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Background: Neuropeptide Y (NPY) is a sympathetic neurotransmitter that acts on multiple receptors involved in cardiovascular remodelling and angiogenesis. Plasma levels of NPY are increased in patients with end-stage renal disease (ESRD) and are independently related to left ventricular hypertrophy (LVH) and incident cardiovascular events in these patients., Objective: To investigate the relationship between NPY receptor Y2 gene polymorphism and left ventricular mass index (LVMI) as well as the interaction between this polymorphism and plasma NPY in determining LVH in 189 ESRD patients., Results: LVMI was significantly higher (+12%, P = 0.03) in patients carrying the C allele than in those without C allele and was linearly associated with plasma NPY (P = 0.01). Interaction analysis showed a significant NPY-LVMI relationship in patients with the C allele, both at univariate (r = 0.27, P = 0.001) and multivariate (r = 0.21, P = 0.01) analyses, whereas no such relationship existed in patients without this allele. In fully adjusted analyses, a 10 pmol/l increase in plasma NPY entailed a 4.9 g/m increase in LVMI in patients with C allele, whereas the same change in NPY levels did not modify the NPY-LVMI link in patients without such allele (P = 0.009)., Conclusion: NPY receptor Y2 polymorphism is independently associated with LVMI and interacts with plasma levels of NPY in explaining the variability of LVH in ESRD. These results offer a genetic basis to the hypothesis that NPY is causally implicated in the pathogenetic pathway leading to LVH in ESRD patients.

Objectives: Vascular endothelial growth factor induces nitric oxide-dependent angiogenic effects and participates in the inflammatory response. This cytokine is over-expressed in the myocardium in experimental models of pressure overload and renal mass ablation, and vascular endothelial growth factor is increased in end-stage renal disease. We investigated the relationship between vascular endothelial growth factor, left ventricular function (by midwall fractional shortening) and mortality in a prospective cohort study in 228 hemodialysis patients., Results: Serum vascular endothelial growth factor concentration was associated directly with interleukin-6 and tumor necrosis factor-alpha (P < 0.01) and inversely with albumin (P = 0.007) but was independent of the endogenous inhibitor of nitric oxide synthesis, asymmetric dimethylarginine. Vascular endothelial growth factor was inversely related with midwall fractional shortening (P = 0.002) and predicted mortality (P = 0.02). In multivariate analyses testing the involvement of this angiogenic cytokine in left ventricular dysfunction and death, these links remained substantially unmodified after adjustment for Framingham risk factors, risk factors peculiar to end-stage renal disease (Hb, Ca, P) and previous cardiovascular complications. However, these links became weaker and not significant when biomarkers of inflammation and asymmetric dimethylarginine were sequentially introduced into the multivariate models. In crude and adjusted analyses, left ventricular function was lowest in patients who displayed both high vascular endothelial growth factor and high asymmetric dimethylarginine, intermediate in patients with either high vascular endothelial growth factor or high asymmetric dimethylarginine and highest in those with low asymmetric dimethylarginine and low vascular endothelial growth factor (P = 0.001)., Conclusion: Vascular endothelial growth factor is associated with left ventricular systolic dysfunction and mortality in hemodialysis patients. Vascular endothelial growth factor appears to be in the pathway whereby inflammation and nitric oxide inhibition lead to cardiomyopathy and death in hemodialysis patients.

Background: End-stage renal disease (ESRD) is a high-risk condition and left ventricular hypertrophy (LVH) is the strongest risk factor in this population., Objective and Methods: Since the prognostic value of left atrial (LA) size in ESRD is still unknown, we performed a prospective cohort study aimed at testing the prognostic value of LA volume in a cohort of 249 ESRD patients., Results: Both un-indexed and indexed LA volume (LAV) was significantly higher in dialysis patients than in healthy subjects (P < 0.001). On multivariate analysis only left ventricular mass index (LVMI), LV ejection fraction (LVEF), ratio of early (E) to late atrial (A) mitral Doppler peak flow velocity (E/A ratio) and antihypertensive treatment maintained an independent association with LAV. During the follow-up 113 patients died. LAV added significant prognostic power to a multivariate Cox model of all-cause death and the model based on height provided the best data fit. Notably, this index maintained an independent predictive value for death (P = 0.03) also when LVMI and LVEF were jointly forced into the Cox's model. Neither crude nor body surface area (BSA)-adjusted LAV had an independent association with death when tested in the Cox model including LVMI and LVEF., Conclusions: In patients with ESRD, LAV indexed for height displays prognostic value beyond and above that provided by LV mass and function.

Objective: Neuropeptide Y (NPY) is released during sympathetic stimulation and mediates the central effects of the adipostatic hormone leptin. The plasma concentration of NPY and leptin is increased in patients with end stage renal disease (ESRD), but it is unknown whether these substances are related to biochemical markers of sympathetic activity and to alterations in left ventricular (LV) mass and function in these patients., Design: We investigated the relationship between NPY, norepinephrine (NE), leptin and echocardiographic measurements in a cross-sectional study in 198 patients with ESRD., Results: NPY was directly related to plasma NE and heart rate but it was largely independent of arterial pressure and of retention of metabolic waste products. NPY was significantly higher in patients with LV hypertrophy and in those with LV systolic dysfunction than in those without these alterations. Of note, NPY emerged as an independent correlate of LV mass index and of LV ejection fraction (LVEF) (both P

Objective: Nocturnal hypoxemia has recently been proposed as a cardiovascular risk factor in patients with chronic renal failure. In this study we have tested the hypothesis that this disturbance is associated with left ventricular hypertrophy (LVH) in dialysis patients., Methods: During a mid-week non-dialysis day, 38 hemodialysis patients underwent continuous monitoring of arterial O2 saturation (SaO2) during night-time as well as 24 h ambulatory blood pressure monitoring and echocardiography., Results: Eighteen patients had one or more episodes of O2 desaturation during night-time (average: 21 episodes; range 1 to 120) while the other 20 had no episode. Neither day-time arterial pressure nor heart rate were significantly associated with nocturnal hypoxemia. However there was a significant correlation between the night/day systolic ratio and the severity of hypoxemia during night-time (r = 0.36, P = 0.03). On multivariate analysis, nocturnal hypoxemia proved to be the stronger independent predictor of relative wall thickness, mean wall thickness and left ventricular mass index, suggesting that nocturnal O2 desaturation is linked to concentric hypertrophy and to concentric geometry of the left ventricle. Accordingly, the proportion of patients with such geometric alteration was higher (chi2 = 4.1, P = 0.04) in patients with a pulse oximetry severity score > 50th percentile [15 of 19 (79%)] than in those below this threshold [nine of 19 (47%)]., Conclusions: Nocturnal hypoxemia is an important correlate of LVH in hemodialysis patients. Such an association is largely independent of arterial pressure. These data further underscore the importance of disturbed respiratory control as a cardiovascular risk factor in dialysis patients.

Objective: To investigate the relationship between inflammatory processes and atherosclerosis in uraemic patients on chronic dialysis., Design: A cross-sectional study in 138 dialysis patients (92 on haemodialysis and 46 on continuous ambulatory peritoneal dialysis)., Methods: Serum C-reactive protein (CRP), IgG anti-Chlamydia pneumoniae antibodies, lipoprotein (a), fibrinogen and plasma homocysteine as well as the intima-media thickness and the number of atherosclerotic plaques of the carotid arteries (by Echo-Colour-Doppler) were measured in each patient, Results: One hundred and eight patients had at least one plaque and 26 had more than six plaques. Serum CRP was above the upper limit of the normal range (5 mg/I) in 85 of 138 patients (62%). IgG anti-Chlamydia pneumoniae antibodies were detectable in 64% of patients (high level in 24%, intermediate in 33% and low in 7%) and undetectable in the remaining 36% of patients. In a multiple regression model age (beta=0.35), serum CRP (beta=0.23), plasma homocysteine (beta=0.19), duration of dialysis (beta=0.19) and pulse pressure (beta=0.18) were independent predictors of intima-media thickness (R=0.54, P < 0.0001). Similarly, age (beta=0.33), serum CRP (beta=0.29), plasma homocysteine (beta=0.20) and serum albumin (beta=-0.18) were independent correlates of the number of atherosclerotic plaques (R = 0.55, P < 0.0001 ). Furthermore, in smokers, the interaction serum CRP-IgG anti-Chlamydia pneumoniae antibodies was the stronger independent predictor (beta=0.43, P=0.0001) of the number of atherosclerotic plaques while no such relationship (P=0.73) was found in non-smokers., Conclusions: In patients on chronic dialysis treatment CRP is independently associated to carotid atherosclerosis and appears at least in part to be explained by IgG anti-Chlamydia pneumoniae antibodies level. These data lend support to the hypothesis that inflammation plays a role in the pathogenesis of atherosclerosis in these patients.

Objective: Arterial hypertension is an established risk factor for left ventricular hypertrophy (LVH) in the uremic population. However, whether 24-h monitoring is a better predictor of LVH than clinic blood pressure and routine pre-dialysis measurements in these patients is still undefined., Methods: This problem was studied in 64 nondiabetic hemodialysis patients without heart failure. The echocardiographic study as well as the clinic and 24-h ambulatory blood pressure (BP) measurements were performed during the day off-dialysis. Pre-dialysis arterial pressure was calculated as the average value of the 12 routine recordings taken during the month preceding the study., Results: In multivariate models, including also sex, body mass index, hematocrit and serum cholesterol, pre-dialysis systolic, diastolic and pulse pressures were the only independent BP determinants of heart geometry. Twenty-four hour ambulatory BP monitoring (ABPM) did add significant (but weak) information to the prediction of left ventricular internal dimension, i.e. it increased by 9% (P = 0.01) the variance already explained by pre-dialysis diastolic BP and other significant covariates. However, 24-h ABPM did not add any significant and independent explanatory information to the corresponding pre-dialysis measurements for the posterior wall and interventricular septum measurements, and for left ventricular mass (-0.6 to +3.9%; average +1.1%)., Conclusions: In dialysis patients, pre-dialysis BP is at least as strong a predictor of left ventricular mass as 24-h ambulatory monitoring. Thus, the average of 12 routine pre-dialysis measurements may be used to predict heart geometry in dialysis patients without any loss of information in comparison with 24-h ambulatory monitoring.