Impaired basal NO activity in patients with glomerular disease and the influence of oxidative stress.

Endothelial dysfunction has been found to be linked to and predictive of cardiovascular events. Whether endothelial function of the renal vasculature is impaired in patients with chronic glomerular disease and whether oxidative stress is of importance in this setting has not yet been determined. In this study, endothelial function of the renal vasculature was investigated in 25 patients with chronic glomerular disease and 50 control subjects matched for age and blood pressure. Renal plasma flow (RPF) and glomerular filtration rate were measured by constant infusion input clearance technique at baseline and following infusions of the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-L-arginine (L-NMMA, 4.25 mg/kg), the substrate of NOS L-arginine (100 mg/kg) and the antioxidant vitamin C (3 g co-infused with L-arginine 100 mg/kg). At baseline, RPF was similar in the two groups. The reduction in RPF in response to L-NMMA was less pronounced in patients with chronic glomerular disease compared to control subjects (-4.6+/-12 vs -9.8+/-9%; P=0.040), indicating reduced basal nitric oxide (NO) activity in chronic glomerular disease. Co-infusion of the antioxidant vitamin C on top of L-arginine induced a more pronounced increase in RPF in patients with chronic glomerular disease than in control subjects (21.7+/-17 vs 10.9+/-22%; P=0.036). Our findings suggest that basal NO activity of the renal vasculature is reduced in patients with chronic glomerular disease compared to age- and blood pressure-matched control subjects. This might be in part related to increased oxidative stress.

The effect of statins on angiotensin II-induced hemodynamic changes in young, mildly hypercholesterolemic men.

BACKGROUND: Angiotensin II type 1 (AT(1)) receptors are well known to mediate angiotensin II (Ang II)-induced pro-atherosclerotic effects. It has been found that hypercholesterolemia influences the expression of AT(1) receptors on vascular smooth muscle cells and that increased density of AT(1) receptors exaggerates the hemodynamic response to Ang II. We analyzed to what extent statins and AT(1) receptor antagonists diminish the vasoconstrictive response to Ang II infusion in hypercholesterolemic patients. METHODS: A total of 24 male patients with LDL cholesterol levels >130 mg/dL were enrolled in a randomized, cross-over study. After baseline evaluation, 12 patients received first cerivastatin (0.3 mg/day) and the other 12 patients initially received candesartan (8 mg/day) for 3 weeks, with subsequent cross-over of the medication for the second 3-week drug period. The vascular response was analyzed by the increase in mean arterial pressure (MAP) and total peripheral resistance (TPR) during infusion of increasing doses of Ang II at baseline and the end of each treatment period. Hemodynamic changes were also compared with those in 24 normocholesterolemic subjects without any therapy. RESULTS: At baseline, Ang II provoked a similar increase of MAP and TPR in patients and control subjects. Treatment with cerivastatin did not affect the response to Ang II compared with baseline. By contrast, treatment with candesartan attenuated significantly the response to Ang II compared with baseline and cerivastatin. CONCLUSIONS: Our hemodynamic data indicate the hypothesis that statins do not reduce the responsiveness to Ang II in resistance arteries of young, mildly hypercholesterolemic patients.

Intensive training of patients with hypertension is effective in modifying lifestyle risk factors.

The burden of insufficiently treated arterial hypertension is still underestimated. In addition to pharmacological therapy, patient training is a valuable therapeutic option. During 1998-1999, the Institute for Preventive Medicine conducted an intensive training programme in cooperation with regional practitioners. The goal of this programme was to educate patients about their disease and motivate them to comply with the therapy. To evaluate the effectivity of this programme, 126 patients with arterial hypertension were trained. They received eight training sessions of 90 min each. In 90 patients blood pressure measurements before and 6 months after training were available. In addition, data concerning health status and lifestyle risk factors were analysed with standardised questionnaires. There was a marked reduction in blood pressure after 6 months (152+/-6/89+/-10 vs. 145+/-12/85+/-8 mmHg, P<0.001). In parallel, mean body weight declined by 0.9 +/- 2.9 kg (P<0.001) and body mass index (BMI) by 0.33+/-1.04 kg/m2 (P<0.001). Further analysis revealed that weight loss was more marked in obese patients (P< 0.01) than in lean subjects. Similarly, the decline of blood pressure was also greater in obese patients, but did not reach statistical significance. The activity score for physical exercise increased overall from 2.1+/-0.4 to 2.8+/-3.1 h/week (P<0.01). Moreover, knowledge about hypertension increased as well (P<0.01). Of all the quality life measurements, the vitality index improved from 53+/-19 to 59+/-19 (P<0.05) according to the patients' self-estimation. In conclusion, training of hypertensive patients has a profound effect on blood pressure control. It motivates patients to change lifestyle risk factors, namely to lose weight, and increases the patients' physical activity level, thereby decreasing the patients' blood pressure. Thus, intensive training programmes are effective and should be used on a widespread basis.

Are conventional cardiovascular risk factors predictive of two-year mortality in hemodialysis patients?

BACKGROUND: In general population hypertension, diabetes mellitus, overweight, hyperlipidemia and smoking are well-established risk factors for cardiovascular disease. However, the effect of these conventional risk factors on cardiovascular disease and mortality of patients on hemodialysis is not well understood. Indeed, some risk factors such as high blood pressure, hyperlipidemia and excess weight have been recently claimed to correlate with improved survival. OBJECTIVE: This study was undertaken to define the prevalence of these conventional risk factors in 453 hemodialysis patients, predominantly African-Americans, to determine their influence on two-year survival. RESULT: High cholesterol was found in 30% of the patients, high LDL-cholesterol in 25% and high triglycerides in 16%. Lipoprotein(a) (LP(a)) was elevated in 68% of the patients. 31% of our patients had predialysis mean arterial blood pressure (MAP) over 114, and 25% were obese based on a body mass index (BMI) over 30, 26% were diabetic and 25% were active smokers. Smoking was more common among our male and Caucasian patients. The aggregate score for the risk factors were 2.4+/-0.1 per patient, which increased to 3.2+/-0.1 in patients with obesity or diabetes, to 3.0+/-0.1 with hypertension and to 2.8+/-0.1 with active smoking. In multivariate Cox model analysis, prealbumin, body weight and blood pressure showed a positive correlation with two-year survival whereas diabetes mellitus had a negative correlation. Hyperlipidemia did not correlate to patients' two-year mortality. Smoking was associated with higher mortality, but that did not reach statistical significance. CONCLUSION: Conventional risk factors at least over a two-year period do not readily account for the higher mortality of a group of predominantly African-American patients on hemodialysis. The lack of prediction is speculated to be partly due to the overriding beneficial effects of better nutrition and due to the presence of other yet to be well-defined factors such as hyperhomocysteinemia, oxidative stress, coronary calcification, hitherto unidentified uremic toxins or a combination of these factors.

Risk factor paradox in hemodialysis: better nutrition as a partial explanation.

The higher mortality rate in patients on hemodialysis is primarily due to the higher rate of cardiovascular disease. Yet, paradoxically, overweight, hypertension, and hyperlipidemia, which are cardiovascular risk factors in the general population, have been reported to correlate with better patient survival in hemodialysis. To examine whether this "risk factor paradox" in hemodialysis is due to the positive influence of accompanying better nutrition, we prospectively obtained data on fasting lipids, biochemical markers of nutrition, body mass index (BMI), and blood pressure (BP) in 453 hemodialysis patients and related them to 1 year mortality. As previously noted, body weight, blood pressure, and certain serum lipids positively correlated with survival. Serum prealbumin, one of the most sensitive and specific biochemical markers for nutrition, correlated positively with hypercholesterolemia (r = 0.30, p < 0.001) and BMI (r = 0.12, p < 0.02), but not with mean arterial pressure (MAP) (r = 0.01, p = NS). By analysis of variance, patients in the upper tertile (i.e., higher levels) of BMI and cholesterol but not MAP had significantly higher serum prealbumin and creatinine compared with those in the lower tertile. Our data lend support to the hypothesis that, in patients on hemodialysis, the positive effect of higher BMI and hyperlipidemia but not of high BP could be partially explained on the basis of the accompanying better nutrition. Although not proven, correcting risk factors while improving nutrition may offer better outcomes for patients on dialysis.

[Results of an intensive training program for hypertension at the Institute for Preventive Medicine]. / Ergebnisse der Intensiv-Hypertonieschulung des Instituts für präventive Medizin.

BACKGROUND AND OBJECTIVE: The burden of insufficiently treated arterial hypertension is still underestimated. During 1998 to 1999 we conducted an intensive training program in cooperation with regional practitioners. The aim of this program was to educate the patients about their disease and motivate them to comply with therapy. The effectivity of this program yet needs to be evaluated. PATIENTS AND METHODS: 146 patients (mean age 62 years; 57 male, 89 female) with arterial hypertension were trained. They received 8 training units of 90 min each. Before training and 6 months after training data concerning health status and life style risk factors were assessed with questionnaires. RESULTS: There was a marked reduction in blood pressure after 6 months (152/89 mmHg vs 145/85 mmHg, p < 0.001). The mean body weight also declined on the average by 0.9 kg (p < 0.001). Physical exercise spent per week increased from mean 2.0 to 2.8 hours (p < 0.01). Moreover, knowledge about hypertension increased (p < 0.001). The established questionnaire SF-36 revealed a better score for vitality (p < 0.05) six months after therapy than before. CONCLUSION: Our intensive training program of patients with arterial hypertension has profound effects on their systolic and diastolic blood pressure. It also motivates patients to change life style. Our data suggest that intensive training programs should be developed on a widespread basis.

Impact of lower delivered Kt/V on the survival of overweight patients on hemodialysis.

UNLABELLED: Impact of lower delivered Kt/V on the survival of overweight patients on hemodialysis. BACKGROUND: A recent study suggests that overweight (OW) patients on hemodialysis are more likely to receive inadequate doses of dialysis. Because underdialysis is associated with higher mortality, OW patients might be at risk for higher mortality. This is in contrast with our recent observation in which survival was better in OW patients on hemodialysis. The objective of this study was to verify whether being OW was associated with underdialysis and to determine the influence of underdialysis on the survival of OW patients. METHOD: Kt/V measurements were obtained in 1151 patients on hemodialysis for two consecutive months, and their survival was prospectively followed for nine months. Body weights were defined by body mass index (BMI): OW if BMI was> 27.5, underweight (UW) if BMI was <20, and normal weight (NW) if BMI was 20 to 27.5. RESULTS: The Kt/V was inversely related to BMI (r = -0. 30, P < 0.0001). Kt/V in the OW patients was significantly lower than Kt/V in the NW or UW patients. By using a Kt/V threshold of 1.2, more patients were underdialyzed in the OW group (24%) than in the NW (15%) or UW (7%) groups. Underdialysis in the whole study group was associated with a 1.6-fold increase in the relative risk (RR) for mortality. The risk was more pronounced (RR, 2.6) in the underdialyzed OW patients compared with adequately dialyzed OW patients. In multivariate analysis, underdialysis in OW patients (RR, 4.3), but not in UW or NW patients, was a significant and independent risk factor for mortality. CONCLUSION: Our results verify that in the current practice of dialysis prescription, OW patients are less likely to receive adequate dialysis, and, to our knowledge for the first time, suggest that such underdialysis in OW patients might exert a negative influence on their survival. Prospective studies are required to test whether ensuring adequate delivery of dialysis in the OW patients might further improve their survival.