Baroreflex effectiveness index and baroreflex sensitivity predict all-cause mortality and sudden death in hypertensive patients with chronic renal failure.

OBJECTIVES: Impaired arterial baroreflex sensitivity (BRS) has been associated with cardiac mortality and non-fatal cardiac arrests after a myocardial infarction. Patients with chronic renal failure (CRF) have a poor prognosis because of cardiovascular diseases, and sudden death is common. The aim of this study was to assess whether BRS or the baroreflex effectiveness index (BEI), a novel index reflecting the number of times the baroreflex is active in controlling the heart rate in response to blood pressure fluctuations, is associated with prognosis in CRF. METHODS: Hypertensive patients with CRF who were treated conservatively, by haemodialysis or peritoneal dialysis were studied. Electrocardiogram and beat-to-beat blood pressures were recorded continuously and BRS and BEI were calculated. Patients were then followed prospectively for 41 +/- 15 months (range 1-64). RESULTS: During follow-up 69 patients died. Cardiovascular diseases and uraemia accounted for the majority of deaths (60 and 20%, respectively), whereas sudden death occurred in 15 patients. In adjunct with established risk factors such as age, diabetes, congestive heart failure and diastolic blood pressure, reduced BEI was an independent predictor of all-cause mortality among CRF patients [relative risk (RR) 0.50, 95% confidence interval (CI) 0.33-0.71 for an increase of one standard deviation in BEI, P < 0.001]. Diabetes and reduced BRS were independent predictors of sudden death (RR 0.29, 95% CI 0.09-0.86 for an increase of one standard deviation in BRS, P=0.022). CONCLUSIONS: Both BEI and BRS convey prognostic information that may have clinical implications for patients with cardiovascular diseases in general.

Reduced baroreflex effectiveness index in hypertensive patients with chronic renal failure.

BACKGROUND: Impaired arterial baroreflex function has been associated with an increased risk of ventricular arrhythmia and sudden death. This has also been suggested for patients with chronic renal failure (CRF) who are at high risk for cardiovascular morbidity. The aim of this study was to investigate the arterial baroreflex function in CRF patients with emphasis on analyzing the time during which the arterial baroreflex is active, the baroreflex effectiveness index (BEI). METHODS: Beat-to-beat blood pressure (measured with Portapres) and electrocardiography were continuously registered during 30 min rest in 216 hypertensive CRF patients on hemodialysis (n=95), continuous ambulatory peritoneal dialysis (n=59), or conservative treatment (n=59). The spontaneous sequence method was used to calculate BRS and BEI. Age-matched healthy subjects (n=43) were examined for comparison. RESULTS: The BRS was reduced by 51% and the BEI by 49% in CRF patients compared with healthy subjects (P<.001 for both). In addition, CRF patients with diabetes showed further reductions compared with patients without diabetes (15% reduction of BRS and 44% of BEI, P<.01 for both). The treatment modality for renal failure had no effect on BRS or BEI. In a multivariate linear regression analysis, age, body mass index, and systolic blood pressure were independent predictors of BRS, whereas age and diabetes were independent predictors of BEI in patients with CRF. CONCLUSIONS: We conclude that BEI, which is markedly reduced in hypertensive patients with CRF, may convey information on arterial baroreflex function that is complementary to BRS.

Elevated temporal QT variability index in patients with chronic renal failure.

Patients with CRF (chronic renal failure) are at increased risk of cardiovascular diseases, and 60% of cardiovascular mortality in CRF is attributed to sudden death. Various abnormalities in myocardial repolarization are associated with the risk of ventricular arrhythmia. The aim of this study was to evaluate an index of temporal myocardial repolarization lability, the temporal QTVI (QT variability index), in patients with CRF. ECGs were recorded in 153 patients with CRF on haemodialysis (n=67), continuous ambulatory peritoneal dialysis (n=43) or conservative treatment (n=43) during 30 min of rest. QTVI was calculated as the logarithm of the ratio between the variances of the normalized QT and RR intervals. Age-matched healthy subjects (n=39) were examined for comparison. QTVI was increased by 47% in CRF patients compared with healthy subjects (-0.82+/-0.56 compared with -1.54+/-0.27 respectively; P<0.01). QTVI did not differ among patients on dialysis or conservative treatment, whereas QTVI was elevated further in patients with diabetes compared with non-diabetic CRF patients (-0.56+/-0.54 compared with -0.94+/-0.52 respectively; P<0.01). In a multiple linear regression analysis, diabetes and a history of coronary artery disease were the only independent predictors of QTVI in the CRF population. The present study demonstrates that elevated QTVI in patients with CRF is associated with diabetes and coronary disease. The present findings are important given that repolarization instability may predispose to ventricular arrhythmia and sudden death, events that occur frequently in CRF patients.

Impaired kidney graft survival is associated with the TNF-alpha genotype.

BACKGROUND: The TNF2 allele at position -308 of the tumor necrosis factor (TNF)-alpha gene is associated with high TNF production. The purpose was to study the association of this gene polymorphism with rejection episodes and graft survival after kidney transplantation. METHODS: A retrospective analysis of transplant outcomes of patients who only had been treated with one single form of immunosuppression consisting of cyclosporine, azathioprine, and prednisolon was performed. RESULTS: We found that 115 (73%) patients had the TNF1/TNF1 genotype, whereas 42 (27%) were TNF2 positive. There was no difference in the overall acute rejection frequency between these two groups (50% in each), but our data showed a non-significant tendency towards a higher frequency of steroid resistant rejections in the TNF2 positive group (57% vs. 40%). There was no significant difference in graft survival between the two genotype groups, although an early tendency towards worse survival was seen in TNF2 recipients. However, the TNF2 positive recipients with rejection episodes had far worse graft survival compared with the TNF1/TNF1 recipients with rejection episodes (P<0.02). No difference was seen between the two genotype groups in patients without rejection episodes. CONCLUSION: Our data propose that potentially high TNF producers with the TNF2 allele do not have an increased risk for rejection episodes, but if rejection episodes occur, they have a significantly increased risk for early graft loss. TNF production may intensify rejection, but is not a primary factor for the induction of such acute immune activation.

Macrovascular disease after simultaneous pancreas and kidney transplantation.

The objective of this study was to evaluate the outcome of simultaneous pancreas and kidney transplantation (SPK) with focus on cardiovascular mortality and morbidity in relation to graft function. From January 1985 through 1999, 87 SPK were performed in the unit. Sixty recipients were males, median age at diabetes onset 13 yr (1-40) and age at transplantation 39 yr (29-54). No case was lost to follow-up. Morbidity and mortality during median 8 yr of follow-up (range 1-15 yr) were recorded. Major macrovascular disease (MVD) was defined as myocardial infarction or sudden death (AMI), stroke or peripheral gangrene requiring amputation of leg, foot or fingers. At the evaluation, 26 of 87 patients (30%) had died, 19 after loss of the pancreas graft and 20 after loss of the kidney. MVD was the dominant cause of death. Non-lethal MVD had previously been recorded in 62%. Of the 61 patients alive, 22 had lost their pancreas graft and 12 the concomitant kidney. MVD had occurred in 32%. Whereas 89% of the concomitant kidneys functioned when the pancreas graft did so, only 37% of the kidneys functioned if the pancreas had been lost, p < 0.0001. The mortality rate was significantly higher among patients who lost both grafts (16/26) than in those who lost only the pancreas graft (3/15), p = 0.01. Progressive MVD is a major clinical problem for SPK transplant patients, particularly if the kidney fails.