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Background: It is well know that arterial stiffness, oxidative stress and inflammation are features of chronic kidney disease. The arterial changes have a multitude of potential interconnected causes including endothelial dysfunction, oxidative stress, inflammation, atherosclerosis and vascular calcification. There is evidence that arterial stiffness becomes progressively worse as CKD progresses. The contribution of the biochemical changes of uremic toxicity to arterial stiffness is less clear. The aim of this study is to elucidate the vascular changes in acute kidney injury. We hypothesise that arterial stiffness will be increased during acute kidney injury and this will return to normal after kidney function recovers., Methods/design: One hundred and forty four patients with acute kidney injury defined as an acute increase in serum creatinine to > 133 micromol/l or urea > 14.3 mmol/l or urine output < 410 ml/day will be recruited. Baseline measures of aortic pulse wave velocity, augmentation index, and brachial and central blood pressure will be recorded along with blood measures for oxidative stress and inflammation. Repeat measures will be taken at six and 12 months after the onset of the acute kidney injury., Discussion: The role and contribution of the biochemical changes to arterial stiffness in the acute phase of kidney disease is not known. This study will primarily assess the time course changes in pulse wave velocity from the onset of acute kidney injury and after recovery. In addition it will assess augmentation index, central blood pressure and oxidative stress and inflammation. This may shed light on the contribution of biochemical kidney toxins on arterial stiffness in both acute kidney injury and chronic kidney disease., Trial Registration: ACTRN 12609000285257.

Hypertension (high blood pressure; BP) is a leading contributor to premature death and disability from cardiovascular disease. Lifestyle modification that includes regular physical activity is often recommended to patients with hypertension as one of the first line treatments for lowering BP, as well as improving overall risk for cardiovascular events. It is recognised that allied health care professionals play an important role in helping patients to achieve BP control by influencing and reinforcing appropriate lifestyle behavior. The minimum amount of exercise that is recommended in patients with hypertension comprises a mix of moderate to vigorous aerobic (endurance) activity (up to 5 days/week) in addition to resistance (strength) training (on 2 or more non-consecutive days/week). However, due to the dose-response relationship between physical activity and health, exercise levels performed beyond the minimum recommendations are expected to confer additional health benefits. Vigorous exercise training is generally safe and well tolerated by most people, including those with hypertension, although some special considerations are required and these are discussed in this review.

Background: Exercise training in hemodialysis patients improves fitness, physical function, quality of life and markers of cardiovascular disease such as arterial stiffness. The majority of trials investigating this area have used supervised exercise training during dialysis (intradialytic), which may not be feasible for some renal units. The aim of this trial is to compare the effects of supervised intradialytic with unsupervised home-based exercise training on physical function and arterial stiffness., Methods and Design: This is a randomised, controlled clinical trial. A total of 72 hemodialysis patients will be randomised to receive either six months of intradialytic exercise training, home-based exercise training or usual care. Intradialytic patients will undergo three training sessions per week on a cycle ergometer and home-based patients will be provided with a walking program to achieve the same weekly physical activity. Primary outcome measures are six-minute walk distance (6 MWD) and aortic pulse wave velocity (PWV). Secondary outcome measures include augmentation index, peripheral and central blood pressures, physical activity and self-reported health. Measures will be made at baseline, three and six months., Discussion: The results of this study will help determine the efficacy of home-based exercise training in hemodialysis patients. This may assist in developing exercise guidelines specific for these patients., Trial Registration: ACTRN12608000247370

Background: Patients with coronary slow flow (CSF) present with a syndrome (often recurrent) of resting angina with no significant coronary stenoses. The nature of myocardial blood flow (MBF), MBF reserve and systemic arterial characteristics may contribute to symptoms in these patients but this has not been examined previously. This study sought to measure MBF, arterial stiffness and wave reflection in patients with CSF and controls., Methods: Ten patients with angiographically proven CSF and 20 controls underwent dipyridamole-exercise stress myocardial contrast echocardiography and arterial waveform analysis. MBF was quantified off-line from 10 mid and apical segments with calculation of myocardial blood volume (A), red cell velocity (beta) and their product, MBF, at rest and post-stress. MBF reserve was calculated as the ratio of peak stress to resting MBF. Central arterial pressure waveforms were derived by radial tonometry, with arterial wave reflection expressed by augmentation index. Arterial stiffness was determined by aortic and brachial pulse wave velocities., Results: There was no significant difference between CSF and control groups in mean resting beta (0.56+/-0.24 versus 0.59+/-0.26), A (7.9+/-1.4 versus 7.9+/-5.2), MBF (4.3+/-1.8 versus 4.4+/-3.6), MBF reserve (3.7+/-2.0 versus 4.0+/-2.0), augmentation index (26+/-12 versus 23+/-9%), aortic (7.4+/-1.8 versus 7.4+/-1.5 m/s) or brachial (8.0+/-0.8 versus 8.1+/-1.3) pulse wave velocity (p>0.4 for all). Similarly, there were no significant haemodynamic differences between groups after exercise (p>0.2 for all)., Conclusions: MBF, large artery stiffness and arterial wave reflection characteristics are normal in CSF patients between their acute episodes.

Central systolic blood pressure (SBP) may differ between individuals with similar brachial SBP, which may have implications for risk assessment. This study aimed to determine the variation and potential clinical value of central SBP between patients with similar brachial SBP. Brachial SBP was measured by sphygmomanometer and central SBP by radial tonometry in 675 people (430 men), comprising healthy individuals (n = 222), patients with known or suspected coronary artery disease (n = 229) and diabetes (n = 224). Individuals were stratified by brachial SBP in accordance with European Society of Hypertension guidelines (optimal, normal, high-normal, grades 1, 2 and 3 hypertension). The potential clinical value of central SBP was determined from the percentage of patients re-classified into different brachial SBP groups due to the difference between brachial and aortic SBP (defined as brachial SBP-central SBP). Central SBP increased with each brachial SBP level (optimal to grade 3 hypertension; P < 0.001 for all). However, large variation in brachial-aortic SBP difference occurred within each brachial SBP group (range 2-33 mm Hg), resulting in sizeable overlap of central SBP between brachial SBP groups. For patients with normal brachial SBP, 96% had central SBP within the range of patients with high-normal brachial SBP, as well as 64% within the range of patients with grade 1 hypertension. We conclude that wide variation in brachial-aortic SBP difference occurs between patients with similar brachial SBP. This results in a significant overlap of central SBP scores between brachial SBP risk groups. This is likely to have treatment implications but remains to be tested.

Background: Central blood pressure (BP) and markers of wave reflection (augmentation index; AIx) measured by radial tonometry have prognostic value independent from brachial BP. The measurement of the central waveform is increasingly used during altered hemodynamics, including exercise, but reliability of the test has not been reported under changed loading conditions. This study aimed to test the technique's reproducibility during major hemodynamic perturbations induced by exercise., Methods: Radial waveforms were recorded (SphygmoCor) in 28 healthy subjects (aged 53 +/- 11 years) at rest, during submaximal exercise (cycling at 50, 60, and 70% of maximal age-predicted heart rate (HR)) and immediately after maximal treadmill exercise on two occasions separated by 9 +/- 5 days. Data were compared between testing days. Waveforms were calibrated with brachial BP measured using a mercury sphygmomanometer. Pulse pressure amplification (PPAmp) was defined as the ratio of brachial to central pulse pressure., Results: There was very good reproducibility between visits at all exercise intensities for all waveform measures, including AIx, central pulse pressure, and PPAmp (intraclass correlations at 50% exercise were 0.93, 0.89, and 0.89, respectively; P < 0.001). The mean difference between tests at this intensity was 0 +/- 4% for AIx, 4 +/- 6 mm Hg for central pulse pressure, and -0.02 +/- 0.09 for PPAmp. There were no significant differences between visits for HR, PPAmp, or AIx at rest or with exercise (P > 0.05 for all)., Conclusions: Radial tonometry is a reproducible technique for measurement of central waveform indices during perturbations induced by exercise. It should, therefore, be suitable for use in intervention studies in which hemodynamics are altered.

Central hemodynamics such as ascending aortic blood pressure (BP), wave reflection and myocardial perfusion are clinically important in the context of cardiovascular health. Ultra-endurance athletes may be at greater risk of cardiovascular abnormalities due to chronically increased physiological stress placed on the cardiovascular system. This study was a cross-sectional investigation that compared central hemodynamics in ultra-endurance athletes and matched controls. Forty-four athletes (36 males; aged mean+/-S.D., 34+/-8 years) undergoing ultra-endurance training (16.3+/-3.7 h/week) were compared to 44 matched recreationally active (1.2+/-0.9 h/week) controls (36 males; aged 34+/-8 years). Brachial BP was measured using an oscillometric device while central hemodynamics including ascending aortic BP, wave reflection (augmentation index, AIx), ejection duration, sub-endocardial perfusion (SEVR) and timing of the reflected wave (T(R)) were determined by applanation tonometry and pulse wave analysis. There were no significant (P>0.05) differences between groups in AIx (athletes and controls; 6+/-12% versus 6+/-13%, respectively), T(R) (athletes and controls; 165+/-22 ms versus 165+/-19 ms, respectively), brachial (athletes and controls; 51+/-9 mmHg versus 48+/-12 mmHg, respectively) or central pulse pressure (33+/-5 mmHg versus 31+/-7 mmHg). However, athletes had significantly increased SEVR (226+/-42% versus 198+/-46%; P<0.001) despite having a longer ejection duration (348+/-19 ms versus 339+/-18 ms; P<0.05). Furthermore, the amount of exercise training volume was significantly related to central (r=-0.46; P=0.002), but not brachial pulse pressure (r=-0.28; P>0.05). Ultra-endurance athletes had increased sub-endocardial perfusion capacity and the quantity of exercise training was associated with central rather than peripheral hemodynamics.

Background: A hypertensive response to exercise has prognostic significance. Patients with type 2 diabetes have vascular abnormalities which may predispose to exaggerated brachial and central blood pressure (BP) during exercise. This study aimed to test this hypothesis and to determine the clinical significance of high exercise BP by examining its relation to left ventricular (LV) mass., Methods: Brachial and central BP were recorded at rest and in response to maximal exercise in 73 diabetic patients (aged 54 +/- 10 years) and 73 controls (aged 53 +/- 12 years). Brachial BP was recorded using mercury sphygmomanometry and LV mass using 2D-echocardiography. Central BP was estimated by radial tonometry using an exercise-validated generalized transfer function., Results: At rest there were no significant (P > 0.05) differences between groups in brachial or central BP. The diabetic patients had significantly increased exercise brachial systolic BP (SBP: 199 +/- 25 mm Hg vs. 185 +/- 21 mm Hg; P = 0.002) and central SBP (158 +/- 17 mm Hg vs. 149 +/- 15 mm Hg; P = 0.002). There was a significantly higher prevalence of an exaggerated exercise BP response (> or =210/105 mm Hg; men and > or =190/105 mm Hg; women) in the diabetic patients (51% vs. 22%; P < 0.01). Compared with those with normal exercise BP, LV relative wall thickness (RWT) was significantly higher (0.41 +/- 0.09 vs. 0.36 +/- 0.08; P < 0.05) and LV hypertrophy was more prevalent (35% vs. 16%; P < 0.05) in those with a hypertensive response. After accounting for other confounding variables, exercise central SBP remained independently associated with LV RWT (beta = 0.22; P = 0.006)., Conclusion: Diabetic patients are more likely to exhibit exaggerated exercise BP. Regardless of disease status, high exercise central SBP may contribute to cardiovascular risk via adverse cardiac remodeling.

NO modulates resting blood pressure and wave reflection. The effect of NO on exercise central hemodynamics is unknown but has important implications relating to cardiovascular risk. The aim of this study was to determine the contribution of NO to pulse pressure (PP) amplification and wave reflection during exercise. Twelve healthy men aged 29+/-1 years (mean+/-SEM) undertook cycle exercise at 60% of their maximal heart rate. Noninvasive measures of central blood pressure, estimated aortic pulse wave velocity, and wave reflection (augmentation index) were obtained by pulse wave analysis during intravenous infusion of saline (control), N(G)-monomethyl-l-arginine (a NO-synthase inhibitor), or noradrenaline (control vasoconstrictor). PP amplification was defined as the ratio of peripheral to central PP. Cardiac output and stroke volume were determined by electric bioimpedance. Both N(G)-monomethyl-l-arginine and noradrenaline caused a significant increase in mean arterial pressure (P<0.01) and augmentation index (P<0.01), as well as reduced ratio of peripheral to central PP (P<0.05) at baseline. Exercise caused a significant increase in the ratio of peripheral to central PP (P<0.001), whereas augmentation index and estimated aortic pulse wave velocity declined (for both P<0.05) during all 3 of the infusion protocols. However, no significant differences were observed in augmentation index, ratio of peripheral to central PP, or estimated aortic pulse wave velocity between infusion procedures (P>0.50) during exercise. Also, heart rate, peripheral vascular resistance, and cardiac output did not differ during exercise between saline, N(G)-monomethyl-l-arginine, or noradrenaline. Although we cannot rule out other vasodilator mechanisms having adjusted for NO blockade, our results indicate that NO does not solely contribute to systemic arterial stiffness or altered blood pressure amplification during light exercise.

Objectives: Exercise brachial blood pressure (BP) is predictive of cardiovascular events. As a result of the amplification of pulse pressure, central BP (a stronger cardiovascular risk factor) differs significantly from peripheral measures. Pulse pressure amplification is reduced with increasing age and hypercholesterolemia at rest, but the effect of exercise on central pressure in these populations is unknown. This study aimed to assess the central and peripheral BP response to exercise with aging and hypercholesterolemia., Methods: Twenty healthy younger (aged 29 +/- 5 years; mean +/- SD), 20 healthy older (aged 57 +/- 5 years) and 12 matched older (aged 59 +/- 7 years) men with hypercholesterolemia exercised (bicycle ergometer) at 60% of their predicted maximal heart rate. Central BP and augmentation index (AIx), a marker of systemic arterial stiffness, were obtained non-invasively using pulse wave analysis. Pulse pressure amplification was defined as the ratio of peripheral to central pulse pressure., Results: The resting haemodynamics of the older men were not significantly different from those with hypercholesterolemia. During exercise, amplification was significantly lower (P < 0.001), and the augmentation index significantly higher (P < 0.001) in the hypercholesterolemic individuals. Younger men had significantly increased amplification (P < 0.01) and reduced AIx (P < 0.001) at rest and during exercise compared with older men. In multiple regression analysis, exercise pulse pressure amplification was independently predicted by age (beta = -0.48; P < 0.001) and total cholesterol (beta = -0.28; P = 0.03)., Conclusion: With increasing age, exercise pulse pressure amplification is significantly attenuated because of increased wave reflection. These effects are exacerbated by hypercholesterolemia and may contribute to cardiovascular risk by mechanisms associated with central hypertension.

Background: The first derivative of left ventricular (LV) pressure over time (dP/dt max) is a marker of LV systolic function that can be assessed during cardiac catheterization and echocardiography. Radial artery dP/dt max has been proposed as a possible marker of LV systolic function and we sought to test this hypothesis., Materials and Methods: We compared simultaneously recorded radial dP/dt max (by high-fidelity tonometry) with LV dP/dt max (by high-fidelity catheter and echocardiography parameters analogous to LV dP/dt max). In study 1, beat-to-beat radial dP/dt max and LV dP/dt max were recorded at rest and during supine exercise in 12 males (aged 61 +/- 12 years) undergoing cardiac catheterization. In study 2, 2D-echocardiography and radial dP/dt max were recorded in 54 patients (separate to study 1; 39 men; aged 64 +/- 10 years) at baseline and peak dobutamine-induced stress. Three basal septum measures were taken as being analogous to LV dP/dt max: 1. Peak systolic strain rate; 2. Strain rate (SR-dP/dt max) during isovolumic contraction (IVCT) and; 3. Tissue velocity during IVCT., Results: In study 1 there was a significant difference between resting LV dP/dt max (1461 +/- 383 mmHg s(-1)) and radial dP/dt max (1182 +/- 319 mmHg s(-1); P < 0.001), and a poor, but statistically significant, correlation between the variables (R(2) = 0.006; P < 0.05). Similar results were observed during exercise. In study 2 there were weak (R(2) = -0.12; P = 0.01) to non-significant associations between radial dP/dt max and all echocardiographic measures analogous to LV dP/dt max at rest or peak stress., Conclusion: Radial pressure waveform dP/dt max is not a reliable marker of LV systolic function.

Left ventricular (LV) diastolic dysfunction and increased arterial stiffness are prevalent in patients with type 2 diabetes mellitus (DM). Because the systemic vasculature plays a pivotal role in myocardial loading, this study aimed to determine the effect of arterial characteristics on LV diastolic function in patients with type 2 DM. Conventional echocardiography and tissue Doppler imaging were performed in 155 patients with type 2 DM (88 men; mean age 55 +/- 11 years) with preserved LV ejection fractions (>50%). Patients were stratified into groups on the basis of LV diastolic function (normal, n = 53; delayed relaxation, n = 79; pseudonormal, n = 23). Arterial wave reflection parameters and central blood pressure were determined by radial tonometry. Arterial (brachial and carotid) structure and function were determined by standard ultrasound methods. There were no significant differences among the groups on central pressure or arterial function. LV filling pressure, determined by the ratio of early transmitral inflow velocity to diastolic early tissue velocity (E/E'), was significantly correlated with central pulse pressure (r = 0.21, p <0.05). Late diastolic inflow velocity (A) was significantly associated with central pulse pressure (r = 0.32, p <0.001), total arterial compliance (r = -0.35, p <0.001), and carotid artery stiffness (r = 0.34, p <0.001). Multiple regression analysis found central but not brachial pulse pressure independently predicted E/E' and A. In conclusion, increased central pulse pressure, possibly due to amplified pressure wave reflections, is independently associated with abnormal LV diastolic function in patients with type 2 DM.

Exercise brachial blood pressure (BP) predicts mortality, but because of wave reflection, central (ascending aortic) pressure differs from brachial pressure. Exercise central BP may be clinically important, and a noninvasive means to derive it would be useful. The purpose of this study was to test the validity of a noninvasive technique to derive exercise central BP. Ascending aortic pressure waveforms were recorded using a micromanometer-tipped 6F Millar catheter in 30 patients (56+/-9 years; 21 men) undergoing diagnostic coronary angiography. Simultaneous recordings of the derived central pressure waveform were acquired using servocontrolled radial tonometry at rest and during supine cycling. Pulse wave analysis of the direct and derived pressure signals was performed offline (SphygmoCor 7.01). From rest to exercise, mean arterial pressure and heart rate were increased by 20+/-10 mm Hg and 15+/-7 bpm, respectively, and central systolic BP ranged from 77 to 229 mm Hg. There was good agreement and high correlation between invasive and noninvasive techniques with a mean difference (+/-SD) for central systolic BP of -1.3+/-3.2 mm Hg at rest and -4.7+/-3.3 mm Hg at peak exercise (for both r=0.995; P<0.001). Conversely, systolic BP was significantly higher peripherally than centrally at rest (155+/-33 versus 138+/-32 mm Hg; mean difference, -16.3+/-9.4 mm Hg) and during exercise (180+/-34 versus 164+/-33 mm Hg; mean difference, -15.5+/-10.4 mm Hg; for both P<0.001). True myocardial afterload is not reliably estimated by peripheral systolic BP. Radial tonometry and pulse wave analysis is an accurate technique for the noninvasive determination of central BP at rest and during exercise.

Objectives: Our study attempted to validate a Doppler index of diastolic filling (E/E') during exercise with simultaneously measured left ventricular diastolic pressure (LVDP), investigate its association with exercise capacity, and understand which patients to select for testing., Background: The ratio of early diastolic transmitral velocity to early diastolic tissue velocity approximates LVDP at rest, but there is limited validation of exercise E/E' with invasive hemodynamic measurement, and its clinical implications are unclear., Methods: The ratio of early diastolic transmitral velocity to early diastolic tissue velocity was measured at rest and during supine cycle ergometry in 37 patients undergoing left heart catheterization. In addition to correlation between invasive and estimated LVDP, the accuracy of different cutoffs for identification of elevated LVDP (>15 mm Hg) was determined at both rest and exercise. Doppler index of diastolic filling was also measured at rest and immediately after maximal treadmill exercise in 166 patients to investigate the association between exercise E/E' and exercise capacity (<8 metabolic equivalents [METs])., Results: In patients undergoing invasive measurement, nine (24%) had elevation of LVDP only during exercise. There was a good correlation between E/E' and LVDP at rest (r = 0.67) and during exercise (r = 0.59), and the regressions at rest and exercise corresponded closely. Receiver-operator curve analysis indicated that a cutoff value of 13 for exercise E/E' identified patients with an elevated LVDP during exercise. A post-exercise E/E' >13 was highly specific (90%) for reduced exercise capacity, and even after classification of resting E/E', exercise E/E' permitted classification of patients with exercise capacity <8 METs or > or =8 METs., Conclusions: The ratio of early diastolic transmitral velocity to early diastolic tissue velocity correlates with invasively measured LVDP during exercise. It can be used to reliably identify patients with elevated LVDP during exercise and reduced exercise capacity.

Background: Brachial blood pressure predicts cardiovascular outcome at rest and during exercise. However, because of pulse pressure amplification, there is a marked difference between brachial pressure and central (aortic) pressure. Although central pressure is likely to have greater clinical importance, very little data exist regarding the central haemodynamic response to exercise. The aim of the present study was to determine the central and peripheral haemodynamic response to incremental aerobic exercise., Materials and Methods: Twelve healthy men aged 31 +/- 1 years (mean +/- SEM) exercised at 50%, 60%, 70% and 80% of their maximal heart rate (HRmax) on a bicycle ergometer. Central blood pressure and estimated aortic pulse wave velocity, assessed by timing of the reflected wave (T(R)), were obtained noninvasively using pulse wave analysis. Pulse pressure amplification was defined as the ratio of peripheral to central pulse pressure and, to assess the influence of wave reflection on amplification, the ratio of peripheral pulse pressure to nonaugmented central pulse pressure (PPP : CDBP-P1) was also calculated., Results: During exercise, there was a significant, intensity-related, increase in mean arterial pressure and heart rate (P < 0.001). There was also a significant increase in pulse pressure amplification and in PPP : CDBP-P(1) (P < 0.001), but both were independent of exercise intensity. Estimated aortic pulse wave velocity increased during exercise (P < 0.001), indicating increased aortic stiffness. There was also a positive association between aortic pulse wave velocity and mean arterial pressure (r = 0.54; P < 0.001)., Conclusions: Exercise significantly increases pulse pressure amplification and estimated aortic stiffness.

Purpose: To quantify the rate of arterial oxygen desaturation during apnea in freedivers., Methods: Ten freedivers and ten controls undertook five maximal face immersion apneas in 10 degrees C water separated by 2 min of recovery. Electrocardiogram (ECG), blood pressure, and pulse oximetry were recorded continuously. Peripheral blood flow was measured by calf plethysmography every 30 s, and venous blood samples were collected at rest and after apneas 1, 3, and 5. The blood was analyzed for hematocrit (Hct), lactate, and hemoglobin (Hb) concentration. The arterial oxygen saturation (SaO(2)) data were curve fitted with both a sigmoid and two-slope continuous function., Results: Apnea duration increased with successive attempts, with freedivers achieving significantly longer maximal apneas (trained 246 +/- 44 s, untrained 129 +/- 39 s, P < 0.001). Compared with controls, freedivers displayed a significant change from baseline in heart rate (trained -27.2 +/- 9.5 bpm, untrained -19.7 +/- 9.3 bpm, P < 0.001) and mean arterial pressure (MAP) (trained 48 +/- 20.7 mm Hg, untrained 37 +/- 10.0 mm Hg, P = 0.002), but no difference existed in peripheral blood flow, Hct, lactate, or Hb. The maximal slope of the SaO(2) sigmoid curve was not significantly different between the groups (trained -0.16 +/- 0.05%.s(-1), untrained -0.15 +/- 0.06%.s(-1), P = 0.26), but the DeltaSaO(2(/Deltat obtained from the two-slope continuous model indicated that 85% of the variance in the freedivers DeltaSaO(2)/Deltat could be explained by the apnea-induced bradycardia, preapnea vital capacity, and Hb concentration., Conclusions: The sigmoidal function provided no quantifiable difference in the rate of oxygen desaturation. The two-slope continuous method, however, indicated that freedivers who had larger oxygen stores and produced the largest bradycardia were able to slow the DeltaSaO(2)/Deltat to two to three times that of the least marked response.

Background: Transplant recipients have elevated oxidative stress, which has prompted suggestions that supplementary antioxidants may be beneficial. However, only a small number of clinical trials have investigated antioxidant supplementation in transplant recipients, with very few data on their effects on patients' immunosuppressive therapy., Methods: A randomized placebo-controlled single-blind crossover trial was conducted in 10 renal transplant recipients (RTRs) taking cyclosporin A (CsA) as part of their immunosuppressive therapy. Each phase of the trial lasted 6 months, with a 6 month wash-out period in between. During one of the phases, patients consumed a tablet twice per day which delivered 400 IU/day of vitamin E, 500 mg/day of vitamin C and 6 mg/day of beta-carotene., Results: During antioxidant supplementation, there was no change in CsA dose. Antioxidant supplementation resulted in a significant decrease (P<0.05) in blood trough CsA by 24% (mean+/-SD, pre- 127.3+/-38.9, post- 97.2+/-30.7 microg/ml) compared with no change while taking the placebo (pre- 132.2+/-50.6, post- 138.6+/-56.0 microg/ml). The glomerular filtration rate was significantly (P<0.05) improved by 12% during antioxidant supplementation (pre- 66.9+/-20.7, post- 75.0+/-20.1 ml/min/1.72 m2), with no change during the placebo phase (pre- 66.8+/-11.8, post- 66.7+/-16.1 ml/min/1.72 m2). There were no significant differences (P>0.05) in markers of oxidative stress (malondialdehyde, susceptibility of plasma to oxidation) or plasma antioxidant enzymes., Conclusion: In CsA-treated RTRs, antioxidant supplementation decreased blood CsA, which may affect adequacy of immunosuppression.

Isolated systolic hypertension is a common condition in individuals aged older than 60 years. However, isolated systolic hypertension has also been described in young individuals, although the mechanisms are poorly understood. We hypothesized that in young adults, isolated systolic hypertension and essential hypertension have different hemodynamic mechanisms and the aim of this study was to test this hypothesis in a cohort of subjects from The ENIGMA Study. Peripheral and central blood pressure, aortic pulse wave velocity, cardiac output, stroke volume, and peripheral vascular resistance were determined in 1008 subjects, aged 17 to 27 years. Compared with normotensive subjects, those with isolated systolic hypertension had significantly higher peripheral, central, and mean blood pressure, aortic pulse wave velocity, cardiac output, and stroke volume (P<0.001 for all comparisons). However, there were no differences in pulse pressure amplification, heart rate, or peripheral vascular resistance between the two groups. Compared with subjects with essential hypertension, mean pressure, heart rate, and peripheral vascular resistance were all significantly lower in isolated systolic hypertensive subjects, but pulse pressure amplification, aortic pulse wave velocity, cardiac output, and stroke volume were higher (P<0.001 for all comparisons). We have demonstrated that in young adults, isolated systolic hypertension and essential hypertension arise from different hemodynamic mechanisms. Isolated systolic hypertension appears to result from an increased stroke volume and/or aortic stiffness, whereas the major hemodynamic abnormality underlying essential hypertension is an increased peripheral vascular resistance. Long-term follow-up of these individuals is now required to determine whether they are at increased risk compared with age-matched normotensive individuals.

Objective: Although physical activity is beneficial to health, people who exercise at high intensities throughout their lifetime may have increased cardiovascular risk. Aerobic exercise increases oxidative stress and may contribute to atherogenesis by augmented oxidation of plasma lipoproteins. The aim of this study was to examine the relationship between aerobic power and markers of oxidative stress, including the susceptibility of plasma to oxidation., Methods and Results: Aerobic power was measured in 24 healthy men aged 29+/-9 years (mean+/-SD). Plasma was analysed from subjects of high aerobic power (HAP; VO2max, 64.6+/-6.1 ml/kg/min) and lower aerobic power (LAP;VO2max, 45.1+/-6.3 ml/kg/min) for total antioxidant capacity (TAC), malondialdehyde (MDA) and susceptibility to oxidation. Three measures were used to quantify plasma oxidizability: (1) lag time to conjugated diene formation (lag time); (2) change in absorbance at 234 nm and; (3) slope of the oxidation curve during propagation (slope). The HAP subjects had significantly lower TAC (1.38+/-0.04 versus 1.42+/-0.06 TEAC units; P < 0.05), significantly higher change in absorbance (1.55+/-0.21 versus 1.36+/-0.17 arbitrary units; P < 0.05), but no difference in MDA (P = 0.6), compared to LAP subjects. There was a significant inverse association between TAC and slope (r = -0.49; P < 0.05). Lipoprotein profiles and daily intake of nutrients did not differ between the groups., Conclusions: These findings suggest that people with high aerobic power, due to extreme endurance exercise, have plasma with decreased antioxidant capacity and higher susceptibility to oxidation, which may increase their cardiovascular risk.

Regular aerobic exercise is recommended by physicians to improve health and longevity. However, individuals exercising in urban regions are often in contact with air pollution, which includes particles and gases associated with respiratory disease and cancer. We describe the recent evidence on the cardiovascular effects of air pollution, and the implications of exercising in polluted environments, with a view to informing clinicians and other health professionals. There is now strong evidence that fine and ultra fine particulate matter present in air pollution increases cardiovascular morbidity and mortality. The main mechanisms of disease appear to be related to an increase in the pathogenic processes associated with atherosclerosis. People exercising in environments pervaded by air contaminants are probably at increased risk, due to an exercise-induced amplification in respiratory uptake, lung deposition and toxicity of inhaled pollutants. We make evidence-based recommendations for minimizing exposure to air-borne toxins while exercising, and suggest that this advice be passed on to patients where appropriate.

Aims: Alpha-lipoic acid (ALA) is a thiol compound with antioxidant properties used in the treatment of diabetic polyneuropathy. ALA may also improve arterial function, but there have been scant human trials examining this notion. This project aimed to investigate the effects of oral and intra-arterial ALA on changes in systemic and regional haemodynamics, respectively., Methods: In study 1, 16 healthy older men aged 58 +/- 7 years (mean +/- SD) received 600 mg of ALA or placebo, on two occasions 1 week apart, in a randomized cross-over design. Repeated measures of peripheral and central haemodynamics were then obtained for 90 min. Central blood pressure and indices of arterial stiffness [augmentation index (AIx) and estimated aortic pulse wave velocity] were recorded non-invasively using pulse wave analysis. Blood samples obtained pre- and post-treatments were analysed for erythrocyte antioxidant enzyme activity, plasma nitrite and malondialdehyde. In study 2 the effects of incremental cumulative doses (0.5, 1.0, 1.5 and 2.0 mg ml(-1) min(-1)) of intra-arterial ALA on forearm blood flow (FBF) were assessed in eight healthy subjects (aged 31 +/- 5 years) by conventional venous occlusion plethysmography., Results: There were no significant changes on any of the central or peripheral haemodynamic measures after either oral or direct arterial administration of ALA. Plasma ALA was detected after oral supplementation (95% confidence intervals 463, 761 ng ml(-1)), but did not alter cellular or plasma measures of oxidative stress., Conclusions: Neither oral nor intra-arterial ALA had any effect on regional and systemic haemodynamics or measures of oxidative stress in healthy men.

Low-density lipoprotein oxidation is implicated in the development of atherosclerosis. Plasma susceptibility to oxidation may be used as a marker of low-density lipoprotein oxidation and thus predict atherosclerotic risk. In this study the authors investigated the relationship between plasma susceptibility to oxidation and exposure to automotive pollution in a group of automobile mechanics (n = 16) exposed to high levels of automotive pollution, vs. matched controls (n = 13). The authors induced plasma oxidation by a free radical initiator and they determined susceptibility to oxidation by (1) change in absorbance at 234 nm, (2) lag time to conjugated diene formation, and (3) linear slope of the oxidation curve. Mechanics had significantly higher values (mean +/- standard error) for change in absorbance (1.60 +/- 0.05 vs. 1.36 +/- 0.05; p < .002), and slope (1.6 x 10(-3) +/- 0.1 x 10(-3) vs. 1.3 x 10(-3) +/- 0.1 x 10(-3); p < .001), compared with controls. These results indicate that regular exposure to automotive pollutants increases plasma susceptibility to oxidation and may, in the long-term, increase the risk of developing atherosclerosis.