The involvement of multiple thrombogenic and atherogenic markers in premature coronary artery disease

OBJECTIVE: To examine the association of atherogenic and thrombogenic markers and lymphotoxin-alfa gene mutations with the risk of premature coronary disease. METHODS: This cross-sectional, case-control, age-adjusted study was conducted in 336 patients with premature coronary disease (<50 years old) and 189 healthy controls. The control subjects had normal clinical, resting, and exercise stress electrocardiographic assessments. The coronary disease group patients had either angiographically documented disease (>50% luminal reduction) or a previous myocardial infarction. The laboratory data evaluated included thrombogenic factors (fibrinogen, protein C, protein S, and antithrombin III), atherogenic factors (glucose and lipid profiles, lipoprotein(a), and apolipoproteins AI and B), and lymphotoxin-alfa mutations. Genetic variability of lymphotoxin-alfa was determined by polymerase chain reaction analysis. RESULTS: Coronary disease patients exhibited lower concentrations of HDL-cholesterol and higher levels of glucose, lipoprotein(a), and protein S. The frequencies of AA, AG, and GG lymphotoxin-alfa mutation genotypes were 55.0%, 37.6%, and 7.4% for controls and 42.7%, 46.0%, and 11.3% for coronary disease patients (p = 0.02), respectively. Smoking, dyslipidemia, family history, and lipoprotein(a) and lymphotoxin-alfa mutations in men were independent variables associated with coronary disease. The area under the curve (C-statistic) increased from 0.779 to 0.802 (p<0.05) with the inclusion of lipoprotein(a) and lymphotoxin-alfa mutations in the set of conventional risk factors. CONCLUSIONS: The inclusion of lipoprotein(a) and lymphotoxin-alfa mutations in the set of conventional risk factors showed an additive but small increase in the risk prediction of premature coronary disease. .

Hypotheses, rationale, design, and methods for prognostic evaluation in type 2 diabetic patients with angiographically normal coronary arteries. The MASS IV-DM Trial.

BACKGROUND: The MASS IV-DM Trial is a large project from a single institution, the Heart Institute (InCor), University of São Paulo Medical School, Brazil to study ventricular function and coronary arteries in patients with type 2 diabetes mellitus. METHODS/DESIGN: The study will enroll 600 patients with type 2 diabetes who have angiographically normal ventricular function and coronary arteries. The goal of the MASS IV-DM Trial is to achieve a long-term evaluation of the development of coronary atherosclerosis by using angiograms and coronary-artery calcium scan by electron-beam computed tomography at baseline and after 5 years of follow-up. In addition, the incidence of major cardiovascular events, the dysfunction of various organs involved in this disease, particularly microalbuminuria and renal function, will be analyzed through clinical evaluation. In addition, an effort will be made to investigate in depth the presence of major cardiovascular risk factors, especially the biochemical profile, metabolic syndrome inflammatory activity, oxidative stress, endothelial function, prothrombotic factors, and profibrinolytic and platelet activity. An evaluation will be made of the polymorphism as a determinant of disease and its possible role in the genesis of micro- and macrovascular damage. DISCUSSION: The MASS IV-DM trial is designed to include diabetic patients with clinically suspected myocardial ischemia in whom conventional angiography shows angiographically normal coronary arteries. The result of extensive investigation including angiographic follow-up by several methods, vascular reactivity, pro-thrombotic mechanisms, genetic and biochemical studies may facilitate the understanding of so-called micro- and macrovascular disease of DM.

Magnetic Resonance Imaging in Chronic Chagas' Disease: Correlation with Endomyocardial Biopsy Findings and Gallium-67 Cardiac Uptake.

BACKGROUND: We studied the correlation among cardiac magnetic resonance imaging (MRI), gallium-67 myocardial uptake, and right ventricular endomyocardial biopsy results in chronic Chagas' disease. To our knowledge, this represents the first attempt to correlate the histological findings with cardiac MRI and gallium-67 myocardial uptake for noninvasive diagnosis of inflammatory activity associated with Chagas' disease. METHODS: Ten male patients with cardiomyopathy secondary to Chagas' disease were studied (mean age, 47.7 +/- 7 years; congestive heart failure New York Heart Association [NYHA] functional class II [two patients], III [six patients], and IV [two patients]; and mean echocardiographic left ventricular [LV] ejection fraction [EF], 36 +/- 6%). The patients underwent right ventricular endomyocardial biopsy, cardiac MRI, and gallium-67 myocardial uptake testing. The results of this group were compared with those of a control group of patients with idiopathic dilated cardiomyopathy who were matched in age (mean age, 46 +/- 10 years), LV function (mean echocardiographic EF, 30 +/- 4%), and NYHA classification (one patient in class II, five patients in class III, and one patient in class IV). RESULTS: All patients with Chagas' disease showed higher signal intensity on MRI after the administration of gadolinium. The intensity of the septal signal changed from 0.90 +/- 0.11 to 1.56 +/- 0.19 (P < 0.001). In the control group, there was no difference in signal intensity with gadolinium (mean septal intensity, 0.94 +/- 0.12 before and 0.99 +/- 0.15 after; NS). On biopsy, eight chagasic patients had evident signs of myocarditis, and two patients had borderline evidence myocarditis. However, only one patient in the control group had a histological diagnosis of borderline myocarditis. Gallium-67 cardiac uptake was positive for myocardial inflammatory process in seven chagasic patients and borderline in one. On the other hand, only one patient in the control group had an uptake that was positive for inflammation, and one had a borderline result. CONCLUSIONS: In conclusion, the data from this study strongly suggest that myocarditis is frequently found in Chagas' disease. Cardiac MRI appears to be an accurate and alternative method for the diagnosis of inflammatory process associated with Chagas' disease.