Cardiovascular biomarkers in sickle cell disease− clinical and echocardiographic correlations in a cross-sectional study with 126 patients

INTRODUCTION: Cardiac biomarkers can be useful in understanding the systemic and heart manifestations of sickle cell disease (SCD). Biomarkers reflect various aspects of heart disease (remodeling, injury and myocardial strain), with discriminatory potential for non-cardiac complications. Patients and METHODS: SCD patients (SS/Sß0) in steady state, were studied, correlating clinical manifestations and echo parameters (myocardial work - MW and speckle tracking), pre-MSCD severity score (integrating clinical and echo data), and cardiac biomarkers (high-sensitivity troponins ­ hs-cTn I and T, NT-pro-BNP, ST2s, and galectin-3 - GAL3). Quantitative characteristics were analyzed by Spearman tests, and qualitative characteristics by Mann-Whitney test. Hemolytic Index (HI) was calculated through Principal Component Analysis. Generalized linear Poisson models were generated for hs-cTn, and γ-distribution models were employed for other markers, with final models selected through the Stepwise Backward method. RESULTS: We studied 126 patients (mean age 37.2 ± 11.6 years), 42.1% male, and 80.2% SS. 47% were on hydroxyurea treatment and 30.2% on a chronic transfusion. NT-pro-BNP was elevated in 44% (> 160 ng/mL in 37%), correlated with female gender (p < 0.001), severity score (p = 0.001), uric acid (p = 0.017), HI (p < 0.001), Global Work Index (GWI) (p = 0.003), left atrial (LA) stiffness (p = 0.003), and ventricular mass (VM) (p = 0.02). ST2s were elevated in 11% and correlated with male gender (p > 0.001), HI (p > 0.001), cardiac index (p = 0.015), and LA strain reservoir function (p = 0.034). GAL3 was elevated in 42.8%, correlated with E/e'ratio (p = 0.006), uric acid (p = 0.005), and absence of chronic pain (p = 0.046). hs-cTn correlated with age (c-TnI p = 0.004; c-TnT p > 0.001), HI (p > 0.001), diastolic dysfunction (p > 0.001), left VM (p < 0.001), increased GWI (p < 0.001), and reduced MW efficiency (p < 0.001). hs-cTn I also correlated with increased LA reservoir function (p < 0.001) with reduced conduit function (p < 0.001). hs-cTn T correlated with uric acid (p = 0.001), and in univariate analysis was also correlated with severity score. The values of both hs-cTn correlated with increased GWI (p < 0.001) and reduced MW efficiency (p < 0.001). DISCUSSION: The biomarkers demonstrated various clinical and pathophysiological aspects of SCD. NT-pro-BNP is a routine marker with correlations similar to literature, except for higher values in females, also observed in non-SCD population. ST2 and GAL3 had limited correlations with echo findings, likely due to their production in extracardiac tissues affected by inflammation/vaso-occlusion. Both were linked to the HI, and the decrease in GAL3 in chronic pain can be attributed to chronic opioid use causing reduced synthesis of it. The elevation of hs-cTn was expected due to the analytical characteristics of high-sensitivity assays, but low in terms of the extent of heart involvement. hs-cTnT was more associated with general severity, like in the general population, where it is associated with overall mortality, while hs-cTnI is more connected to heart disease. MW in SCD is optimized to the maximum with a very low Global Work Wasted, and hs-cTn elevation is associated with reduced MW efficiency, indicating mecano-energetic uncoupling and subtle systolic dysfunction. CONCLUSION: Our study demonstrates that cardiac biomarkers can be used for clinical and pathophysiological evaluation, with NT-pro-BNP confirming its role in clinical stratification. ST2s and GAL3 may reveal new pathophysiological pathways in hemolysis and the interaction of opioids and chronic pain. Troponins are promising as prospective tool and may unveil ischemic damage resulting from myocardial mecano-energetic dissociation.

Short-term follow-up of exercise training program and beta-blocker treatment on quality of life in dogs with naturally acquired chronic mitral valve disease.

This study aimed to evaluate the effects of carvedilol treatment and a regimen of supervised aerobic exercise training on quality of life and other clinical, echocardiographic, and biochemical variables in a group of client-owned dogs with chronic mitral valve disease (CMVD). Ten healthy dogs (control) and 36 CMVD dogs were studied, with the latter group divided into 3 subgroups. In addition to conventional treatment (benazepril, 0.3-0.5 mg/kg once a day, and digoxin, 0.0055 mg/kg twice daily), 13 dogs received exercise training (subgroup I; 10.3 ± 2.1 years), 10 dogs received carvedilol (0.3 mg/kg twice daily) and exercise training (subgroup II; 10.8 ± 1.7 years), and 13 dogs received only carvedilol (subgroup III; 10.9 ± 2.1 years). All drugs were administered orally. Clinical, laboratory, and Doppler echocardiographic variables were evaluated at baseline and after 3 and 6 months. Exercise training was conducted from months 3-6. The mean speed rate during training increased for both subgroups I and II (ANOVA, P>0.001), indicating improvement in physical conditioning at the end of the exercise period. Quality of life and functional class was improved for all subgroups at the end of the study. The N-terminal pro-brain natriuretic peptide (NT-proBNP) level increased in subgroup I from baseline to 3 months, but remained stable after training introduction (from 3 to 6 months). For subgroups II and III, NT-proBNP levels remained stable during the entire study. No difference was observed for the other variables between the three evaluation periods. The combination of carvedilol or exercise training with conventional treatment in CMVD dogs led to improvements in quality of life and functional class. Therefore, light walking in CMVD dogs must be encouraged.

Short-term follow-up of exercise training program and beta-blocker treatment on quality of life in dogs with naturally acquired chronic mitral valve disease

This study aimed to evaluate the effects of carvedilol treatment and a regimen of supervised aerobic exercise training on quality of life and other clinical, echocardiographic, and biochemical variables in a group of client-owned dogs with chronic mitral valve disease (CMVD). Ten healthy dogs (control) and 36 CMVD dogs were studied, with the latter group divided into 3 subgroups. In addition to conventional treatment (benazepril, 0.3-0.5 mg/kg once a day, and digoxin, 0.0055 mg/kg twice daily), 13 dogs received exercise training (subgroup I; 10.3±2.1 years), 10 dogs received carvedilol (0.3 mg/kg twice daily) and exercise training (subgroup II; 10.8±1.7 years), and 13 dogs received only carvedilol (subgroup III; 10.9±2.1 years). All drugs were administered orally. Clinical, laboratory, and Doppler echocardiographic variables were evaluated at baseline and after 3 and 6 months. Exercise training was conducted from months 3-6. The mean speed rate during training increased for both subgroups I and II (ANOVA, P>0.001), indicating improvement in physical conditioning at the end of the exercise period. Quality of life and functional class was improved for all subgroups at the end of the study. The N-terminal pro-brain natriuretic peptide (NT-proBNP) level increased in subgroup I from baseline to 3 months, but remained stable after training introduction (from 3 to 6 months). For subgroups II and III, NT-proBNP levels remained stable during the entire study. No difference was observed for the other variables between the three evaluation periods. The combination of carvedilol or exercise training with conventional treatment in CMVD dogs led to improvements in quality of life and functional class. Therefore, light walking in CMVD dogs must be encouraged.

Gender differences in serum CK-MB mass levels in healthy Braziliansubjects

The creatine kinase-isoenzyme MB (CK-MB) mass assay is one of the laboratory tests used for the diagnosis of myocardial infarction. It is recommended, however, that reference limits should take gender and race into account. In the present study, we analyzed the plasma CK-MB mass and troponin levels of 244 healthy volunteers without a personal history of coronary artery disease and with no chronic diseases, muscular trauma or hypothyroidism, and not taking statins. The tests were performed with commercial kits, CK-MB mass turbo kit and Troponin I turbo kit, using the Immulite 1000 analyzer from Siemens Healthcare Diagnostic. The values were separated according to gender and showed significant differences by the Mann-Whitney test. Mean (± SD) CK-MB mass values were 2.55 ± 1.09 for women (N = 121; age = 41.20 ± 10.13 years) and 3.49 ± 1.41 ng/mL for men (N = 123; age = 38.16 ± 11.12 years). Gender-specific reference values at the 99th percentile level, according to the Medicalc statistical software, were 5.40 ng/mL for women and 7.13 ng/mL for men. The influence of race was not considered because of the high miscegenation of the Brazilian population. The CK-MB values obtained were higher than the 5.10 mg/mL proposed by the manufacturer of the laboratory kit. Therefore, decision limits should be related to population and gender in order to improve the specificity of this diagnostic tool, avoiding misclassification of patients.

Gender differences in serum CK-MB mass levels in healthy Brazilian subjects.

The creatine kinase-isoenzyme MB (CK-MB) mass assay is one of the laboratory tests used for the diagnosis of myocardial infarction. It is recommended, however, that reference limits should take gender and race into account. In the present study, we analyzed the plasma CK-MB mass and troponin levels of 244 healthy volunteers without a personal history of coronary artery disease and with no chronic diseases, muscular trauma or hypothyroidism, and not taking statins. The tests were performed with commercial kits, CK-MB mass turbo kit and Troponin I turbo kit, using the Immulite 1000 analyzer from Siemens Healthcare Diagnostic. The values were separated according to gender and showed significant differences by the Mann-Whitney test. Mean (± SD) CK-MB mass values were 2.55 ± 1.09 for women (N = 121; age = 41.20 ± 10.13 years) and 3.49 ± 1.41 ng/mL for men (N = 123; age = 38.16 ± 11.12 years). Gender-specific reference values at the 99th percentile level, according to the Medicalc statistical software, were 5.40 ng/mL for women and 7.13 ng/mL for men. The influence of race was not considered because of the high miscegenation of the Brazilian population. The CK-MB values obtained were higher than the 5.10 mg/mL proposed by the manufacturer of the laboratory kit. Therefore, decision limits should be related to population and gender in order to improve the specificity of this diagnostic tool, avoiding misclassification of patients.

Anxiety and high plasma catecholamines do not impair pharmaco-induced erection of psychogenic erectile dysfunctional patients.

The aim of this study was to assess the influence of anxiety and plasma catecholamines on the pharmaco-induced erection of psychogenic erectile dysfunction (ED) patients. A total of 23 patients with psychogenic ED aged from 19 to 43 y were submitted to: (1) anxiety evaluation by the Spielberger's State and Trait Anxiety Inventory-STAI; (2) intracavernous injection of PGE1 10 microg+phentolamine 1 mg with the response monitored by Rigiscan; (3) blood sampling from cavernous bodies and cubital vein for adrenaline and noradrenaline levels determination by high performance liquid chromatography. The whole procedure was done in a single clinical setting at the same day. We found no significant correlation between the erection rigidity and the cavernous or peripheral catecholamines or between erection rigidity and anxiety scores. Some patients showed rigid erections despite high anxiety scores or penile catecholamine levels while others, with incomplete erections, had much smaller levels. These results are suggestive of a more complex mechanism controlling the penile sympathetic responsiveness in psychogenic ED patients.

Acute and chronic pleural changes after the intrapleural instillation of mitoxantrone in rabbits.

A previous study demonstrated that the intrapleural injection of 2 mg/kg mitoxantrone in rabbits resulted in a degree of pleurodesis which is comparable to that seen after 35 mg/kg tetracycline but that the animals had a high mortality rate after this dose of mitoxantrone. The objective of the present study was to assess the acute pleural fluid findings, the acute gross and microscopic pleural findings, and the chronic gross and microscopic findings in rabbits that received mitoxantrone. Mitoxantrone, 1.5 mg/kg, was instilled intrapleurally in 70 lightly anesthetized male rabbits. Groups of rabbits were sacrificed 1, 2, 4, 7, 15, 28, and 60 days after the injection. The intrapleural injection of mitoxantrone resulted in an exudative effusion on day 1. The pleural fluid contained predominantly neutrophils and had a mean lactate dehydrogenase (LDH) level that exceeded 4,000 IU/liter. Over the following week the volume of fluid diminished, the predominant cell became the macrophage, and the LDH levels decreased to less than 400 IU/liter. Macroscopic examination of the pleural space revealed that the mean degree of pleurodesis increased progressively over the 60-day observation period. With microscopy, the mean degree of pleural fibrosis also increased progressively. There were also substantial fibrosis and inflammation of the underlying lung and the contralateral lung. The mortality rates were low in the first 28 days (3/70) but subsequently increased and exceeded 80% in the period between 60 and 120 days. This experimental model of pleurodesis should be useful in future studies directed toward uncovering the mechanisms of pleurodesis.

Oral glucose ingestion increases endurance capacity in normal and diabetic (type I) humans.

The effects of an oral glucose administration (1 g/kg) 30 min before exercise on endurance capacity and metabolic responses were studied in 21 type I diabetic patients [insulin-dependent diabetes mellitus (IDDM)] and 23 normal controls (Con). Cycle ergometer exercise (55-60% of maximal O2 uptake) was performed until exhaustion. Glucose administration significantly increased endurance capacity in Con (112 +/- 7 vs. 125 +/- 6 min, P < 0.05) but only in IDDM patients whose blood glucose decreased during exercise (70.8 +/- 8.2 vs. 82.8 +/- 9.4 min, P < 0.05). Hyperglycemia was normalized at 15 min of exercise in Con (7.4 +/- 0.2 vs. 4.8 +/- 0.2 mM) but not in IDDM patients (12.4 +/- 0.7 vs. 15.6 +/- 0.9 mM). In Con, insulin and C-peptide levels were normalized during exercise. Glucose administration decreased growth hormone levels in both groups. In conclusion, oral glucose ingestion 30 min before exercise increases endurance capacity in Con and in some IDDM patients. In IDDM patients, in contrast with Con, exercise to exhaustion attenuates hyperglycemia but does not bring blood glucose levels to preglucose levels.

[Precision and accuracy of blood lipid analyses by a portable device (Cholestech-LDX)]. / Precisão e exatidão das dosagens dos lípides sangüíneos em equipamento portátil (Cholestech-LDX).

PURPOSE: To verify whether precision and accuracy of lipids analyses by a new portable device, Cholestech-lipid desktop analyzer (LDX), were in agreement with the guidelines of the National Cholesterol Education Program (NCEP). METHODS: Serum samples from 45 outpatients were collected for the determination of total Cholesterol (TC), HDL-cholesterol (HDL-C) and triglycerides (TG). These samples were analysed simultaneously by the Cholestech-LDX, and by the automatic enzymatic methods routinely used at the Heart Institute's laboratory. Precision was determined by repeating 20 times the evaluation of the same sample of venous blood. Accuracy was established confronting the values of the lipids variables obtained with Cholestech-LDX against the values determined by the automatic enzymatic routine. RESULTS: Accuracy for TC was 1.60% (NCEP < or = 3%), for HDL-C was -2.74% (NCEP < or = 6%) and for TG was 2.11% (NCEP < or = 5%). Precision for CT was 3.05% (NCEP < or = 3%), for HDL-C was 1.05% (NCEP < or = 6%) and for TG was 2.65% (NCEP < 5%). CONCLUSION: Precision and accuracy of lipids evaluation by the Cholestech-LDX are within the guidelines of the National Cholesterol Education Program. Therefore the cholestech-LDX seems to be a reliable alternative to the conventional biochemical routine, allowing population screenings.

Glycosaminoglycan distribution in atherosclerotic saphenous vein grafts.

Glycosaminoglycan composition of normal saphenous veins and atherosclerotic saphenous vein grafts is reported. Dermatan sulfate is the main glycosaminoglycan present in both normal saphenous veins and saphenous vein grafts. These tissues also contain chondroitin sulfate and heparan sulfate. Although the total amount of glycosaminoglycans decreased in the grafts (compared with normal saphenous veins), the grafts showed an increase in the relative amounts of dermatan sulfate and chondroitin sulfate. Heparan sulfate was decreased, compared with normal controls. These findings suggest the involvement of blood vessel glycosaminoglycans (not only the arterial glycosaminoglycans) in the process of atherosclerosis.

Low cord blood levels of catecholamine from a newborn of a pheochromocytoma patient.

Association of pheochromocytoma and pregnancy is rare and usually related to high maternal and fetal mortality rates. Maternal effects of the tumor have been studied extensively and the clinical outcome has markedly improved during the last decade. However, the role of excess catecholamines on fetal development has been discussed very little. We report here a case of pheochromocytoma during pregnancy. In which catecholamine levels from the cord blood were low despite simultaneous elevated maternal values (1.93 and 29.46 nmol/l norepinephrine, respectively), possibly owing to the high activity of the catecholamine degradative enzymes monoamine oxidase and COMT at the placental level. We suggest that in pregnancies complicated by pheochromocytoma, fetal well-being may be related mainly to good control of maternal blood pressure instead of the amount of catecholamines in the fetal circulation, because the placenta performs a protective role through an effective process of hormone inactivation.

Renal denervation normalizes pressure and baroreceptor reflex in high renin hypertension in conscious rats.

High renin hypertension is usually accompanied by impairment of the baroreceptor reflexes. This feature has been mostly ascribed to overactivity of the renin-angiotensin system. However, renal nerves could also modulate the baroreceptor reflexes. In the present experiments, the effect of renal denervation on the depressed baroreceptor reflexes was studied in rats subjected to aortic ligation between the renal arteries. Renal denervation of the ischemic kidney was performed at the same time as aortic ligation. The resulting effects on arterial pressure, heart rate, plasma renin activity, and baroreceptor reflex control of heart rate were studied 10-12 days after ligation and denervation. Aortic ligation induced high levels of mean arterial pressure (166 +/- 6 versus 110 +/- 3 mm Hg in controls), heart rate (380 +/- 9 versus 352 +/- 8 beats per minute in controls), and plasma renin activity (44 +/- 5 versus 6 +/- 1.2 ng angiotensin I/ml/hr). The baroreceptor reflex sensitivity for bradycardia and tachycardia was significantly reduced (-0.18 +/- 0.04 and -0.18 +/- 0.05, respectively, versus -2.3 +/- 0.01 and -2.4 +2- 0.1 beats per minute per mm Hg in controls). Denervation of the ischemic kidney attenuated the development of hypertension in aortic-ligated rats (122 +/- 3 mm Hg), lowering heart rate (319 +/- 8 beats per minute) and normalizing baroreceptor reflex sensitivity to bradycardia (-2.0 +/- 0.2 beats per minute per mm Hg) and to tachycardia (-4.0 +/- 0.1 beats per minute per mm Hg). Plasma renin activity was also normalized (4.3 +/- 2.4 ng angiotensin I/ml/hr).(ABSTRACT TRUNCATED AT 250 WORDS)

[Lipoprotein (a) plasma levels in normal subjects and patients with coronary disease confirmed by coronary cineangiography]. / Níveis plasmáticos de lipoproteína (a) em indivíduos normais e portadores de doença coronariana confirmada por cinecoronariografia.

PURPOSE: To evaluate the plasma concentration of lipoprotein (a) (Lp(a) in subjects with normal or altered coronary angiography, as a risk factor of atherosclerosis in a Brazilian population. PATIENTS AND METHOD: Lp(a) plasma levels were determined by radioimmunoassay in 31 subjects with normal angiography and in 131 subjects with atherosclerosis. Plasma cholesterol, triglycerides, apolipoprotein A, A1 and B were also determined as well as risk factors like systemic arterial hypertension, smoking habit, diabetes and physical activity. RESULTS: Subjects with coronary disease had Lp(a) plasma levels of 41.9 mg/dl, compared to 23.9 mg/dl found in the normal group. Coronary artery disease risk was increased 2.3 times in those with plasma Lp(a) levels equal or above 25 mg/dl, compared to those with levels below this boundary. As to other known risk factors, only smoking habit has shown correlation with coronary artery disease. CONCLUSION: We confirmed the value of Lp(a) as a risk factor of coronary heart disease.

Sulfated glycosaminoglycan and collagen patterns in parietal yolk sac carcinoma (PYSC).

Electrophoretic analyses of collagenous material have shown that the parietal yolk sac carcinoma (PYSC) ascitic tumour synthesizes polypeptide chains that migrate as type IV procollagen. Having molecular weights of 185,000 and 160,000, these polypeptides are sensitive to collagenase. When the PYSC cells are injected subcutaneously, they form a solid tumour, and type I collagen predominates. The electrophoretic analyses of sulfated glycosaminoglycans and enzymatic degradation have shown a predominance of heparan sulfate in the ascitic tumour, and of chondroitin sulfate B in the solid tumour. Cells cultured from ascitic tumours have maintained the same collagen and sulfated glycosaminoglycan patterns as the original cells, whereas in the solid tumour culture only chondroitin sulfate AC has been detected.