Relations of inflammatory markers to lipid levels and autonomic tone in patients with moderate and severe chronic kidney disease and in patients under maintenance hemodialysis.

BACKGROUND AND AIMS: Chronic kidney disease is associated with enhanced inflammatory response and autonomic dysfunction. Evidence exists of a potential interaction of inflammation and nervous system. We sought to investigate determinants of heart rate variability (HRV) and relations between the inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6) and autonomic tone in patients with moderate and severe chronic kidney disease and in maintenance hemodialysis patients, and relations of CRP and IL-6 with clinical characteristics and lipid levels. METHODS: This was a cross-sectional study of 51 hemodialysis and 53 moderate and severe chronic kidney disease patients. Autonomic tone was assessed using 24-hour HRV analysis in time and frequency domain. All patients underwent measurements of high sensitivity CRP, IL-6 and lipid levels. RESULTS: CRP and IL-6 were elevated in the non-dialysis group at levels similar to hemodialysis patients. Hemodialysis patients had lower total cholesterol, LDL cholesterol and apolipoprotein B levels (p < 0.05), and in this group of patients lipids were related to CRP and IL-6 (p < 0.05). The inflammatory marker IL-6 was associated to HRV in the moderate and severe chronic kidney disease group (R = -0.4, p < 0.01 for standard deviation of RR intervals and very low frequency power, R = -0.5, p < 0.01 for standard deviation of all five-minute RR intervals, R = 0.35, p < 0.05, for total power and low frequency power). Adequacy of dialysis, but not the inflammatory markers, was associated to HRV in the hemodialysis group (R = 0.6, p < 0.01 for high frequency power). CONCLUSION: Enhanced inflammatory response occurs already in stages 3 and 4 chronic kidney disease. IL-6 is related to HRV in these patients, but not in the hemodialysis group, suggesting that IL-6 may interact with autonomic tone in that stage of disease.

Raised concentrations of macrophage colony stimulating factor in severe unstable angina beyond the acute phase are strongly predictive of long term outcome.

OBJECTIVE: To evaluate the long term prognostic value of macrophage colony stimulating factor (MCSF), interleukin-6 (IL-6), and tumour necrosis factor alpha (TNFalpha) measured in serum six weeks after the occurrence of unstable angina. SUBJECTS: 119 consecutive patients, mean (SD) age 58 (10) years, with severe unstable angina (Braunwald class IIIb); controls were 96 subjects of similar age and sex distribution. DESIGN: MCSF, IL-6, and TNFalpha were measured on admission, at discharge, and six weeks later, and the patients were followed for two years. Clinical end points were: cardiac death, readmission for acute coronary syndromes, and revascularisation. SETTING: District general hospital. RESULTS: 113 patients completed follow up, during which two died of non-cardiac causes. Of the remaining 111 patients, 39 (35.1%) had a cardiac event (two deaths, 15 revascularisations, and 22 readmissions for acute coronary syndromes). MCSF and IL-6 concentrations at six weeks were higher in patients with cardiac events than in those without (424 v 306 pg/ml, p = 0.0008, and 6.6 v 4.5 pg/ml, p = 0.01, respectively). Cytokine concentrations at six weeks were also significantly higher than in the control group. Logistic regression analysis showed that MCSF concentrations were the only independent predictors of future events, with an adjusted odds ratio for events of 4.1 (95% confidence interval 1.1 to 14.8; p = 0.03). The two year survival free of cardiac events was significantly lower in patients with MCSF concentrations in the highest tertile (values > or = 468 pg/ml) than in those with values < 468 pg/ml. CONCLUSIONS: Increased MCSF concentrations beyond the acute phase are strongly predictive of long term outcome in patients with severe unstable angina.

Prospective randomized trial of external versus internal transcatheter cardioversion in patients with chronic atrial fibrillation.

To evaluate the safety and long-term efficacy of internal transcatheter cardioversion, forty patients with chronic, lone atrial fibrillation were studied. The patients were randomised to internal transcatheter cardioversion or to conventional external cardioversion. In cases where the procedure was unsuccessful, cross-over to the alternate method was performed. Oral anticoagulation therapy was started three weeks prior to the procedure and was maintained for another three weeks following successful cardioversion. Sinus rhythm was restored in 16/18 patients (88%) in the internal cardioversion group, versus 9/22 patients (40%) in the external cardioversion group (p < 0.01). In addition, 8/13 (61%) patients who were crossed-over to internal cardioversion were successfully cardioverted to sinus rhythm. In contrast, both patients who were crossed-over to external cardioversion remained in atrial fibrillation. During a mean follow-up period of 23 months, 13 (39.3%) patients maintained sinus rhythm. Using the intention to treat principle, the recurrence rate was not statistically different between the two methods. It is concluded that internal cardioversion is more effective in acutely restoring sinus rhythm compared to external cardioversion. However, both methods have similar long-term recurrence rates.

Comparison of endothelin-1 levels at rest and during exercise between patients with cardiac syndrome-X and healthy people.

Several previous studies have shown that endothelin-1 (ET 1) plasma levels are raised in cases of endothelial abnormality and microvascular dysfunction. Syndrome-X constitutes an important clinical entity characterized by angina-like pain and normal coronary arteries which is believed to reflect microvascular dysfunction. The aim of the present study was to investigate the role of ET 1 in the pathophysiology of the above syndrome. For that purpose the plasma ET 1 concentrations, measured by radioimmunoassay, between 28 X-syndrome patients (group A) and 10 age-matched normal control subjects (group B) at rest and at the peak of the exercise testing were compared. We specify that all individuals of group A were referred to our Department for effort angina and were found to have normal coronary arteriograms, negative ergonovine and hyperventilation test and positive exercise test. Our results showed that while at rest ET 1 plasma concentrations did not differ significantly between the two groups, at the peak of the exercise test its levels were found to be significantly higher in syndrome-X patients as compared with those of normal subjects (p< 0.001). In addition, in healthy control subjects ET 1 levels decreased during exercise as compared with the baseline values and that difference was found to be statistically significant (p approximately 0.01). The above finding suggests opposite kinetics during exercise of ET 1 between the two groups studied, which could explain effort angina onset in patients with syndrome-X.

Intracoronary cyclic-GMP and cyclic-AMP during percutaneous transluminal coronary angioplasty.

We investigated intracoronary cyclic-guanosine monophosphate (c-GMP) levels during percutaneous transluminal coronary angioplasty (PTCA) since experimental studies have shown the endothelial origin of c-GMP production. Intracoronary c-GMP and cyclic adenosine monophosphate (c-AMP) were measured during coronary angioplasty in 24 patients with chronic coronary artery disease. Four coronary blood samples were taken through a catheter from the coronary artery the first sample before coronary angiography and the other three from distal to coronary obstruction, as follows: before the balloon inflation, at the maximum inflation and 5 min after restoration of coronary flow. c-GMP increased from 7.9 +/- 1.0 pmol/ml and 7.5 +/- 0.9 pmol/ml before angiography and balloon inflation to 11.1 +/- 1.3 pmol/ml at the maximum inflation (P < 0.01), with a trend to decrease 5 min after the end of the intervention (9.5 +/- 1.0 pmol/ml, P: NS). Intracoronary c-AMP levels remained almost unchanged. Five venous samples were taken to measure c-AMP before coronary angiography, before PTCA, and 5 min, 2 h and 24 h after PTCA. c-AMP values 2 and 24 h after PTCA (17.8 +/- 1.7 pmol/ml and 17.5 +/- 1.7 pmol/ml, respectively) were lower than the highest value (22.1 +/- 2.1 pmol/ml) found 5 min after PTCA, (P < 0.001). c-GMP increases distal to coronary obstructive lesion during PTCA at the time of balloon inflation, while c-AMP remains unchanged. c-AMP rises in venous circulation only. PTCA stimulates the mechanism of c-GMP release, while systemic c-AMP increase seems to be related to the stress occurring during catheterisation and PTCA.