Feasibility of an Intradialytic Combined Exercise Program Targeting Older Adults With End-Stage Renal Disease.

Intradialytic exercise is feasible and yields substantial clinical benefits in middle-aged patients. However, evidence is scarce in older hemodialysis patients. OBJECTIVE: To assess the feasibility and clinical benefits of supervised, intradialytic exercise in older patients. METHODS: Multicenter one-arm feasibility study. The main outcome was feasibility (ease of recruitment, dropout rate, adherence, affective valence, and adverse events). The secondary outcomes were physical capacity (five-repetition sit-to-stand, 60-s sit-to-stand tests, and grip strength), quality of life (36-Item Short-Form Health Survey), quality of sleep (Pittsburgh Sleep Quality Index), depressive symptoms (Beck Depression Inventory), and dialysis efficacy (Kt/V and urea reduction ratio). RESULTS: About 79% of the screened patients agreed to participate (n = 25, 73 [66-77] years). The dropout rate was high (32%), but adherence remained high among the participants who completed the study (94%). Improvements were found in the five-repetition sit-to-stand (p < .001), 60-s sit-to-stand tests (p = .028), 36-Item Short-Form Health Survey mental component score (p = .008), depressive symptoms (p = .006), and quality of sleep (p = .035). CONCLUSION: Supervised intradialytic exercise seems safe and beneficial in older patients.

Determinants of Increased Central Excess Pressure in Dialysis: Role of Dialysis Modality and Arteriovenous Fistula.

BACKGROUND: Arterial reservoir-wave analysis (RWA)-a new model of arterial hemodynamics-separates arterial wave into reservoir pressure (RP) and excess pressure (XSP). The XSP integral (XSPI) has been associated with increased risk of clinical outcomes. The objectives of the present study were to examine the determinants of XSPI in a mixed cohort of hemodialysis (HD) and peritoneal dialysis (PD) patients, to examine whether dialysis modality and the presence of an arteriovenous fistula (AVF) are associated with increased XSPI. METHOD: In a cross-sectional study, 290 subjects (232 HD and 130 with AVF) underwent carotid artery tonometry (calibrated with brachial diastolic and mean blood pressure). The XSPI was calculated through RWA using pressure-only algorithms. Logistic regression was used for determinants of XSPI above median. Through forward conditional linear regression, we examined whether treatment by HD or the presence of AVF is associated with higher XSPI. RESULTS: Patients with XSPI above median were older, had a higher prevalence of diabetes and cardiovascular disease, had a higher body mass index, and were more likely to be on HD. After adjustment for confounders, HD was associated with a higher risk of higher XSPI (odds ratio = 2.39, 95% confidence interval: 1.16-4.98). In a forward conditional linear regression analysis, HD was associated with higher XSPI (standardized coefficient: 0.126, P = 0.012), but on incorporation of AVF into the model, AVF was associated with higher XSPI (standardized coefficient: 0.130, P = 0.008) and HD was excluded as a predictor. CONCLUSION: This study suggests that higher XSPI in HD patients is related to the presence of AVF.

Prognostic Value of Carotid and Radial Artery Reservoir-Wave Parameters in End-Stage Renal Disease.

Background Reservoir-wave approach is an alternative model of arterial hemodynamics based on the assumption that measured arterial pressure is composed of volume-related (reservoir pressure) and wave-related components (excess pressure). However, the clinical utility of reservoir-wave approach remains debatable. Methods and Results In a single-center cohort of 260 dialysis patients, we examined whether carotid and radial reservoir-wave parameters were associated with all-cause and cardiovascular mortality. Central pulse pressure and augmentation index at 75 beats per minute were determined by radial arterial tonometry through generalized transfer function. Carotid and radial reservoir-wave analysis were performed to determine reservoir pressure and excess pressure integral. After a median follow-up of 32 months, 171 (66%) deaths and 88 (34%) cardiovascular deaths occurred. In Cox regression analysis, carotid excess pressure integral was associated with a hazard ratio of 1.33 (95% CI , 1.14-1.54; P<0.001 per 1 SD) for all-cause and 1.45 (95% CI : 1.18-1.75; P<0.001 per 1 SD) for cardiovascular mortality. After adjustments for age, heart rate, sex, clinical characteristics and carotid-femoral pulse wave velocity, carotid excess pressure integral was consistently associated with increased risk of all-cause (hazard ratio per 1 SD, 1.30; 95% CI : 1.08-1.54; P=0.004) and cardiovascular mortality (hazard ratio per 1 SD, 1.31; 95% CI : 1.04-1.63; P=0.019). Conversely, there were no significant associations between radial reservoir-wave parameters, central pulse pressure, augmentation index at 75 beats per minute, pressure forward, pressure backward and reflection magnitude, and all-cause or cardiovascular mortality after adjustment for comorbidities. Conclusions These observations support the clinical value of reservoir-wave approach parameters of large central elastic vessels in end-stage renal disease.

Association of interleukin-6 with aortic stiffness in end-stage renal disease.

Cardiovascular disease (CVD) is the leading cause of mortality in patients with chronic kidney disease (CKD). Aortic stiffness, a nontraditional risk factor, is associated with high rate of mortality in CKD. Using a CKD animal model with medial vascular calcification, we previously reported increased mRNA expression of interleukin-6 (IL-6), tumor necrosis factor (TNF), and interleukin-1ß (IL-1ß) in calcified aorta. The aim of the study was to investigate the association between IL-6, TNF, IL-1ß, and aortic stiffness in end-stage renal disease patients. In a cross-sectional study, we enrolled 351 patients on dialysis. Aortic stiffness was assessed by carotid-femoral pulse wave velocity (cf-PWV), while central pulse pressure and augmentation index were assessed using generalized transfer function applied to the radial artery pressure wave form. Plasma IL-6, TNF, and IL-1ß were measured by enzyme-linked immunosorbent assay. IL-6 was associated with cf-PWV adjusted for mean blood pressure (MBP) (standardized ß = 0.270; P < .001). In a multivariate adjusted model for age, diabetes, hypertension, CVD, and MBP, IL-6 was still associated with cf-PWV (standardized ß = 0.096; P = .026). The impact of age, diabetes, and CVD on cf-PWV was partially mediated by IL-6 in a mediation analysis. However, there were no associations between TNF, IL-1ß, and aortic stiffness. While IL-6 was associated with augmentation index (standardized ß = 0.224; P < .001) and central pulse pressure (standardized ß = 0.162; P = .001) when adjusted for MBP and heart rate, this relationship was not significant after adjusting for potential confounders.This study suggests a potential role of IL-6 for CKD-related aortic stiffness.

Acute effects of cinacalcet on arterial stiffness and ventricular function in hemodialysis patients: A randomized double-blinded crossover study.

BACKGROUND: Serum calcium concentration (Ca) plays an essential role in a vascular muscle tone and myocardial contractility. Previously, we showed that acutely lowering Ca by hemodialysis reduced arterial stiffness. Cinacalcet is a calcimimetic that lowers Ca and parathyroid hormone (PTH). The aim of the present study was to examine whether acute lowering of Ca by cinacalcet improves vascular stiffness and myocardial diastolic dysfunction. METHOD: This is a double-blinded randomized placebo-controlled crossover study that included 21 adult patients with end-stage kidney disease undergoing chronic hemodialysis. Subjects were assigned to placebo-cinacalcet (30 mg) or cinacalcet-placebo sequence. After each treatment period (7 days), aortic, brachial, and carotid stiffness were determined by examining carotid-femoral pulse wave velocity (cf-PWV), carotid-radial PWV (cr-PWV), and carotid distension. A central pulse wave profile was determined by radial artery tonometry and cardiac function was evaluated by echocardiography. RESULTS: Cinacalcet reduced PTH (483 [337-748] to 201 [71-498] ng/L, P < .001) and ionized Ca (1.11 [1.08-1.15] to 1.05 [1.00-1.10] mmol/L, P = .04). Cinacalcet did not reduced cf-PWV significantly (12.2 [10.4-15.4] to 12.2 [11.0-14.6] m/s, P = .16). After adjustments for mean blood pressure, sequence, carryover, and treatment effects, cf-PWV was not significantly lowered by cinacalcet (-0.35 m/s, P = .139). There were no significant changes in central blood pressures, brachial and carotid stiffness, and echocardiographic parameters. CONCLUSION: In this study, 30 mg daily cinacalcet for 1 week did not have any significant impact on peripheral and central blood pressures, arterial stiffness parameters, or cardiac function (NCT01250405).

Aortic-Brachial Pulse Wave Velocity Ratio: A Blood Pressure-Independent Index of Vascular Aging.

Aortic stiffness, a cardiovascular risk factor, depends on the operating mean arterial pressure (MAP). The impact of aortic stiffness on cardiovascular outcomes is proposed to be mediated by the attenuation or the reversal of the arterial stiffness gradient. We hypothesized that arterial stiffness gradient is less influenced by changes in MAP. We aimed to study the relationship between MAP and aortic stiffness, brachial stiffness, and arterial stiffness gradient. In a cross-sectional study of a dialysis cohort (group A, n=304) and a cohort of hypertensive or kidney transplant recipient with an estimated glomerular filtration rate of >45 mL/min/1.73 m2 (group B, n=114), we assessed aortic and brachial stiffness by measuring carotid-femoral and carotid-radial pulse wave velocities (PWV). We used aortic-brachial PWV ratio as a measure of arterial stiffness gradient. Although there was a positive relationship between MAP and carotid-femoral PWV (R2=0.10 and 0.08; P<0.001 and P=0.003) and MAP and carotid-radial PWV (R2=0.22 and 0.12; P<0.001 and P<0.001), there was no statistically or clinically significant relationship between MAP and aortic-brachial PWV ratio (R2=0.0002 and 0.0001; P=0.8 and P=0.9) in group A and B, respectively. Dialysis status and increasing age increased the slope of the relationship between MAP and cf-PWV. However, we found no modifying factor (age, sex, dialysis status, diabetes mellitus, cardiovascular disease, and class of antihypertensive drugs) that could affect the lack of relationship between MAP and aortic-brachial PWV ratio. In conclusion, these results suggest that aortic-brachial PWV ratio could be considered as a blood pressure-independent measure of vascular aging.

Aortic-brachial stiffness mismatch and mortality in dialysis population.

We hypothesized that increased aortic stiffness (central elastic artery) combined with a decrease in brachial stiffness (peripheral muscular artery) leads to the reversal of the physiological stiffness gradient (ie, mismatch), promoting end-organ damages through increased forward pressure wave transmission into the microcirculation. We, therefore, examined the effect of aortic-brachial stiffness mismatch on mortality in patients in need of dialysis. In a prospective observational study, aortic-brachial arterial stiffness mismatch (pulse wave velocity ratio) was assessed using carotid-femoral pulse wave velocity divided by carotid-radial pulse wave velocity in 310 adult patients on dialysis. After a median follow-up of 29 months, 146 (47%) deaths occurred. The hazard ratio (HR) for mortality related to PWV ratio in a Cox regression analysis was 1.43 (95% confidence interval [CI], 1.24-1.64; P<0.001 per 1 SD) and was still significant after adjustments for confounding factors, such as age, dialysis vintage, sex, cardiovascular disease, diabetes mellitus, smoking status, and weight (HR, 1.23; 95% CI: 1.02-1.49). The HRs for changes in 1 SD of augmentation index (HR, 1.35; 95% CI, 1.12-1.63), carotid-femoral pulse wave velocity (HR, 1.29; 95% CI, 1.11-1.50), and carotid-radial pulse wave velocity (HR, 0.80; 95% CI, 0.67-0.95) were statistically significant in univariate analysis, but were no longer statistically significant after adjustment for age. In conclusion, aortic-brachial arterial stiffness mismatch was strongly and independently associated with increased mortality in this dialysis population. Further studies are required to confirm these finding in lower-risk groups.

The impact of warfarin on the rate of progression of aortic stiffness in hemodialysis patients: a longitudinal study.

BACKGROUND: Accelerated progression of aortic stiffness in patients with advanced chronic kidney disease is not well explained by the traditional cardiovascular risk factors. We hypothesized that vitamin K deficiency may result in an accelerated progression of aortic stiffness in the pro-calcifying uremic milieu. METHOD: Eighteen hemodialysis (HD) patients on warfarin were matched to 54 HD patients without warfarin (control). Aortic stiffness was determined by carotid-femoral pulse wave velocity (cf-PWV) at baseline and after a mean follow-up of 1.2 years. In the control group, spontaneous vitamin K deficiency was defined as proteins induced by vitamin K deficiency/absence-II >median. RESULTS: At baseline, clinical characteristics and cf-PWV were similar. Adjusted cf-PWV increased by 0.86 ± 1.87 m/s in control and by 2.24 ± 2.68 m/s in warfarin group (P = 0.024). After adjustments for confounders, warfarin therapy was independently associated with progression of aortic stiffness (P = 0.016). The rate of progression of aortic stiffness showed a linear trend in response to vitamin K status and warfarin therapy, suggesting that at least part of the effects are mediated through reduced availability of vitamin K. The unadjusted and adjusted hazard ratio (HR) of warfarin therapy on mortality were, respectively, 2.40 (P = 0.006) and 2.53 (P = 0.006). In a forward conditional Cox regression analysis, age, albumin, augmentation index (AIx) and a cf-PWV > 13.8 m/s at the time of follow-up (HR: 2.11, P = 0.05) were independent determinants of mortality, whereas warfarin use was not retained as an independent factor. Finally, control patients with poor vitamin K status had an intermediate survival as compared with controls with better vitamin K status and patients with warfarin (P = 0.01). CONCLUSION: This is the first study to show a temporal association between warfarin, functional vitamin K deficiency and progression of aortic stiffness in HD patients. These findings suggest that the net cardiovascular benefit of long-term warfarin therapy may need to be reevaluated in this population.

Obesity in chronic obstructive pulmonary disease: is fatter really better?

BACKGROUND: Overweight/obesity is associated with longer survival in chronically ill patients, a phenomenon referred to as the 'obesity paradox'. OBJECTIVE: To investigate whether the obesity paradox in patients with chronic obstructive pulmonary disease (COPD) is due to fat accumulation or confounding factors. METHODS: A total of 190 patients with stable COPD who underwent a mean (± SD) follow-up period of 72±34 months were enrolled. Anthropometry, pulmonary function tests, midthigh muscle cross-sectional area obtained using computed tomography (MTCSACT), arterial blood gas and exercise testing data were measured at baseline. Patients were categorized into two subgroups according to body mass index (BMI) <25 kg/m2 or ≥25 kg/m2 (normal and overweight/obese, respectively). RESULTS: Seventy-two patients (38%) died during the follow-up period. Survival tended to be better in the overweight/obese patients but this difference did not reach statistical significance. Overweight/obese patients had better lung function and a larger MTCSACT than those with normal BMI (P<0.001). Overweight/obese patients also had a significantly higher peak work rate than patients with normal BMI (P<0.001). PaO2 and PaCO2 were not significantly different in the two groups. When adjusted for PaCO2, peak work rate and MTCSACT, the tendency for improved survival in overweight/obese patients disappeared. In fact, when these variables were considered in the survival analysis, patients with lower BMI tended to have better survival. CONCLUSION: These results suggest that important confounders, such as hypercapnia, exercise capacity and muscle mass, should be considered when interpreting the association between increased BMI and survival in patients with COPD.

Active vitamin D and accelerated progression of aortic stiffness in hemodialysis patients: a longitudinal observational study.

BACKGROUND: We hypothesized that high-dose active vitamin D therapy in the form of alphacalcidol (α-calcidol), used to treat secondary hyperparathyroidism in chronic kidney disease, could lead to vascular calcification and accelerated progression of aortic stiffness. METHODS: We conducted an observational study in 85 patients on chronic hemodialysis, among which 70 were taking a weekly dose of α-calcidol of <2 µg and 15 were taking a weekly dose of ≥2 µg (pharmacological dose). Parathyroid hormone, 25-hydroxyvitamin D, fibroblast growth factor 23, and α-klotho were determined. Aortic stiffness was assessed by determination of carotid-femoral pulse wave velocity (cf-PWV) at baseline and after a mean follow-up of 1.2 years. A multivariable regression model was used to evaluate the impact of pharmacological dose of α-calcidol on the progression of aortic stiffness. RESULTS: At baseline, clinical, biological, and hemodynamic parameters were similar. At follow-up, cf-PWV increased more in patients with pharmacological dose of α-calcidol (0.583±2.291 m/s vs. 1.948±1.475 m/s; P = 0.04). After adjustment for changes in mean blood pressure and duration of follow-up, pharmacological dose of α-calcidol was associated with a higher rate of progression of cf-PWV (0.969 m/s; 95% confidence interval = 0.111-1.827; P = 0.03), and this association persisted after further adjustments for parameters of mineral metabolism. CONCLUSIONS: In this study, pharmacological dose of α-calcidol was associated with accelerated progression of aortic stiffness. This study suggest that the vascular safety of active vitamin D posology may need to be specifically addressed in the treatment of chronic kidney disease-related bone mineral disorder.

Advanced glycation end products, aortic stiffness, and wave reflection in peritoneal dialysis as compared to hemodialysis.

BACKGROUND: Modification of vascular extracellular matrix by advanced glycation end products (AGEs) may result in vascular stiffness. Because of higher exposure to glucose, we hypothesized that patients on peritoneal dialysis (PD) may have higher tissue levels of AGEs, increased vascular stiffness, and enhanced central augmentation pressure as compared to hemodialysis patients (HD). METHODS: In a cross-sectional study, 43 PD were matched to 43 HD based on age, gender, diabetes, and dialysis vintage. Tissue levels of AGEs were assessed by skin autofluorescence (skin AF). Aortic stiffness was measured by carotid-femoral pulse wave velocity (cf-PWV), and heart rate-adjusted augmentation pressure (AP@75) was performed by arterial tonometry. RESULTS: Baseline characteristics were similar in both groups except for lower prevalence of cardiovascular disease (CVD) and higher exposure to smoking in PD. Skin AF and cf-PWV were not statistically different, but PD patients had a lower AP@75 (P = 0.023). However, after adjustments for prevalence of CVD and smoking status, skin AF was higher in PD by 0.587 AU (95 % CI 0.091-1.215, P = 0.020), and cf-PWV was higher in PD by 2.20 m/s (95 % CI 0.56-3.84, P = 0.009), while AP@75 was not different. Overall, there was a significant association between skin AF and cf-PWV and AP@75. CONCLUSION: Skin AF and aortic stiffness were higher in PD after adjustments for imbalances in baseline characteristics. Independent of dialysis modality, there was a positive association between skin AF, aortic stiffness, and enhanced wave reflection.

Determinants of progression of aortic stiffness in hemodialysis patients: a prospective longitudinal study.

Aortic stiffness is associated with increased cardiovascular mortality in patients with chronic kidney disease. However, the rate of progression of arterial stiffness and the role of cardiovascular risk factors in the progression of arterial stiffness has never been established in a longitudinal study. In a prospective, longitudinal, observational study, carotid-femoral pulse wave velocity and carotid-radial pulse wave velocity were assessed in 109 hemodialysis patients at baseline and after a mean follow-up of 1.2 years. We examined the impact of age, atherosclerotic cardiovascular disease, diabetes mellitus, dialysis vintage, and pentosidine (a well-characterized, advanced glycation end products) on the rate of progression of aortic stiffness. The annual rate of changes in carotid-femoral pulse wave velocity and carotid-radial pulse wave velocity were 0.84 m/s per year (95% confidence interval, 0.50-1.12 m/s per year) and -0.66 m/s per year (95% confidence interval, -0.85 to -0.47 m/s per year), respectively. Older subjects, and patients with diabetes mellitus or atherosclerotic cardiovascular disease had higher aortic stiffness at baseline, however, the rate of progression of aortic stiffness was only determined by plasma pentosidine levels (P=0.001). The degree of baseline aortic stiffness was a significant determinant of the regression of brachial stiffness (P<0.001) suggesting that the regression of brachial stiffness occurs in response to central aortic stiffness. These findings suggest that traditional cardiovascular risk factors may play some role in the progression of aortic stiffness before development of advanced chronic kidney disease, and that the enhanced rate of progression of aortic stiffness in chronic kidney disease patients on dialysis are probably determined by more specific chronic kidney disease-related risk factors such as advanced-glycation end products.

Age-related and blood pressure-independent reduction in aortic stiffness after kidney transplantation.

OBJECTIVES: Aortic stiffness is a novel cardiovascular risk factor in patients with chronic kidney disease (CKD). The purpose of the present study is to examine whether there is a blood pressure-independent improvement in aortic stiffness 3 months after successful kidney transplantation (KTx), and whether this improvement is age-dependent. METHOD: In this prospective, longitudinal observational study, we studied hemodynamic and biological parameters prior to and 3 months after a KTx in 52 stage 5 CKD patients. Aortic stiffness was measured by carotido-femoral pulse wave velocity (c-f PWV) and enhanced central wave reflection was evaluated by the heart rate-adjusted central augmentation index (AIx) by means of arterial tonometry. Endothelin-1, L-arginine, asymmetric dimethylarginine (biomarkers of endothelial dysfunction), pentosidine (advanced glycation end-products) and mineral metabolism parameters were also measured. RESULTS: After adjusting for the reduction in mean blood pressure, c-f PWV decreased significantly from 12.1 ± 3.3 to 11.6 ± 2.3 m/s (P < 0.05). In an analysis stratified by age, this improvement was only present in patients older than 50 years of age as compared with patients younger than 50 years of age (-5.5 ± 2.2 vs. 2.1 ± 1.9%, P < 0.05). AIx decreased from 22 ± 11 to 14 ± 13% (P < 0.01), but this reduction was not age-dependent. We also observed a similar degree of improvement in the biomarker levels of endothelial dysfunction and pentosidine in both groups. CONCLUSION: This study shows for the first time that there is an age-dependent improvement in aortic stiffness after KTx. These observations suggest that older patients may have an added cardiovascular risk reduction after a successful KTx.

Reduced heart rate variability in patients with chronic obstructive pulmonary disease independent of anticholinergic or ß-agonist medications.

Reduced heart rate variability (HRV) is a predictor of poor outcome in several pathologies and in general population. Whether HRV is altered during normal daily activities or influenced by anticholinergic and ß-adrenergic medications in chronic obstructive pulmonary disease (COPD) remains unknown. Forty-one clinically stable COPD patients and 19 healthy controls matched for age, sex and smoking history underwent a 24-hour ambulatory ECG recording during normal daily activities. HRV was assessed by standardized temporal and spectral analysis. COPD patients showed a reduced HRV (LF/HF ratio) compared with healthy controls (median [interquartile range]) during daytime (2.6 [1.5-3.8] vs. 3.5 [2.9-5.6]), nighttime (1.8 [1.1-4.3] vs. 4.2 [2.7-6.9]) as well as during the entire 24-hour (1.9 [1.5-3.4] vs. 3.9 [3.2-5.6]) recordings (all P < 0.005). There was no significant difference between the two groups in the time domain and in the low frequency or high frequency domain for the 24-hour period analysis. In COPD patients, the 24-hour LF/HF ratio positively correlated with forced expiratory volume in 1 second (FEV(1)) (r = 0.342, P = 0.028) and negatively correlated with age (r = -0.317, P = 0.044). In multiple regression analysis, LF/HF ratio was associated with FEV(1) (P = 0.05) but not with age (P = 0.08). There was no difference of HRV between patients using or not anticholinergic or ß-agonist medications. These results demonstrate that COPD patients have a reduced sympatho-vagal balance compared with healthy subjects. HRV correlates with disease severity and does not seem to be influenced by anticholinergic or adrenergic medications.

Effects of aerobic exercise training and irbesartan on blood pressure and heart rate variability in patients with chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVES: The present pilot study was undertaken to evaluate the efficacy of an aerobic exercise training (AET) program alone or combined with an antihypertensive agent (irbesartan) to reduce blood pressure (BP) and enhance heart rate variability (HRV) in chronic obstructive pulmonary disease patients. METHODS: Twenty-one patients were randomly assigned to a double-blind treatment with exercise and placebo (n=11) or exercise and irbesartan (n=10). Subjects underwent 24 h BP monitoring and 24 h electrocardiographic recording before and after the 12-week AET. HRV was investigated using three indexes from the power spectral analysis and three indexes calculated from the time domain. The AET program consisted of exercising on a calibrated ergocycle for 30 min three times per week. Five patients in the placebo group were excluded during follow-up because they were not compliant. RESULTS: There was no change in 24 h systolic and diastolic BP before (130+/-14 mmHg and 70+/-3 mmHg, respectively) and after (128+/-8 mmHg and 70+/-8 mmHg, respectively) exercise training in the placebo group, whereas in the irbesartan group systolic and diastolic BP decreased from 135+/-9 mmHg and 76+/-9 mmHg to 126+/-12 mmHg and 72+/-8 mmHg, respectively (P<0.02). There were no changes in HRV parameters in either group. CONCLUSIONS: The present study suggests that a 12-week AET program is not associated with a significant reduction in BP or enhancement in HRV, whereas an AET program combined with irbesartan is associated with a reduction in 24 h BP.

Impact of diabetes, chronic heart failure, congenital heart disease and chronic obstructive pulmonary disease on acute and chronic exercise responses.

Several chronic diseases are known to negatively affect the ability of an individual to perform exercise. However, the altered exercise capacity observed in these patients is not solely associated with the heart and lungs dysfunction. Exercise has also been shown to play an important role in the management of several pathologies encountered in the fields of cardiology and pneumology. Studies conducted in our institution regarding the influence of diabetes, chronic heart failure, congenital heart disease and chronic pulmonary obstructive disease on the acute and chronic exercise responses, along with the beneficial effects of exercise training in these populations, are reviewed.

Chronic obstructive pulmonary disease in women.

BACKGROUND: Little is known about the comparative impact of chronic obstructive pulmonary disease (COPD) between women and men and about women's response to pulmonary rehabilitation. OBJECTIVES: To compare lung function, disability, mortality and response to pulmonary rehabilitation between women and men with COPD. METHODS: In the present retrospective study, 68 women (mean age 62.5+/-8.9 years) and 168 men (mean age 66.3+/-8.4 years) were evaluated by means of pulmonary function testing and an incremental symptom-limited cycle exercise test. Forty women and 84 men also participated in a 12-week pulmonary rehabilitation program. A 6 min walking test and the chronic respiratory questionnaire were used to assess the effects of pulmonary rehabilitation. Survival status was also evaluated. RESULTS: Compared with men, women had a smaller tobacco exposure (31+/-24 versus 48+/-27 pack-years, P<0.05), displayed better forced expiratory volume in 1 s (44+/-13 versus 39+/-14 % predicted, P<0.05), a higher functional residual capacity (161+/-37 versus 149+/-36 % predicted, P<0.05) and total lung capacity (125+/-20 versus 115+/-19 % predicted, P<0.001). Peak oxygen consumption was not different between women and men when expressed in predicted values but lower in women when expressed in absolute values. Pulmonary rehabilitation resulted in significant improvements in 6 min walking test and quality of life in both sexes, but women had a greater improvement in chronic respiratory questionnaire dyspnea. Survival status was similar between sexes, but predictors of mortality were different between sexes. CONCLUSIONS: Women may be more susceptible to COPD than men. The clinical expression of COPD may differ between sexes with greater degree of hyperinflation in women, who also benefit from pulmonary rehabilitation.

The metabolic syndrome in patients with chronic obstructive pulmonary disease.

PURPOSE: This study was undertaken to evaluate the presence of the metabolic syndrome in COPD patients who participated in a cardiopulmonary rehabilitation program. The metabolic syndrome is characterized by the presence of abdominal obesity, atherogenic dyslipidemia, raised blood pressure, presence of insulin resistance, and prothrombotic and inflammatory states that predispose to cardiovascular diseases. METHODS: Thirty-eight COPD patients (age: 66 +/- 7 years, [mean +/- SD], FEV1: 43 +/- 16% predicted) and 34 control participants matched for age and gender are included in this study. The criteria for the identification of the metabolic syndrome include 3 or more of the following features: abdominal obesity (waist circumference: > 102 cm in men, > 88 cm in women), triglycerides levels (>or= 1.69 mmol/L), high-density lipoprotein cholesterol levels (< 1.0 mmol/L in men, < 1.3 mmol/L in women), blood pressure (>or= 130/ >or= 85 mm Hg), and fasting glucose levels (>or= 6.1 mmol/L). RESULTS: Forty-seven percent of COPD patients and 21% of control participants presented 3 or more determinants of the metabolic syndrome. CONCLUSIONS: The presence of metabolic syndrome is frequent in patients with COPD who participated in a cardiopulmonary program. Hence, this population should be considered for screening for the metabolic syndrome.

Post-exercise heart rate recovery and mortality in chronic obstructive pulmonary disease.

Abnormal heart rate recovery (HRR) after exercise, a marker of cardiac autonomic dysfunction, is associated with poor prognosis in various populations. As chronic obstructive pulmonary disease (COPD) is associated with cardiac autonomic dysfunction, we tested the hypothesis that patients with COPD have a lower HRR than healthy people, and evaluated whether a delay in HRR is associated with an increased risk of mortality in COPD. The records of 147 COPD patients were reviewed (65.1+/-9.1 years, mean+/-sd, 42 women/105 men, forced expiratory volume in 1s (FEV1): 42+/-15% predicted) and compared to 25 healthy subjects (61.6+/-4.5 years, 5 women/20 men, FEV1: 100+/-14% predicted) during recovery after an exercise test. Heart rate was measured at peak exercise and at 1-min recovery, the difference between the two being defined as HRR (11+/-9 beats in COPD patients vs. 20+/-9 beats in healthy subjects, P < 0.0001). During a mean follow-up of 43.1+/-22.0 months, 32 patients died. Abnormal HRR (14 beats) was a strong predictor of mortality in COPD patients (adjusted hazard ratio: 5.12, 95% CI [1.54-17.00]). In conclusion, COPD patients have a lower HRR than healthy subjects, and have a worse prognosis when presenting abnormal HRR.

Catabolic/anabolic balance and muscle wasting in patients with COPD.

BACKGROUND: The mechanisms leading to muscle wasting in patients with COPD are still uncertain. This study was undertaken to evaluate the relationships among circulating levels of catabolic factors (ie, interleukin [IL]-6 and cortisol), anabolic factors (ie, bioavailable testosterone [Tbio], dehydroepiandrosterone sulfate [DHEAS], and insulin-like growth factor [IGF]-I), and mid-thigh muscle cross-sectional area (MTCSA) in patients with COPD. METHODS: Serum levels of the above factors were measured in 45 men with COPD (mean [+/- SEM] FEV(1), 43 +/- 3% predicted; mean age, 67 +/- 1 years) and 16 sedentary healthy men of similar age. MTCSA was quantified using CT scanning. Patients with COPD were subdivided into two groups according to the MTCSA (< 70 or >or= 70 cm(2)). RESULTS: There was a greater prevalence of hypogonadism (ie, Tbio, < 2 nmol/L) in patients with COPD compared to control subjects (22% vs 0%, respectively). Patients with an MTCSA of < 70 cm(2) had significantly reduced levels of DHEAS compared to those in healthy subjects (p < 0.01). IL-6 levels were significantly higher in both subgroups of COPD patients compared to those in control subjects (p < 0.005). The cortisol/DHEAS, IL-6/DHEAS, IL-6/Tbio, and IL-6/IGF-I ratios were significantly greater in COPD patients with an MTCSA of < 70 cm(2) compared to those in control subjects (p < 0.05). The cortisol/DHEAS and IL-6/DHEAS ratios were also significantly greater in COPD patients with an MTCSA of < 70 cm(2) than in COPD patients with an MTCSA of >or= 70 cm(2) (p < 0.05). In a stepwise multiple regression analysis, the IL-6/DHEAS ratio explained 20% of the variance in MTCSA (p < 0.005). CONCLUSION: Catabolic/anabolic disturbances were found in COPD patients leading to a shift toward catabolism and possibly to the development of peripheral muscle wasting.