Association of aortic stiffness and wave reflections with coronary flow reserve in women without obstructive coronary artery disease: An ancillary study from the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE).

BACKGROUND: Increased aortic stiffness and reduced coronary flow reserve (CFR) independently predict adverse outcomes. But information about relationships between arterial properties and CFR in subjects without obstructive coronary artery disease (CAD) is limited. METHODS: CFR was measured (Doppler flow wire and intracoronary adenosine) in 50 women (age 53 ± 11 years) with symptoms and signs of myocardial ischemia without obstructive CAD. Aortic pulse wave velocity (aPWV), a measure of aortic stiffness, was obtained via catheter pullback; radial artery pressure waves were measured by applanation tonometry and central aortic pressure synthesized. RESULTS: Overall, CFR (mean 2.61 ± 0.47) was significantly correlated with aPWV (r = -0.51), pulse wave amplification (r = 0.45), augmented pressure (r = -0.48), augmentation index (AIx, r = -0.44), aortic systolic pressure (r = -0.49), left ventricular wasted energy (LVEw, r = -0.47) (all P < .001), systolic pressure time index (r = -0.37, P < .008), and rate pressure product (r = -0.29, P < .04). In the multiple regression model including aPWV, CFR was still significantly correlated with aPWV (P < .008) and aortic systolic pressure (P < .01). No other measures contributed significant additional information. Women with CFR ≤2.5 versus those with CFR >2.5 had greater aPWV (894 ± 117 vs 747 ± 93 cm/s, P < .001), augmented pressure (14 ± 4.9 vs 11 ± 4.1 mmHg, P < .008), AIx (32 ± 6.6 vs 27 ± 6.6%, P < .003), LVEw (30 ± 12 vs 21 ± 10 dyne-s/cm(2) × 10(2), P < .02) and reduced pulse pressure amplification (1.20 ± .07 vs 1.26 ± .10, P < .008) and pressure wave travel time (133 ± 7.3 vs 138 ± 6.9 milliseconds, P < .04). CONCLUSIONS: Among symptomatic women without obstructive CAD, CFR was inversely related to aortic systolic pressure and indices of aortic stiffness. These changes in arterial properties increase left ventricular afterload requiring the ventricle to generate additional, but wasted, energy that increases indices of myocardial oxygen demand, reduces CFR and increases vulnerability to ischemia.

Enhanced external counterpulsation improves peripheral artery flow-mediated dilation in patients with chronic angina: a randomized sham-controlled study.

BACKGROUND: Mechanisms responsible for anti-ischemic benefits of enhanced external counterpulsation (EECP) remain unknown. This was the first randomized sham-controlled study to investigate the extracardiac effects of EECP on peripheral artery flow-mediated dilation. METHODS AND RESULTS: Forty-two symptomatic patients with coronary artery disease were randomized (2:1 ratio) to thirty-five 1-hour sessions of either EECP (n=28) or sham EECP (n=14). Flow-mediated dilation of the brachial and femoral arteries was performed with the use of ultrasound. Plasma levels of nitrate and nitrite, 6-keto-prostaglandin F(1α), endothelin-1, asymmetrical dimethylarginine, tumor necrosis factor-α, monocyte chemoattractant protein-1, soluble vascular cell adhesion molecule, high-sensitivity C-reactive protein, and 8-isoprostane were measured. EECP increased brachial (+51% versus +2%) and femoral (+30% versus +3%) artery flow-mediated dilation, the nitric oxide turnover/production markers nitrate and nitrite (+36% versus +2%), and 6-keto-prostaglandin F(1α) (+71% versus +1%), whereas it decreased endothelin-1 (-25% versus +5%) and the nitric oxide synthase inhibitor asymmetrical dimethylarginine (-28% versus +0.2%) in treatment versus sham groups, respectively (all P<0.05). EECP decreased the proinflammatory cytokines tumor necrosis factor-α (-16% versus +12%), monocyte chemoattractant protein-1 (-13% versus +0.2%), soluble vascular cell adhesion molecule-1 (-6% versus +1%), high-sensitivity C-reactive protein (-32% versus +5%), and the lipid peroxidation marker 8-isoprostane (-21% versus +1.3%) in treatment versus sham groups, respectively (all P<0.05). EECP reduced angina classification (-62% versus 0%; P<0.001) in treatment versus sham groups, respectively. CONCLUSIONS: Our findings provide novel mechanistic evidence that EECP has a beneficial effect on peripheral artery flow-mediated dilation and endothelial-derived vasoactive agents in patients with symptomatic coronary artery disease.

Relationship between endogenous concentrations of vasoactive substances and measures of peripheral vasodilator function in patients with coronary artery disease.

1. The aim of the present study was to determine the relationship between plasma concentrations of nitrite/nitrate (NO(x)) and endothelin (ET)-1 and non-invasive measures of peripheral vasodilator function in patients with coronary artery disease (CAD). 2. Twenty-two patients with angiographic CAD underwent non-invasive measurement of peripheral vasodilator function in the brachial conduit artery (flow-mediated dilation (FMD) testing via ultrasound) and in the forearm resistance arteries (via venous occlusion plethysmography) during reactive hyperaemia after 5 min ischaemia. In addition, plasma NO(x) and ET-1 concentrations were determined. 3. The plasma concentration of NO(x) was related to the peak brachial FMD response when expressed as either the relative (%) or absolute (mm) change in diameter (r = 0.73, P < 0.001; and r = 0.64, P < 0.01, respectively). Moreover, plasma concentrations of NO(x) demonstrated a relationship with forearm vasodilation estimated by total forearm blood flow following 5 min ischaemia (r = 0.63, P < 0.01) and the flow debt repayment of the forearm (r = 0.54, P < 0.01). Finally, ET-1 concentrations were inversely related to FMD% (r = -0.45, P < 0.05). 4. The findings of the present study demonstrate a relationship between the plasma concentrations of NO(x) and measures of vascular reactivity in conduit and resistance arteries in patients with CAD. Therefore, measurement of plasma NO(x) may serve as a reliable marker for peripheral vasodilator dysfunction in patients with CAD.

Maternal Cardiovascular Dysregulation During Early Pregnancy After In Vitro Fertilization Cycles in the Absence of a Corpus Luteum.

Commonly used in vitro fertilization protocols produce pregnancies without a corpus luteum (CL), a major source of reproductive hormones. In vitro fertilization pregnancies without a CL showed deficient gestational increases of central (aortic) arterial compliance during the first trimester and were at increased risk for developing preeclampsia. Here, we investigated whether there was generalized impairment of cardiovascular adaptation in in vitro fertilization pregnancies without a CL compared with pregnancies conceived spontaneously or through ovarian stimulation, which lead to 1 and >1 CL, respectively (n=19-26 participants per cohort). Prototypical maternal cardiovascular adaptations of gestation were serially evaluated noninvasively, initially during the follicular phase before conception, 6× in pregnancy, and then, on average, 1.6 years post-partum. The expected increases of cardiac output, left atrial dimension, peak left ventricular filling velocity in early diastole (E wave velocity), peripheral/central arterial pulse pressure ratio, and global AC, as well as decrease in augmentation index were significantly attenuated or absent during the first trimester in women who conceived without a CL, when compared with the 1 and >1 CL cohorts, which were comparable. Thereafter, these cardiovascular measures showed recovery in the 0 CL group except for E wave velocity, which remained depressed. These results provided strong support for a critical role of CL factor(s) in the transformation of the maternal cardiovascular system in early gestation. Regimens that lead to the development of a CL or replacement of missing CL factor(s) may be indicated to improve cardiovascular function and reduce preeclampsia risk in in vitro fertilization pregnancies.

Increased Preeclampsia Risk and Reduced Aortic Compliance With In Vitro Fertilization Cycles in the Absence of a Corpus Luteum.

In vitro fertilization involving frozen embryo transfer and donor oocytes increases preeclampsia risk. These in vitro fertilization protocols typically yield pregnancies without a corpus luteum (CL), which secretes vasoactive hormones. We investigated whether in vitro fertilization pregnancies without a CL disrupt maternal circulatory adaptations and increase preeclampsia risk. Women with 0 (n=26), 1 (n=23), or >1 (n=22) CL were serially evaluated before, during, and after pregnancy. Because increasing arterial compliance is a major physiological adaptation in pregnancy, we assessed carotid-femoral pulse wave velocity and transit time. In a parallel prospective cohort study, obstetric outcomes for singleton livebirths achieved with autologous oocytes were compared between groups by CL number (n=683). The expected decline in carotid-femoral pulse wave velocity and rise in carotid-femoral transit time during the first trimester were attenuated in the 0-CL compared with combined single/multiple-CL cohorts, which were similar (group-time interaction: P=0.06 and 0.03, respectively). The blunted changes of carotid-femoral pulse wave velocity and carotid-femoral transit time from prepregnancy in the 0-CL cohort were most striking at 10 to 12 weeks of gestation ( P=0.01 and 0.006, respectively, versus 1 and >1 CL). Zero CL was predictive of preeclampsia (adjusted odds ratio, 2.73; 95% CI, 1.14-6.49) and preeclampsia with severe features (6.45; 95% CI, 1.94-25.09) compared with 1 CL. Programmed frozen embryo transfer cycles (0 CL) were associated with higher rates of preeclampsia (12.8% versus 3.9%; P=0.02) and preeclampsia with severe features (9.6% versus 0.8%; P=0.002) compared with modified natural frozen embryo transfer cycles (1 CL). In common in vitro fertilization protocols, absence of the CL perturbed the maternal circulation in early pregnancy and increased the incidence of preeclampsia.

Effect of enhanced external counterpulsation on inflammatory cytokines and adhesion molecules in patients with angina pectoris and angiographic coronary artery disease.

Cardiovascular disease is associated with chronic low-level inflammation, as evidenced by elevated circulating proinflammatory cytokines. Experimental evidence suggests that inflammation can be suppressed under conditions of high shear stress. This study was conducted to examine the effects of enhanced external counterpulsation (EECP), a noninvasive therapy that increases endothelial shear stress, on circulating levels of inflammatory biomarkers and adhesion molecules in patients with angina pectoris. Twenty-one patients were randomly assigned to either 35 1-hour treatments at cuff pressures of 300 mm Hg (EECP; n=12) or 75 mm Hg (sham; n=9). Plasma tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and soluble vascular cell adhesion molecule-1 were measured before and after 35 1-hour sessions of treatment or sham. Patients in the EECP group demonstrated reductions in tumor necrosis factor-alpha (6.9+/-2.7 vs 4.9+/-2.5 pg/ml, p<0.01; -29%) and monocyte chemoattractant protein-1 (254.9+/-55.9 vs 190.4+/-47.6 pg/ml, p<0.01; -19%) after treatment, whereas there was no change in the sham group. Changes in soluble vascular cell adhesion molecule-1 were not observed in either group. In conclusion, 35 sessions of EECP decreased circulating levels of proinflammatory biomarkers in patients with symptomatic coronary artery disease.

Impact of aging on central pressure wave reflection characteristics during exercise.

BACKGROUND: Age is associated with increases in elastic artery stiffness and pulse wave velocity, which cause profound changes in arterial pressure waves, including increases in the augmentation index (AIx) and wasted left ventricular (LV) energy. We examined the impact of aging on the central blood pressure (BP) waveform and wave reflection responses during exercise. METHODS: Central BP and wave reflection characteristics were measured non-invasively using radial artery applanation tonometry at rest and during cycling exercise (45-65% of age predicted maximal heart rate (HR)) in 16 older (48 +/- 2 years) and 14 younger (24 +/- 1 years) men. RESULTS: Older men had increased central pressure values and AIx (26 +/- 2% vs. 12 +/- 2%) and lower pulse pressure amplification (PPA; 1.29 +/- 0.03 vs. 1.50 +/- 0.04) than their younger counterparts at rest (P < 0.05). Central pressure values and AIx (10 +/- 3% vs. -8 +/- 3%) continued to be greater, while PPA (1.61 +/- 0.04 vs. 1.85 +/- 0.03) was lower in the older group compared with the younger group during exercise (P < 0.05). However, the relative changes from baseline for central pressure values, AIx (-15 +/- 2 vs. -19 +/- 3), and PPA (0.32 +/- 0.03 vs. 0.35 +/- 0.04) were similar for both groups (P > 0.05). CONCLUSIONS: The findings of this study suggest that older men have a greater central BP and AIx and lower PPA during exercise. However, the magnitude of the central hemodynamic responses (i.e., change from baseline) during exercise does not differ between older and younger men.

Association between wasted pressure effort and left ventricular hypertrophy in hypertension: influence of arterial wave reflection.

BACKGROUND: Wave reflection during the systole increases left ventricular (LV) pressure, tension-time index (TTI) and myocardial oxygen requirement. The purpose of this study was to extract that component of extra myocardial oxygen requirement that is due to early systolic wave reflection, define it as wasted effort (DeltaE(w)), and examine its relationship to LV hypertrophy (LVH). METHODS: Radial artery pressure waveforms were recorded using applanation tonometry and central aortic waveforms generated in 98 patients with untreated hypertension. Aortic augmentation index (AI(a)), wave reflection amplitude (i.e., aortic augmented pressure (AG)) and systolic duration (ED-Tr), ejection duration (ED) and round-trip travel time of the pressure wave (Tr) were calculated from the aortic waveform, and DeltaE(w) estimated as 2.09 AG (ED-Tr). Carotid-femoral pulse wave velocity (PWV(e)) was also measured and LV mass index (LVMI) determined by echocardiography. RESULTS: DeltaE(w) was significantly correlated with age, body height, and LVMI. Women had greater DeltaE(w) than men. The correlation between DeltaE(w) and LVMI was independent of age, gender and body height (P = 0.003). Patients with LVH (LVH (+) group) showed greater DeltaE(w) than patients without LVH (LVH (-) group) (P = 0.003), and this difference remained significant when adjusted for confounding factors. Also, AI(a) and AG were higher in the LVH (+) than in the LVH (-) group (both P < 0.01). In contrast, PWV(e) was not different between the groups, and Tr showed only a marginal difference (P = 0.07). CONCLUSIONS: DeltaE(w) appears to be directly and positively associated with LVH in untreated hypertensive patients. The amplitude and duration of the reflected wave, rather than its travel time, are probably responsible for this association.

Effects of arterial stiffness, pulse wave velocity, and wave reflections on the central aortic pressure waveform.

Brachial systolic and pulse blood pressures (BPs) are better predictors of adverse cardiovascular (CV) events than diastolic BP in individuals older than 50 years. The principal cause of increased systolic and pulse BP is increased stiffness of the elastic arteries as a result of degeneration and hyperplasia of the arterial wall. Recent studies have shown that central BP, the pressure exerted on the heart, brain, and kidneys, is a better predictor of CV risk than brachial BP. As stiffness increases, reflected wave amplitude increases and augments pressure in late systole, producing an increase in left ventricular afterload and myocardial oxygen demand. Vasoactive drugs have little direct effect on large human elastic arteries but can markedly modify wave reflection by altering stiffness of the muscular arteries and changing pulse wave velocity of the reflected wave from the periphery to the heart. Vasodilators decrease the amplitude and increase the travel time (or delay) of the reflected wave, causing a generalized decrease in systolic BP. The decrease in systolic BP brought about by this mechanism is grossly underestimated when systolic BP is measured in the brachial artery.

Wave reflections and global arterial compliance during normal human pregnancy.

Profound changes occur in the maternal circulation during pregnancy. Routine measures of arterial function - central systolic pressure (CSP) and augmentation index (AIx) - decline during normal human pregnancy. The objectives of this study were twofold: (1) explore wave reflection indices besides CSP and AIx that are not routinely reported, if at all, during normal human pregnancy; and (2) compare wave reflection indices and global arterial compliance (gAC) obtained from carotid artery pressure waveforms (CAPW) as a surrogate for aortic pressure waveforms (AOPW) versus AOPW synthesized from radial artery pressure waveforms (RAPW) using a generalized transfer function. To our knowledge, a comparison of these two methods has not been previously evaluated in the context of pregnancy. Ten healthy women with normal singleton pregnancies were studied using applanation tonometry (SphygmoCor) at pre-conception, and then during 10-12 and 33-35 gestational weeks. CSP and AIx declined, and gAC increased during pregnancy as previously reported. As a consequence of the rise in gAC, the return of reflected waves of lesser magnitude from peripheral reflection sites to the aorta was delayed that, in turn, reduced systolic duration of reflected waves, augmentation index, central systolic pressure, LV wasted energy due to reflected waves, and increased brachial-central pulse pressure. For several wave reflection indices, those derived from CAPW as a surrogate for AOPW versus RAPW using a generalized transfer function registered greater gestational increases of arterial compliance. This discordance may reflect imprecision of the generalized transfer function for some waveform parameters, though potential divergence of carotid artery and aortic pressure waveforms during pregnancy cannot be excluded.

Role of heart failure etiology on arterial wave reflection in heart transplant recipients: relation with C-reactive protein.

OBJECTIVES: Aortic augmentation index (AIa), a measure of arterial pressure wave reflection related to central and peripheral arterial stiffness, is elevated in many heart transplant recipients. We investigated whether the increase in wave reflection observed in some heart transplant recipients is influenced by the etiology of antecedent heart failure and circulating pro-inflammatory proteins early in the post-transplantation period. METHODS: Two months after heart transplantation, 20 heart transplant recipients underwent noninvasive measurement of aortic pressure and wave reflection properties and measurement of plasma pro-inflammatory proteins. RESULTS: AIa adjusted to a heart rate of 75 beats/min (AIaHR75) was higher in heart transplant recipients with ischemic (n = 12) compared with nonischemic (n = 8) heart failure (P < 0.01). Similarly, circulating C-reactive protein, a marker of systemic inflammation and an independent predictor of allograft vasculopathy and death in heart transplant recipients, was higher in heart transplant recipients with ischemic than with nonischemic heart failure (log-transformed, P < 0.05). Moreover, there was a significant relation between log C-reactive protein and AIaHR75 (r = 0.68, P < 0.05), augmented pressure (r = 0.60, P < 0.01), roundtrip time of the reflected wave to the peripheral reflecting sites and back (r = -0.62; P < 0.01), and left ventricular wasted energy (r = 0.55, P < 0.01). Multiple regression analysis revealed that log C-reactive protein explained 43% of the variance in AIaHR75 and the difference in AIaHR75 between groups was abolished when adjusted for log C-reactive protein. CONCLUSIONS: Heart transplant recipients with antecedent ischemic heart failure demonstrated increased AIaHR75 compared with nonischemic heart transplant recipients and AIaHR75 was associated with higher circulating C-reactive protein concentration. Whether elevated arterial wave reflection and associated systemic low-grade inflammation early after transplantation have clinical implications in ischemic heart transplant recipients requires further investigation.

Arterial-wave reflections are increased in heart failure patients with a left-ventricular assist device.

BACKGROUND: Chronic heart failure (HF) is associated with increased central arterial pulse-wave reflections, which may contribute to increased myocardial oxygen demand. Although the treatment of HF via left-ventricular assist device (LVAD) placement has recently become widespread, the effects of LVAD therapy on central arterial pulse-wave reflections are unknown. METHODS: Central aortic pulse-wave analysis was performed on patients with end-stage HF awaiting cardiac transplantation and on healthy age-matched controls using the SphygmoCor (Akor Medical, Sydney, Australia) system. Arterial pulse-wave data were compared between patients receiving LVAD support versus those receiving intravenous inotropic drugs and healthy control patients. RESULTS: Five patients on LVAD support were compared with 10 patients on inotropic drugs and 10 healthy control patients. Aortic augmented pressure and the aortic augmentation index (AI(a)) were higher in LVAD patients compared with inotrope and control patients, despite similar brachial and aortic blood pressures between groups. The AI(a) was significantly higher in LVAD patients than in patients on inotropic drugs (28.2% +/- 10% v 7.9% +/- 9%, P < or = .01). Additionally, there was a significantly higher aortic systolic tension time index, an index of left-ventricular myocardial oxygen demand, in the LVAD group compared with the inotrope group (2655 +/- 298 mm Hg/sec/min v 1748 +/- 303 mm Hg/sec/min, P < .01). CONCLUSIONS: Central arterial pressure-wave reflection is increased in end-stage HF patients on LVAD support compared with those on inotropic drugs, leading to an increase in aortic augmented pressure, AI(a), and systolic tension time index. The AI(a) is also higher in LVAD patients than in healthy controls. This increased central arterial-wave reflection places an additional hemodynamic load on the LVAD device and may have relevance to the medical management of patients after LVAD placement and to the longevity of the LVAD device itself.

The pathophysiology of chronic ischemic heart disease.

With our success in management of acute coronary syndromes (ACS), aging population and epidemics of diabetes and obesity, the management of patients with chronic coronary artery disease is becoming an increasing important part of clinical practice. Although the rates of death and myocardial infarction (MI) in this group of patients are not high as a group, a subgroup has very high risk but many have poor quality of life related to limiting angina. The purpose of this article is to review the pathophysiology of the chronic angina syndrome to provide an improved understanding of the basis for the comprehensive management required to yield patient benefits. Where possible, targets for novel therapeutic approaches are highlighted.

All-Extremity Exercise Training Improves Arterial Stiffness in Older Adults.

Large elastic arteries stiffen with age, which predisposes older adults to increased risk for cardiovascular disease. Aerobic exercise training is known to reduce the risk for cardiovascular disease, but the optimal exercise prescription for attenuating large elastic arterial stiffening in older adults is not known. PURPOSE: The purpose of this randomized controlled trial was to compare the effect of all-extremity high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on aortic pulse wave velocity (PWV) and carotid artery compliance in older adults. METHODS: Forty-nine sedentary older adults (age = 64 ± 1 yr), free of overt major clinical disease, were randomized to HIIT (n = 17), MICT (n = 18), or nonexercise controls (CONT; n = 14). HIIT (4 × 4 min at 90% HRpeak interspersed with 3 × 3 min active recovery at 70% HRpeak) and isocaloric MICT (70% HRpeak) were performed on an all-extremity non-weight-bearing ergometer, 4 d·wk for 8 wk under supervision. Aortic (carotid to femoral PWV [cfPWV]) and common carotid artery compliance were assessed at pre- and postintervention. RESULTS: cfPWV improved by 0.5 m·s in MICT (P = 0.04) but did not significantly change in HIIT and CONT (P > 0.05). Carotid artery compliance improved by 0.03 mm·mm Hg in MICT (P = 0.001), but it remained unchanged in HIIT and CONT (P > 0.05). Improvements in arterial stiffness in response to MICT were not confounded by changes in aortic or brachial blood pressure, HR, body weight, total and abdominal adiposity, blood lipids, or aerobic fitness. CONCLUSION: All-extremity MICT, but not HIIT, improved central arterial stiffness in previously sedentary older adults free of major clinical disease. Our findings have important implications for aerobic exercise prescription in older adults.

Influence of the central-to-peripheral arterial stiffness gradient on the timing and amplitude of wave reflections.

In individuals with compliant aortas, peripheral muscular artery stiffness exceeds central elastic artery stiffness. With aging, central stiffness increases with little change in peripheral stiffness, resulting in a reversal of the normal stiffness gradient. This reversal may reduce the wave reflection amplitude due to the movement of the major 'effective' reflection site further from the heart. To test this phenomenon, we investigated the relationship among arterial stiffness gradients (normal and reversed), wave reflection amplitude and reflection site distance. Subjects aged ⩾50 years were recruited from the Anglo-Cardiff Collaborative Trial. Central stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV). In Study 1, peripheral PWV was also measured in the arm (carotid-radial pulse wave velocity) and, in Study 2, in the leg (femoral-dorsalis pedis). Reflection site distance was calculated from cfPWV and the reflected wave Tr. Subjects were dichotomized into those with a normal stiffness gradient (peripheral >central PWV) or a reversed gradient (peripheral

American Society of Hypertension position paper: central blood pressure waveforms in health and disease.

A number of devices are available which noninvasively estimate central aortic blood pressure using a variety of approaches such as tonometry or oscillometry. In this position paper, we discuss how the central pressure waveform is generated and measured, how central pressure waveforms appear in health and disease, the predictive value of central blood pressure measurements, the effects of interventions on waveforms, and areas of future need in this field of clinical and research endeavor.

Accuracy of commercial devices and methods for noninvasive estimation of aortic systolic blood pressure a systematic review and meta-analysis of invasive validation studies.

BACKGROUND: Although compelling evidence has established the physiological and clinical relevance of aortic SBP (a-SBP), no consensus exists regarding the validity of the available methods/techniques that noninvasively measure it. OBJECTIVES: The systematic review and meta-analysis aimed to determine the accuracy of commercial devices estimating a-SBP noninvasively, which have been validated by invasive measurement of a-SBP. Moreover their optimal mode of application, in terms of calibration, as well as specific technique and arterial site of pulse wave acquisition were further investigated. METHODS: The study was performed according to the PRISMA guidelines; 22 eligible studies were included, which validated invasively 11 different commercial devices in 808 study participants. RESULTS: Overall, the error in a-SBP estimation (estimated minus actual value) was -4.49 mmHg [95% confidence interval (CI): -6.06 to -2.92 mmHg]. The estimated (noninvasive) a-SBP differed from the actual (invasive) value depending on calibration method: by -1.08 mmHg (95% CI: -2.81, 0.65 mmHg) and by -5.81 mmHg (95% CI: -7.79, -3.84 mmHg), when invasively and noninvasively measured brachial BP values were used respectively; by -1.83 mmHg, (95% CI: -3.32, -0.34 mmHg), and by 7.78 mmHg (95% CI: -10.28, -5.28 mmHg), when brachial mean arterial pressure/DBP and SBP/DBP were used, respectively. CONCLUSION: Automated recording of waveforms, calibrated noninvasively by brachial mean arterial pressure/DBP values seems the most promising approach that can provide relatively more accurate, noninvasive estimation of a-SBP. It is still uncertain whether a specific device can be recommended as 'gold standard'; however, a consensus is currently demanding.

Clinical measurement of arterial stiffness obtained from noninvasive pressure waveforms.

Aortic pulse wave velocity (PWV) and augmentation index are independent predictors of adverse cardiovascular events, including mortality. In hypertension and aging, central elastic arteries become stiffer, diastolic pressure decreases, and central systolic and pulse pressures are augmented due to increased PWV and early return of reflected waves to the heart from the periphery. Valuable information on arterial properties such as stiffness can be obtained from both central (aortic) and peripheral (radial artery) pressure waveforms, but absolute values of wave reflection amplitude and wasted left ventricular (LV) pressure energy can only be obtained from the central arterial pressure waveform. As the arterial system becomes stiffer, there is a marked increase in central systolic and pulse pressures and wasted LV energy, along with a decrease in pulse pressure amplification. The increase in aortic systolic and pulse pressures are due primarily to increases in PWV and wave reflection amplitude with a small increase in incident wave amplitude. In individuals with very stiff elastic arteries (eg, in older persons with isolated systolic hypertension), there is a decrease in diastolic pressure. These changes in pressure components increase LV afterload and myocardial oxygen demand and therefore cause an undesirable mismatch between ventricle emptying and arterial pulse wave transmission, which promotes ventricular hypertrophy. High systolic and pulse pressures resulting from advanced age or hypertension increase circumferential arterial wall stress, which likely causes breakdown of medial elastin and increases the possibility of local fatigue, endothelial damage and development of atherosclerosis. Vasodilator drugs may have little direct effect on large central elastic arteries, but at the same time, their effects on peripheral muscular arteries reduce wave reflection amplitude and markedly lower systolic and pulse pressures and ventricular afterload. These beneficial effects on central arterial pressure can occur with or without a reduction in cuff blood pressure (BP) and may explain the apparent "pressure-independent" effects of drugs such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Therefore, optimal treatment of high BP and its complications should include consideration of arterial stiffness, augmentation of aortic pressure, and LV wasted energy, all of which should be reduced to the lowest possible level.

Radial artery tonometry demonstrates arterial stiffness in children with type 1 diabetes.

OBJECTIVE: To determine if children with type 1 diabetes have increased arterial stiffness by estimating augmentation index with the simple noninvasive technique of radial artery tonometry. RESEARCH DESIGN AND METHODS: We studied 98 type 1 diabetic children and 57 healthy control subjects, ages 10-18 years, matched for age, sex, race, and BMI, generating 43 matched pairs. Radial artery tonometry was performed, and blood was collected for analysis of fasting lipids, HbA1c, glucose, and cytokines in all children. RESULTS: Children with diabetes had a significantly higher augmentation index corrected to a heart rate of 75 (AI75) than their matched control subjects. Mean AI75 in type 1 diabetic subjects was 1.11 +/- 10.15 versus -3.32 +/- 10.36 in control subjects. The case-control difference was 5.20 +/- 11.02 (P=0.0031). CONCLUSIONS: Children with type 1 diabetes have increased arterial stiffness compared with healthy control subjects. Radial artery tonometry is a simple noninvasive technique that could be added to the armamentarium of tests used to provide cardiovascular risk stratification in children with type 1 diabetes.