Aortic elastic properties in patients with hypertensive response to exercise.

BACKGROUND: The aim of this study was to evaluate whether there is a relationship between aortic elastic properties in patients with a suggestive response to treadmill exercise testing. METHODS AND RESULTS: The study group comprised 32 patients suggesting hypertensive response to exercise and 20 patients suggesting normal blood pressure response to treadmill exercise testing. Baseline demographic characteristics were similar in both groups. However, the mean aortic stiffness index of patients suggesting hypertensive response to treadmill exercise testing was significantly higher (4.8+/-1.26 vs 2.36+/-1.09; p=0.001) whereas aortic distensibility was significantly lower (12.82 +/-5.84 vs 22.64+/-14.54; p=0.001) than the control group. The aortic strain of patients with hypertensive response to exercise was lower than the control group (12+/-3% vs 19.2+/-5%, p<0.001). The left ventricular mass (LVM) of these patients was also higher than control group (206.5+/-46.3 vs 134.2+/-19.97; p=0.01). A negative correlation between LVM and distensibility was found (r=-0.64; p=0.001) well as a positive correlation between LVM and aortic stiffness index (r=0.51; p=0.004) in patients suggesting hypertensive response to exercise. Pressure--rate product was also found to be correlated with LVM (r=0.47; p=0.006). CONCLUSION: Elastic properties of the aorta may be impaired in subjects showing exaggerated blood pressure response to exercise long before clinically manifest hypertension, particularly if the LVM is increased.     

Disturbed hemodynamic cardiac exercise stress test response in non-smoking, normolipidemic, normotensive, diabetic subjects

OBJECTIVE: The hemodynamic response to exercise is affected by diverse factors such as age, gender and exercise load as well as concomitant pathogenic conditions including smoking, hyperlipidemia, hypertension and possibly diabetes. In this study the hemodynamic response to a graded exercise has been evaluated in diabetic and non-diabetic individuals. DESIGN AND METHOD: In 3170 consecutive non-smoker normolipidemic normotensive patients, referred for the treadmill exercise test (age 25-70 years), the exercise-induced change in heart rate (DeltaHR) and blood pressure (DeltaSBP and DeltaDBP) was evaluated in 176 diabetics (DM) compared to non-diabetics (NDM). RESULTS: The results demonstrated that while resting HR and SBP were higher in DM, they had an impaired DeltaHR (62.1+/-20.5 versus 76.4+/-24.2; P<0.0001), DeltaSBP (35.5+/-29.3 versus 42.2+/-24.5; P<0.01) and DeltaDBP (-0.4+/-9.8 versus 2.1+/-15.9; P<0.05) in response to exercise compared to NDM, even among individuals with negative results for exercise test. DM had also lower heart rate reserve, circulatory power and rate-pressure product than NDM (all P<0.0001). While DM were slightly older (57 versus 54.5) and had lower exercise capacity (7.1 versus 8.6 MET) than NDM (both P<0.01), the impact of DM on the hemodynamic changes remained independent and significant after multivariate adjustment for age, exercise load and gender for DeltaHR and DeltaSBP (P<0.01). Exercise-induced DeltaSBP was directly correlated with exercise load and inversely associated with resting pulse pressure (rPP) (P<0.0001). Furthermore, rPP was the second strongest independent predictor for DeltaSBP (beta=-0.22, p<0.0001). CONCLUSION: The impaired hemodynamic response of DM to exercise and its inverse association with rPP supports the early development of arterial and ventricular stiffness in DM, unrelated to other likely risk factors such as hypertension and hyperlipidemia.     

Relationship between small-artery structure and systolic, diastolic and pulse pressure in essential hypertension

OBJECTIVE: Studies of cerebral arterioles have suggested that pulse pressure may be a more important determinant of small-artery structure than systolic, diastolic or mean blood pressure in stroke-prone spontaneously hypertensive rats and in rats with an arterio-venous shunt. A study of small arteries has suggested that this is not the case in human essential hypertension. We therefore investigated the role of hemodynamic determinants on small-artery structure in hypertensive patients. DESIGN AND METHODS: To determine whether pulse pressure contributes to structural alterations in human essential hypertension, small arteries (lumen < 300 microns) were obtained from gluteal subcutaneous biopsies of 40 normotensive subjects aged 40.7 +/- 1.2 years and 45 untreated essential hypertensive humans aged 46.5 +/- 1.3 years. The relationship between the media: lumen ratio of the small arteries and levels of systolic, diastolic and mean blood pressure and pulse pressure was investigated. RESULTS: The media: lumen ratio (5.33 +/- 0.001%) of small gluteal subcutaneous arteries of normotensive subjects was significantly smaller and the lumen diameter (306 +/- 13 microns) significantly larger than in untreated hypertensive patients (7.42 +/- 0.001% and 244 +/- 9.7 microns respectively, P < 0.001). The media: lumen ratio of both groups examined together correlated with systolic blood pressure (r = 0.45, P < 0.001), diastolic blood pressure (r = 0.56, P < 0.001) and mean arterial pressure (r = 0.55, P < 0.001). The media: lumen ratio of vessels from hypertensive patients correlated with diastolic blood pressure (r = 0.22, P < 0.01) but not with systolic or mean blood pressure. There was no correlation between the media: lumen ratio of small gluteal subcutaneous arteries and pulse pressure in this population of normotensive and hypertensive subjects, examined together or separately. CONCLUSION: These results suggest that in 30- to 65-year-old humans with systolodiastolic essential hypertension, pulse pressure does not appear to be an important determinant of small-artery structure.     

Correlation of plasma homocysteine level with arterial stiffness and pulse pressure in hemodialysis patients

Elevated plasma homocysteine, arterial stiffness, and increased pulse pressure (PP) are independently associated with higher cardiovascular risk in patients with end-stage renal disease. The aim of this study is to investigate the influence of plasma homocysteine on arterial stiffness and PP in hemodialysis (HD) patients. One hundred and nine HD patients were stratified into three groups by plasma homocysteine levels: low (11.2-20.8 micromol/L), middle (21.2-25.1 micromol/L), and high tertiles of plasma homocysteine (Hcy) group (25.2-43.9 micromol/L). Using a computerized oscillometry, we measured the arterial stiffness index (ASI) and blood pressure (BP) hemodynamic parameters in the brachial artery. The high Hcy group exhibited a higher ASI (110.4+/-129.5 versus 46.2+/-17.5, mean+/-S.E., P<0.01), PP (59.7+/-23.1 versus 43.3+/-16.3 mmHg, P<0.01), and age (57.8+/-14.1 versus 49.9+/-12.7 years, P<0.05) compared with the low Hcy group. Plasma homocysteine was significantly correlated with ASI (r=0.25, P<0.001), PP (r=0.33, P<0.001), systolic BP (r=0.31, P<0.001), and age (r=0.24, P<0.05). Serum ferritin was significantly correlated with ASI (r=0.24, P<0.05) and PP (r=0.23, P<0.05). ASI was also correlated with PP (r=0.64, P<0.001). Multiple regression analyses showed that both plasma homocysteine and serum ferritin had significant associations with ASI (beta=4.246, P=0.007 and beta=0.024, P=0.006, respectively), and with PP (beta=1.089, P=0.002 and beta=0.005, P=0.005, respectively) independent of other classic risk factors for atherosclerosis. In conclusion, plasma homocysteine, along with serum ferritin, may act as an important predictor for arterial stiffness and PP in HD patients.     

Comparison of ST segment depression in upright treadmill and supine bicycle exercise testing

Significant differences in the hemodynamic response to upright and supine exercise have been reported in patients with coronary artery disease. The purpose of the present study was to compare the degree of myocardial ischemia as assessed by ST segment depression during upright treadmill and supine bicycle exercise in 98 patients with coronary artery disease and in 34 patients with normal coronary arteries. The amount of ST segment depression at maximal exercise in patients with coronary artery disease was 0.90 +/- 0.80 mm for treadmill and 1.34 +/- 1.09 mm for supine bicycle (p less than 0.001). The amount of ST segment depression during treadmill and supine bicycle exercise tests was also compared at highest similar heart rates (0.68 +/- 0.77 versus 1.17 +/- 1.01, p less than 0.001), at highest similar rate-pressure products (0.71 +/- 0.77 versus 1.08 +/- 1.04, p less than 0.001), at highest similar metabolic equivalents of oxygen consumption (MET) levels (0.69 +/- 0.75 versus 1.20 +/- 1.05 mm, p less than 0.001) and at the onset of angina (0.84 +/- 0.73 versus 1.18 +/- 0.88 mm, p less than 0.001). The rate-pressure product achieved at maximal exercise was similar in both tests (18.74 +/- 5.80 x 10(3) versus 18.81 +/- 5.17 x 10(3), p = NS). The occurrence of angina during treadmill and supine bicycle exercise tests was similar (47 of 98 versus 48 of 98, respectively, p = NS). For the detection of coronary artery disease, the sensitivity was 50.0% for treadmill and 63.3% for supine bicycle (p less than 0.05) and the specificity was 73.5 versus 70.6%, respectively (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

Muscular strength training is associated with low arterial compliance and high pulse pressure.

Aerobic exercise training increases arterial compliance and reduces systolic blood pressure, but the effects of muscular strength training on arterial mechanical properties are unknown. We compared blood pressure, whole body arterial compliance, aortic impedance, aortic stiffness (measured by beta-index and carotid pulse pressure divided by normalized systolic expansion [Ep]), pulse wave velocity, and left ventricular parameters in 19 muscular strength-trained athletes (mean+/-SD age, 26+/-4 years) and 19 sedentary controls (26+/-5 years). Subjects were healthy, non-steroid-using, nonsmoking males, and athletes had been engaged in a strength-training program with no aerobic component for a minimum of 12 months. There was no difference in maximum oxygen consumption between groups, but handgrip strength (mean+/-SEM, 44+/-2 versus 56+/-2 kg; P<0.01) and left ventricular mass (168+/-8 versus 190+/-8 g; P<0.05) were greater in athletes. Arterial stiffness was higher in athletes, as evidenced by lower whole body arterial compliance (0.40+/-0.04 versus 0.54+/-0.04 arbitrary compliance units; P=0.01), higher aortic characteristic impedance (1.55+/-0.13 versus 1.18+/-0.08 mm Hg. s. cm-1; P<0.05), beta-index (4.6+/-0.2 versus 3.8+/-0.4; P<0. 05), and ln Ep (10.86+/-0.06 versus 10.60+/-0.08; P<0.01). Femoral-dorsalis pedis pulse wave velocity was also higher in the athletes, but carotid-femoral pulse wave velocity was not different. Furthermore, both carotid (56+/-3 versus 44+/-2 mm Hg; P<0.001) and brachial (60+/-3 versus 50+/-2 mm Hg; P<0.01) pulse pressures were higher in the athletes, but mean arterial pressure and resting heart rate did not differ between groups. These data indicate that both the proximal aorta and the leg arteries are stiffer in strength-trained individuals and contribute to a higher cardiac afterload.     

Effect of maintenance digoxin therapy on aerobic performance and exercise left ventricular function in mild to moderate heart failure due to coronary artery disease: a randomized, placebo-controlled, crossover trial

Despite 200 years of use, the ability of digitalis glycosides to improve exercise capacity in patients with congestive heart failure remains controversial, partly because of imprecise end points and suboptimal study design. Therefore, this question was examined in 10 ambulatory patients (8 men and 2 women) aged 46 to 70 years (mean 57.8) in sinus rhythm with mild to moderate chronic stable congestive heart failure due to coronary artery disease and systolic left ventricular dysfunction (ejection fraction 32 +/- 12). All underwent maximal treadmill exercise with respiratory gas analysis and upright cycle ergometry with gated radionuclide angiography after 4 weeks of digoxin or placebo therapy, administered in a randomized double-blind crossover protocol. Neither treadmill exercise duration (7.7 +/- 2.3 versus 7.3 +/- 2.7 min) nor peak oxygen consumption (18.7 +/- 3.7 versus 18.4 +/- 5.4 ml/kg per min) differed between digoxin and placebo regimens. However, the change in peak oxygen consumption induced by digoxin was inversely related to the peak oxygen consumption during placebo therapy (r = -0.64, p less than 0.05). At maximal treadmill effort, heart rate (138 +/- 16 versus 141 +/- 21 beats/min), oxygen pulse (10.3 +/- 2.1 versus 9.9 +/- 2.2 ml/beat), ventilation (40.3 +/- 10.6 versus 42.0 +/- 10.8 liters/min) and ventilatory equivalent (29.4 +/- 4.8 versus 31.5 +/- 6.8) did not differ between digoxin and placebo treatment, although systolic blood pressure was higher during digoxin therapy (163.0 +/- 23.1 versus 153.2 +/- 25.3 mm Hg, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulse pressure amplification during exercise is significantly reduced with age and hypercholesterolemia

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.     

Usefulness of arterial compliance in the thigh in predicting exercise capacity in individuals without coronary heart disease

This study examined the relation between arterial compliance of the lower extremities and aerobic capacity in patients with a broad spectrum of cardiovascular risk but without overt coronary heart disease (CHD). Local arterial compliance was noninvasively measured in the thigh and calf in 104 men and 99 women using air plethysmography. Subjects also underwent maximal exercise treadmill testing as a measure of aerobic capacity. In univariate analysis, age (r = -0.49, p <0.001), systolic blood pressure at rest (r = -0.27, p <0.001), pulse pressure (r = -0.39, p <0.001), total cholesterol (r = -0.25, p <0.001), triglycerides (r = -0.025, p <0.001), non-high-density lipoprotein cholesterol (r = -0.23, p <0.001), high-sensitivity C-reactive protein (r = -0.21, p = 0.002), and low-density lipoprotein cholesterol (r = -0.15, p = 0.03) all demonstrated a significant inverse association with treadmill time. Thigh and calf compliance demonstrated a significant positive association with treadmill time (r = 0.48, p <0.001; r = 0.46, p <0.001). In multivariate analysis, thigh compliance (p = 0.003), age (p <0.001), gender (p = 0.005), and triglycerides (p = 0.017) were independent predictors of treadmill time. In conclusion, thigh compliance measured with a simple-to-use, fully automated device independently predicts aerobic fitness in patients with a wide range of cardiovascular risk but without CHD.     

Relation between renal function within the normal range and central and peripheral arterial stiffness in hypertension

Chronic kidney disease is accompanied by increased large-artery stiffness, but the relation between glomerular filtration rate within the reference range and central or peripheral arterial stiffness has been understudied. The link between renal function and arterial stiffness was assessed in 305 patients with never-treated essential hypertension (men: 58%; age: 48+/-11 years, blood pressure: 151/95+/-20/11 mm Hg), free from overt cardiovascular disease and with serum creatinine values <1.4 mg/dL (men) and <1.2 mg/dL (women), who underwent noninvasive aortic and upper-limb pulse wave velocity (PWV) determination. Aortic PWV was strongly related to age (r=0.55; P<0.001), whereas upper-limb PWV had a weaker nonlinear relation with age (beta=1.392; P<0.001 for age; beta=-1.312; P<0.001 for age squared) and a weak relation with aortic PWV (r=0.22; P<0.001). Glomerular filtration rate (GFR), estimated according to the Mayo clinic equation for healthy subjects, was inversely correlated with large-artery stiffness, as assessed by aortic PWV (r=-0.34; P<0.001), and with peripheral artery stiffness, as assessed by upper-limb PWV (r=-0.25; P<0.001). In a multivariate linear regression, aortic PWV was independently predicted by age (beta=0.48; P<0.001), mean arterial pressure (beta=0.14; P=0.013), and GFR (beta=-0.13, P=0.029). Upper-limb PWV was predicted by GFR (beta=-0.24; P<0.001) and mean arterial pressure (beta=0.20; P<0.001). We conclude that, in hypertensive patients with normal renal function, an inverse relationship exists between GFR and stiffness of both central elastic and peripheral muscular arteries. These relations are in part independent from the effect of several confounders, including age, sex, and blood pressure values.     

Smaller aortic dimensions do not fully account for the greater pulse pressure in elderly female hypertensives

This study examined the importance of aortic dimensions in determining pulse pressure in elderly hypertensives participating in the 2nd Australian National Blood Pressure Study, including a substantial number not previously receiving blood pressure lowering medication. Aortic dimensions were determined by ultrasound at the transverse arch and at the insertion of the aortic valve. Unadjusted data showed negative (P<0.001) correlations between central (carotid) and (brachial) peripheral pulse pressure and both arch (-0.200, -0.181) and outflow tract (-0.238, -0.238) diameters. Correlations were similar in those previously treated with blood pressure lowering medication and in the treatment na?ve. Central pulse pressure (84+/-26 versus 75+/-28 mm Hg, P<0.001) was higher and aortic dimensions (transverse arch 2.56+/-0.31 versus 2.88+/-0.35 mm, P<0.001) smaller in women than men. Women had greater aortic stiffness (beta index 29.4+/-36.1 versus 22.1+/-21.3, P<0.03). Other bivariate correlates of central pulse pressure were age, mean arterial pressure, height, heart rate, augmentation index, aortic stiffness (all P<0.001), and weight (P=0.027). In multivariate analyses gender remained a predictor of central pulse pressure (P<0.001) even with inclusion of aortic dimensions (P=0.013) height and weight. Other significant terms were age, heart rate, mean blood pressure, and aortic stiffness (all P<0.001). These findings demonstrate an independent inverse relation between aortic size and pulse pressure in older hypertensive subjects. Differences in aortic dimensions and stiffness between genders do not fully account for the observed blood pressure differences, suggesting that a contributory factor to gender differences in pulse pressure is an increased age-related mismatch in ventricular function and aortic stiffness in women compared with men.     

Increased aortic pulse wave velocity is associated with silent cerebral small-vessel disease in hypertensive patients

Aortic stiffness predicts an excess risk of stroke, supposedly via cerebral small-vessel disease. White matter hyperintensities, silent lacunar infarcts, and brain microbleeds, manifestations of cerebral small-vessel disease on neuroimaging, may precede overt cerebrovascular disease. Therefore, we assessed whether aortic stiffness is also related to such lesions. In 167 hypertensive patients (85 men) without a history of cardiovascular or cerebrovascular disease, a mean age of 51.8+/-13.1 years, and untreated office blood pressure levels of 169+/-25/104+/-12 mm Hg, we determined aortic pulse wave velocity and office and ambulatory 24-hour pulse pressure (off medication), as well as the volume of white matter hyperintensities and the presence of lacunar infarcts and microbleeds using brain MRI. Linear and logistic regression analyses were performed to assess the relationships between the arterial stiffness measures and brain lesions. Aortic stiffness and pulse pressure were significantly related to each of the brain lesions in univariate analyses (P<0.05). Multivariate analyses, adjusted for age, sex, brain volume, mean arterial pressure, and heart rate, showed that a higher pulse wave velocity was significantly associated with a greater volume of white matter hyperintensities (unstandardized regression coefficient: 0.041; 95% CI: 0.005 to 0.078; P<0.05) and the presence of lacunar infarcts (odds ratio [per SD increase in pulse wave velocity]: 1.78; 95% CI: 1.06 to 2.99; P<0.05) but not with microbleeds. The models for pulse pressure failed to reach statistical significance in multivariate analyses. In conclusion, aortic stiffness is independently associated with manifestations of cerebral small-vessel disease in hypertensive patients, linking systemic large- to cerebral small-artery disease.     

Relation of left ventricular chamber stiffness at rest to exercise capacity in hypertrophic cardiomyopathy

The degree of exercise capacity is poorly predicted by conventional markers of disease severity in patients with hypertrophic cardiomyopathy (HC). The principal mechanism of exercise intolerance in patients with HC is the failure of stroke volume augmentation due to left ventricular (LV) diastolic dysfunction. The role of LV chamber stiffness, assessed noninvasively, as a determinant of exercise tolerance is unknown. Sixty-four patients with HC were studied with Doppler echocardiography, exercise testing, and gadolinium cardiac magnetic resonance. The LV chamber stiffness index was determined as the ratio of pulmonary capillary wedge pressure (derived from the E/Ea ratio) to LV end-diastolic volume (assessed by cardiac magnetic resonance). Maximal exercise tolerance was defined as achieved METs. There were inverse correlations between METs achieved and age (r = -0.38, p = 0.003), heart rate deficit (r = -0.39, p = 0.002), LV outflow tract gradient (r = -0.33, p = 0.009), the E/Ea ratio (r = -0.4, p = 0.001), mean LV wall thickness (r = -0.26, p = 0.04), and LV stiffness (r = -0.56, p <0.001) and a positive correlation between METs achieved and LV end-diastolic volume (r = 0.33, p = 0.01). On multivariate analysis, only LV chamber stiffness was associated with exercise capacity. A LV stiffness level of 0.18 mm Hg/ml had 100% sensitivity and 75% specificity (area under the curve 0.84) for predicting < or =7 METs achieved. In conclusion, LV diastolic dysfunction at rest, as manifested by increased LV chamber stiffness, is a major determinant of maximal exercise capacity in patients with HC.     

The effect of left ventricular systolic function on maximal aerobic exercise capacity in asymptomatic patients with coronary artery disease

The purpose of this study was to examine the relationship between maximal O2 uptake (VO2max) and left ventricular systolic function in patients with coronary artery disease. We studied 27 patients, age 50 +/- 10 years (mean +/- SD), who were asymptomatic and able to attain true VO2max. VO2max was defined by the leveling-off criterion and/or a respiratory exchange ratio of 1.15 or greater. Left ventricular ejection fraction was determined by gated cardiac blood pool imaging. In patients whose ejection fraction decreased with exercise, VO2max was 21 +/- 4 vs 27 +/- 4 ml/kg/min in those whose ejection fraction increased (p less than .001). Systolic blood pressure/end-systolic volume relation was shifted upward and to the right in the former group in response to peak exercise. In contrast, the pressure-volume relation was shifted upward and to the left in patients whose ejection fraction increased with exercise. Ejection fraction at rest did not correlate with VO2max. There was a significant but weak correlation between peak exercise ejection fraction and VO2max (r = .43, p less than .025). Left ventricular exercise reserve, i.e., the change in ejection fraction from rest to exercise, correlated with VO2max (r = .77, p less than .0002), maximal O2 pulse (r = .50, p less than .005), and maximal heart rate during treadmill exercise (r = .61, p less than .001). Maximal heart rate during treadmill exercise correlated with VO2max (r = .70, p less than .0002).(ABSTRACT TRUNCATED AT 250 WORDS)     

Endothelial dysfunction and decreased exercise tolerance in interferon-alpha therapy in chronic hepatitis C: relation between exercise hyperemia and endothelial function

BACKGROUND: We previously reported that reversible endothelial dysfunction is caused by interferon-alpha therapy (IFN) in patients with chronic hepatitis C. In experimental studies, limb blood flow during exercise is reported to be dependent on endothelium-derived nitric oxide. HYPOTHESIS: The purpose of this study was to confirm the effect of IFN on endothelial function and to investigate whether exercise hyperemia is dependent on endothelial function in humans. METHODS: We performed symptom-limited exercise treadmill testing and measured flow-mediated vasodilation (FMD, endothelium-dependent vasodilation) and sublingual glyceryl-trinitrate-induced dilation (GTN-D, 0.3 mg, endothelium-independent vasodilation) in the brachial artery by using high-resolution ultrasound in 10 patients with chronic active hepatitis C (age 53 +/- 11 years, 2 men, 8 women) before and immediately after administration of recombinant interferon 2b (10 million U/day) for 4 weeks. RESULTS: There were no significant abnormal findings in any patients in routine studies of 24-h ambulatory electrocardiogram monitoring, two-dimensional echocardiography, and exercise treadmill testing both before and after treatment. Leg fatigue and exhaustion were the reasons for termination of exercise treadmill testing in each patient. Pressure rate product was calculated at rest and peak exercise. Interferon-alpha therapy significantly (p<0.05) decreased FMD (6.8 +/- 3.1 vs. 1.9 +/- 2.6%), exercise treadmill testing tolerance time (437 +/- 89 vs. 395 +/- 62 s) and peak pressure rate product (283 +/- 41 vs. 241 +/- 47 mmHg x beats/min x 10(-2)), but not GTN-D (13.4 +/- 5.4 vs. 17.0 +/- 5.5%). The change of FMD due to IFN significantly and highly correlated with exercise treadmill testing tolerance time (r = 0.86, p<0.001), but not with change of peak pressure rate product, suggesting that FMD is more closely related to the condition of the peripheral circulation than is cardiac performance. CONCLUSION: These results suggest that IFN in patients with chronic hepatitis C impairs endothelial function and exercise tolerance, and that endothelial function might be at least partly involved in exercise hyperemia in humans.     

Validation of a generalized transfer function to noninvasively derive central blood pressure during exercise

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.     

Inspiratory muscle training using an incremental endurance test alleviates dyspnea and improves functional status in patients with chronic heart failure.

BACKGROUND: The benefits of inspiratory muscle training (IMT) in patients with chronic heart failure (CHF) have been inadequately studied. DESIGN AND METHODS: Using a prospective, age and sex-matched controlled study, we investigated 35 patients with moderate to severe CHF (NYHA class II-III and left ventricular ejection fraction 24.4+/-1.3% [mean+/-SEM]). An incremental respiratory endurance test using a fixed respiratory workload was provided by software with an electronic mouth pressure manometer interfaced with a computer. The training group (n=20) exercised at 60% of individual sustained maximal inspiratory pressure (SMIP) and the control group (n=15) at 15% of SMIP. All patients exercised three times weekly for 10 weeks. Pulmonary function, exercise capacity, dyspnea and quality of life were assessed, pre- and post-training. RESULTS: The training group significantly increased both maximum inspiratory pressure (Pimax), (111+/-6.8 versus 83+/-5.7 cmH2O, P<0.001), and SMIP (527822+/-51358 versus 367360+/-41111 cmH2O/sec x 10(-1), P<0.001). Peak VO2 increased after training (17.8+/-1.2 versus 15.4+/-0.9 ml/kg/min, P<0.005), as did the six-minute walking distance (433+/-16 versus 367+/-22 meters, P<0.001). Perceived dyspnea assessed using the Borg scale was reduced for both the treadmill (12.7+/-0.57 versus 14.2+/-0.48, P<0.005) and the walking (9+/-0.48 versus 10.5+/-0.67, P<0.005) exercise tests and the quality of life score was also improved (21.1+/-3.5 versus 25.2+/-4, P<0.01). Resting heart rate was significantly reduced with training (77+/-3.3 versus 80+/-3 beats/min, P<0.05). The control group significantly increased Pimax (86.6+/-6.3 versus 78.4+/-6.9 cmH2O, P<0.05), but decreased SMIP (274972+/-32399 versus 204661+/-37184 cmH2O/sec x 10(1), P<0.005). No other significant effect on exercise capacity, heart rate, dyspnea, or quality of life was observed in this group. CONCLUSION: Inspiratory muscle training using an incremental endurance test, successfully increases both inspiratory strength and endurance, alleviates dyspnea and improves functional status in CHF.     

人体质量指数与运动血压的相关性研究

目的：观察人体质量指数（BMI）不同的患者行平板运动试验时运动血压的变化。方法：BMI正常患者224例（正常对照组）,肥胖患者109例（肥胖组）,行平板运动实验检查,比较两组之间运动血压的差别,并分析BMI和运动血压之间的相关性。结果：肥胖组患者静息血压（收缩压、舒张压）,运动峰值血压（收缩压、舒张压）,恢复期血压（收缩压、舒张压）和恢复期脉压均明显高于正常对照组（P〈0.05）。肥胖组患者运动高血压的发生率明显高于正常对照组（9.2%比3.6%,P〈0.05）,且BMI与运动血压呈明显正相关（r=0.123～0.205,P〈0.05）。结论：肥胖患者运动中血压变化异常,提示肥胖患者有血管舒缩功能障碍和心脏自主神经功能紊乱。     

Early recovery of oxygen kinetics after submaximal exercise test predicts functional capacity in patients with chronic heart failure.

BACKGROUND: Oxygen (O2) uptake at peak exercise (VO2 peak) is an objective measurement of functional capacity in patients with chronic heart failure (CHF). The significance of recovery O2 kinetics parameters in predicting exercise capacity, and the parameters of submaximal exercise testing have not been thoroughly examined. METHODS AND RESULTS: Thirty-six patients (mean age = 48+/-14 years) with CHF and New York Heart Association functional class I, II, or III, and eight healthy volunteers (mean age = 39+/-13 years) were studied with maximal and submaximal cardiopulmonary exercise testing (CPET). The first degree slope of O2 uptake decay during early recovery from maximal (VO2/t-slope), and submaximal exercise (VO2/t-slope)(sub), were calculated, along with VO2 half-time (T(1/2)VO2). Patients with CHF had a longer recovery of O2 uptake after exercise than healthy volunteers, expressed by a lower VO2/t-slope (0.616+/-0.317 vs. 0.956+/-0.347 l min(-1) min(-1), P=0.029) and greater T(1/2)VO2 (1.28+/-0.30 vs. 1.05+/-0.15 min, P = 0.005). VO2/t-slope correlated with the VO2 peak (r = 0.84, P<0.001), anaerobic threshold (r = 0.79, P<0.001), and T(1/2)VO2, a previously established estimate of recovery O2 kinetics (r = -0.59, P<0.001). (VO2/t-slope)(sub) was highly correlated with VO2/t-slope after maximal exercise (r=0.87, P<0.001), with the VO2 peak (r=0.87, P<0.001) and with T(1/2)VO2 after maximal exercise (r=-0.62, P<0.001). VO2/t-slope after maximal and submaximal exercise was reduced in patients with severe exercise intolerance (F=9.3, P<0.001 and F=12.8, P<0.001, respectively). CONCLUSIONS: Early recovery O2 kinetics parameters after maximal and submaximal exercise correlate closely with established indices of exercise capacity in patients with CHF and in healthy volunteers. These findings support the use of early recovery O2 kinetics after submaximal exercise testing as an index of functional capacity in patients with CHF.     

Contribution of lung function to exercise capacity in patients with chronic heart failure

BACKGROUND: The importance of exercise capacity as an indicator of prognosis in patients with heart disease is well recognized. However, factors contributing to exercise limitation in such patients have not been fully characterized and in particular, the role of lung function in determining exercise capacity has not been extensively investigated. OBJECTIVE: To examine the extent to which pulmonary function and respiratory muscle strength indices predict exercise performance in patients with moderate to severe heart failure. METHODS: Fifty stable heart failure patients underwent a maximal symptom-limited cardiopulmonary exercise test on a treadmill to determine maximum oxygen consumption (VO2max), pulmonary function tests and maximum inspiratory (PImax) and expiratory (PEmax) pressure measurement. RESULTS: In univariate analysis, VO2max correlated with forced vital capacity (r = 0.35, p = 0.01), forced expiratory volume in 1 s (r = 0.45, p = 0.001), FEV1/FVC ratio (r = 0.37, p = 0.009), maximal midexpiratory flow rate (FEF25-75, r = 0. 47, p < 0.001), and PImax (r = 0.46, p = 0.001), but not with total lung capacity, diffusion capacity or PEmax. In stepwise linear regression analysis, FEF25-75 and PImax were shown to be independently related to VO2max, with a combined r and r2 value of 0. 56 and 0.32, respectively. CONCLUSIONS: Lung function indices overall accounted for only approximately 30% of the variance in maximum exercise capacity observed in heart failure patients. The mechanism(s) by which these variables could set exercise limitation in heart failure awaits further investigation.