carotid-femoral pulse-wave velocity (CFPWV), have not been conducted. AimTo study long-term exposure to ambient fine particles (PM2.5), proximity to roadway, and short-term air pollution exposures in relation to multiple measures of arterial stiffness in the Framingham Heart Study. MethodsWe assessed central arterial stiffness using CFPWV, forward pressure wave amplitude, mean arterial pressure and augmentation index. We investigated long-and short-term air pollution exposure associations with arterial stiffness with linear regressions using long-term residential PM2.5 (2003 average from a spatiotemporal model using satellite data) and proximity to roadway in addition to short-term averages of PM2.5, black carbon, particle number, sulfate, nitrogen oxides, and ozone from stationary monitors. ResultsWe examined 5842 participants (mean age 51 ± 16, 54% women). Living closer to a major roadway was associated with higher arterial stiffness (0.11 m/s higher CFPWV [95% CI: 0.01, 0.22] living <50 m vs 400 ≤ 1000 m). We did not observe association between arterial stiffness measures and long-term PM2.5 or short-term levels of PM2.5, particle number, sulfate or ozone. Higher levels of black carbon and nitrogen oxides in the previous days were unexpectedly associated with lower arterial stiffness. ConclusionsLong-term exposure to PM2.5 was not associated with arterial stiffness but positive associations with living close to a major road may suggest that pollutant mixtures very nearby major roads, rather than PM2.5, may affect arterial stiffness. Furthermore, short-term air pollution exposures were not associated with higher arterial stiffness.

The Effect of Lower Body Aerobic Exercise on Forward and Backward Pressure Wave Amplitude

The Effect of Lower Body Aerobic Exercise on Forward and Backward Pressure Wave Amplitude

Metabolic Predictors of Change in Vascular Function: Prospective Associations From a Community-Based Cohort.

Vascular function varies with age because of physiological and pathological factors. We examined relations of longitudinal change in vascular function with change in metabolic traits. Longitudinal changes in vascular function and metabolic traits were examined in 5779 participants (mean age, 49.8±14.5 years; 54% women) who attended sequential examinations of the Framingham Offspring, Third Generation, and Omni-1 and Omni-2 cohorts. Multivariable regression analysis related changes in vascular measures (dependent variables), including carotid-femoral pulse wave velocity (CFPWV), forward pressure wave amplitude, characteristic impedance, central pulse pressure, and mean arterial pressure (MAP), with change in body mass index, fasting total:high-density lipoprotein cholesterol ratio, serum triglycerides, and blood glucose. Analyses accounted for baseline value of each vascular and metabolic measure, MAP change, and multiple comparisons. On follow-up (mean, 5.9±0.6 years), aortic stiffness (CFPWV, 0.2±1.6 m/s), and pressure pulsatility (forward pressure wave, 1.2±12.4 mm Hg; characteristic impedance, 23±73 dyne×sec/cm5; central pulse pressure, 2.6±14.7 mm Hg; all P<0.0001) increased, whereas MAP fell (-3±10 mm Hg; P<0.0001). Worsening of each metabolic trait was associated with increases in CFPWV and MAP (P<0.0001 for all associations) and an increase in MAP was associated with an increase in CFPWV. Overall, worsening metabolic traits were associated with worsening aortic stiffness and MAP. Opposite net change in aortic stiffness and MAP suggests that factors other than distending pressure contributed to the observed increase in aortic stiffness. Change in metabolic traits explained a greater proportion of the change in CFPWV and MAP than baseline metabolic values.

Relations of Arterial Stiffness With Postural Change in Mean Arterial Pressure in Middle-Aged Adults: The Framingham Heart Study.

Impaired regulation of blood pressure on standing can lead to adverse outcomes, including falls, syncope, and disorientation. Mean arterial pressure (MAP) typically increases on standing; however, an insufficient increase or a decline in MAP on standing may result in decreased cerebral perfusion. Orthostatic hypotension has been reported in older people with increased arterial stiffness, whereas the association between orthostatic change in MAP and arterial stiffness in young- to middle-aged individuals has not been examined. We analyzed orthostatic blood pressure response and comprehensive hemodynamic data in 3205 participants (1693 [53%] women) in the Framingham Heart Study Third Generation cohort. Participants were predominantly middle aged (mean age: 46±9 years). Arterial stiffness was assessed using carotid-femoral pulse wave velocity, forward pressure wave amplitude, and characteristic impedance of the aorta. Adjusting for standard cardiovascular disease risk factors, orthostatic change in MAP (6.9±7.7 mm Hg) was inversely associated with carotid-femoral pulse wave velocity (partial correlation, rp=-0.084; P<0.0001), forward wave amplitude (rp=-0.129; P<0.0001), and characteristic impedance (rp=-0.094; P<0.0001). The negative relation between forward wave amplitude and change in MAP on standing was accentuated in women (P=0.002 for sex interaction). Thus, higher aortic stiffness was associated with a blunted orthostatic increase in MAP, even in middle age. The clinical implications of these findings warrant further study.

Misinterpretation of the Determinants of Elevated Forward Wave Amplitude Inflates the Role of the Proximal Aorta.

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.

Relations of circulating GDF-15, soluble ST2, and troponin-I concentrations with vascular function in the community: The Framingham Heart Study

Background and aimsGrowth differentiation factor-15 (GDF-15), soluble (s)ST2, and high-sensitivity troponin-I (hs-TnI) are associated with incident cardiovascular disease (CVD) including heart failure, yet the underlying mechanisms are not fully understood. We investigated if GDF-15, sST2, and hs-TnI are related to subclinical vascular dysfunction in the community, which may explain the relations of these biomarkers with CVD. MethodsWe evaluated 1823 Framingham Study participants (mean age 61 ± 10 years, 54% women) who underwent routine assessment of vascular function. We related circulating GDF-15, sST2, and hs-TnI concentrations to measures of arterial stiffness (carotid-femoral pulse wave velocity, CFPWV; augmentation index; and forward pressure wave amplitude, FW), endothelial-dependent vasodilation (flow-mediated dilation, FMD), and baseline and hyperemic brachial flow velocities using linear regression adjusting for standard risk factors. ResultsAfter multivariable adjustment, GDF-15 levels were positively associated with CFPWV (0.044 [95% confidence interval 0.007–0.081] standard deviation [SD] change per SD increase in loge[GDF-15], p = 0.02) and FW (0.076 [0.026–0.126] SD change per SD increase in loge[GDF-15], p = 0.003) and inversely related to FMD (−0.051 [−0.101–0.0003] SD change per SD increase in loge[GDF-15], p = 0.048). sST2 was positively associated with CFPWV (0.032 [0.0005–0.063] SD change per SD increase in loge[sST2], p = 0.046), and hs-TnI inversely associated with hyperemic flow velocity (−0.041 [−0.082–0.0004] SD change per SD increase in loge[hs-TnI], p = 0.048). ConclusionIn our community-based investigation, individual cardiac stress biomarkers were differentially related to select aspects of vascular function. These findings may contribute to the associations of circulating GDF-15, sST2, and hs-TnI with incident CVD and heart failure.

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

Elevated blood pressure is the leading modifiable risk factor for cardiovascular disease (CVD) and premature death. The blood pressure waveform consists of discrete hemodynamic components, derived from measured central pressure and flow, which may contribute separately to risk for an adverse outcome. However, pressure-flow measures have not been studied in a large, community-based sample. We used proportional hazards models to examine the association of incident CVD with forward pressure wave amplitude, mean arterial pressure, and global reflection coefficient derived from wave separation analysis and echocardiography in 2492 participants (mean age 66±9 years, 56% women) in the Framingham Heart Study. During follow-up (0.04-6.8 years), 149 participants (6%) had a CVD event. In multivariable models adjusting for age, sex, antihypertensive therapy, body mass index, heart rate, total and high-density lipoprotein cholesterol concentrations, smoking, and the presence of diabetes mellitus, forward pressure wave amplitude (hazard ratio, 1.40; 95% confidence interval, 1.16-1.67; P=0.0003) was associated with incident CVD, whereas mean arterial pressure (hazard ratio, 1.10; 95% confidence interval, 0.94-1.29; P=0.25) and global wave reflection (hazard ratio, 0.93; 95% confidence interval, 0.78-1.12; P=0.58) were not. After adding systolic blood pressure and carotid-femoral pulse wave velocity to the model, forward pressure wave amplitude persisted as a correlate of events (hazard ratio, 1.33; 95% confidence interval, 1.05-1.68; P=0.02). Higher forward pressure wave amplitude (a measure of proximal aortic geometry and stiffness) was associated with increased risk for incident CVD, whereas mean arterial pressure and relative wave reflection (correlates of resistance vessel structure and function) were not associated with increased risk for incident CVD.

Arterial stiffness and hypertension: chicken or egg?

Hypertension is highly prevalent in the United States and worldwide. In the United States, 1 in 3 adults (≈73 million people) have hypertension. The financial and human costs of hypertension are substantial. The estimated costs attributable to hypertension in the United States alone in 2010 were $70 billion direct costs for medical treatments and $24 billion indirect costs because of lost productivity.1 Awareness and treatment of hypertension have improved considerably during the past several decades: >80% of all people with hypertension are aware of the condition and 75% are using antihypertensive medications.2,3 However, despite enormous effort and treatment-related expenditures, only 53% of those with documented hypertension have their blood pressure controlled.3 Older age (Figure 1), left ventricular hypertrophy, and obesity are important risk factors for uncontrolled or drug-resistant hypertension.4 Importantly, the foregoing are also risk factors for increased aortic stiffness.5 Figure 1. Hypertension prevalence and control rates as a function of age in the National Health and Nutrition Examination Survey 2003 to 2004. Data derived from Wong et al.44 During the past 2 decades, measures of aortic stiffness have emerged as important risk factors for progression of blood pressure and incident cardiovascular disease. Carotid femoral pulse wave velocity (CFPWV), a measure of aortic wall stiffness, increases markedly with age, particularly after midlife. For example, Framingham Heart Study investigators have shown that the prevalence of CFPWV ≥12 m/s increases from a few percentage before 50 years of age to ≥60% after 70 years of age (Figure 2A). Importantly, elevated CFPWV is associated with high risk for incident hypertension (Figure 2B) and cardiovascular disease (Figure 2C). Figure 2C should be interpreted within the context that a normal value (<95th percentile) for CFPWV in a healthy Framingham Heart Study reference sample <50 years of age was 8.1 …

Relations of Exercise Blood Pressure Response to Cardiovascular Risk Factors and Vascular Function in the Framingham Heart Study

Exercise blood pressure (BP) is an important marker of left ventricular hypertrophy, incident hypertension, and future cardiovascular events. Although impaired vascular function is hypothesized to influence the BP response during exercise, limited data exist on the association of vascular function with exercise BP in the community. Framingham Offspring cohort participants (n=2115, 53% women, mean age 59 years) underwent a submaximal exercise test (first 2 stages of the Bruce protocol), applanation tonometry, and brachial artery flow-mediated dilation testing. We related exercise systolic and diastolic BP at second stage of the Bruce protocol to standard cardiovascular risk factors and to vascular function measures. In multivariable linear regression models, exercise systolic BP was positively related to age, standing BP, standing heart rate, smoking, body mass index, and the total cholesterol-to-high-density cholesterol ratio (P≤0.01 for all). Similar associations were observed for exercise diastolic BP. Carotid-femoral pulse wave velocity (P=0.02), central pulse pressure (P<0.0001), mean arterial pressure (P=0.04), and baseline brachial flow (P=0.002) were positively associated with exercise systolic BP, whereas flow-mediated dilation was negatively associated (P<0.001). For exercise diastolic BP, forward pressure wave amplitude was negatively related (P<0.0001), whereas mean arterial pressure was positively related (P<0.0001). Increased arterial stiffness and impaired endothelial function are significant correlates of a higher exercise systolic BP response. Our findings suggest that impaired vascular function may contribute to exaggerated BP responses during daily living, resulting in repetitive increments in load on the heart and vessels and increased cardiovascular disease risk.

Augmented aortic forward pressure wave amplitude contributes to increased left ventricular mass in overweight adolescents

Augmented aortic forward pressure wave amplitude contributes to increased left ventricular mass in overweight adolescents

Hemodynamic Correlates of Blood Pressure Across the Adult Age Spectrum

Background— Systolic blood pressure and pulse pressure are substantially higher in older adults. The relative contributions of increased forward versus reflected pressure wave amplitude or earlier arrival of the reflected wave to elevated pulse pressure remain controversial. Methods and Results— We measured proximal aortic pressure and flow, forward pressure wave amplitude, global wave reflection, reflected wave timing, and pulse wave velocity noninvasively in 6417 (age range, 19 to 90 years; 53 women) Framingham Heart Study Third Generation and Offspring participants. Variation in forward wave amplitude paralleled pulse pressure throughout adulthood. In contrast, wave reflection and pulse pressure were divergent across adulthood: In younger participants, pulse pressure was lower and wave reflection was higher with advancing age, whereas in older participants, pulse pressure was higher and wave reflection was lower with age. Reflected wave timing differed modestly across age groups despite considerable differences in pulse wave velocity. Forward wave amplitude explained 80 (central) and 66 (peripheral) of the variance in pulse pressure in younger participants (&lt;50 years) and 90 and 84 in the older participants (≥50 years; all P &lt;0.0001). In a stepwise model that evaluated age–pulse pressure relations in the full sample, the late accelerated increases in central and peripheral pulse pressure were markedly attenuated when variation in forward wave amplitude was considered. Conclusions— Higher pulse pressure at any age and higher pulse pressure with advancing age is associated predominantly with a larger forward pressure wave. The influence of wave reflection on age-related differences in pulse pressure was minor.

Arterial Stiffness in Mild-to-Moderate CKD

Whether arterial stiffness correlates with mild-to-moderate CKD and albuminuria in the community is unclear. We studied the association between arterial stiffness and mild-to-moderate CKD and albuminuria in the Framingham Heart Study. CKD was present in 6.7% (181 of 2682) of participants and microalbuminuria was present in 8.2% (479 of 5818). The measures of arterial stiffness were the carotid femoral pulse wave velocity, forward pressure wave amplitude, central pulse pressure, augmentation pressure, augmentation index, and mean arterial pressure. In cross-sectional analyses, arterial stiffness did not associate with CKD (defined by estimated GFR <60 ml/min/1.73 m(2)) in either age- and gender-adjusted or multivariable-adjusted linear regression models. Carotid femoral pulse wave velocity associated with both urinary albumin-to-creatinine ratio and microalbuminuria (P < 0.0001 after multivariable adjustment). In longitudinal analyses, we used logistic regression models to examine the associations between baseline arterial stiffness measures (exposure variables) and incident CKD or microalbuminuria (n = 1675 for CKD analyses and n = 1252 for microalbuminuria analyses). Baseline arterial measures did not associate with incident CKD or incident microalbuminuria. In summary, arterial stiffness correlates with albuminuria but not with mild-to-moderate CKD.

Clinical Summaries

Clinical Summaries

Multimarker Approach to Evaluate Correlates of Vascular Stiffness

Arterial stiffness increases with age and contributes to the pathogenesis of systolic hypertension and cardiovascular disease in the elderly. Knowledge about the pathophysiological processes that determine arterial stiffness may help guide therapeutic approaches. We related 7 circulating biomarkers representing distinct biological pathways (C-reactive protein, aldosterone-to-renin ratio, N-terminal proatrial natriuretic peptide and B-type natriuretic peptide, plasminogen activator inhibitor-1, fibrinogen, and homocysteine) to 5 vascular function measures (central pulse pressure, carotid-femoral pulse-wave velocity, mean arterial pressure, forward pressure wave amplitude [all measures of conduit artery stiffness], and augmented pressure, an indicator of wave reflection) in 2000 Framingham Offspring Study participants (mean age, 61 years; 55% women). Tonometry measures were obtained on average 3 years after the biomarkers were measured. In multivariable linear regression models adjusting for covariates, the biomarker panel was significantly associated with all 5 vascular measures (P<0.003 for all). On backward elimination, the aldosterone-to-renin ratio was positively associated with each stiffness measure (P< or =0.002 for all). In addition, C-reactive protein was positively related to augmented pressure (P=0.0003), whereas plasminogen activator inhibitor-1 was positively associated with mean arterial pressure (P=0.003), central pulse pressure (P=0.001), and forward pressure wave (P=0.01). Our cross-sectional data on a community-based sample suggest a distinctive pattern of positive associations of biomarkers of renin-angiotensin-aldosterone system activation with pan-arterial vascular stiffness, plasminogen activator inhibitor-1 with central vascular stiffness indices, and C-reactive protein with wave reflection. These observations support the notion of differential influences of biological pathways on vascular stiffness measures.