Predictors of cardiovascular events in patients with end-stage renal disease: an analysis from the Fosinopril in dialysis study.

BACKGROUND: Cardiovascular events (CVE) are a major cause of morbidity and mortality in end-stage renal disease (ESRD) patients. These patients are often excluded from CV clinical trials, and the prognostic factors associated with CVE in patients with ESRD have not been fully explored. A risk prediction model was created from the FOSIDIAL trial to identify factors predictive of CVE and to evaluate the relative strength of known predictors when considered together in a multivariate model. METHODS: FOSIDIAL was a prospective, randomized, double-blind study with 2-year follow-up and CVE adjudication. The study enrolled 397 patients with ESRD and left ventricular hypertrophy (LVH). CVE included cardiovascular death, non-fatal myocardial infarction, unstable angina, stroke, revascularization, heart failure hospitalization, resuscitated cardiac arrest and confirmed stroke. The model was built using a forward selection of all baseline variables. A structural equation model (SEM) was used to identify factors with an indirect association with CVE. RESULTS: CV history was the most important prognostic factor, followed by C-reactive protein (CRP), left ventricular mass index, diabetes and age. Smoking, low HDL, female gender and Kt/V were indirectly associated with CVE. CONCLUSION: Prior CV disease, elevated CRP, LVH, diabetes or advanced age identifies patients at the highest risk for CVE. These data may be useful to detect high risk patients, to define potential targets for pharmacologic intervention, and to plan future studies in ESRD. Further research is needed to identify effective approaches that reduce the rate of CVE in these patients.

D-lactate is not a reliable marker of gut ischemia-reperfusion in a rat model of supraceliac aortic clamping.

OBJECTIVE: D-lactate is the dextrorotatory form of L-lactate. L-lactate is the isomer routinely tested in clinical practice to assess cell hypoxemia. D-lactate has been recently proposed as a specific marker of gut ischemia-reperfusion (IR), particularly after surgery for ruptured aortic aneurysms. We sought to assess D-lactate as a reliable marker of gut IR in a rat model of supraceliac aortic clamping. DESIGN: Prospective, randomized trial. SETTING: Animal research center. SUBJECTS: Male Wistar rats. INTERVENTIONS: After general anesthesia, rats were randomized into two groups (n = 8 in each). The IR group underwent a laparotomy, aortic clamping for 40 mins, and 1 hr of reperfusion. The control group underwent the same procedure, except for aortic clamping. MEASUREMENTS AND MAIN RESULTS: The following variables were tested after 1 hr of reperfusion (IR group) or after the equivalent time (control group): 1) tissue and cell insult via ileum morphometry and electron microscopy, serum glutamic transaminases (serum glutamic-oxaloacetic transaminase and serum glutamic-pyruvic transaminase), pH, and L-lactate; 2) systemic inflammatory response via tumor necrosis factor-alpha; and 3) D-lactate levels. After IR, mucous membrane thickness and villi height decreased significantly, respectively by 30% and 45%, and electron-microscopic examination showed typical IR mucous membrane cell insult. IR also caused lactic acidosis (pH = 7.16 +/- 0.05 vs. 7.31 +/- 0.02, p < .01; L-lactate = 7.1 +/- 1.6 vs. 1.6 +/- 0.4 mmol/L, p = .001) and increased blood levels of transaminases. Concurrently, the inflammatory response was characterized by an increase in tumor necrosis factor-alpha (213 +/- 129 vs. 47 +/- 32 pg/mL, p < .05). However, blood levels of D-lactate never increased after IR. CONCLUSIONS: D-lactate is not a reliable marker of gut IR in our model of supraceliac aortic clamping in rats.

FOSIDIAL: a randomised placebo controlled trial of the effects of fosinopril on cardiovascular morbidity and mortality in haemodialysis patients. Study design and patients' baseline characteristics.

The prevalence of end stage renal disease (ESRD) is growing in western countries. Patients with ESRD are more frequently elderly and diabetic and are exposed to very high cardiovascular morbidity and mortality. The main aim of the FOSIDIAL study is to assess the efficacy and safety of fosinopril, an angiotensin converting enzyme (ACE) inhibitor, in reducing the mortality and cardiovascular events in haemodialysis patients presenting with left ventricular hypertrophy. A total number of 397 patients are included in the study. They are aged 50-80 years (average 66.7 years) and have been undergoing haemodialysis for 4.8 years. All have left ventricular hypertrophy with cardiac mass index > 100 g/m2 in women and > 130 g/m2 in men, measured within 3 months prior to inclusion. Baseline cardiac mass index is 174 g/m2. After a 2 week placebo period, the patients are randomised into two groups receiving either fosinopril 5-20 mg/day, or a placebo for a duration of 24 months. The target dose is reached at the sixth, seventh or eighth week of treatment. Depending on tolerance, 300 patients reached the maximum recommended dose. Patients are subsequently assessed clinically every 3 months until the end of the study. The primary outcome is a composite endpoint of fatal and nonfatal major cardiovascular events. Secondary endpoints are individual cardiovascular events, event-free survival, overall mortality and all-cause hospitalisations. The trial began in October 1998. All patients were included by December 2000 and follow-up is ongoing. The last visit for the last patient is scheduled for 30 December 2002. We report here on the study design and the baseline characteristics of the study population.