José Jayme Galvão de Lima

Rosuvastatin and Cardiovascular Events in Patients Undergoing Hemodialysis

BACKGROUND Statins reduce the incidence of cardiovascular events in patients at high cardiovascular risk. However, a benefit of statins in such patients who are undergoing hemodialysis has not been proved. METHODS We conducted an international, multicenter, randomized, double-blind, prospective trial involving 2776 patients, 50 to 80 years of age, who were undergoing maintenance hemodialysis. We randomly assigned patients to receive rosuvastatin, 10 mg daily, or placebo. The combined primary end point was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Secondary end points included death from all causes and individual cardiac and vascular events. RESULTS After 3 months, the mean reduction in low-density lipoprotein (LDL) cholesterol levels was 43% in patients receiving rosuvastatin, from a mean baseline level of 100 mg per deciliter (2.6 mmol per liter). During a median follow-up period of 3.8 years, 396 patients in the rosuvastatin group and 408 patients in the placebo group reached the primary end point (9.2 and 9.5 events per 100 patient-years, respectively; hazard ratio for the combined end point in the rosuvastatin group vs. the placebo group, 0.96; 95% confidence interval [CI], 0.84 to 1.11; P=0.59). Rosuvastatin had no effect on individual components of the primary end point. There was also no significant effect on all-cause mortality (13.5 vs. 14.0 events per 100 patient-years; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P=0.51). CONCLUSIONS In patients undergoing hemodialysis, the initiation of treatment with rosuvastatin lowered the LDL cholesterol level but had no significant effect on the composite primary end point of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. (ClinicalTrials.gov number, NCT00240331.)

Coronary Angiography Is the Best Predictor of Events in Renal Transplant Candidates Compared With Noninvasive Testing

Abstract—Guidelines for the detection of coronary artery disease (CAD) and assess of risk in renal transplant candidates are based on the results of noninvasive testing, according to data originated in the nonuremic population. We evaluated prospectively the accuracy of 2 noninvasive tests and risk stratification in detecting CAD (≥70% obstruction) and assessing cardiac risk by using coronary angiography (CA). One hundred twenty-six renal transplant candidates who were classified as at moderate (≥50 years) or high (diabetes, extracardiac atherosclerosis, or clinical coronary artery disease) coronary risk underwent myocardial scintigraphy (SPECT), dobutamine stress echocardiography, and CA and were followed for 6 to 48 months. The prevalence of CAD was 42%. The sensitivities and negative predictive values for the 2 noninvasive tests and risk stratification were <75%. After 6 to 48 months, there were 18 cardiac events, 9 fatal. Risk stratification (P =0.007) and CA (P =0.0002) predicted the crude probability of surviving free of cardiac events. The probability of event-free survival at 6, 12, 24, 36, and 48 months were 98%, 98%, 94%, 94%, and 94% in patients with <70% stenosis on CA and 97%, 87%, 61%, 56%, and 54% in patients with ≥70% stenosis. Multivariate analysis showed that the sole predictor of cardiac events was critical coronary lesions (P =0.003). Coronary angiography may still be necessary for detecting CAD and determining cardiac risk in renal transplant candidates. The data suggest that current algorithms based on noninvasive testing in this population should be revised.

Screening for significant coronary artery disease in high-risk renal transplant candidates.

BackgroundRenal transplant candidates are at an increased risk for coronary artery disease (CAD), a strong predictor of cardiovascular events [major adverse coronary events (MACE)]. Coronary angiography is a costly, risky, invasive procedure. We sought to determine clinical predictors of significant CAD (stenosis ≥70%) in high-risk renal transplant candidates. MethodsClinical evaluation and coronary angiography were performed in 301 patients (57±8 years, 73% men) on hemodialysis for 32 months (median). Patients were followed-up for 22 months (median). Inclusion criteria were diabetes (type 1 or 2), evidence of cardiovascular disease, or age ≥50 years. Risk factors included hypertension (93.7%), overweight/obesity (54.3%), dyslipidemia (44.9%), diabetes (42.1%), and smoking (24.3%). Cardiovascular disease was found as follows: peripheral arterial disease (PAD) (31.2%), angina (28.1%), stroke (12.9%), myocardial infarction (MI) (10.3%), and heart failure (9.3%). ResultsSignificant CAD was found in 136 individuals (45.2%). Diabetes [odds ratio (OR)=1.82; 95% confidence interval (CI)=1.08–3.07], PAD (OR=2.50; 95% CI=1.44–4.37), and previous MI (OR=7.75; 95% CI=3.03–23.98) were associated with significant CAD. The prevalence of significant CAD increased with the number of clinical predictors from 26% (none) to 100% (all present) (P<0.0001). The incidence of fatal/nonfatal MACE increased two, four, and sixfold in those with diabetes, PAD, or previous MI, respectively (P<0.0001). ConclusionsIn high-risk patients with end-stage renal disease, the prevalence of CAD and the incidence of MACE were high. Significant CAD or cardiovascular complications were not related to the majority of classic risk factors. Patients with diabetes, PAD, or previous MI are at higher risk of CAD, MACE, or both and, thus, must be referred for invasive diagnostic procedures.

Blood pressure and the risk of complex arrhythmia in renal insufficiency, hemodialysis, and renal transplant patients☆

Complex arrhythmia is frequent in hemodialysis patients but it is not clear if this is a consequence of dialysis or uremia or is secondary to the hemodynamic and cardiovascular alterations often associated with chronic renal failure. The incidence of complex ventricular arrhythmia (frequent multiform premature beats, couplets, and runs) in 31 subjects who had their uremic status recently corrected by renal transplant (Group 1) and in 23 predialysis (Group 2) and 73 hemodialysis (Group 3) chronic renal failure patients were studied with 24-h Holter monitoring. Patients were not receiving antiarrhythmic drugs or digitalis and significant coronary artery disease was excluded by clinical and noninvasive methods. Complex arrhythmia was two times more frequent in dialysis patients but the difference did not reach statistical significance (Group 1: 16%; Group 2: 17%; Group 3: 34%; chi2 4.9, P = .086). The stepwise model of logistic regression analysis identified systolic blood pressure (odds ratio 1.015, 95% confidence interval [CI] 1.001-1.027, P = .03) and left ventricular systolic dysfunction (odds ratio 7.04, 95% CI 1.3-36.7, P = .02) as the only factors that independently influenced the probability of complex arrhythmia. Age, gender, race, diabetes, smoking status, body mass index, diastolic blood pressure, serum creatinine, hematocrit, left ventricular mass index, and use of diuretics, beta-blockers, angiotensin converting enzyme (ACE) inhibitors, sympatolytics, and calcium channel blockers did not influence the occurrence of complex arrhythmia. The data indicate that blood pressure and myocardial dysfunction are more important determinants of complex arrhythmia than dialysis or uremia in chronic renal disease patients.

Blood Pressure Influences the Occurrence of Complex Ventricular Arrhythmia in Hemodialysis Patients

We investigated the relationship between blood pressure and the occurrence of complex ventricular arrhythmias (multiform, couplets, or runs) as assessed by 48-hour Holter monitoring in 74 stable long-term hemodialysis patients (44.5 +/- 12 years old; 54% men; 74% whites; dialysis duration, 51.3 +/- 36.1 months; systolic pressure, 146.6 +/- 19.3 mm Hg; diastolic pressure, 89.2 +/- 12.1 mm Hg; prevalence of arterial hypertension, 33.8%). Systolic and diastolic pressures represented the average of all predialysis determinations during the 3 months preceding the tests. Hemodialysis was performed midway through the Holter monitoring period. M-mode and bidimensional echocardiograms and myocardial perfusion tests were also obtained from all patients. Complex arrhythmias were observed in 37 individuals (50%). Univariate analysis showed that systolic pressure (P < .001), diastolic pressure (P < .05), age (P < .001), left ventricular posterior wall thickness (P < .01), left ventricular mass index (P < .05), and ischemic alterations on myocardial perfusion tests (P < .005) were significantly associated with complex arrhythmias. With the use of a multivariate model (stepwise logistic regression analysis) only systolic pressure (P < .01) and age (P < .05) were independently associated with complex arrhythmias. Sex; angina; dialysis duration; New York Heart Association functional class; use of digitalis; plasma levels of creatinine, sodium, potassium, calcium, and phosphate; hematocrit; left ventricular fractional shortening; left ventricular diastolic diameter; and ST segment deviation were not correlated with complex arrhythmias. The severity and frequency of complex arrhythmias were not influenced by hemodialysis. At follow-up (5 to 80 months) 5 patients had died of sudden death, 4 of whom were hypertensive and older than 45 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Oxidative stress and endothelial dysfunction in chronic kidney disease

FUNDAMENTO: La enfermedad renal cronica (ERC) se caracteriza por la alta prevalencia de aterosclerosis Siendo el estres oxidativo y la disfuncion endotelial promotores de la aterosclerosis, es interesante verificar si las dos condiciones estan asociadas en pacientes con ERC, aun sin enfermedad cardiovascular (ECV) clinica. OBJETIVO: Evaluar las relaciones entre el estres oxidativo y la funcion endotelial en pacientes con ERC estado 5, sin ECV. METODOS: Se estudiaron 22 pacientes con ERC, no diabeticos, no fumadores, sin ECV y tratados por hemodialisis; ademas de 22 individuos normales. En todos los individuos se evaluaron la reactividad vascular, dependiente e independiente de endotelio (ecografia de alta resolucion de la arteria braquial), y el estres oxidativo (niveles plasmaticos de sustancias reactivas al acido tiobarbiturico - TBARS). RESULTADOS: La reactividad vascular dependiente de endotelio (6,0 ± 4,25% vs. 11,3 ± 4,46%, p <0,001) y la reactividad independiente de endotelio (11,9 ± 7,68% vs. 19,1 ± 6,43%, p <0,001) se redujeron en la ERC, mientras el estres oxidativo (2,63 ± 0,51 vs. 1,49 ± 0,43, p <0,001) se vio aumentado. Los niveles de TBARS, cuando se utiliza en la totalidad de individuos del estudio (pacientes y controles), se correlacionaron con la reactividad vascular dependiente de endotelio (r = -0,56, p<0,001) y con la presion arterial sistolica (r = 0,48, p = 0,002). CONCLUSION: El estres oxidativo esta asociado a la disfuncion endotelial. Pacientes con ERC presentan aumento del estres oxidativo y compromiso de la reactividad vascular. Los resultados sugieren ademas que el estres oxidativo y la disfuncion endotelial pueden estar involucrados en la susceptibilidad exagerada de la ERC a las complicaciones cardiovasculares.BACKGROUND Chronic kidney disease (CKD) is characterized by the high prevalence of atherosclerosis. Considering that endothelial dysfunction and oxidative stress are promoters of atherosclerosis, it is of interest to verify whether the two conditions are associated in CKD patients still free of clinical cardiovascular disease (CVD). OBJECTIVE To evaluate the association between oxidative stress and endothelial function in end-stage CKD patients without clinically evident CVD. METHODS We studied 22 nondiabetic, nonsmoker CKD patients without clinical CVD treated by maintenance hemodialysis and 22 healthy controls. Endothelium- dependent and independent vascular reactivity and oxidative stress, as determined by the plasma levels of thiobarbituric acid-reactive substances--TBARS, were evaluated in all subjects. RESULTS Endothelium-dependent (6.0 +/- 4.25 vs. 11.3 +/- 4.46%, p<0.001) and endothelium-independent (11.9 +/- 7.68 vs. 19.1% +/- 6.43%, p<0.001) vascular reactivity were reduced, while TBARS (2.63 +/- 0.51 vs. 1.49 +/- 0.42 nmols/mL) was increased in CKD patients when compared to controls. TBARS levels were significantly related to endothelium-dependent vascular reactivity (r=-0.56, p<0.001) and to systolic blood pressure (r=-0.48, p=0.002). CONCLUSION Oxidative stress is increased in CKD patients free of CVD and is associated with endothelial dysfunction in patients and controls. The results suggest that oxidative stress and endothelial dysfunction may be involved in the increased susceptibility of CKD patients to CVD and cardiovascular complications.

Treatment of coronary artery disease in hemodialysis patients evaluated for transplant-a registry study.

Background. We assessed the results of a noninvasive therapeutic strategy on the long-term occurrence of cardiac events and death in a registry of patients with chronic kidney disease (CKD) and coronary artery disease (CAD). Methods. We analyzed 519 patients with CKD (56±9 years, 67% men, 67% whites) on maintenance hemodialysis with clinical or scintigraphic evidence of CAD by using coronary angiography. Results. In 230 (44%) patients, coronary angiography revealed significant CAD (lumen reduction≥70%). Subjects with significant CAD were kept on medical treatment (MT; n=184) or referred for myocardial revascularization (percutaneous transluminal coronary angioplasty/coronary artery bypass graft—intervention; n=30) according to American College of Cardiology/American Heart Association guidelines. In addition, 16 subjects refused intervention and were also followed-up. Event-free survival for patients on MT at 12, 36, and 60 months was 86%, 71%, and 57%, whereas overall survival was 89%, 71%, and 50% in the same period, respectively. Patients who refused intervention had a significantly worse prognosis compared with those who actually underwent intervention (events: hazard ratio=4.50; % confidence interval=1.48–15.10; death: hazard ratio=3.39; % confidence interval 1.41–8.45). Conclusions. In patients with CKD and significant CAD, MT promotes adequate long-term event-free survival. However, failure to perform a coronary intervention when necessary results in an accentuated increased risk of events and death.

Baseline variables associated with early death and extended survival on dialysis

Patients who die during the first three months on dialysis are not systematically included in the American and European statistics. In contrast, only a few patients survive more than 10 years on this modality of renal replacement therapy. The factors determining these two extreme forms of outcome are poorly understood. We tested the hypothesis that a few variables, easily obtainable at the initiation of dialysis, would identify those individuals at high and low risk of early death. We retrospectively studied 23 patients who died within 90 days of initiating dialysis and 20 patients who survived more than 10 years. These patients were admitted for dialysis to a Brazilian center between July 1, 1976 and February 28, 1997. The baseline variables assessed which were thought to influence survival, were: age, sex, race, body weight, etiology of renal disease, blood pressure, comorbid conditions, hematocrit and serum electrolytes, albumin, creatinine, urea, and urea/creatinine ratio. Univariate analysis showed that patients who died early were older (56.2 +/- 15.6 vs. 42.1 +/- 10.4 years, p < 0.01), had lower serum creatinine (10.6 +/- 2.9 vs. 13.7 +/- 3.7 mg/dL, p < 0.01) and albumin (3.3 +/- 0.9 vs. 4.0 +/- 0.5 g/dL) and a higher urea/creatinine ratio (18.4 +/- 5.8 vs. 13.5 +/- 4.8, p < 0.01) compared with subjects surviving more than 10 years. Early death patients also had more cases of diabetes (35% vs. 0%, p < 0.01) and less chronic glomerulonephritis (9% vs. 35%, p < 0.05). Multivariate analysis showed that age (p < 0.01, CI 1.02 to 1.15, odds ratio 1.1) and urea/creatinine ratio (p < 0.01, CI 1.03 to 1.38, odds ratio 1.2) were positively and independently related to outcome. In the early death group, malnutrition was an important cause of death (17% of all deaths). Compared to baseline data, long-term survivors, at the last follow up, presented reduced systolic blood pressure and increased hematocrit and unchanged body weight, serum albumin and urea/creatinine ratio. These results, based on easily accessible initial variables, suggest that early death on dialysis is influenced by age and by indices related to the nutritional condition of the patients. They also highlight the importance of a potentially correctable risk factor in a population with an elevated prevalence of premature death.

High dose of N-acetylcystein prevents acute kidney injury in chronic kidney disease patients undergoing myocardial revascularization.

BACKGROUND The renoprotective effect of N-acetylcystein in patients undergoing coronary artery bypass graft surgery is controversial. METHODS We assessed the renoprotective effect of the highest dose of N-acetylcystein sanctioned for clinical use in a prospective, double-blind, placebo-controlled study including 70 chronic kidney disease patients, stage 3 or 4, who underwent coronary artery bypass graft surgery, on cardiopulmonary bypass (CPB) and off CPB, and were randomly allocated to receive either N-acetylcystein 150 mg/kg followed by 50 mg/kg for 6 hours in 0.9% saline or only 0.9% saline. Acute kidney injury was defined by the Acute Kidney Injury Network classification. RESULTS The incidence of kidney injury was reduced in the N-acetylcystein group (57.1% versus 28.6%, p=0.016). Nonuse of N-acetylcystein (relative risk 3.58, 95% confidence interval: 1.04 to 12.33, p=0.04) and cardiopulmonary bypass (relative risk 4.55, 95% confidence interval: 1.28 to 16.15, p=0.02) were independent predictors of kidney injury. In patients treated with CPB, N-acetylcystein reduced the incidence of kidney injury from 63% to 46%. Oxidative stress was increased in control subjects (p=0.01) and abolished in patients receiving N-acetylcystein. CONCLUSIONS Maximum intravenous doses of N-acetylcystein reduce the incidence of acute kidney injury in patients with kidney disease undergoing coronary artery bypass graft surgery, abolish oxidative stress, and mitigate the negative effect of CPB on renal function.

Cardiac MRI for Detection of Unrecognized Myocardial Infarction in Patients With End-Stage Renal Disease: Comparison With ECG and Scintigraphy

OBJECTIVE The purposes of this study were to use the myocardial delayed enhancement technique of cardiac MRI to investigate the frequency of unrecognized myocardial infarction (MI) in patients with end-stage renal disease, to compare the findings with those of ECG and SPECT, and to examine factors that may influence the utility of these methods in the detection of MI. SUBJECTS AND METHODS We prospectively performed cardiac MRI, ECG, and SPECT to detect unrecognized MI in 72 patients with end-stage renal disease at high risk of coronary artery disease but without a clinical history of MI. RESULTS Fifty-six patients (78%) were men (mean age, 56.2 +/- 9.4 years) and 16 (22%) were women (mean age, 55.8 +/- 11.4). The mean left ventricular mass index was 103.4 +/- 27.3 g/m(2), and the mean ejection fraction was 60.6% +/- 15.5%. Myocardial delayed enhancement imaging depicted unrecognized MI in 18 patients (25%). ECG findings were abnormal in five patients (7%), and SPECT findings were abnormal in 19 patients (26%). ECG findings were false-negative in 14 cases and false-positive in one case. The accuracy, sensitivity, and specificity of ECG were 79.2%, 22.2%, and 98.1% (p = 0.002). SPECT findings were false-negative in six cases and false-positive in seven cases. The accuracy, sensitivity, and specificity of SPECT were 81.9%, 66.7%, and 87.0% (not significant). During a period of 4.9-77.9 months, 19 cardiac deaths were documented, but no statistical significance was found in survival analysis. CONCLUSION Cardiac MRI with myocardial delayed enhancement can depict unrecognized MI in patients with end-stage renal disease. ECG and SPECT had low sensitivity in detection of MI. Infarct size and left ventricular mass can influence the utility of these methods in the detection of MI.