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We examined the influence of arterial stiffening and ventricular ejection dynamics on the age-related increase in central pulse pressure. A total of 2033 women aged 18 to 91 years from the Twins UK cohort were studied. Aortic flow and central blood pressure were measured by Doppler sonography and carotid tonometry, respectively. Measured values of central pulse pressure were compared with values predicted from aortic pulse wave velocity and ventricular ejection characteristics. Central pulse pressure at the first shoulder ( P1 ) increased with age from 29.2±8.0 in those 70 years (means±SD; P P2 , usually equal to peak central pulse pressure) increased to a greater extent with age: from 29.1±7.8 mm Hg for those 70 years ( P P2/P1 closely mirrored the ratio of ejection volume to ejection velocity at corresponding time points, and the proportionately greater increase in P2 compared with P1 was explained by increased ventricular ejection up to the time of P2 . This increased from 52.5±13.1 to 59.3±17.8 mL ( P

Background Basal release of nitric oxide ( NO ) from the vascular endothelium regulates the tone of muscular arteries and resistance vasculature. Effects of NO on muscular arteries could be particularly important during exercise when shear stress may stimulate increased NO synthesis. Methods and Results We investigated acute effects of NO synthase inhibition on exercise hemodynamics using N G ‐monomethyl‐ l ‐arginine ( l ‐ NMMA ), a nonselective NO synthase ‐inhibitor. Healthy volunteers (n=10, 5 female, 19–33 years) participated in a 2‐phase randomized crossover study, receiving l ‐ NMMA (6 mg/kg, iv over 5 minutes) or placebo before bicycle exercise (25–150 W for 12 minutes). Blood pressure, cardiac output (measured by dilution of soluble and inert tracers) and femoral artery diameter were measured before, during, and after exercise. At rest, l ‐ NMMA reduced heart rate (by 16.2±4.3 bpm relative to placebo, P P P l ‐ NMMA and placebo, P l ‐ NMMA had no significant effect on peripheral resistance, cardiac output, or on femoral artery diameter. Conclusions These results suggest that NO plays little role in modulating muscular artery function during exercise but that it may mediate changes in muscular artery tone immediately before exercise.

We investigated whether expression of genes previously implicated in arterial stiffening associates with cross-sectional and longitudinal measures of arterial stiffness. Women from the Twins UK cohort (n=470, aged 39–81 years) had gene expression in lymphoblastoid cell lines measured using an Illumina microarray. Arterial stiffness was measured by carotid-femoral pulse wave velocity and carotid distensibility. A subsample (n=121) of women had repeat vascular measures after a mean±SD follow-up of 4.3±1.4 years. Associations of arterial phenotypes with gene expression levels were examined for 52 genes identified from previous association studies. The gene transcript most closely associated with pulse wave velocity in cross-sectional analysis was ectonucleotide pyrophosphatase/phosphodiesterase ( P =0.012). Pleiotropic genetic effects accounted for 14% of the phenotypic correlation between ectonucleotide pyrophosphatase/phosphodiesterase expression and pulse wave velocity. Progression of pulse wave velocity during the follow-up period best related to expression of ectonucleotide pyrophosphatase/phosphodiesterase (β=0.19, P =0.008) and collagen type IV α 1 (β=0.32, P P =0.005), angiotensin-converting enzyme (β=–0.15, P =0.035), and B-cell CLL/lymphoma11B (β=0.18, P =0.010). Expression levels of angiotensin-converting enzyme also related to progression in carotid diameter (β=0.21, P =0.012). Expression levels of ectonucleotide pyrophosphatase/phosphodiesterase, involved in arterial calcification, and collagen type IV α 1, involved in collagen formation, correlate with aortic stiffening. These genes may be functional mediators of arterial stiffening.

Background Interactions between the left ventricular (LV) and the arterial system, (ventricular-arterial coupling) are key determinants of cardiovascular function. However, most of studies covered multiple cardiovascular risk factors, which also contributed to the morphological and functional changes of LV. The aim of this study was to examine the relationship between arterial stiffness and LV structure and function in healthy women with a low burden of risk factors. Methods Healthy women from the Twins UK cohort (n = 147, mean age was 54.07 ± 11.90 years) were studied. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (cf-PWV). LV structure and function were assessed by two-dimensional speckle tracking echocardiography. Results cf-PWV was significantly associated with most measures of LV geometry and function, including relative wall thickness (RWT), E/e’ ratio, global circumferential and radial strain, apical rotation and LV twist (each p

Background— Inorganic nitrite dilates small resistance arterioles via hypoxia-facilitated reduction to vasodilating nitric oxide. The effects of nitrite in human conduit arteries have not been investigated. In contrast to nitrite, organic nitrates are established selective dilators of conduit arteries. Methods and Results— We examined the effects of local and systemic administration of sodium nitrite on the radial artery (a muscular conduit artery), forearm resistance vessels (forearm blood flow), and systemic hemodynamics in healthy male volunteers (n=43). Intrabrachial sodium nitrite (8.7 μmol/min) increased radial artery diameter by a median of 28.0% (25th and 75th percentiles, 25.7% and 40.1%; P −1 ·100 mL −1 tissue (95% confidence interval, 0.5–1.8). Nitrite-induced radial artery dilation was enhanced by administration of acetazolamide (oral or intra-arterial) and oral raloxifene ( P =0.0248, P P =0.0006, respectively) but was inhibited under hypoxia ( P P =0.0006) compared with normoxia. Systemic intravenous administration of sodium nitrite (8.7 μmol/min) dilated the radial artery by 10.7% (95% confidence interval, 6.8–14.7) and reduced central systolic blood pressure by 11.6 mm Hg (95% confidence interval, 2.4–20.7), augmentation index, and pulse wave velocity without changing peripheral blood pressure. Conclusions— Nitrite selectively dilates conduit arteries at supraphysiological and near-physiological concentrations via a normoxia-dependent mechanism that is associated with cGMP production and is enhanced by acetazolamide and raloxifene. The selective central blood pressure–lowering effects of nitrite have therapeutic potential to reduce cardiovascular events.

AimsVascular ageing is characterized by arterial stiffening, dilation, and arterial wall thickening. We investigated the extent to which these changes are related and their heritability during 5 year follow-up in the Twins UK cohort.Methods and resultsCarotid-femoral pulse wave velocity (PWVcf), carotid diameter, carotid distensibility, and carotid intima-media thickness (IMT) were measured in 762 female twins (mean age 57.9 ± 8.6 years) at two time-points over an average follow-up of 4.9 ± 1.5 years. Magnetic resonance imaging (MRI) was performed in a sub-sample of 38 women to measure aortic pulse wave velocity (PWVaorta), diameter, and wall thickness. Heritability of changes in arterial wall properties was estimated using structural equation modelling. Annual increases in PWVcf, carotid diameter, distensibility, and IMT were 0.139 m/s, 0.028 mm, −0.4 kPa−1, and 0.011 mm per year, respectively. In regression analysis, predictors of progression in PWVcf included age, mean arterial pressure (MAP), and heart rate (HR) at baseline, and progression in MAP, HR, and body mass index (BMI). Predictors of progression in IMT included progression in MAP, BMI, and triglyceride levels. Progression of PWV and distensibility correlated with progression in carotid diameter but not with IMT. Heritability of progression of PWVcf, diameter, and IMT was 55%, 21%, and 8%, respectively. In a sub-sample of women that underwent MRI, aortic wall thickness increased by 0.19 mm/year, but aortic wall thickening was not correlated with an increase in lumen diameter or PWVaorta.ConclusionArterial stiffening, as measured by PWVcf, and dilation are heritable but independent of arterial wall thickening. Genetic and cardiovascular risk factors contribute differently to progression of PWV and IMT.

Background/objectives There are few studies investigating the long-term association between childhood blood pressure (BP) and adult cardiovascular remodeling. We seek to examine the effect of elevated childhood BP on cardiovascular remodeling in early or middle adulthood. Methods We used the "Beijing BP Cohort Study", where 1259 subjects aged 6–18years old were followed over 24years from childhood (1987) to early or middle adulthood (2011). Anthropometric measures and BP were obtained at baseline and follow-up examinations. Carotid–femoral pulse wave velocity (cfPWV), carotid intima-media thickness (cIMT), and left ventricular mass index (LVMI) were measured to assess cardiovascular remodeling in early or middle adulthood. Multiple logistic regression models were used to assess the odds ratio (OR) and 95% confidence interval (CI) for cardiovascular remodeling. Results 82 out of 384 children with elevated BP (21.4%) had adult hypertension. Compared to those with normal BP, children with elevated BP were at 2.1 times (95% CI: 1.4–3.1) likely to develop hypertension in early or middle adulthood. Compared to those with normal BP, children with elevated BP were at higher OR of developing high cfPWV (OR=1.8, 95% CI=1.3–2.4), high cIMT (1.4, 1.0–1.9), or high LVMI (1.4, 1.0–1.9) in early or middle adulthood. The ORs for remodeling (for any measures) were 1.4 (0.9–2.0) in early adulthood for children age 6–11years, and 1.6 (1.1–2.4) in middle adulthood for those aged 12–18years. Conclusions Children with elevated BP from 6years old have accelerated remodeling on both cardiac and arterial system in early or middle adulthood.

Pulsatile components of blood pressure may arise from forward (ventricular generated) or backward wave travel in the arterial tree. The objective of this study was to determine the relative contributions of forward and backward waves to pulsatility. We used wave intensity and wave separation analysis to determine pulsatile components of blood pressure during inotropic and vasopressor stimulation by dobutamine and norepinephrine in normotensive subjects and compared pulse pressure components in hypertensive (mean±SD, 48.8±11.3 years; 165±26.6/99±14.2 mm Hg) and normotensive subjects (52.2±12.6 years; 120±14.2/71±8.2 mm Hg). Dobutamine (7.5 μg/kg per minute) increased the forward compression wave generated by the ventricle and increased pulse pressure from 36.8±3.7 to 59.0±3.4 mm Hg (mean±SE) but had no significant effect on mean arterial pressure or the midsystolic backward compression wave. By contrast, norepinephrine (50 ng/kg per minute) had no significant effect on the forward compression wave but increased the midsystolic backward compression wave. Despite this increase in the backward compression wave, and an increase in mean arterial pressure, norepinephrine increased central pulse pressure less than dobutamine (increases of 22.1±3.8 and 7.2±2.8 mm Hg for dobutamine and norepinephrine, respectively; P P

Background Haemoglobin scavenges nitric oxide, and a previous study has shown a negative association between flow-mediated vasodilation (FMD), a measure of nitric oxide (NO)-dependent vasomotor function and haemoglobin concentrations [Hb]. Circulating erythropoietin (EPO) is also negatively associated with [Hb] and could influence availability of NO. The purpose of this study was to examine the association of FMD with [Hb] and EPO concentrations and to determine whether these contribute to the sex difference in FMD. FMD (by high-resolution ultrasound), [Hb], circulating immunoreactive EPO and cardiovascular risk factors were measured in 317 healthy middle-aged men and women (183 women, 33 premenopausal, mean age ± SD, 55 ± 6·8 years) participating in a dietary study. Results In the whole mixed-sex group, FMD was negatively correlated with [Hb] (R = −0·23, P

Objectives The goal of this study was to examine the progression of central arterial pulse pressure (cPP) in women and the degree to which this can be reversed by nitrovasodilation. Background cPP can be partitioned into height of the first systolic shoulder (P1), generated by a forward pressure wave and related to arterial stiffness, and augmentation pressure (AP), thought to be influenced by pressure wave reflection from muscular arteries and/or aortic reservoir. Methods Using a longitudinal cohort design, cPP, P1, and AP were estimated (using the SphygmoCor System [AtCor Medical Pty Ltd., West Ryde, Australia]) in 411 female twins over a mean follow-up of 10.8 years. In a subsample (n = 42), cPP, arterial stiffness (using pulse wave velocity [PWV]) and arterial diameters (using ultrasonography) were measured before and after nitroglycerin administration (400 μg s/l). Results cPP increased more than peripheral pulse pressure (10.3 and 9.2 mm Hg, respectively; p Conclusions Age-related widening of cPP is driven in large part by an increase in AP, which can be reversed by selective dilation of muscular arteries, independent of PWV.

Flow-mediated dilation of the brachial or radial artery in response to transient hyperaemic flow, the most widely used test of endothelial function, is only manifest after flow decays back to baseline. We examined whether this dissociation of flow and diameter might be explained by a reduction in transmural pressure generated by high flow. Studies were performed in healthy subjects 20 to 55 years of age. Flow-mediated dilation was measured in the radial artery using a standard protocol and after flow interruption at peak hyperemia during brachial artery infusion of saline and the NO synthase inhibitor N G -monomethyl- l -arginine (8 μmol/min). Flow interruption 20 seconds after cuff release (during high flow but no dilatation) produced an immediate increase in radial artery diameter of 5.36±2.12%, inhibited by N G -monomethyl- l -arginine to 1.09±0.67% (n=8; P P

Objectives Our aim was to examine the relationship of arterial stiffness to measures of atherosclerosis, arterial calcification, and bone mineral density (BMD); the heritability of these measures; and the degree to which they are explained by common genetic influences. Background Arterial stiffening relates to arterial calcification, but this association could result from coexistent atherosclerosis. A reciprocal relationship between arterial stiffening/calcification and BMD could explain the association between cardiovascular morbidity and osteoporosis. Methods We examined, in 900 women from the Twins UK cohort, the relationship of carotid-femoral pulse wave velocity (cfPWV) to measures of atherosclerosis (carotid intima-media thickening; carotid/femoral plaque), calcification (calcified plaque [CP]; aortic calcification by computed tomography, performed in subsample of 40 age-matched women with low and high cfPWV), and BMD. Results The cfPWV independently correlated with CP but not with intima-media thickness or noncalcified plaque. Total aortic calcium, determined by computed tomography, was significantly greater in subjects with high cfPWV (median Agatston score 450.4 compared with 63.2 arbitrary units in subjects with low cfPWV, p = 0.001). There was no independent association between cfPWV and BMD. Adjusted heritability estimates of cfPWV and CP were 0.38 (95% confidence interval: 0.19 to 0.59) and 0.61 (95% confidence interval: 0.04 to 0.83), respectively. Shared genetic factors accounted for 92% of the observed correlation (0.38) between cfPWV and CP. Conclusions These results suggest that the association between increased arterial stiffness and the propensity of the arterial wall to calcify is explained by a common genetic etiology and is independent of noncalcified atheromatous plaque and independent of BMD.

Objectives: Patients with rheumatoid arthritis (RA) have increased cardiovascular mortality. Tumour necrosis factor α (TNFα)-blocking therapy has been shown to reduce RA disease activity measures and joint damage progression. Some observational studies suggest that TNFα blockade reduces mortality and incidence of first cardiovascular events. The mechanisms contributing to these outcomes are unclear. This study assessed the effects of infliximab treatment on vascular stiffness and structure in patients with RA. Methods: A post hoc analysis of longitudinal data from a randomised placebo controlled study evaluated the effect of infliximab on vascular assessments. 26 patients received intravenous infliximab (3 mg/kg) at weeks 0, 2, 6 and every 8 weeks thereafter to week 54. Patients were followed up to 56 weeks of infliximab therapy with assessments of RA disease activity, cardiovascular risk factors, vascular stiffness (pulse wave velocity (PWV)), carotid intima media thickness (CIMT) and carotid artery plaque (CAP). Univariate analyses of changes over time by repeated measures analysis of variance (ANOVA) were followed by multivariate time-series regression analysis (TSRA) if changes were seen. Results: PWV was significantly lower (better) after 56 weeks of treatment with infliximab (ANOVA p

Postprandial lipemia impairs endothelial function possibly via an oxidative stress mechanism. A stearic acid-rich triacylglycerol (TAG) (shea butter) results in a blunted postprandial increase in plasma TAG compared with an oleic acid-rich TAG; however, its acute effects on endothelial function and oxidative stress are unknown. A randomized crossover trial (n = 17 men) compared the effects of 50 g fat, rich in stearic acid [shea butter blend (SA)] or oleic acid [high oleic sunflower oil (HO)], on changes in endothelial function [brachial artery flow-mediated dilatation (FMD)], arterial tone [pulse wave analysis (PWA), and carotid-femoral pulse wave velocity (PWV(c-f))], and oxidative stress (plasma 8-isoprostane F2alpha) at fasting and 3 h following the test meals. The postprandial increase in plasma TAG was lower (66% lower incremental area under curve) following the SA meal [28.3 (9.7, 46.9)] than after the HO meal [83.4 (57.0, 109.8); P < 0.001] (geometric means with 95% CI, arbitary units). Following the HO meal, there was a decrease in FMD [-3.0% (-4.4, -1.6); P < 0.001] and an increase in plasma 8-isoprostane F2alpha [10.4ng/L (3.8, 16.9); P = 0.005] compared with fasting values, but no changes followed the SA meal. The changes in 8-isoprostane F2alpha and FMD differed between meals and were 14.0 ng/L (6.4, 21.6; P = 0.001) and 1.75% (0.10, 3.39; P = 0.02), respectively. The reductions in PWA and PWV c-f did not differ between meals. This study demonstrates that a stearic acid-rich fat attenuates the postprandial impairment in endothelial function compared with an oleic acid-rich fat and supports the hypothesis that postprandial lipemia impairs endothelial function via an increase in oxidative stress.

Arterial calcification leading to increased arterial stiffness, a powerful risk factor for cardiovascular disease, may underlie the association of osteoporosis with cardiovascular disease in postmenopausal women. Osteoprotegerin (OPG), an indirect inhibitor of osteoclastogenesis, may be involved in arterial calcification. We examined relationships between calcification of subclinical atherosclerotic plaque and arterial stiffness with bone mineral density (BMD) and OPG in a group of 54 postmenopausal women referred for routine osteoporosis screening by dual-energy X-ray absorptiometric scanning of the lumbar spine and hip. Presence of calcified and noncalcified plaque in carotid and femoral arteries was examined using ultrasonography. Pulse wave velocity (PWV), a measure of arterial stiffness, was determined by sequential tonometry over the carotid and femoral region. Fifty-nine percent of osteoporotic women had calcified (echogenic) plaque at one or more sites compared with 42% and 20% for women with osteopenia and normal BMD, respectively (P = 0.04). There was a significant negative correlation between PWV and hip BMD (r = -0.35, P = 0.01), which remained significant when age, mean arterial pressure, and serum lipids were taken into account (P = 0.05). No significant relationships were observed between serum concentrations of OPG and lumbar spine or total hip BMD or with the number of arterial sites with calcified or noncalcified plaque. However, there was a strong correlation between OPG and PWV (r = 0.44, P = 0.001), which remained significant when adjusted for age (P = 0.01). These findings suggest that decreased BMD is associated with arterial calcification and stiffening and raise the possibility that OPG is a marker of arterial stiffening, independent of any association with BMD.

Pulse wave velocity (PWV), the speed of propagation of arterial pressure waves through the arterial tree, is related to arterial stiffness and is an important prognostic marker for cardiovascular events. In clinical practice PWV is commonly determined by arterial tonometry, with a noninvasive pressure sensor applied sequentially over carotid and femoral arteries. The electrocardiogram (ECG) is used as a timing reference to determine the time delay or "transit time" between the upstroke of carotid and femoral pulse waveforms. Commercially available vascular ultrasound scanners provide a pulsed wave (PW) Doppler velocity signal, which should allow determination of carotid-femoral transit time and hence PWV. We compared carotid-femoral PWV measured by tonometry and by PW Doppler ultrasound (Seimens, Apsen scanner with 7 MHz linear transducer) in asymptomatic subjects (n = 62, 26 male, aged 21 to 72 y). To test for intra-subject and inter-observer variation, ten subjects were scanned by one observer on two occasions 2 wk apart and by two observers on same day. PWV by tonometry ranged from 5.3 to 15.0 m/s. There was no significant difference between mean values of PWV obtained by the two techniques (mean difference: 0.3 m/s, standard deviation of difference: 1.5 m/s), which were closely correlated (r = 0.83). The coefficient of variation for repeated measures on the same subject by the same observer was 10.1% and the inter-observer coefficient of variation was 5.8%. These results suggest a commercial ultrasound scanner can be used to measure PWV, giving results that are reproducible and closely correlated with those obtained by arterial tonometry. (E-mail: ben_yu.jiang@kcl.ac.uk).

Objective To overall evaluate the change of global cardiac systolic performance and diastolic filling in hypovoleamia by LBNP. Methods 10 healthy male subjects were placed in a standard LBNP chamber. Baseline haemodynamic and echocardiographic measure- ments were made after a period of least 10 min resting supine within the chamber. Pressure was then decreased to -10,-20 and -30 mmHg, with each pressure maintained for 15 min. The indices offour transvalvular and SVC flow were measured using Doppler echocardiography. Results The results showed that S wave, Re wave, and VTI of SVC progressively decreased with increasing LBNP. At -30 mmHg stage, S wave decreased by 35.4 %(change of 0.21+0.03 m/s, P P −1 at -30 mmHg LBNP, P P P P P Conclusion Doppler indices changes in different LBNP stage can roughly reflect the degree of hypovoleamia caused by blood volume redistribution. The indices of Doppler echocardiography are more sensitive than traditional physiological indexes in evaluating cardiovascular responses of LBNP. Echocardiography techniques overall can evaluate the global cardiac function including systolic performance and diastolic filling.

Objectives— The objective of this study was to examine determinants of excess coronary artery disease risk in UK South Asians, more prevalent in this population than UK Caucasians, by examining differences in risk factors, vascular function, and endothelial progenitor cells (EPCs). Methods and Results— 24 South Asian and 25 Caucasian healthy age-matched nonsmoking men were studied. Vascular function was assessed by flow-mediated and GTN brachial artery dilatation and blood flow responses to infusion of ACh, SNP, and L-NMMA. EPC number and function were measured by flow cytometry (CD34, CD133, and KDR positive cells), and CFU/migration assays. Traditional risk factors and anthropometric measurements were similar in the groups. South Asians had higher fasting insulin levels (6.01 versus 3.62 μU/mL; P =0.02). South Asians had lower FMD (6.9 versus 8.5%; P =0.003), L-NMMA response (0.8 versus 1.3 mL/min/100 mL; P =0.03), mean SNP response (9.5±0.6 versus 11.6±0.6; P =0.02), EPC number (0.046±0.005% versus 0.085±0.009%; P =< 0.001), and CFU ability (CFU 4.29±1.57 versus 18.86±4.00; P =0.005). EPC number was the strongest predictor of FMD. Ethnicity was the strongest predictor of EPC number. Conclusions— Healthy South Asian men are more insulin resistant, and demonstrate endothelial dysfunction and reduced EPC number and function compared with Caucasians. These abnormalities may contribute to their increased CAD risk.

Rheumatoid arthritis (RA) is associated with increased cardiovascular disease (CVD) risk that has been attributed to endothelial dysfunction and inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs) and cyclo-oxygenase (COX)-2 inhibitors have been shown in some studies to improve endothelial function in subjects without RA. The aim of this study was to investigate the effects of COX inhibition on endothelial function in patients with RA.Patients with RA (n = 37) were randomized to receive a 2-week course of either indomethacin (75 mg bd), rofecoxib (12.5 mg bd), or placebo in a double-blind study. Endothelial function was measured using flow-mediated dilation (FMD) of the brachial artery in response to reactive hyperaemia. Arterial stiffness was also assessed using pulse wave analysis (PWA) through the measurement of the aortic augmentation index (AIx). Measurements of vascular function and inflammatory markers were taken before and at the end of the treatment period.There were no significant differences in changes in FMD, AIx, blood pressure (BP), serum creatinine, erythrocyte sedimentation rate (ESR), or high-sensitivity C-reactive protein (hsCRP) between groups. However, compared with the other treatment groups, there was a tendency for systolic BP to decrease in the placebo group (p = 0.063) and for creatinine to increase in the indomethacin and rofecoxib groups after treatment (p = 0.054).This study suggests that COX inhibition by indomethacin or rofecoxib do not improve endothelial function in patients with RA.

Stiffness of large elastic arteries is elevated in subjects with hypertension, an effect that could potentially be explained by increased distending pressure. We examined effects of an acute change in blood pressure on carotid-femoral pulse wave velocity and carotid artery distensibility (inversely related to stiffness) in normotensive control subjects (n20, mean age 42) with mean arterial pressure (MAP) 841.7 mm Hg (meanSE) and subjects with essential hypertension (n20, mean age 45, MAP 1042.0 mm Hg). Normotensive subjects received intravenous nitroglycerin (NTG) and angiotensin II to lower/increase blood pressure. Hypertensive subjects received NTG to lower blood pressure. Pulse wave velocity was 24% (95% CI: 12% to 35%) higher and carotid distensibility 47% (95% CI: 32% to 63%) lower in hypertensive subjects compared with controls. In normotensive subjects, acute changes in blood pressure produced expected changes in stiffness. However, in hypertensive subjects, despite reducing MAP by 22 mm Hg to the same level as in normotensive subjects, there was no detectable reduction in arterial stiffness: pulse wave velocity remained 24% (95% CI: 10% to 38%) higher and carotid distensibility 48% (95% CI: 31% to 63%) lower in hypertensive compared with normotensive subjects. Because blood pressure-independent effects of NTG are, if anything, to reduce stiffness, these results indicate that elevated carotid and aortic stiffness in hypertensive subjects is not explained by elevated blood pressure but relates to structural change in the arterial wall. (Hypertension. 2006; 48:404-410.)

Objective— Autopsy studies show that intimal lipid accumulations in arteries are often present at birth, suggesting that the prenatal environment plays a role in the pathogenesis of atherosclerosis. In animal models, a restricted or unbalanced maternal diet during gestation can influence susceptibility to atherosclerosis, but the relation in humans between maternal diet during pregnancy and atherogenesis is unknown. Methods and Results— We measured carotid intima–media thickness (IMT) in 216 nine-year-old children whose mothers had participated in a study of nutrition during pregnancy. IMT was greater in boys, in children who were heavier, in those with higher systolic blood pressure, and in those who took less exercise. Increased IMT was associated with a lower maternal energy intake in early ( P =0.029) or late ( P =0.006) pregnancy, after adjustment for these factors. Mean IMT of children whose mothers were in the lowest quarter of the distribution of energy intake in late pregnancy was 0.027 mm (95% confidence interval, 0.004 to 0.049) greater than that of those whose mothers were in the highest quarter of the distribution. Conclusion— Lower maternal energy intake during pregnancy may increase the susceptibility to atherogenesis of the child.

Background: Nitroglycerin (NTG) reduces cardiac pre-load and after-load through venodilation and arterial dilation respectively but the relative contributions of these effects to reduction in myocardial wall stress is unknown. Methods: We estimated myocardial wall stress from transthoracic echocardiographic imaging of the left ventricle (LV) and LV pressure estimated from carotid tonometry during systole. Nineteen subjects aged 43.3 ± 2.7 (mean ± SE) years were studied before and 7–12 min after NTG (400 ìg sublingually). Carotid pressure calibrated by mean and diastolic blood pressure (BP) was used to calculate time-varying LV wall stress from endocardial and epicardial volumes obtained from Tomtec wall tracking analysis. The relative contributions of reductions in systolic pressure and in LV volumes and to overall reduction in LV wall stress were calculated assuming that volume or pressures after NTG were identical to baseline values. Results: NTG decreased peak LV stress (pre: 387±22; post: 329±22kdynes/cm2, P

Purpose/ background/ objectives: People with or at risk of Type II diabetes (T2DM) are at increased risk of vascular disease and arterial stiffness (AS). We hypothesized that spironolactone and dietary nitrate (beetroot juice) separately and together would reduce AS, measured as cardiac-ankle vascular index (CAVI Fukuda Denshi, Japan mainly BP-independent) or aortic pulse wave velocity (PWV). Methods: 126 (60% T2DM) were randomized, double-blind to spironolactone (≤50mg) or doxazosin (control ≤16mg) and active/ placebo juice (≤9/0mmol) daily. AS and echocardiographic measures (on a subgroup) were performed. Intention-to-treat analysis adjusted for between-group blood pressure (BP) change over time was performed using SAS. Results: Change in (Δ)BP was not different between spironolactone and doxazosin (mean -6.7mmHg), nor between the juices. ΔCAVI was marginally reduced on doxazosin compared to spironolactone (−0.11[−0.30,0.08] vs. 0.14[−0.06,0.34] units, p=0.080) but more for aortic PWV (−0.44 [−0.69,−0.20] vs. −0.07 [−0.32,0.18]ms−2, p=0.04). Dietary nitrate had no impact, but did rise in plasma. Spironolactone improved Δrelative wall thickness vs. doxazosin (0.01[−0.02,−0.0], p

Arterial tone in muscular conduit arteries may influence pressure wave reflection through changes in diameter and pulse wave velocity. We examined the relative specificity of vasodilator drugs for radial artery and forearm resistance vessels during intrabrachial arterial infusion. The nitric oxide (NO) donors, nitroglycerine and nitroprusside, and brain natriuretic peptide were compared with the α-adrenergic antagonist phentolamine, calcium-channel antagonist verapamil, and hydralazine. Radial artery diameter was measured by high resolution ultrasound, forearm blood flow by strain gauge plethysmography, and pulse wave velocity by pressure recording cuffs placed over the distal brachial and radial arteries. Norepinephrine was used to constrict the radial artery to generate a greater range of vasodilator tone when examining pulse wave velocity. Despite dilating resistance vasculature, phentolamine and verapamil had little effect on radial artery diameter (mean dilation R =−0.89, P

Although a high intake of some flavonoid subclasses may reduce cardiovascular disease mortality, data regarding the in vivo mechanisms of action are limited.We examined associations between habitual flavonoid intakes and direct measures of arterial stiffness, central blood pressure, and atherosclerosis.In a cross-sectional study of 1898 women aged 18-75 y from the TwinsUK registry, intakes of total flavonoids and their subclasses (flavanones, anthocyanins, flavan-3-ols, polymers, flavonols, and flavones) were calculated from validated food-frequency questionnaires by using an updated and extended USDA database. Direct measures of arterial stiffness and atherosclerosis included central systolic blood pressure (cSBP), central diastolic blood pressure, mean arterial pressure (MAP), augmentation index, pulse wave velocity (PWV), and intima-media thickness.In multivariate analyses, a higher anthocyanin intake was associated with significantly lower cSBP (mean ± SE: -3.0 ± 1.4 mm Hg for quintile 5 compared with quintile 1; P-trend = 0.02), MAP (-2.3 ± 1.2 mm Hg for quintile 5 compared with quintile 1; P-trend = 0.04), and PWV (-0.4 ± 0.2 m/s for quintile 5 compared with quintile 1; P-trend = 0.04), whereas a higher flavone intake was associated with a lower PWV (-0.4 ± 0.2 m/s for quintile 5 compared with quintile 1; P-trend = 0.04). Although a higher wine and berry intake was associated with a lower PWV, no associations were observed for total and other flavonoid subclasses.These data, which include direct measures of arterial stiffness and thickness, suggest that higher intake of anthocyanins and flavones are inversely associated with lower arterial stiffness. The intakes of anthocyanins associated with these findings could be incorporated into the diet by the consumption of 1-2 portions of berries daily and are, therefore, relevant for public health strategies to reduce cardiovascular disease risk.

We thank Turner1 for drawing attention to the likely contribution of the Bernoulli effect as contributing, in addition to the resistive pressure loss, to the drop in mean hydrostatic intra-arterial pressure in the upper limb during …

The goal of this study was to examine the progression of central arterial pulse pressure (cPP) in women and the degree to which this can be reversed by nitrovasodilation.cPP can be partitioned into height of the first systolic shoulder (P1), generated by a forward pressure wave and related to arterial stiffness, and augmentation pressure (AP), thought to be influenced by pressure wave reflection from muscular arteries and/or aortic reservoir.Using a longitudinal cohort design, cPP, P1, and AP were estimated (using the SphygmoCor System [AtCor Medical Pty Ltd., West Ryde, Australia]) in 411 female twins over a mean follow-up of 10.8 years. In a subsample (n = 42), cPP, arterial stiffness (using pulse wave velocity [PWV]) and arterial diameters (using ultrasonography) were measured before and after nitroglycerin administration (400 μg s/l).cPP increased more than peripheral pulse pressure (10.3 and 9.2 mm Hg, respectively; p0.0001). In women60 years of age at follow-up, AP contributed more to the increase in cPP than did P1 (increases of 6.5 ± 6.4 mm Hg and 4.2 ± 7.8 mm Hg, respectively). P1 was significantly positively correlated to PWV (p0.0001); AP was correlated to aorto-femoral tapering (p0.0001) but not PWV. Nitroglycerin reduced cPP by 10.0 ± 6.0 mm Hg (p0.0001), equivalent to a decade of aging. The reduction in cPP was entirely explained by a decrease in AP, with no significant change in P1 or PWV but an increase in large artery diameters of 4% to 18% (p0.0001).Age-related widening of cPP is driven in large part by an increase in AP, which can be reversed by selective dilation of muscular arteries, independent of PWV.

Background: Within the general population, levels of C-reactive protein (CRP) are positively associated with atherosclerotic cardiovascular disease (CVD). Whether CRP is causally implicated in atherogenesis or is the results of atherosclerosis is disputed. A role of CRP to protect endothelium-derived nitric oxide (EDNO) has been suggested. We examined the association of CRP with EDNO-dependent vasomotor function and subclinical measures of atherosclerosis and arteriosclerosis in patients with raised CRP resulting from rheumatoid arthritis (RA).Methodology/Principal Findings: Patients with RA (n = 59) and healthy control subjects (n = 123), underwent measures of high sensitivity CRP, flow-mediated dilation (FMD, dependent on EDNO), intima-media thickness (IMT, a measure of subclinical atherosclerosis) and aortic pulse wave velocity (PWV, a measure of arteriosclerosis). IMT and PWV were elevated in patients with RA compared to controls but FMD was similar in the two groups. In patients with RA, IMT and PWV were not correlated with CRP but FMD was positively independently correlated with CRP (P