Hyperhomocyst(e)inemia in chronic stable renal transplant patients

PURPOSE: Hyperhomocyst(e)inaemia is an important risk factor for atherosclerosis, which is currently a major cause of death in renal transplant patients. The aim of this study was to assess the influence of immunosuppressive therapy on homocyst(e)inemia in renal transplant recipients. METHODS: Total serum homocysteine (by high performance liquid chromatography), creatinine, lipid profile, folic acid (by radioimmunoassay-RIA) and vitamin B12 (by RIA) concentrations were measured in 3 groups. Group I patients (n=20) were under treatment with cyclosporine, azathioprine, and prednisone; group II (n=9) were under treatment with azathioprine and prednisone; and group III (n=7) were composed of renal graft donors for groups I and II. Creatinine, estimated creatinine clearance, cyclosporine trough level, lipid profile, folic acid, and vitamin B12 concentrations and clinical characteristics of patients were assessed with the aim of ascertaining determinants of hyperhomocyst(e)inemia. RESULTS: Patient ages were 48.8 ± 15.1 yr (group I), 43.3 ± 11.3 yr (group II); and 46.5 ± 14.8 yr (group III). Mean serum homocyst(e)ine (tHcy) concentrations were 18.07 ± 8.29 mmol/l in renal transplant recipients; 16.55 ± 5.6 mmol/l and 21.44 ± 12.1 mmol/l respectively for group I (with cyclosporine) and group II (without cyclosporine) (NS). In renal donors, tHcy was significantly lower (9.07 ± 3.06 mmol/l; group I + group II vs. group III, p<0.008). There was an unadjusted correlation (p<0.10) between age (r=0.427; p<0.005) body weight (r=0.412; p<0.05), serum creatinine (r=0.427; p<0.05), estimated creatinine clearance (r=0.316; p<0.10), and tHcy in renal recipients (group I +II). Independent regressors (r²=0.46) identified in the multiple regression model were age (coefficient= 0.253; p=0.009) and serum creatinine (coefficient=8.07; p=0.045). We found no cases of hyperhomocyst(e)inemia in the control group. In contrast, 38% of renal recipients had hyperhomocyst(e)inemia: 7 cases (35%) on cyclosporine and 4 (45%) without cyclosporine, based on serum normal levels. CONCLUSIONS: Renal transplant recipients frequently have hyperhomocyst(e)inemia. Hyperhomocyst(e)inemia in renal transplant patients is independent of the scheme of immunosuppression they are taking. The older the patients are and the higher are their serum creatinine levels, the more susceptible they are to hyperhomocyst(e)inemia following renal transplantation.

Aortofemoral thromboendarterectomy

PURPOSE: To study whether endarterectomy is feasible in all patients with aortofemoral atherosclerotic obstruction, considering early and late results. METHODS: A clinical, prospective, and descriptive study carried out in a university hospital. Inclusion criteria were atherosclerotic aortofemoral obstructive disease, clinical status compatible with major surgery, and absence of prior restorative procedure. Exclusion criteria were aneurysm, inflammatory arterial disease, and prior restorative procedure found during surgery. Eighty patients entered the protocol, but 9 were excluded (11.2%). Seventy-one patients, mean age of 57.3 years, underwent endarterectomy. Operative indications were intermittent claudication and critical ischemia. A ring-stripper endarterectomy technique was employed in all patients. Results were related to age, gender, symptoms, presence of diabetes mellitus, extension of endarterectomy, and extent of obstructive disease. Chi square or Fisher exact tests were used when appropriate, and the Wilkoxon (Gehan) test was used to compare survival curves. RESULTS: Sixty-eight (100%) endarterectomies were patent at discharge. The mortality rate was 4.2%. The amputation rate (4.3%) was higher in diabetic patients and when there was associated femoropopliteal obstruction. The 5-year survival rate was 83.3%, and late deaths were mostly cardiovascular. Diabetes mellitus, age above 65 years, and associated femoropopliteal obstruction lowered the survival rate. The 5-year patency rate was 87.0%. Critical ischemia and less extensive endarterectomies were associated with a lower patency rate. There were no anastomotic aneurysms or deep infections. CONCLUSIONS: Aortofemoral thromboendarterectomy is feasible in 90% of patients, early mortality rate is low, diabetic patients and those with associated femoropopliteal obstructive disease have a higher mortality rate, amputation rate is low, late deaths are mostly cardiovascular, and late patency rate is high, and even higher in the intermittent claudication group.

Natural history of stenosis in the iliac arteries in patients with intermittent claudication undergoing clinical treatment

PURPOSE: Inspite of the long experience with the treatment of intermittent claudication, little is known about the natural history of stenotic lesions in the iliac segment. With the advent of endovascular treatment, this knowledge has become important. METHODS: Fifty-two stenosis, diagnosed using arteriography, in 38 claudicant patients were analyzed. After a minimum time interval of 6 months, a magnetic resonance angiography was performed to determine whether there was arterial occlusion. The primary factors that could influence the progression of a stenosis were analyzed, such as risk factors (smoking, hypertension, diabetes, sex, and age), compliance with clinical treatment, initial degree of stenosis, site of the stenosis, and length of follow-up. RESULTS: The average length of follow-up was 39 months. From the 52 lesions analyzed, 13 (25%) evolved to occlusion. When occlusion occurred, there was clinical deterioration in 63.2% of cases. This association was statistically significant (P = .002). There was no statistically significant association of the progression of the lesion with the degree or site of stenosis, compliance with treatment, or length of follow-up. Patients who evolved to occlusion were younger (P = .02). The logistic regression model showed that the determinant factors for clinical deterioration were arterial occlusion and noncompliance with clinical treatment. CONCLUSIONS: The progression of a stenosis to occlusion, which occurred in 25% of the cases, caused clinical deterioration. Clinical treatment was important, but it did not forestall the arterial occlusion. Prevention of occlusion could be achieved by early endovascular intervention or with the development of drugs that might stabilize the atherosclerotic plaque.

Criação de um sistema de apoio para o suporte avançado de vida

Dissertação de mestrado integrado em Engenharia Biomédica (área de especialização em Eletrónica Médica)

Great amount of C.pneumoniae in ruptured plaque vessel segments at autopsy. A comparative study with stable plaques

A possible relationship between C.pneumoniae (CP) infection, atherosclerosis and acute myocardial infarction is a debated matter. Now we performed the search of CP in histological segments of fatal ruptured plaques and of stable plaques by histochemistry (Macchiavello stain), immunohistochemistry and in situ hybridization techniques. Electron microscopy and confocal laser microscopy techniques were used in two additional cases. The semi-quantitification of CP + cells (0-4+) and quantification of lymphocytes demonstrated greater amount of CP + cells and more inflammation in the adventitia of vulnerable plaque vessel segments than of stable ones, larger amount of CP + cells in adventitia than in the plaque and high frequency of CP + cells in all groups studied. This preliminary study strongly suggests a direct pathogenetic involvement of adventitial CP in the rupture of the atheromatous plaque, development of acute myocardial infarction and also in the development of atherosclerosis.

Myocardial revascularization with coronary endarterectomy. Stratification of risk factors for early mortality

OBJECTIVE: To determine the risk factors for mortality related to myocardial revascularization when performed in association with coronary endarterectomy. METHODS: We assessed retrospectively 353 patients who underwent 373 coronary endarterectomies between January '89 and November '98, representing 3.73% of the myocardial revascularizations in this period of time. The arteries involved were as follows: right coronary artery in 218 patients (58.45%); left anterior descending in 102 patients (27.35%); circumflex artery in 39 patients (10.46%); and diagonal artery in 14 patients (3.74%). We used 320 (85.79%) venous grafts and 53 (14.21%) arterial grafts. RESULTS: In-hospital mortality among our patients was 9.3% as compared with 5.7% in patients with myocardial revascularizations without endarterectomy (p=0.003). Cause of death was related to acute myocardial infarction in 18 (54.55%) patients. The most significant risk factors for mortality identified were as follows: diabetes mellitus (p=0.001; odds ratio =7.168), left main disease (<0.001; 9.283), female sex (0.01; 3.111), acute myocardial infarction (0.02; 3.546), ejection fraction <35% (<0.001; 5.89), and previous myocardial revascularization (<0.001; 4.295). CONCLUSION: Coronary endarterectomy is related to higher mortality, and the risk factors involved are important elements of a poor outcome.

PANDORA - Survey of Brazilian cardiologists about cholesterol reduction

OBJECTIVE: To report about a group of physicians' understanding of the recommendations of the II Brazilian Guidelines Conference on Dyslipidemias, and about the state of the art of primary and secondary prevention of atherosclerosis. METHODS: Through the use of a questionnaire on dyslipidemia, atherosclerosis prevention, and recommendations for lipid targets established by the II Brazilian Guidelines Conference on Dyslipidemias, 746 physicians, 98% cardiologists, were evaluated. RESULTS:Eighty-seven percent of the respondents stated that the treatment of dyslipidemia changes the natural history of coronary disease. Although most of the participants followed the total cholesterol recommendations (<200mg/dL for atherosclerosis prevention), only 55.8% would adopt the target of LDL-C <100 mg/dL for secondary prevention. Between 30.5 and 36.7% answered, in different questions, that the recommended level for HDL-C should be <35mg/dL. Only 32.7% would treat their patients indefinitely with lipid- lowering drugs. If the drug treatment did not reach the proposed target, only 35.5% would increase the dosage, and 29.4% would change the medication. Participants did not know the targets proposed for diabetics. CONCLUSION: Although the participating physicians valued the role played by lipids in the prevention of atherosclerosis, serious deficiencies exist in their knowledge of the recommendations given during the II Brazilian Guidelines Conference on Dyslipidemias.

Arterial distensibility as a possible compensatory mechanism in chronic aortic regurgitation

OBJECTIVE: To evaluate elastic properties of conduit arteries in asymptomatic patients who have severe chronic aortic regurgitation. METHODS: Twelve healthy volunteers aged 30±1 years (control group) and 14 asymptomatic patients with severe aortic regurgitation aged 29±2 years and left ventricular ejection fraction of 0.61±0.02 (radioisotope ventriculography) were studied. High-resolution ultrasonography was performed to measure the systolic and diastolic diameters of the common carotid artery. Simultaneous measurement of blood pressure enabled the calculation of arterial compliance and distensibility. RESULTS: No differences were observed between patients with aortic regurgitation and the control group concerning age, sex, body surface, and mean blood pressure. Pulse pressure was significantly higher in the aortic regurgitation group compared with that in the control group (78±3 versus 48±1mmHg, P<0.01). Arterial compliance and distensibility were significantly greater in the aortic regurgitation group compared with that in the control group (11.0±0.8 versus 8.1±0.7 10-10 N-1 m4, P=0.01 e and 39.3±2.6 versus 31.1±2.0 10-6 N-1 m², P=0.02, respectively). CONCLUSION: Patients with chronic aortic regurgitation have increased arterial distensibility. Greater vascular compliance, to lessen the impact of systolic volume ejected into conduit arteries, represents a compensatory mechanism in left ventricular and arterial system coupling.

Trends in the risk of mortality due to cardiovascular diseases in five Brazilian geographic regions from 1979 to 1996

OBJECTIVE - To analyze the trends in risk of death due to cardiovascular diseases in the northern, northeastern, southern, southeastern, and central western Brazilian geographic regions from 1979 to 1996. METHODS - Data on mortality due to cardiovascular, cardiac ischemic, and cerebrovascular diseases in 5 Brazilian geographic regions were obtained from the Ministry of Health. Population estimates for the time period from 1978 to 1996 in the 5 Brazilian geographic regions were calculated by interpolation with the Lagrange method, based on the census data from 1970, 1980, 1991, and the population count of 1996, for each age bracket and sex. Trends were analyzed with the multiple linear regression model. RESULTS - Cardiovascular diseases showed a declining trend in the southern, southeastern, and northern Brazilian geographic regions in all age brackets and for both sexes. In the northeastern and central western regions, an increasing trend in the risk of death due to cardiovascular diseases occurred, except for the age bracket from 30 to 39 years, which showed a slight reduction. This resulted from the trends of cardiac ischemic and cerebrovascular diseases. The analysis of the trend in the northeastern and northern regions was impaired by the great proportion of poorly defined causes of death. CONCLUSION - The risk of death due to cardiovascular, cerebrovascular, and cardiac ischemic diseases decreased in the southern and southeastern regions, which are the most developed regions in the country, and increased in the least developed regions, mainly in the central western region.

Comparison between Adventitial and Intimal Inflammation of Ruptured and Nonruptured Atherosclerotic Plaques in Human Coronary Arteries

OBJECTIVE: To verify the possible role of adventitial inflammation in atherosclerotic plaque vulnerability and coronary artery remodelling. METHODS: We compared the mean numbers of lymphocytes in the adventitia and in the plaque of ruptured thrombosed and stable equi-stenotic coronary segments of 34 patients who died due to acute myocardial infarction. We also analysed adventitial microvessels, adventitial fibrosis and the external elastic membrane. RESULTS: In the adventitia, the numbers of lymphocytes and microvessels/mm² were 69.5±88.3 and 60.9± 32.1 in culprit lesions and 16.4 ± 21.1 and 44.3±16.1 in stable lesions (p<0.05); within the plaques, the mean number of lymphocytes was 24±40.8 in culprit lesions and 10.9±13.2 in stable ones (p=0.17). The mean percent area of adventitial fibrosis/cross-sectional area of the vessel was significantly lower in unstable plaques (p<0.001). The confocal images showed holes in the external elastic membrane. CONCLUSION: Unstable plaques exhibit chronic pan-arteritis, accompanied by enlargement, medial thinning, and less fibrosis than in stable lesions, which is compatible with vessel aneurysm. Adventitial inflammation may contribute significantly to atheroma instability.

Myocardial revascularization in renal transplant patients

OBJECTIVE: To assess the results of surgical myocardial revascularization in renal transplant patients. METHODS: From 1991 to 2000, 11 renal transplant patients, whose ages ranged from 36 to 59 (47.5±8) years, 8 males and 3 females, underwent myocardial revascularization. The time interval between renal transplantation and myocardial revascularization ranged from 25 to 120 (mean of 63.8±32.7) months. RESULTS: The in-hospital mortality rate was 9%. One patient died on the 4th postoperative day from septicemia and respiratory failure. The mean graft/patient ratio was 2.7±0.8. Only 1 patient required slow hemodialysis during 24 hours in the postoperative period, and no patient had a definitive renal lesion or lost the transplanted kidney. The actuarial survival curves after 1, 2, and 3 years were, respectively, 90.9%, 56.8%, and 56.8%. CONCLUSION: Renal transplant patients may undergo myocardial revascularization with no lesion in or loss of the transplanted kidney.

Lipid peroxidation and nitric oxide inactivation in postmenopausal women

OBJECTIVE: To assess the effect of endogenous estrogens on the bioavailability of nitric oxide (·NO) and in the formation of lipid peroxidation products in pre- and postmenopausal women. METHODS: NOx and S-nitrosothiols were determined by gaseous phase chemiluminescence, nitrotyrosine was determined by ELISA, COx (cholesterol oxides) by gas chromatography, and cholesteryl linoleate hydroperoxides (CE18:2-OOH), trilinolein (TG18:2-OOH), and phospholipids (PC-OOH) by HPLC in samples of plasma. RESULTS: The concentrations of NOx, nitrotyrosine, COx, CE18:2-OOH, and PC-OOH were higher in the postmenopausal period (33.8±22.3 mM; 230±130 nM; 55±19 ng/mL; 17±8.7 nM; 2775±460 nM, respectively) as compared with those in the premenopausal period (21.1±7.3 mM; 114±41 nM; 31±13 ng/mL; 6±1.4 nM; 1635±373 nM). In contrast, the concentration of S-nitrosothiols was lower in the postmenopausal period (91±55 nM) as compared with that in the premenopausal p in the premenopausal period (237±197 nM). CONCLUSION: In the postmenopausal period, an increase in nitrotyrosine and a reduction of S-nitrosothiol formation, as well as an increase of COx, CE18:2-OOH and PC-OOH formation occurs. Therefore, •NO inactivation and the increase in lipid peroxidation may contribute to endothelial dysfunction and to the greater risk for atherosclerosis in postmenopausal women.

Acute myocardial infarction: predictors of mortality at a public hospital in the city of Fortaleza, Ceará state

OBJECTIVE: To identify the clinical and demographic predictors of in-hospital mortality in acute myocardial infarction with elevation of the ST segment in a public hospital, in the city of Fortaleza, Ceará state, Brazil. METHODS: A retrospective study of 373 patients experiencing their first episode of acute myocardial infarction was carried out. Of the study patients, 289 were discharged from the hospital (group A) and 84 died (group B). Both groups were analyzed regarding: sex; age; time elapsed from the beginning of the symptoms of myocardial infarction to assistance at the hospital; use of streptokinase; risk factors for atherosclerosis; electrocardiographic location of myocardial infarct; and Killip functional class. RESULTS: In a univariate analysis, group B had a greater proportion of the following parameters as compared with group A: non-Killip I functional class; diabetes; age >70 years; infarction of the inferior wall associated with right ventricular impairment; time between symptom onset and treatment at the hospital >12 h; anteroseptal or extensive anterior infarction; no use of streptokinase; and no tobacco use. In a multivariate logistic regression analysis, only non-Killip I functional class, diabetes, and age >70 years persisted as independent factors for death. CONCLUSION: Non-Killip I functional class, diabetes, and age >70 years were independent predictors of mortality in acute myocardial infarction with elevation of the ST segment.

National alert campaign about increased cholesterol: determination of cholesterol levels in 81,262 Brazilians

OBJECTIVE: To determine the levels of total cholesterol in a significant sample of the Brazilian population. METHODS: Blood cholesterol was determined in 81.262 individuals > 18 years old (51% male, 44.7 ± 15.7 years), using Accutrend equipment, in the cities São Paulo, Campinas, Campos do Jordão, São José dos Campos, Santos, Santo André, Ribeirão Preto, Porto Alegre, Rio de Janeiro, Belo Horizonte, Curitiba, Brasília, Salvador and documented in the presence of other risk factors (RF) for coronary artery disease (CAD) (systemic hypertension, CAD in the family, smoking, and diabetes). Participants were classified according to sex, age, and the presence or absence of RF, respectively, as 0 RF, 1 RF and > 2 RF. The percentage of individuals with cholesterol > 200 mg/dL and > 240 mg/dL was evaluated. RESULTS: The prevalence of individuals with 0, 1, and > 2 risk factors was 30% (n = 24,589), 36% (n =29,324), and 34% (n = 27,349) respectively, (P=0.657), and the mean total cholesterol of the population was 199.0 ± 35.0 mg/dL. Cholesterol levels above 200 and 240 mg/dL were found, respectively, in 40% (n = 32,515) and 13% (10.942) of individuals. The greater the number of risk factors the higher the levels of cholesterol (P<0.0001) and the greater the proportion of individuals with cholesterol > 200 mg/dL (P=0.032). No difference existed in the proportion of individuals with cholesterol > 240 mg/dL (P=0.11). CONCLUSION: A great percentage of individuals with cholesterol levels above those recommended to prevent coronary artery disease was found.

Coinfection with Mycoplasma Pneumoniae and Chlamydia Pneumoniae in ruptured plaques associated with acute myocardial infarction

OBJECTIVE: To study atheromas, Mycoplasma pneumoniae (M. pneumoniae), and Chlamydia pneumoniae (C. pneumoniae). METHODS: C. pneumoniae was studied with immunohistochemistry and M. pneumoniae with in situ hybridization (ISH), in segments of coronary arteries (SCA) as follows: group A - thrombosed ruptured plaques (TRP) of 23 patients who died due to acute myocardial infarction (AMI); group B - 23 nonruptured plaques (NRP) of group A patients; group C - NRP of 11 coronary patients who did not die due to AMI; and group D - 11 SCA from patients with dilated cardiomyopathy or Chagas' disease without atherosclerosis. RESULTS: The mean number of C. pneumoniae+ cells/400x in groups A, B, C, and D was, respectively, 3.3±3.6; 1.0±1.3; 1.2±2.4; and 0.4±0.3; and the percentage of M. pneumoniae area was, respectively, 3.9±3.5; 1.5± 1.6; 0.9±0.9; and 0.4±0.2. More M. pneumoniae and C. pneumoniae were found in of group A than in group B (P<0.01). Good correlation was seen between the area of the vessel and the M. pneumoniae area in the plaque (r = 0.46; P=0.001) and between C. pneumoniae+ cells and CD4+ T lymphocytes (r = 0.42; P<0.01). The number of C. pneumoniae+ cells correlated with CD20+ B cells (r=0.48; P<0.01). CONCLUSION: M. pneumoniae and C. pneumoniae are more frequently found in TRP correlate with the intensity of the inflammation and diameter of the vessel (positive remodeling).