Protective effects of ascorbic acid on arterial hemodynamics during acute hyperglycemia

Mortality increases when acute coronary syndromes are complicated by stress-induced hyperglycemia. Early pulse wave reflection can augment central aortic systolic blood pressure and increase left ventricular strain. Altered pulse wave reflection may contribute to the increase in cardiac risk during acute hyperglycemia. Chronic ascorbic acid (AA) supplementation has recently been shown to reduce pulse wave reflection in diabetes. We investigated the in vivo effects of acute hyperglycemia, with and without AA pretreatment, on pulse wave reflection and arterial hemodynamics. Healthy male volunteers were studied. Peripheral blood pressure (BP) was measured at the brachial artery, and the SphygmoCor pulse wave analysis system was used to derive central BP, the aortic augmentation index (AIx; measure of systemic arterial stiffness), and the time to pulse wave refection (Tr; measure of aortic distensibility) from noninvasively obtained radial artery pulse pressure (PP) waveforms. Hemodynamics were recorded at baseline and then every 30 min during a 120-min systemic hyperglycemic clamp (14 mmol/l). The subjects, studied on two separate occasions, were randomized in a double-blind, crossover manner to placebo or 2 g intravenous AA before the initiation of hyperglycemia. During hyperglycemia, AIx increased and Tr decreased. Hyperglycemia did not change peripheral PP but did magnify central aortic PP and diminished the normal physiological amplification of PP from the aorta to the periphery. Pulse wave reflection, as assessed from peripheral pulse wave analysis, is enhanced during acute hyperglycemia. Pretreatment with AA prevented the hyperglycemia-induced hemodynamic changes. By protecting hemodynamics during acute hyperglycemia, AA may have therapeutic use.     

Postprandial Vascular Reactivity in Obese and Normal Weight Young Adults

As humans spend a significant amount of time in the postprandial state, we examined whether vascular reactivity (a key indicator of cardiovascular health) was different after a high‐fat meal in 11 obese (median BMI 46.4, age 32.1 ± 6.3 years, 7 men) and 11 normal weight (median BMI 22.6) age‐ and sex‐matched controls. At baseline and 1 and 3 h postmeal, blood pressure (BP), heart rate (HR), reactive hyperemia peripheral artery tonometry (RH‐PAT) index, radial augmentation index adjusted for HR (AIx75), brachial pulse wave velocity (PWV_b), glucose, insulin, total and high‐density lipoprotein (HDL) cholesterol, and triglycerides were measured. Brachial flow‐mediated dilatation (FMD) and, by venous plethysmography, resting and hyperemic forearm blood flows (FBFs) were measured at baseline and 3 h. At baseline, obese subjects had higher systolic BP, HR, resting FBF, insulin and equivalent FMD, RH‐PAT, hyperemic FBF, AIx75, PWV_b, glucose, total cholesterol, triglycerides, and lower HDL cholesterol. In obese and lean subjects, FMD at baseline and 3 h was not significantly different (6.2 ± 1.7 to 5.8 ± 4.3% for obese and 4.7 ± 4.1 to 4.3 ± 3.9% for normal weight, P = 0.975 for group × time). The meal did not produce significant changes in RH‐PAT, hyperemic FBF, and PWV_b in either group (P > 0.1 for the effect of time and for group × time interactions). In conclusion, the vascular responses to a high‐fat meal are similar in obese and normal weight young adults. An exaggerated alteration in postprandial vascular reactivity is thus unlikely to contribute importantly to the increased cardiovascular risk of obesity.     

Relationships between high-sensitive C-reactive protein and markers of arterial stiffness in hypertensive patients. Differences by sex

ABSTRACT: BACKGROUND: The present study was designed to evaluate the relationship between high-sensitivity Creactive protein (hs-CRP) and arterial stiffness according to sex in patients with arterial hypertension. METHODS: A case-series study was carried out in 258 hypertensive patients without antecedents of cardiovascular disease or diabetes mellitus. Nephelometry was used to determine hs-CRP. Office or clinical and home blood pressures were measured with a validated OMRON model M10 sphygmomanometer. Ambulatory blood pressure monitoring was performed with the SpaceLabs 90207 system. Pulse wave velocity (PWV) and central and peripheral augmentation index (AIx) were measured with the SphygmoCor system, and a Sonosite Micromax ultrasound unit was used for automatic measurements of carotid intima-media thickness (IMT). Ambulatory arterial stiffness index and home arterial stiffness index were calculated as "1-slope" from the within-person regression analysis of diastolic-on-systolic ambulatory blood pressure. RESULTS: Central and peripheral AIx were greater in women than in men: 35.31 +/- 9.95 vs 26.59 +/- 11.45 and 102.06 +/- 20.47 vs 85.97 +/- 19.13, respectively. IMT was greater in men (0.73 +/- 0.13 vs 0.69 +/- 0.10). hs-CRP was positively correlated to IMT (r = 0.261), maximum (r = 0.290) and to peripheral AIx (r = 0.166) in men, and to PWV in both men (r = 0.280) and women (r = 0.250). In women, hs-CRP was negatively correlated to central AIx (r = 0.222). For each unit increase in hs-CRP, carotid IMT would increase 0.05 mm in men, and PWV would increase 0.07 m/sec in men and 0.08 m/sec in women, while central AIx would decrease 2.5 units in women. In the multiple linear regression analysis, hs-CRP explained 10.2 % and 6.7 % of PWV variability in women and men, respectively, 8.4 % of carotid IMT variability in men, and 4.9 % of central AIx variability in women. CONCLUSIONS: After adjusting for age, other cardiovascular risk factors and the use of antihypertensive and lipid-lowering drugs, hs-CRP was seen to be positively correlated to carotid IMT in men, and negatively correlated to central AIx in women. The association of hs-CRP to arterial stiffness parameters differs between men and women.     

Ascorbic acid does not affect large elastic artery compliance or central blood pressure in young and older men

Large elastic artery compliance is reduced and arterial blood pressure (BP) is increased in the central (cardiothoracic) circulation with aging. Reactive oxygen species may tonically modulate central arterial compliance and BP in humans, and oxidative stress may contribute to adverse changes with aging. If so, antioxidant administration may have beneficial effects. Young (Y; 26 +/- 1 yr, mean +/- SE) and older (O; 63 +/- 2 yr, mean +/- SE) healthy men were studied at baseline and during acute (intravenous infusion; Y: n = 13, O: n = 12) and chronic (500 mg/day for 30 days; Y: n = 10, O: n = 10) administration of ascorbic acid (vitamin C). At baseline, peripheral (brachial artery) BP did not differ in the two groups, but carotid artery compliance was 43% lower (1.2 +/- 0.1 vs. 2.1 +/- 0.1 mm(2)/mmHg x 10(-1), P < 0.01) and central (carotid) BP (systolic: 116 +/- 5 vs. 101 +/- 3 mmHg, P < 0.05, and pulse pressure: 43 +/- 4 vs. 36 +/- 3 mmHg, P = 0.16), carotid augmentation index (AIx; 27.8 +/- 7.8 vs. -20.0 +/- 6.6%, P < 0.001), and aortic pulse wave velocity (PWV; 950 +/- 88 vs. 640 +/- 38 cm/s, P < 0.01) were higher in the older men. Plasma ascorbic acid concentrations did not differ at baseline (Y: 71 +/- 5 vs. O: 61 +/- 7 micromol/l, P = 0.23), increased (P < 0.001) to supraphysiological levels during infusion (Y: 1240 +/- 57 and O: 1,056 +/- 83 micromol/l), and were slightly elevated (P < 0.001 vs. baseline) with supplementation (Y: 96 +/- 5 micromol/l vs. O: 85 +/- 6). Neither ascorbic acid infusion nor supplementation affected peripheral BP, heart rate, carotid artery compliance, central BP, carotid AIx, or aortic PWV (all P > 0.26). These results indicate that the adverse changes in large elastic artery compliance and central BP with aging in healthy men are not 1). mediated by ascorbic acid-sensitive oxidative stress (infusion experiments) and 2). affected by short-term, moderate daily ascorbic acid (vitamin C) supplementation.     

Interrelationships among noninvasive measures of postischemic macro- and microvascular reactivity.

The clinical importance of vascular reactivity as an early marker of atherosclerosis has been well established, and a number of established and emerging techniques have been employed to provide measurements of peripheral vascular reactivity. However, relations between these methodologies are unclear as each technique evaluates different physiological aspects related to micro- and macrovascular reactive hyperemia. To address this question, a total of 40 apparently healthy normotensive adults, 19-68 yr old, underwent 5 min of forearm suprasystolic cuff-induced ischemia followed by postischemic measurements. Measurements of vascular reactivity included 1) flow-mediated dilatation (FMD), 2) changes in pulse wave velocity between the brachial and radial artery (DeltaPWV), 3) hyperemic shear stress, 4) reactive hyperemic flow, 5) reactive hyperemia index (RHI) assessed by fingertip arterial tonometry, 6) fingertip temperature rebound (TR), and 7) skin reactive hyperemia. FMD was significantly and positively associated with RHI (r=0.47) and TR (r=0.45) (both P<0.01) but not with reactive hyperemic flow or hyperemic shear stress. There was no correlation between two measures of macrovascular reactivity (FMD and DeltaPWV). Skin reactive hyperemia was significantly associated with RHI (r=0.55) and reactive hyperemic flow (r=0.35) (both P<0.05). There was a significant association between reactive hyperemia and RHI (r=0.30; P<0.05). In more than 75% of cases, vascular reactivity measures were not significantly associated. We concluded that associations among different measures of peripheral micro- and macrovascular reactivity were modest at best. These results suggest that different physiological mechanisms may be involved in changing different measures of vascular reactivity.     

The importance of indicators of the initial phase of atherosclerosis in patients with microvascular angina

Endothelial dysfunction (ED) is generally considered to be the initial step in the progression to atherosclerosis but there is still much uncertainty about the role of the microvascular form of angina in patients with a normal coronary angiogram with regard to ED. The authors investigated the extent of endothelial perturbation and thereby whether the microvascular form of angina precedens macroscopic atherosclerosis by means of non-invasive ultrasound measurement of the intima-media thickening (IMT) in common carotid artery and flow mediated dilatation (FMD) in the brachial artery. 28 patients with stable angina with positive exercise test and ST segment depression (22 females, 6 males, average age 54 years) were compared with a control group consisting of 28 patients with no clinical signs of coronary artery disease (18 females, 10 males, average age 53 years). No significant difference in FMD% (7.3 vs. 10.8, p = 0.07) was found between the groups, though specific measurements (average dilatation of the brachial artery induced by ischemic insult, peak blood flow and peak hyperemic flow) differed considerably. Also IMT did not vary significantly between the groups (0.74 vs. 0.65, p = 0.08). In patients with IMT > 0.8 mm (6 patients in each group) a significant decrease of FMD was found as compared with patients with normal IMT (p < 0.05). It was concluded that in patients with increased IMT an inverse relationship between FMD and IMT exists both in patients with microvascular angina and in the healthy control subjects whereas in the group of patients with normal IMT no ED was demonstrated. This supports the hypothesis that the microvascular form of angina is the early stage of coronary artery atherosclerosis and this escapes angiographic recognition.     

Progressive resistance training without volume increases does not alter arterial stiffness and aortic wave reflection

Endurance exercise is efficacious in reducing arterial stiffness. However, the effect of resistance training (RT) on arterial stiffening is controversial. High-intensity, high-volume RT has been shown to increase arterial stiffness in young adults. We tested the hypothesis that an RT protocol consisting of progressively higher intensity without concurrent increases in training volume would not elicit increases in either central or peripheral arterial stiffness or alter aortic pressure wave reflection in young men and women. The RT group (n = 24; 21 +/- 1 years) performed two sets of 8-12 repetitions to volitional fatigue on seven exercise machines on 3 days/week for 12 weeks, whereas the control group (n = 18; 22 +/- 1 years) did not perform RT. Central and peripheral arterial pulse wave velocity (PWV), aortic pressure wave reflection (augmentation index; AIx), brachial flow-mediated dilation (FMD), and plasma levels of nitrate/nitrite (NOx) and norepinephrine (NE) were measured before and after RT. RT increased the one-repetition maximum for the chest press and the leg extension (P < 0.001). RT also increased lean body mass (P < 0.01) and reduced body fat (%; P < 0.01). However, RT did not affect carotid-radial, carotid-femoral, and femoral-distal PWV (8.4 +/- 0.2 vs. 8.0 +/- 0.2 m/sec; 6.5 +/- 0.1 vs. 6.3 +/- 0.2 m/sec; 9.5 +/- 0.3 vs. 9.5 +/- 0.3 m/sec, respectively) or AIx (2.5% +/- 2.3% vs. 4.8% +/- 1.8 %, respectively). Additionally, no changes were observed in brachial FMD, NOx, NE, or blood pressures. These results suggest that an RT protocol consisting of progressively higher intensity without concurrent increases in training volume does not increase central or peripheral arterial stiffness or alter aortic pressure wave characteristics in young subjects.     

Acute effects of cold exposure on central aortic wave reflection.

The purpose of this study was to determine the effects of acute cold exposure on the timing and amplitude of central aortic wave reflection and central pressure. We hypothesized that cold exposure would result in an early return of reflected pressure waves from the periphery and an increase in central aortic systolic pressure as a result of cold-induced vasoconstriction. Twelve apparently healthy men (age 27.8 +/- 2.0 yr) were studied at random, in either temperate (24 degrees C) or cold (4 degrees C) conditions. Measurements of brachial artery blood pressure and the synthesis of a central aortic pressure waveform (by noninvasive radial artery applanation tonometry and use of a generalized transfer) were conducted at baseline and after 30 min in each condition. Central aortic augmentation index (AI), an index of wave reflection, was calculated from the aortic pressure waveform. Cold induced an increase (P < 0.05) in AI from 3.4 +/- 1.9 to 19.4 +/- 1.8%. Cold increased (P < 0.05) both brachial and central systolic pressure; however, the magnitude of change in central systolic pressure was greater (P < 0.05) than brachial (13 vs. 2.5%). These results demonstrate that cold exposure and the resulting peripheral vasoconstriction increase wave reflection and central systolic pressure. Additionally, alterations in central pressure during cold exposure were not evident from measures of brachial blood pressure.     

Physical exercise capacity is associated with coronary and peripheral vascular function in healthy young adults

Short-term exercise training has been shown to improve cardiovascular function, whereas long-term effects of a physically active lifestyle, on coronary artery function in particular, are still not well studied. We explored possible relationships between physical exercise capacity and coronary and peripheral vascular function in healthy young adults. Twenty-nine healthy young male and female volunteers participated in the study. They underwent 1) basic clinical and echocardiographic characterization, 2) coronary flow velocity reserve (CFVR) measurement of the left anterior descending coronary artery (LAD), 3) common carotid artery (CCA) intima-media thickness (IMT) measurement, 4) assessment of CCA stiffness index (SI), 5) forearm flow-mediated vasodilation (FMD), and 6) submaximal exercise test. The calculated weight-adjusted maximal oxygen uptake capacity (Vo(2 max)(c)) was positively correlated to LAD CFVR and inversely correlated to IMT and SI. Also, subjects with high compared with moderate exercise capacity had higher FMD. In addition, subjects with LAD CFVR in the upper median had greater ratios between endothelium-dependent and -independent vasodilation in the forearm and lower SI in CCA. High exercise capacity due to a physically active lifestyle is associated with high coronary and peripheral artery function, indicating an early protective role of physical exercise for cardiovascular health.     

Validity and application of noninvasive measurement of blood pressure in hamsters.

The aim of this study was to examine both the validity and application of noninvasive measurement of blood pressure (BP) at the brachial artery in hamsters. There were significant correlations between noninvasive and invasive values for systolic BP (SBP), mean BP, and diastolic BP (r = 0.96, r = 0.93, r = 0.88, respectively, all p < 0.0001). Furthermore, SBP appeared to be the most accurate noninvasive BP index because both proportional and constant systematic errors were the least among the three indices. Peripheral vascular resistance calculated by combination with echocardiographic indices actually reflected the prominent alpha 1-adrenergic drive induced by beta-adrenergic blockers. In conclusion, noninvasive BP measurement at the brachial artery can provide useful information regarding the integrated cardiovascular function in hamsters.     

Assessment of central haemomodynamics from a brachial cuff in a community setting

ABSTRACT: BACKGROUND: Large artery stiffening and wave reflections are independent predictors of adverse events. To date, their assessment has been limited to specialised techniques and settings. A new, more practical method allowing assessment of central blood pressure from waveforms recorded using a conventional automated oscillometric monitor has recently been validated in laboratory settings. However, the feasibility of this method in a community based setting has not been assessed. METHODS: One-off peripheral and central haemodynamic (systolic and diastolic blood pressure (BP) and pulse pressure) and wave reflection parameters (augmentation pressure (AP) and index, AIx) were obtained from 1,903 volunteers in an Austrian community setting using a transferfunction like method (ARCSolver algorithm) and from waveforms recorded with a regular oscillometric cuff. We assessed these parameters for known differences and associations according to gender and age deciles from <30 years to >80 years in the whole population and a subset with a systolic BP < 140 mmHg. RESULTS: We obtained 1,793 measures of peripheral and central BP, PP and augmentation parameters. Age and gender associations with central haemodynamic and augmentation parameters reflected those previously established from reference standard non-invasive techniques under specialised settings. Findings were the same for patients with a systolic BP below 140 mmHg (i.e. normotensive). Lower values for AIx in the current study are possibly due to differences in sampling rates, detection frequency and/or averaging procedures and to lower numbers of volunteers in younger age groups. CONCLUSION: A novel transfer-function like algorithm, using brachial cuff-based waveform recordings, provides robust and feasible estimates of central systolic pressure and augmentation in community-based settings.     

Impact of Body Mass Index on Changes in Common Carotid Artery Wall Thickness

Objective: To examine associations between changes in body mass index (BMI) and changes in carotid artery intima-media thickness (IMT) in a community-based sample. Research Methods and Procedures: Carotid artery IMT and BMI were assessed at baseline (between 1987 and 1990) and in three subsequent examinations at 3-year intervals in participants in the Atherosclerosis Risk in Communities cohort. The 9316 African-American and white men and women in the analysis were 45 to 64 years of age at baseline. Cross-sectional associations between BMI and IMT were assessed using general linear models. Longitudinal associations were examined using mixed models analysis. Results: Cross-sectional associations between BMI and IMT were confirmed. At baseline, a 1-kg/m² increase in BMI was associated with an increase in IMT that ranged from 2.5 to 7.5 μm among the ethnic-gender groups examined. Changes in BMI were not associated with changes in IMT in models that adjusted for aging and other covariates. Results were similar across ethnic-gender groups. Discussion: Among free-living, 45- to 64-year-old adults, changes in common carotid artery IMT associated with changes in BMI are either very small or absent.     

Aerobic run training improves brachial artery flow-mediated dilation

The purpose of this study was to assess the relationship between aerobic exercise training and brachial artery flow-mediated dilation (FMD) in healthy subjects. Healthy controls (HC) and aerobically-trained (T) subjects were studied with high-resolution vascular ultrasound at baseline, and during a 5-minute period of hyperemia following forearm cuff occlusion. Training was defined by self-reported participation in recreational or competitive run training. Forearm cuff occlusion was held at 200 mm Hg for 5 minutes. At baseline, both brachial artery flow and diameter were greater in T than in HC (p < 0.05). Resting heart rate was lower in T than in HC (p < 0.05). Peak hyperemic flow (15 seconds postocclusion) was significantly greater in T than in HC (HC; 539 +/- 75 ml x min(-1) vs. T; 832 +/- 103 ml x min(-1), p < 0.05) and correlated well with V(.-)O2peak (r = 0.67, p = 0.008). Flow-mediated dilation was significantly greater in T vs. HC throughout the 5-minute postocclusion phase (p < 0.05). Maximal brachial artery dilation was greater in T than in HC (HC; 3 +/- 1% of baseline vs. T; 8 +/- 3% of baseline; p < 0.05) and moderately correlated with V(.-)O2peak (r = 0.55, p < 0.05). These data suggest that the greater FMD observed in trained subjects may be due, in part, to an augmentation of peak hyperemic flow.     

High dietary salt intake increases carotid blood pressure and wave reflection in normotensive healthy young men

Dietary salt intake is associated with high brachial blood pressure (BP) and increased risk of cardiovascular disease. We investigated whether changes in dietary salt intake are associated with changes in central BP and wave reflection in healthy volunteers. Ten healthy normotensive male volunteers (22-40 yr) participated in a 6-wk double-blind randomized crossover study to compare a low-dietary salt intake (60-80 mmol sodium/day) with a high-salt intake (low salt intake supplemented with 128 mmol sodium/day) on central BP and wave reflection. Brachial and carotid BP, carotid blood flow velocity, forward (P(f)) and backward (P(b)) pressure, wave intensity, body weight, and urinary electrolyte excretion were measured at the end of each crossover period. High salt intake significantly increased carotid systolic BP [98 (SD 11) vs. 91 mmHg (SD 13), P < 0.01] and increased wave reflection [ratio of backward to forward pressure (P(b)/P(f)) 0.13 (SD 0.02) vs. 0.11 (SD 0.03), P = 0.04] despite only small effects on brachial BP [114 (SD 9) vs. 112 mmHg (SD 6), P = 0.1]. Urinary sodium excretion and body weight were also increased following high salt intake. High salt intake disproportionately increases central BP compared with brachial BP as a result of enhanced wave reflection. These effects may contribute to the adverse effect of high dietary salt intake on the risk of cardiovascular disease.     

Limitations of Augmentation Index in the Assessment of Wave Reflection in Normotensive Healthy Individuals

Objectives

Augmentation index (AIx) is widely used as a measure of wave reflection. We compared the relationship between AIx and age, height and sex with ‘gold standard’ measures of wave reflection derived from measurements of pressure and flow to establish how well AIx measures wave reflection.

Materials and Methods

Measurements of carotid pressure and flow velocity were made in the carotid artery of 65 healthy normotensive individuals (age 21–78 yr; 43 male) and pulse wave analysis, wave intensity analysis and wave separation was performed; waveforms were classified into type A, B or C. AIx, the time of the first shoulder (T_s), wave reflection index (WRI) and the ratio of backward to forward pressure (P_b/P_f) were calculated.

Results

AIx did not correlate with log WRI or P_b/P_f. When AIx was restricted to positive values AIx and log WRI were positively correlated (r = 0.33; p = 0.04). In contrast log WRI and P_b/P_f were closely correlated (r = 0.66; p<0.001). There was no correlation between the T_s and the timing of P_b or the reflected wave identified by wave intensity analysis. Wave intensity analysis showed that the morphology of type C waveforms (negative AIx) was principally due to a forward travelling (re-reflected) decompression wave in mid-systole. AIx correlated positively with age, inversely with height and was higher in women. In contrast log WRI and P_b/P_f showed negative associations with age, were unrelated to height and did not differ significantly by gender.

Conclusions

AIx has serious limitations as a measure of wave reflection. Negative AIx values derived from Type C waves should not be used as estimates of wave reflection magnitude.     

Sex differences in carotid baroreflex control of arterial blood pressure in humans: relative contribution of cardiac output and total vascular conductance

It is presently unknown whether there are sex differences in the magnitude of blood pressure (BP) responses to baroreceptor perturbation or if the relative contribution of cardiac output (CO) and total vascular conductance (TVC) to baroreflex-mediated changes in BP differs in young women and men. Since sympathetic vasoconstrictor tone is attenuated in women, we hypothesized that carotid baroreflex-mediated BP responses would be attenuated in women by virtue of a blunted vascular response (i.e., an attenuated TVC response). BP, heart rate (HR), and stroke volume were continuously recorded during the application of 5-s pulses of neck pressure (NP; carotid hypotension) and neck suction (NS; carotid hypertension) ranging from +40 to -80 Torr in women (n = 20, 21 ± 0.5 yr) and men (n = 20, 21 ± 0.4 yr). CO and TVC were calculated on a beat-to-beat basis. Women demonstrated greater depressor responses to NS (e.g., -60 Torr, -17 ± 1%baseline in women vs. -11 ± 1%baseline in men, P < 0.05), which were driven by augmented decreases in HR that, in turn, contributed to larger reductions in CO (-60 Torr, -15 ± 2%baseline in women vs. -6 ± 2%baseline in men, P < 0.05). In contrast, pressor responses to NP were similar in women and men (e.g., +40 Torr, +14 ± 2%baseline in women vs. +10 ± 1%baseline in men, P > 0.05), with TVC being the primary mediating factor in both groups. Our findings indicate that sex differences in the baroreflex control of BP are evident during carotid hypertension but not carotid hypotension. Furthermore, in contrast to our hypothesis, young women exhibited greater BP responses to carotid hypertension by virtue of a greater cardiac responsiveness.     

Early atherosclerosis in systemic sclerosis and its relation to disease or traditional risk factors

Introduction  

Several systemic autoimmune diseases are associated with an increased prevalence of atherosclerosis which could not be explained by traditional risk factors alone. In systemic sclerosis (SSc), microvascular abnormalities are well recognized. Previous studies have suggested an increased prevalence of macrovascular disease as well. We compared patients with SSc to healthy controls for signs of early atherosclerosis by measuring intima-media thickness (IMT) of the common carotid artery in relation to traditional risk factors and markers of endothelial activation.     

Effect of lower limb exercise on forearm vascular function: contribution of nitric oxide

We examined vascular function in an inactive muscle bed, the forearm, during lower limb exercise and determined the contribution of endothelium-derived nitric oxide (NO) to the hyperemic response. Eight young males were randomized to participate in two studies, each consisting of two bouts of lower limb exercise, separated by a 30-min recovery. Peak forearm blood flow (PFBF) and mean blood flow (MFBF) were continuously recorded at baseline and during exercise using continuous high-resolution vascular ultrasound and Doppler flow velocity measurement. During one session, the brachial artery was cannulated to allow continuous infusion of saline or N(G)-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthase. The alternate session was performed to control for possible effects of repeated exercise. At 60, 100, and 160 W, L-NMMA significantly decreased both PFBF and MFBF compared with the saline infusion. These results suggest that systemic production of NO occurs during exercise in resting vessel beds, which do not feed metabolically active tissue. This finding provides a plausible explanation for the antiatherogenic benefits of exercise.     

Why is flow-mediated dilation dependent on arterial size? Assessment of the shear stimulus using phase-contrast magnetic resonance imaging

Flow-mediated dilation (FMD) is strongly dependent on arterial size, but the reasons for this phenomenon are poorly understood. We have previously shown that FMD is greater in small brachial arteries because the shear stress stimulus is greater in small brachial arteries. However, it is unclear why the shear stimulus is greater in small arteries. Furthermore, this relationship has not been investigated in other, differently sized arterial beds. Postischemic systolic shear stress and resulting FMD were evaluated in the brachial and femoral arteries of 24 young, healthy adults using phase-contrast magnetic resonance imaging. Arterial shear and radius were calculated from the velocity profile via a best-fit parabola before and after occlusion. Summing the velocity pixels provided hyperemic systolic flow. FMD was proportional to hyperemic shear in the brachial and femoral arteries (P < 0.0001, r = 0.60). Hyperemic systolic flow was proportional to radius2 (P < 0.0001, r = 0.93). Applying this relationship to the Poiseuille equation (shear is proportional to flow/radius3) shows that hyperemic shear is proportional to radius2/radius3 and, therefore, explains why hyperemic shear is proportional to 1/radius. We conclude that FMD is proportional to hyperemic systolic shear stress in both the brachial and the femoral arteries. The hyperemic shear stimulus for FMD is greater in small arteries due to the dependence of postischemic systolic flow on radius squared. Therefore, greater FMD in small arteries does not necessarily reflect better conduit artery endothelial function. Evaluating the shear stimulus using phase-contrast magnetic resonance imaging enhances the understanding of mechanisms underlying FMD.     

超声检查颈动脉粥样硬化情况和肱动脉FMD 对稳定性心绞痛的价值

目的:探讨无创超声检查颈动脉粥样硬化情况和肱动脉FMD对SAP的价值。方法:将选取的65例SAP患者分为轻度狭窄组、中度狭窄组和重度狭窄组,超声检测所有病例的肱动脉FMD和颈总动脉IMT,并作Califf危险评分和As积分,分析观察指标间的关系。结果:Califf危险评分和As积分都随着冠脉狭窄程度的加深而增大,且二者呈正相关(P<0.05);颈总动脉IMT随着狭窄程度的加深而增大,肱动脉FMD则随着狭窄程度的加深而降低,二者呈负相关(P<0.05)。结论:无创监测颈总动脉IMT和肱动脉FMD,可指导SAP临床风险的控制。