Abdominal Obesity and Association With Atherosclerosis Risk Factors: The Uberlândia Heart Study.

Ectopic visceral fat (VF) and subcutaneous fat (SCF) are associated with cardiovascular risk factors. Gender differences in the correlations of cardiovascular disease risk factors and ectopic fat in the Brazilian population still lacking. Cross-sectional study with 101 volunteers (50.49% men; mean age 56.5 ±â€Š18, range 19-74 years) drawn from the Uberlândia Heart Study underwent ultrasonography assessment of abdominal visceral adipose tissue with convex transducer of 3.5 MHz of frequency. The thickness of VF was ultrasonographically measured by the distance between the inner face of the abdominal muscle and the posterior face of abdominal aorta, 1 cm above the umbilicus. The SCF thickness was measured with a 7.5 MHz linear transducer transversely positioned 1 cm above the umbilical scar. The exams were always performed by the same examiner. Ectopic fat volumes were examined in relation to waist circumference, blood pressure, and metabolic risk factors. The VF was significantly associated with the levels of triglycerides (P < 0.01, r = 0.10), HDL cholesterol (P < 0.005, r = 0.15), total cholesterol (P < 0.01, r = 0.10), waist circumference (P < 0.0001, r = 0.43), systolic blood pressure (P < 0.001, r = 0.41), and diastolic blood pressure (P < 0.001, r = 0.32) in women, and with the levels of triglycerides (P < 0.002, r = 0,14), HDL cholesterol (P < 0.032, r = 0.07), glucose (P < 0.001, r = 0.15), alanine aminotransferase (ALT) (P < 0.008, r = 0.12), gamma-GT (P < 0.001, r = 0.30), waist circumference (P < 0.001, r = 0.52), systolic blood pressure (P < 0.001, r = 0.32), and diastolic blood pressure (P < 0.001, r = 0.26) in men. SCF was significantly associated with the levels of triglycerides (P < 0.01, r = 0.34), LDL cholesterol (P < 0.001, r = 0.36), total cholesterol (P < 0.05, r = 0.36), waist circumference (P < 0.0001, r = 0.62), systolic and diastolic blood pressure (P < 0.05, r = 0.34) in women, and with the waist circumference (P < 0.001, r = 0.065)), and MetS (P < 0.05, r = 0.11) in men. The VF and SCF were correlated with most cardiovascular risk factors in both genders but our findings support the idea that there are gender differences in the correlations between ectopic fat deposition and the cardiovascular risk factors.

Perirenal Fat and Association With Metabolic Risk Factors: The Uberlândia Heart Study.

Perirenal fat (PRF) is associated with cardiovascular risk factors. Gender differences in the correlations of cardiovascular disease risk factors and PRF in the Brazilian population are lacking.Cross-sectional study with 101 (50.49% men; mean age 56.5 ±â€Š18, range 19-74 years) drawn from the Uberlândia Heart Study underwent ultrasonography assessment of abdominal adipose. For the PRF, a 3.5 MHz transducer was measured in the middle third of the right kidney, with the transducer positioned at the axillary midline. The examinations were always performed by the same examiner. The PRF thickness was examined in relation to waist circumference, blood pressure, and metabolic risk factors. The PRF was significantly associated with the levels of gamma-glutamyl transferase (P < 0.05, r = 0.08), fasting plasma glucose (P < 0.05, r = 0.07), waist circumference (P < 0.05, r = 0.10), and metabolic syndrome (P < 0.001, r = 0.38) in men, and with the levels of fasting plasma glucose (P < 0.05) in women.The PRF was correlated with most cardiovascular risk factors in men and only in glucose at the women.

Increased circulating levels of matrix metalloproteinase (MMP)-8, MMP-9, and pro-inflammatory markers in patients with metabolic syndrome.

BACKGROUND: Metabolic syndrome (MetS) predisposes to cardiovascular complications. Increased concentrations of pro-inflammatory mediators and imbalanced concentrations of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) may reflect the pathophysiology of MetS. We compared the circulating levels of MMPs, TIMPs, and inflammatory mediators in MetS patients with those found in healthy controls. METHODS: We studied 25 healthy subjects and 25 MetS patients. The plasma levels of pro-MMP-2 and pro-MMP-9 were determined by gelatin zymography. The plasma concentrations of MMP-8, MMP-3, TIMP-1, TIMP-2, monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), intercellular adhesion molecule (sICAM-1), and sP-selectin were measured by ELISA kits. RESULTS: We found higher sP-selectin, sICAM-1, MCP-1, and IL-6 (all P<0.05) concentrations in MetS patients compared with healthy controls. No differences in pro-MMP-2, MMP-3, and TIMP-2 levels were found (all P>0.05). However, we found higher pro-MMP-9, MMP-8, and TIMP-1 levels in MetS patients compared with healthy controls (all P<0.05). CONCLUSIONS: Patients with MetS have increased circulating concentrations of pro-MMP-9, MMP-8, and TIMP-1 that are associated with increased concentrations of pro-inflammatory mediators and adhesion molecules. These findings suggest that MMPs may have a role in the increased cardiovascular risk of MetS patients. Pharmacological interventions targeting MMPs, especially MMP-9 and MMP-8 deserve further investigation in MetS patients.

Prognostic value of left atrial volume in patients who underwent dobutamine stress echocardiography for known or suspected coronary artery disease.

BACKGROUND: Left atrial volume indexed (LAVI) has been reported as a predictor of cardiovascular events. We sought to determine the prognostic value of LAVI for predicting the outcome of patients who underwent dobutamine stress echocardiography (DSE) for known or suspected coronary artery disease (CAD). METHODS: From January 2000 to July 2005, we studied 981 patients who underwent DSE and off-line measurements of LAVI. The value of DSE over clinical and LAVI data was examined using a stepwise log-rank test. RESULTS: During a median follow-up of 24 months, 56 (6%) events occurred. By univariate analysis, predictors of events were male sex, diabetes mellitus, previous myocardial infarction, left ventricular ejection fraction (LVEF), left atrial diameter indexed, LAVI, and abnormal DSE. By multivariate analysis, independent predictors were LVEF (relative risk [RR] = 0.98, 95% CI 0.95-1.00), LAVI (RR = 1.04, 95% CI 1.02-1.05), and abnormal DSE (RR = 2.70, 95% CI 1.28-5.69). In an incremental multivariate model, LAVI was additional to clinical data for predicting events (chi(2) 36.8, P < .001). The addition of DSE to clinical and LAVI yielded incremental information (chi(2) 55.3, P < .001). The 3-year event-free survival in patients with normal DSE and LAVI < or =33 mL/m(2) was 96%; with abnormal DSE and LAVI < or =33 mL/m(2), 91%; with normal DSE and LAVI >34 mL/m(2), 83%; and with abnormal DSE and LAVI >34 mL/m(2), 51%. CONCLUSION: Left atrial volume indexed provides independent prognostic information in patients who underwent DSE for known or suspected CAD. Among patients with normal DSE, those with larger LAVI had worse outcome, and among patients with abnormal DSE, LAVI was still predictive.

Prognostic value of dobutamine stress echocardiography with early injection of atropine with versus without chronic beta-blocker therapy in patients with known or suspected coronary heart disease.

Although a new protocol of dobutamine stress echocardiography with the early injection of atropine (EA-DSE) has been demonstrated to be useful in reducing adverse effects and increasing the number of effective tests and to have similar accuracy for detecting coronary artery disease (CAD) compared with conventional protocols, no data exist regarding its ability to predict long-term events. The aim of this study was to determine the prognostic value of EA-DSE and the effects of the long-term use of beta blockers on it. A retrospective evaluation of 844 patients who underwent EA-DSE for known or suspected CAD was performed; 309 (37%) were receiving beta blockers. During a median follow-up period of 24 months, 102 events (12%) occurred. On univariate analysis, predictors of events were the ejection fraction (p <0.001), male gender (p <0.001), previous myocardial infarction (p <0.001), angiotensin-converting enzyme inhibitor therapy (p = 0.021), calcium channel blocker therapy (p = 0.034), and abnormal results on EA-DSE (p <0.001). On multivariate analysis, the independent predictors of events were male gender (relative risk [RR] 1.78, 95% confidence interval [CI] 1.13 to 2.81, p = 0.013) and abnormal results on EA-DSE (RR 4.45, 95% CI 2.84 to 7.01, p <0.0001). Normal results on EA-DSE with beta blockers were associated with a nonsignificant higher incidence of events than normal results on EA-DSE without beta blockers (RR 1.29, 95% CI 0.58 to 2.87, p = 0.54). Abnormal results on EA-DSE with beta blockers had an RR of 4.97 (95% CI 2.79 to 8.87, p <0.001) compared with normal results, while abnormal results on EA-DSE without beta blockers had an RR of 5.96 (95% CI 3.41 to 10.44, p <0.001) for events, with no difference between groups (p = 0.36). In conclusion, the detection of fixed or inducible wall motion abnormalities during EA-DSE was an independent predictor of long-term events in patients with known or suspected CAD. The prognostic value of EA-DSE was not affected by the long-term use of beta blockers.

Modulation of cardiac metabolism during myocardial ischemia.

Metabolic modulation during myocardial ischemia is possible by the use of specific drugs, which may induce a shift from free fatty acid towards predominantly glucose utilization by the myocardium to increase ATP generation per unit oxygen consumption. Three agents (trimetazidine, ranolazine, and perhexiline) have well-documented anti-ischaemic effects. However, perhexiline, the most potent agent currently available, requires plasma-level monitoring to avoid hepato-neuro-toxicity. Besides, the long-term safety of trimetazidine and ranolazine has yet to be established. In addition to their effect in ischemia, the potential use of these drugs in chronic heart failure is gaining recognition as clinical and experimental data are showing the improvement of myocardial function following treatment with several of them, even in the absence of ischemia. Future applications for this line of treatment is promising and deserves additional research. In particular, large, randomised, controlled trials investigating the effects of these agents on mortality and hospitalization rates due to coronary artery disease are needed.

Enhanced concentrations of relevant markers of nitric oxide formation after exercise training in patients with metabolic syndrome.

Metabolic syndrome (MetS) denotes a clustering of risk factors that may affect nitric oxide (NO) bioavailability and predispose to cardiovascular diseases, which are delayed by exercise training. However, no previous study has examined how MetS affects markers of NO formation, and whether exercise training increases NO formation in MetS patients. Here, we tested these two hypotheses. We studied 48 sedentary individuals: 20 healthy controls and 28 MetS patients. Eighteen MetS patients were subjected to a 3-month exercise training (E+group), while the remaining 10 MetS patients remained sedentary (E-group). The plasma concentrations of nitrite, cGMP, and ADMA (asymmetrical dimethylarginine; an endogenous nitric oxide synthase inhibitor), and the whole blood nitrite concentrations were determined at baseline and after exercise training using an ozone-based chemiluminescence assay, and commercial enzyme immunoassays. Thiobarbituric acid reactive species (TBA-RS) were measured in the plasma to assess oxidative stress using a fluorometric method. We found that, compared with healthy subjects, patients with MetS have lower concentrations of markers of NO formation, including whole blood nitrite, plasma nitrite, and plasma cGMP, and increased oxidative stress (all P<0.05). Exercise training increased the concentrations of whole blood nitrite and cGMP, and decreased both oxidative stress and the circulating concentrations of ADMA (both P<0.05). These findings show clinical evidence for lower endogenous NO formation in patients with MetS, and for improvements in NO formation associated with exercise training in MetS patients.

Bases experimentais da utilizaçäo da cardiomioplastia no tratamento da insuficiência miocárdica / Experimental bases of the use of cardiomyoplasty in tho treatment of myocardial insufficiency

A cardiomioplastia é uma técnica que utiliza exertos musculares esqueléticos, estimulados sincronamente ao coraçäo, para substituir, ou envolver o miocárdio. O objetivo deste trabalho foi analisar as características contráteis e a resistência a fadiga do músculo grande dorsal normal e estimulado cronicamente, bem como avaliar a eficiência da cardiomioplastia como método de suporte circulatório. Treze cäes foram estudados, após condicionamento elétrico do músculo grande dorsal esquerdo, por período de 6 semanas. Sete deles foram submetidos a medida isométrica da força exercida pelos músculos condicionados e pelos controles contralaterais e a estudo morfológico. Os parâmetros ideais de estimulaçäo foram semelhantes para os músculos normais e os condiconados. Os músculos condicionados, constituídos, predominantemente, de fibras de açäo lenta, apresentaram uma força de amplitude menor (-27%) e um tempo de contraçäo mais longo (+32%). Por outro lado, as curvas de fadiga dos músculos normais, constituídos de fibras mistas, mostraram a queda inicial da força de contraçäo e valores estáveis, após 30 minutos, inversamente proporcionais a freqüência das contraçöes, resultados em um mesmo índice tensäo-tempo (18 ñ 2 KgF. seg/min). Já os músculos condicionados apresentaram um desempenho estável nas mesmas freqüências, mantendo um índice tensäo-tempo elevado (68 ñ 6 KgF. seg/min). Os outros 6 animais foram submetidos a cardiomioplastia, sendo estudados hemodinâmica e ecocardiograficamente, após a induçäo de disfunçäo miocárdica. Com a estimulaçäo do músculo esquelético, observou-se a elevaçäo do índice cardíaco em 35ñ4% (p < 0,01), associada a queda da pressäo capilar pulmonar. O aumento da fraçäo de ejeçäo foi documentado (51 ñ 3%), inclusive quando o enxerto foi colocado apenas sobre o ventrículo esquerdo (p < 0,01). Em conclusäo: 1) os músculos esqueléticos säo capazes de manter atividade semelhante ao trabalho cardíaco, com um desempenho que depende de sua capacidade aeróbica; 2) estimulaçäo crônica leva a transformaçäo adaptativa das fibras musculares, aumentando a sua capacidade de trabalho aeróbico; 3) a cardiomioplastia pode ser um método alternativo, no tratamento da insuficiência miocárdica, mesmo quando é possível apenas o envolvimento parcial do coraçäo pelo enxerto

Ventricular fibrillation in acute experimental myocardial ischemia: protection by magnesium sulfate

The efficacy of magnesium sulfate for prevention of ventricular fibrillation was compared with that of the calcium blocker verapamil and other antiarrhythmic drugs in 54 open-chested anesthetized dogs during a 3-h ligation of the circumflex coronary artery. Latency time to fibrillation, incidence of fibrillation and hemodynamic parameters were assessed. 2. Ventricular fibrillation ocurred in 11 of 14(79%) control dogs, in 2 of 8(25%) dogs treated with magnesium sulfate (100 mg/Kg) and in none of 8 animals treated with verapamil (0.2 mg/Kg) (P = 0.014 and P = 0.0004, respectively, in comparison with controls); lidocaine (60 mg followed by 4 mg/min), amiodarone (5mg/kg) and propafenone (4mg/Kg) had no effect on the incidence of fibrillation. 3. The latency time to fibrillation was 11.6 ñ 9.1 min in controls and it was shortened to 4.0 ñ 3.8 min (P = 0.039) in dogs treated with propafenone, but was unaffected by other drugs. 4. There was no correlation between pre-occlusion heart rate or blood pressure and fibrillation incidence. 5. In this experimental model, magnesium sulfate infusion had a protective effect against ventricular fibrillation that was similar to verapamil, suggesting that magnesium sulfate may be useful as an antifibrillatory agent during acute ischemia