Liz Andréa Villela Baroncini

Appropriateness of carotid plaque and intima-media thickness assessment in routine clinical practice

ObjectivesTo describe the findings and evaluate appropriateness of a carotid artery study including the measurement of IMT, the presence of atherosclerotic plaque, and their correlation with cardiovascular risk factors.Methods555 patients (220 men; 67.06 ± 12.44 years) were included in the study. 120 patients (21.62%) presented carotid plaque: 108 (19.45%) in patients with at least one risk factor and 12 (2.1%) in patients without risk factors. With respect to appropriateness of the present studies: 65% were appropriate, 22% were uncertain and 13% were inappropriate. The IMT medians were higher in males (0.0280; 95% CI, 00.82 to 0.478; p = 0.0057) and in hypertensive patients (0.391; 95% CI, 0.0190 to 0.0592; p = 0,001). There was a linear increase in mean IMT for each year increased in age (0.0059; 95% CI; 0.0050 to 0.0067). Carotid plaque was more frequent in patients with CAD (p = 0.0002), diabetes (p = 0.024) and hypertension (p = 0.036).ConclusionAssessment of carotid arteries identified increased incidence of plaque in patients with CAD, diabetes and hypertension. IMT was increased in older patients, hypertensive patients and males. Forty-five percent of the patients were studied based on uncertain and inappropriate reasons.

Olmesartan severely weakened the development of NASH in an animal model of hypercholesterolemia

BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is characterized by a broad spectrum of liver damage. In a rat model of non-alcoholic steatohepatitis (NASH), olmesartan attenuated steatosis and fibrosis. OBJECTIVE To assess the potential preventive action of olmesartan, an angiotensin II type 1 receptor blocker, on NAFLD in hypercholesterolemic rabbits. METHODS Thirty-four white adult male rabbits were selected. The animals were divided into three groups: group I (GI), control group, 13 rabbits; group II (GII), olmesartan group, 12 rabbits; and group III (GIII), normal group, 9 rabbits. The animals from GI and GII were fed with a specific diet plus 1% cholesterol. Animals from GIII were fed only with a specific diet. The GII animals were treated with olmesartan. RESULTS Steatosis was present in all animals from GI and GII; no steatosis was observed in animals from GIII. When GI and GII where compared, the steatosis had higher scores in GI (p < 0.013). Perisinusoidal and periportal fibrosis occurred in 46.2% of the animals from GI. There was no fibrosis in GII or GIII. Lobular inflammation occurred in 84.6% of the animals from GI. Animals from GII and GIII had no inflammation. The NAFLD activity score was higher in animals from GI when compared to animals from GII and GIII (p < 0.001 for both groups); the NAFLD score was significantly higher in animals from GII when compared to animals from GIII (p < 0.001). CONCLUSIONS In hypercholesterolemic rabbits, olmesartan significantly attenuated hepatic steatosis and prevented the development of lobular inflammation and liver fibrosis. Based on the NAFLD activity score, olmesartan significantly weakened the development of NASH in rabbits fed a high cholesterol diet.

Assessment of MMP-9, TIMP-1, and COX-2 in normal tissue and in advanced symptomatic and asymptomatic carotid plaques

BackgroundMature carotid plaques are complex structures, and their histological classification is challenging. The carotid plaques of asymptomatic and symptomatic patients could exhibit identical histological components.ObjectivesTo investigate whether matrix metalloproteinase 9 (MMP-9), tissue inhibitor of MMP (TIMP), and cyclooxygenase-2 (COX-2) have different expression levels in advanced symptomatic carotid plaques, asymptomatic carotid plaques, and normal tissue.MethodsThirty patients admitted for carotid endarterectomy were selected. Each patient was assigned preoperatively to one of two groups: group I consisted of symptomatic patients (n = 16, 12 males, mean age 66.7 ± 6.8 years), and group II consisted of asymptomatic patients (n = 14, 8 males, mean age 67.6 ± 6.81 years). Nine normal carotid arteries were used as control. Tissue specimens were analyzed for fibromuscular, lipid and calcium contents. The expressions of MMP-9, TIMP-1 and COX-2 in each plaque were quantified.ResultsFifty-eight percent of all carotid plaques were classified as Type VI according to the American Heart Association Committee on Vascular Lesions. The control carotid arteries all were classified as Type III. The median percentage of fibromuscular tissue was significantly greater in group II compared to group I (p < 0.05). The median percentage of lipid tissue had a tendency to be greater in group I than in group II (p = 0.057). The percentages of calcification were similar among the two groups. MMP-9 protein expression levels were significantly higher in group II and in the control group when compared with group I (p < 0.001). TIMP-1 expression levels were significantly higher in the control group and in group II when compared to group I, with statistical difference between control group and group I (p = 0.010). COX-2 expression levels did not differ among groups. There was no statistical correlation between MMP-9, COX-2, and TIMP-1 levels and fibrous tissue.ConclusionsMMP-9 and TIMP-1 are present in all stages of atherosclerotic plaque progression, from normal tissue to advanced lesions. When sections of a plaque are analyzed without preselection, MMP-9 concentration is higher in normal tissues and asymptomatic surgical specimens than in symptomatic specimens, and TIMP-1 concentration is higher in normal tissue than in symptomatic specimens.

Oxidative stress and inflammatory response increase during coronary artery bypass grafting with extracorporeal circulation.

INTRODUCTION Thiobarbituric acid-reactive substance is a marker of oxidative stress and has cytotoxic and genotoxic actions. C- reactive protein is used to evaluate the acute phase of inflammatory response. OBJECTIVES To assess the thiobarbituric acid-reactive substance and C-reactive protein levels during extracorporeal circulation in patients submitted to cardiopulmonary bypass. METHODS Twenty-five consecutive surgical patients (16 men and nine women; mean age 61.2 ± 9.7 years) with severe coronary artery disease diagnosed by angiography scheduled for myocardial revascularization surgery with extracorporeal circulation were selected. Blood samples were collected immediately before initializing extracorporeal circulation, T0; in 10 minutes, T10; and in 30 minutes, T30. RESULTS The thiobarbituric acid-reactive substance levels increased after extracorporeal circulation (P=0.001), with average values in T0=1.5 ± 0.07; in T10=5.54 ± 0.35; and in T30=3.36 ± 0.29 mmoles/mg of serum protein. The C-reactive protein levels in T0 were negative in all samples; in T10 average was 0.96 ± 0.7 mg/dl; and in T30 average was 0.99 ± 0.76 mg/dl. There were no significant differences between the dosages in T10 and T30 (P=0.83). CONCLUSIONS C-reactive protein and thiobarbituric acid-reactive substance plasma levels progressively increased during extracorporeal circulation, with maximum values of thiobarbituric acid-reactive substance at 10 min and of C-reactive protein at 30 min. It suggests that there are an inflammatory response and oxidative stress during extracorporeal circulation.

Use of rosiglitazone before and after vascular injury in hypercholesterolemic rabbits: Assessment of neointimal formation

ObjectivesTo analyse the effects of rosiglitazone administered at different times on neointimal formation in hypercholesterolemic rabbits following vascular injury.MethodsThirty-nine rabbits on a hypercholesterolemic diet were included. The animals underwent balloon catheter injury to the right iliac artery on day 14. They were divided into three groups as follows: control group, 13 rabbits without rosiglitazone; group I, 13 rabbits treated with rosiglitazone (3 mg/Kg body weight/day) for 28 days after the vascular injury; and group II, 13 rabbits treated with rosiglitazone (3 mg/Kg body weight/day) during all the experiment (42 days). Histological analysis was done by an experienced pathologist who was unaware of the rosiglitazone treatment. Histomorphometric parameters were performed by calculation of the luminal and intimal layer area, and intima/media layer area ratio (the area of the intimal layer divided by the area of the medial layer).ResultsIntimal area was significantly lower in group II vs. CG (p = 0.024) and group I (p = 0.006). Luminal layer area was higher in group II vs. CG (p < 0.0001) and group I (p < 0.0001). Intima/media layer area ratio was equal between CG and group I. Intima/media layer ratio area was significantly lower in group II vs. control group (p < 0.021) and group I (p < 0.003). There was a significant reduction of 65% and 71% in intima/media layer area ratio in group II vs. control group and group I, respectively.ConclusionPretreatment with rosiglitazone in hypercholesterolemic rabbits submitted to vascular injury significantly reduces neointimal formation.

Assessment of Intima-Media Thickness in Healthy Children Aged 1 to 15 Years

Background Carotid intima-media thickness (CIMT) has been shown to be increased in children and adolescents with traditional cardiovascular risk factors such as obesity, hypertension, and chronic kidney disease, compared with those of healthy children. Objective To assess the influence of sex, age and body mass index (BMI) on the CIMT in healthy children and adolescents aged 1 to 15 years. Methods A total of 280 healthy children and adolescents (males, n=175; mean age, 7.49±3.57 years; mean BMI, 17.94±4.1 kg/m2) were screened for CIMT assessment. They were divided into 3 groups according to age: GI, 1 to 5 years [n=93 (33.2%); males, 57; mean BMI, 16±3 kg/m2]; GII, 6 to 10 years [n=127 (45.4%); males, 78; mean BMI, 17.9±3.7 kg/m2], and GIII, 11 to 15 years [n=60 (21.4%); males, 40; mean BMI, 20.9±4.5 kg/m2]. Results There was no significant difference in CIMT values between male and female children and adolescents (0.43±0.06 mm vs. 0.42±0.05 mm, respectively; p=0.243). CIMT correlated with BMI neither in the total population nor in the 3 age groups according to Pearson correlation coefficient. Subjects aged 11 to 15 years had the highest CIMT values (GI vs. GII, p=0.615; GI vs. GIII, p=0.02; GII vs. GIII, p=0.004). Conclusions CIMT is constant in healthy children younger than 10 years, regardless of sex or BMI. CIMT increases after the age of 10 years.

Rosiglitazona e lesão vascular em coelhos hipercolesterolêmicos: avaliação da formação neointimal

FUNDAMENTO: El uso de rosiglitazona ha estado siendo el objeto de extensas discusiones. OBJETIVO: Evaluar los efectos de la rosiglitazona en las arterias iliacas, en el local de la injuria y en la arteria contralateral, de conejos hipercolesterolemicos sometidos a la lesion por cateter-balon. METODOS: Conejos blancos machos recibieron una dieta hipercolesterolemica a traves de gavage oral por 6 semanas y se los dividieron en 2 grupos: grupo rosiglitazona (GR - 14 conejos tratados con rosiglitazona por 6 semanas) y grupo control (GC - 18 conejos sin rosiglitazona). Los animales se sometieron a lesion por cateter-balon en la arteria iliaca derecha en el 14o dia. RESULTADOS: En la arteria iliaca contralateral, no hubo diferencia significativa en la razon entre las areas intima y media (RIM) entre los grupos GR y GC. La rosiglitazona no redujo la probabilidad de lesiones tipo I, II o III (72,73% vs 92,31%; p=0,30) y lesiones tipo IV o V (27,27% vs 7,69%; p=0,30). En la arteria iliaca homolateral, el area intima era significantemente menor en el GR cuando comparado al GC (p = 0,024). El area luminal era mayor en el GR cuando comparado al GC (p < 0,0001). Hubo una reduccion significante del 65% en la IMR en el GR cuando comparado al GC (p = 0,021). Ningun de los criterios histologicos para lesiones ateroscleroticas tipos I a V (American Heart Association) se encontraron en la arteria iliaca homolateral. CONCLUSION: Estos hallazgos demuestran que la administracion de rosiglitazona por 6 semanas impide la aterogenesis en el local de la lesion, pero no en un vaso distante del sitio de la lesion.BACKGROUND Rosiglitazone has been the focus of extensive discussion. OBJECTIVE To evaluate the effects of rosiglitazone on iliac arteries, both at the injury site and the contralateral artery, of hypercholesterolemic rabbits undergoing balloon catheter injury. METHODS White male rabbits were fed a hypercholesterolemic diet by oral gavage for 6 weeks and divided into two groups as follows: rosiglitazone group (14 rabbits treated with rosiglitazone during 6 weeks) and the control group (18 rabbits without rosiglitazone). Animals underwent balloon catheter injury of the right iliac artery on the 14th day. RESULTS In the contralateral iliac artery, there was no significant difference in the intima/media layer area ratio (IMR) between the control and rosiglitazone groups. Rosiglitazone did not reduce the probability of type I, II, or III lesions (72.73% vs 92.31%; p=0.30) and type IV or V lesions (27.27% vs 7.69%; p=0.30). As for the homolateral iliac artery, the intimal area was significantly lower in the rosiglitazone group, as compared to the control group (p = 0.024). The luminal layer area was higher in the rosiglitazone group vs. the control group (p < 0.0001). There was a significant reduction of 65% in the IMR in the rosiglitazone group vs the control group (p = 0.021). None of the histological criteria for type I-V atherosclerotic lesions (American Heart Association) were found in the homolateral iliac artery. CONCLUSION These findings demonstrate that rosiglitazone given for 6 weeks prevents atherogenesis at the injury site, but not in a vessel distant from the injury site.

Rosiglitazone and vascular injury in hypercholesterolemic rabbits: neointimal formation assessment

FUNDAMENTO: El uso de rosiglitazona ha estado siendo el objeto de extensas discusiones. OBJETIVO: Evaluar los efectos de la rosiglitazona en las arterias iliacas, en el local de la injuria y en la arteria contralateral, de conejos hipercolesterolemicos sometidos a la lesion por cateter-balon. METODOS: Conejos blancos machos recibieron una dieta hipercolesterolemica a traves de gavage oral por 6 semanas y se los dividieron en 2 grupos: grupo rosiglitazona (GR - 14 conejos tratados con rosiglitazona por 6 semanas) y grupo control (GC - 18 conejos sin rosiglitazona). Los animales se sometieron a lesion por cateter-balon en la arteria iliaca derecha en el 14o dia. RESULTADOS: En la arteria iliaca contralateral, no hubo diferencia significativa en la razon entre las areas intima y media (RIM) entre los grupos GR y GC. La rosiglitazona no redujo la probabilidad de lesiones tipo I, II o III (72,73% vs 92,31%; p=0,30) y lesiones tipo IV o V (27,27% vs 7,69%; p=0,30). En la arteria iliaca homolateral, el area intima era significantemente menor en el GR cuando comparado al GC (p = 0,024). El area luminal era mayor en el GR cuando comparado al GC (p < 0,0001). Hubo una reduccion significante del 65% en la IMR en el GR cuando comparado al GC (p = 0,021). Ningun de los criterios histologicos para lesiones ateroscleroticas tipos I a V (American Heart Association) se encontraron en la arteria iliaca homolateral. CONCLUSION: Estos hallazgos demuestran que la administracion de rosiglitazona por 6 semanas impide la aterogenesis en el local de la lesion, pero no en un vaso distante del sitio de la lesion.BACKGROUND Rosiglitazone has been the focus of extensive discussion. OBJECTIVE To evaluate the effects of rosiglitazone on iliac arteries, both at the injury site and the contralateral artery, of hypercholesterolemic rabbits undergoing balloon catheter injury. METHODS White male rabbits were fed a hypercholesterolemic diet by oral gavage for 6 weeks and divided into two groups as follows: rosiglitazone group (14 rabbits treated with rosiglitazone during 6 weeks) and the control group (18 rabbits without rosiglitazone). Animals underwent balloon catheter injury of the right iliac artery on the 14th day. RESULTS In the contralateral iliac artery, there was no significant difference in the intima/media layer area ratio (IMR) between the control and rosiglitazone groups. Rosiglitazone did not reduce the probability of type I, II, or III lesions (72.73% vs 92.31%; p=0.30) and type IV or V lesions (27.27% vs 7.69%; p=0.30). As for the homolateral iliac artery, the intimal area was significantly lower in the rosiglitazone group, as compared to the control group (p = 0.024). The luminal layer area was higher in the rosiglitazone group vs. the control group (p < 0.0001). There was a significant reduction of 65% in the IMR in the rosiglitazone group vs the control group (p = 0.021). None of the histological criteria for type I-V atherosclerotic lesions (American Heart Association) were found in the homolateral iliac artery. CONCLUSION These findings demonstrate that rosiglitazone given for 6 weeks prevents atherogenesis at the injury site, but not in a vessel distant from the injury site.

Effects of rosiglitazone on contralateral iliac artery after vascular injury in hypercholesterolemic rabbits

BackgroundThe objective was to evaluate the effects of rosiglitazone on iliac arteries of hypercholesterolemic rabbits undergoing balloon catheter injury in the contralateral iliac arteries.MethodsWhite male rabbits were fed a hypercholesterolemic diet for 6 weeks and divided into two groups as follows: rosiglitazone group, 14 rabbits treated with rosiglitazone (3 mg/Kg body weight/day) during 6 weeks; and control group, 18 rabbits without rosiglitazone treatment. All animals underwent balloon catheter injury of the right iliac artery on the fourteenth day of the experiment.ResultsThere was no significant difference in intima/media layer area ratio between the control group and the rosiglitazone group. Rosiglitazone did not reduce the probability of lesions types I, II, or III (72.73% vs. 92.31%; p = 0.30) and types IV or V (27.27% vs. 7.69%; p = 0.30). There were no differences in the extent of collagen type I and III deposition or in the percentage of animals with macrophages in the intima layer. The percentage of rabbits with smooth muscle cells in the intima layer was higher in rosiglitazone group (p = 0.011).ConclusionThese findings demonstrate that rosiglitazone given for 6 weeks did not prevent atherogenesis at a vessel distant from the injury site.

Carotid intima-media thickness and carotid plaque represent different adaptive responses to traditional cardiovascular risk factors

Aim To assess the effects of each traditional cardiovascular risk factor (hypertension, diabetes mellitus, dyslipidemia, and smoking), including the presence of coronary artery disease (CAD), on carotid intima-media thickness (CIMT) and to assess the degree of carotid plaque occurrence. Methods A total of 553 outpatients (216 men and 337 women; mean age 67.06 ± 12.44 years) who underwent a carotid artery ultrasound were screened for carotid plaque and CIMT measurements. Results The CIMT medians were higher in males (P < .001) and in patients with hypertension (P < .001). A linear increase occurred in mean CIMT of 0.0059 mm for each year of increase in age. The presence of plaque indicated a tendency to correlate with CIMT (P = .067). The presence of hypertension associated with diabetes (P = .0061; estimated difference 0.0494 mm) or dyslipidemia (P = .0016; estimated difference 0.0472 mm) or CAD (P = .0043; estimated difference 0.0527 mm) increased the mean CIMT measurements. The probability of plaque occurrence in carotid arteries is influenced by the age (P < .001) and is higher in patients with dyslipidemia (P = .008) and CAD (P < .001). Conclusions Hypertension is the strongest cardiovascular risk factor that increases CIMT, followed by age and male sex. Age and dyslipidemia increase the probability of carotid plaque. Increased CIMT and plaque could be present in the same patient caused by different risk factors and with independent effects on the artery wall and different clinical prognoses.