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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.

Background/Objectives: We previously demonstrated a different regional stiffness response of elastic and muscular arteries after the administration of nitroglycerin, leading to an alteration of aortic-brachial stiffness gradient. Regional stiffness of smaller arteries may respond differently to vasodilation drugs. The objectives of this study were 1- to assess the feasibility of measuring arterial stiffness of the hand, i.e. radial-finger pulse wave velocity (RF-PWV) using piezoelectric sensors, and 2- to measure RF-PWV and its response to nitroglycerin. Methods: This exploratory study was conducted in 11 healthy participants (55% were men, mean age was 33.6 ± 10.6 yrs). Piezoelectric sensors (Complior) were placed simultaneously on carotid and radial arteries, and tip of the third finger, to obtain carotid-radial PWV (CR-PWV) and RF-PWV (in triplicates), before and after 4 minutes of 0.4 mg NTG sublingual spray. Results: Visually, pressure curves at the finger and detection of the foot of the wave were obtained with a similar quality than radial and carotid pressure curves. The RF-PWV intra-session coefficient of variation was 7.3%. At baseline, mean CR-PWV and RF-PWV were respectively of 9.07 ± 1.24 m/s and 4.80 ± 1.42 m/s. After NTG, CR-PWV decreased (7.75 ± 1.32 m/s) and RF-PWV increased (6.75 ± 2.58 m/s), both significantly (p < 0.01). Conclusion: This first attempt to measure small arteries stiffness shows that it is possible to measure hand PWV. Again, we observed opposite changes in regional stiffness of different vascular territories with a vasodilator drug. These results may open up the path to a better understanding of microcirculation consequences of an altered stiffness gradient.

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 CI : 1.18–1.75; P 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.

Purpose/Background/Objectives: According to reservoir-wave theory, excess pressure (XSP) is analogous to flow and related to excess cardiac workload. In end-stage renal disease (ESRD) patients, we have shown that XSPI is associated with increased mortality and is higher in patients with arteriovenous fistula (AVF). Recently AVF has been proposed treatment for treatment of resistant hypertension. However, this benefit may be mitigated through an increase in cardiac output. Therefore, we examine whether XSPI increases after creation of an AVF in ESRD patients. Methods: Hemodynamic assessments were performed within 1 month before and 6 months after creation of AVF in ESRD patients. Carotid pressure waves were recorded using arterial tonometry, calibrated using brachial diastolic and mean arterial pressure. Using pressure only approach, reservoir-wave analysis was used to derive reservoir pressure (RP), XSP and their integrals (RPI, XSPI). Results: 38 patients (63% male, mean age 59 ± 15 years) were assessed 3.9 ± 1.2 months Post-AVF. Carotid RP decreased slightly (115 ± 18 vs 109 ± 24, p = 0.060), due to the reduction of diastolic BP (79 ± 10 vs 73 ± 12 mm Hg, p = 0.003). While, carotid systolic BP (123 ± 20 vs 119 ± 27 mm Hg, p = 0.380) remained unchanged, XSP and XSPI increased (XSP: 14 [12–19] to 17 [12–22] mmHg, p = 0.031; XSPI: 275 [212–335] to 334 [241–349] kPa.s, p = 0.015). Conclusion: While AVF creation reduced diastolic BP, it resulted in higher XSPI, which has been associated with increased mortality. Therefore, the long-term efficacy of AVF in reducing clinical outcomes should be specifically addressed.

Purpose/Background/Objective: Cognitive decline is highly prevalent amongst end-stage renal disease (ESRD) patients and is accelerated upon initiation of hemodialysis (HD) [1]. ESRD increases aortic stiffness and blood flow pulsatility, which may damage small vessels of target organs like the brain [2]. In this pilot study, we aimed to evaluate the acute effect of HD on cerebral blood flow and its relation to arterial stiffness. Methods: Before, every hour during and after HD (T0–T4), we measured cerebral flow velocity (FV) using transcranial Doppler, blood pressure (BP) via digital finger cuff (Nexfin), cardiac activity using ECG and aortic pulse wave velocity (PWV) with Mobile-O-Graph. FV pulsatility index (PI) and transit times between ECG peak and the foot of both FV and BP waveforms (cerebral dT; digital dT) were computed using in house MATLAB-based analysis. Changes during HD were evaluated with Generalized Estimating Equation models adjusting for multiple comparisons in SPSS 26.0. Results: In eight participants aged 63 ± 17 y. old (4 diabetics, 3 women), peak FV decreased from baseline at T1 and T2 (−11.2 cm/s, p = 0.007; −12.2 cm/s, p < 0.001), PI decreased at T1 (0.81 to 0.77, p = 0.005), whilst minimum FV, mean BP and partial pressure of CO2 remained unchanged. Digital dT increased at T3 (0.19 to 0.22, p < 0.001) and cerebral dT increased throughout HD (T1–T4, p < 0.005), whereas aortic PWV did not change. Conclusions: During hemodialysis, cerebral and digital transit times increased, suggesting decreased stiffness of small peripheral vessels, without significant changes in aortic stiffness. Reduced stiffness of cerebral arteries may partially explain decreased cerebral flow pulsatility.

We performed a case-control study on 130 age- and sex-matched hemodialysis patients. In multivariate analysis, we observed that FGF23 levels were associated with fracture incidence and that soluble α-klotho levels were associated with the aortic-brachial arterial stiffness ratio. New bone markers such as sclerostin, Dickkopf-related protein 1 (DKK1), fibroblast growth factor-23 (FGF23), and α-klotho have been identified as potential key players in bone and vascular abnormalities of chronic kidney disease. Therefore, we aimed to assess whether these markers are associated with fractures, bone metabolism, and vascular stiffness in dialysis patients. In a prospective hemodialysis cohort, where plasma samples and vascular assessment were performed at baseline, we matched patients who experienced a fracture during follow-up with sex- and age-matched non-fractured patients on a 1:4 ratio. Sclerostin, DKK1, α-klotho, FGF23, and markers of bone formation (alkaline phosphatase and procollagen type 1-N terminal propeptide [P1NP]) and bone resorption (tartrate-resistant acid phosphatase 5b [TRAP5b]) were measured in baseline plasma samples. Aortic-brachial pulse wave velocity ratio, a blood pressure independent measure of arterial stiffness, was used to assess vascular stiffness at baseline. We included 130 hemodialysis patients (26 fractured, 104 non-fractured) with a median follow-up of 42 months and a median age of 72 years. In multivariate Cox regression models, high FGF23 levels were associated with increased fracture incidence (adjusted HR = 2.97; 95% CI 1.18, 7.43). α-Klotho levels were associated with bone formation but not resorption markers. In both univariate and multivariable adjusted models, α-klotho levels were inversely associated with the aortic-brachial pulse wave velocity ratio (β = − 0.070; 95% CI − 0.133, − 0.006). These results suggest a role for FGF23/klotho axis on bone and vascular metabolism in dialysis populations.

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-1β (IL-1β) in calcified aorta. The aim of the study was to investigate the association between IL-6, TNF, IL-1β, 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-1β were measured by enzyme-linked immunosorbent assay. IL-6 was associated with cf-PWV adjusted for mean blood pressure (MBP) (standardized β = 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 β = 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-1β, and aortic stiffness. While IL-6 was associated with augmentation index (standardized β = 0.224; P < .001) and central pulse pressure (standardized β = 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.

Cardiovascular disease is the leading cause of death in patients with advanced chronic kidney disease (CKD). The risk of cardiovascular mortality in hemodialysis patients is 10–20 times higher than in the general population, even after stratification for traditional cardiovascular risk factors.1 Aortic stiffness, a nontraditional cardiovascular risk factor that results in increased central pulse pressure, cardiac workload, and left ventricular hypertrophy, has been shown to be a strong predictor for cardiovascular morbidity and mortality in CKD.2–4 Even in earlier stages of CKD, the decline in renal function is associated with a higher degree of aortic stiffness at follow-up.5,6 In a longitudinal study with repeated measurements of aortic stiffness, we have shown that the rate of progression of aortic stiffness is accelerated in patients undergoing hemodialysis. Our findings suggested that, although traditional cardiovascular risk factors may play some role in the progression of aortic stiffness before development of advanced CKD, the increased rate of progression of aortic stiffness in CKD patients on dialysis is probably determined by specific CKD-related risk factors.7 The mechanisms of aortic stiffness in CKD still remain poorly understood. However, vascular calcification seems to play a dominant role in the alteration of biomechanical properties of the arterial wall.8–10 CKD mineral and bone disorder and, more specifically, hyperphosphatemia play key roles in the transdifferentiation of vascular smooth muscle cells into an osteoblastic phenotype, therefore promoting vascular calcification.11 In CKD, because there is a lack of activation of vitamin D by a reduction in 1-α-hydroxylase activity that is usually performed by the kidney, the use of 1-α-hydroxy-vitamin D (α-calcidol) or other forms of active vitamin D have become the cornerstone of therapy for the treatment of CKD mineral and bone disorder.12–14 However, the impact of high-dose (pharmacological) active vitamin D therapy on vascular health is at best controversial. In a procalcifying media in vitro, active vitamin D therapy can stimulate vascular smooth muscle cell transdifferentiation into osteoblast-like cells and promote vascular calcification.15–21 In the context of this study, we hypothesized that pharmacological dose of active vitamin D may result in accelerated progression of aortic stiffness in CKD. Therefore, we examined the impact of active vitamin D therapy on the rate of progression of aortic stiffness in a group of hemodialysis patients.

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) 2or ≥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 MTCSACTthan those with normal BMI (PPaO2andPaCO2were not significantly different in the two groups. When adjusted forPaCO2, 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.

Objective:Arteriovenous fistula (AVF) is the vascular access of choice in patients with end-stage kidney disease (ESKD) requiring hemodialysis (HD). AVF adds a high flow and low resistance circuit into the arterial system. We had previously shown that AVF is associated with a reduction in blood pres

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 m 2 (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 ( R 2 =0.10 and 0.08; P P =0.003) and MAP and carotid–radial PWV ( R 2 =0.22 and 0.12; P P R 2 =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.

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 (PCONCLUSIONS: 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 irbe-sartan is associated with a reduction in 24 h BP.

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, PCONCLUSIONS: 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.

Background: Arterial stiffness has been considered as an index of vascular ageing. However, the relationship between age and stiffness of various segments of the arterial tree is heterogeneous. Moreover, the hemodynamic impact of vascular stiffness is thought to be related to the attenuation or even reversal of the physiological arterial stiffness gradient. The objectives of the present study were to evaluate the impact of age on aortic (central elastic artery) and brachial (muscular conduit artery) stiffness and to assess hemodynamic correlates of the arterial stiffness gradient. Method/results: In 310 dialysis patients (67 years [25th-75thpercentiles: 56–76], 185(60%) men, 134(43%) diabetes and 162(52%) cardiovascular disease), we measured aortic and brachial stiffness by pulse wave velocity of carotid-femoral (cf-PWV) and carotid-radial (cr-PWV) using direct distances (Complior). Arterial stiffness gradient was determined by cf-PWV/cr-PWV (PWV ratio). Central pulse wave parameters were obtained through generalized transfer function applied to the radial artery pulse profile (Sphygmocor). Mean cf-PWV, cr-PWV and PWV ratio were respectively of 13.52 ±4.07m/s, 8.76 ±1.68m/s and 1.59 ±0.52m/s. Cr-PWV decreased with age (β=−0.031, R=−0.274, P0.001), while cf-PWV (β=0.144, R=0.529, P0.001) and PWV ratio (β=0.021, R=0.613, P0.001) increased. In contrast to cf-PWV and cr-PWV, PWV ratio was not associated with MBP (P=0.997). Conclusion: The use of PWV ratio may be a more logical choice for risk determination than aortic stiffness as it provides a better estimation of the loss of arterial stiffness gradient and is not influenced by MBP in this population.

Summary 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 1 s (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.

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.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).Forty-seven percent of COPD patients and 21% of control participants presented 3 or more determinants of the metabolic syndrome.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.

Backgroud: 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] FEV1 ,4 3 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 cm 2 ). Results: There was a greater prevalence of hypogonadism (ie, Tbio, 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. (CHEST 2003; 124:83– 89)

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). Th

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.

Objective. We have shown that regression of brachial stiffness is inversely related to aortic stiffness in dialysis patients. In this study, we sequentially examine the impact of aortic stiffness, brachial stiffness and aortic-brachial stiffness mismatch on mortality in dialysis patients. Design and Method. This is a prospective longitudinal study conducted in 310 adult dialysis patients (mean age 65 ± 15). Aortic and brachial stiffness were respectively measured by determination of carotid-femoral (cf-PWV) and carotid-radial pulse wave velocity (cr-PWV) (CompliorSP-direct measurement technique). Aortic-brachial stiffness mismatch was defined by cf-PWV/cr-PWV mismatch. Central pulse wave profile was determined by radial applanation tonometry. After a mean follow-up of 3.6 ± 1.7 years mortality status was assessed. ROC curve analysis was performed to evaluate the impact of central pulse pressure (PP), heart rate adjusted augmentation index (AIx), cf-PWV, cr-PWV and the cf-PWV/cr-PWV ratio on mortality. Results. The cf-PWV was 13.5 ± 4.1 m/s, cr-PWV was 8.7 ± 1.7 m/s, cf-PWV/cr-PWV ratio was 1.6 ± 0.5, central PP was 49 ± 21 mmHg and the AIx 26.8 ± 11.1%. During follow-up, 160 (49%) deaths occurred. Area under the curve was largest for cf-PWV/cr-PWV ratio (0.694, p < 0.001), followed by cf-PWV (0.627, p < 0.001), AIx (0.617, p < 0.001), PP (0.598, P = 0.003) and cr-PWV (0.371, p < 0.001). Figure 1 shows patient survival according to tertiles of aortic-brachial stiffness ratio. In univariate and various adjusted models using Cox regression model, aortic-brachial stiffness was independently associated with increased risk of mortality. Conclusion. Aortic-brachial stiffness mismatch was better that aortic stiffness alone in predicting clinical outcome in this population.

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). 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. 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. 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.

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

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 β-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 β-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.

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.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.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 (P0.05). 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%, P0.05). AIx decreased from 22 ± 11 to 14 ± 13% (P0.01), 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.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.

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.

This study was undertaken to test the hypothesis that a reduction in midthigh muscle cross-sectional area obtained by CT scan (MTCSA(CT)) is a better predictor of mortality in chronic obstructive pulmonary disease (COPD) than low body mass index (BMI). We also wished to evaluate whether anthropometric measurements could be used to estimate MTCSA(CT). One hundred forty-two patients with COPD (age = 65 +/- 9 years, mean +/- SD, 26 F, BMI = 26 +/- 6 kg/m(2), FEV(1) = 42 +/- 16% predicted) were recruited from September 1995 to April 2000 with a mean follow-up of 41 +/- 18 months. The primary end-point was all-cause mortality during the study period. A Cox proportional hazards regression model was used to predict mortality using the following independent variables: age, sex, daily use of corticosteroid, FEV(1), DL(CO), BMI, thigh circumference, MTCSA(CT), peak exercise workrate, Pa(O2), and Pa(CO2). Only MTCSA(CT) and FEV(1) were found to be significant predictors of mortality (p = 0.0008 and p = 0.01, respectively). A second analysis was also performed with FEV(1) and MTCSA(CT) dichotomized. Patients were divided into four subgroups based on FEV(1) (oror= 50% predicted) and MTCSA(CT) (oror= 70 cm(2)). Compared with patients with an FEV(1)or= 50% predicted and a MTCSA(CT)or= 70 cm(2), those with an FEV(1)50% predicted and a MTCSA(CT)or= 70 cm(2) had a mortality odds ratio of 3.37 (95% confidence interval, 0.41-28.00), whereas patients with an FEV(1)50% predicted and a MTCSA(CT)70 cm(2) had a mortality odds ratio of 13.16 (95% confidence interval, 1.74-99.20). MTCSA(CT) could not be estimated with sufficient accuracy from anthropometric measurements. In summary, we found in this cohort of patients with COPD that (1) MTCSA(CT) was a better predictor of mortality than BMI, and (2) MTCSA had a strong impact on mortality in patients with an FEV(1)50% predicted. These findings suggest that the assessment of body composition may be useful in the clinical evaluation of these patients.

Introduction La bronchopneumopathie obstructive chronique (BPCO) affecte principalement la fonction respiratoire. Or, cette maladie est frequemment associee a d’autres problemes de sante appeles manifestations systemiques. Notamment, les patients atteints d’une BPCO presentent un risque eleve de maladies cardiovasculaires. Etat des connaissances La majeure partie des connaissances actuelles en ce qui a trait aux problemes cardiovasculaires chez les patients atteints d’une BPCO porte sur les arythmies cardiaques. Outre les arythmies, l’hypertension arterielle, les maladies cardiovasculaires, l’insuffisance cardiaque et les accidents vasculaires cerebraux font partie des problemes cardiovasculaires qui surviennent chez ces patients. Ce manuscrit a essentiellement pour objectif de dresser le portrait des maladies cardiovasculaires qui surviennent chez les patients atteints d’une BPCO. Il exclut le champ relatif a l’hypertension pulmonaire et ses consequences cardiaques droites. Perspectives et conclusion De plus en plus, la communaute medicale s’interesse aux manifestations systemiques dont les problemes cardiovasculaires chez les patients atteints d’une BPCO. D’autres etudes seront toutefois necessaires afin d’approfondir les connaissances a ce propos. Celles-ci permettront une meilleure prise en charge des patients souffrant d’une BPCO.