Polymorphisms of the interleukin-1beta gene affect the risk of myocardial infarction and ischemic stroke at young age and the response of mononuclear cells to stimulation in vitro.

OBJECTIVE: To investigate the role of interleukin-1beta (IL-1beta) gene polymorphisms as a link between inflammation, coagulation, and risk of ischemic vascular disease at young age. METHODS AND RESULTS: A total of 406 patients with myocardial infarction (MI) at young age, frequency-matched for age, sex, and recruitment center, with 419 healthy population-based controls and 134 patients with ischemic stroke at young age, matched by age and sex, with 134 healthy population-based controls, were studied. Subjects carrying the TT genotype of the -511C/T IL-1beta polymorphism showed a decreased risk of MI (odds ratio [OR], 0.36; 95% CI, 0.20 to 0.64) and stroke (OR, 0.32; 95% CI, 0.13 to 0.81) after adjustment for conventional risk factors. In both studies, the T allele showed a codominant effect (P=0.0020 in MI; P=0.021 in stroke). Mononuclear cells from volunteers carrying the T allele showed a decreased release of IL-1beta and a decreased expression of tissue factor after stimulation with lipopolysaccharide compared with CC homozygotes. The presence of a monoclonal antibody against IL-1beta during cell stimulation resulted in a marked reduction of tissue factor activity expression. CONCLUSIONS: -511C/T IL-1beta gene polymorphism affects the risk of MI and ischemic stroke at young age and the response of mononuclear cells to inflammatory stimulation.

Residual exertional ischemia and unfavorable left ventricular remodeling in patients with systolic dysfunction after anterior myocardial infarction.

OBJECTIVES: This study investigated whether exercise-induced myocardial ischemia influences left ventricular remodeling after anterior myocardial infarction. BACKGROUND: The effects of acute and recurrent ischemia on ventricular function are well established. However, to our knowledge the role of exertional ischemia in the remodeling response after infarction has not been investigated. METHODS: Ninety-one patients with a first anterior Q wave myocardial infarction were studied at 5 weeks by rest echocardiography and exercise scintigraphy. The echocardiographic examination was repeated 6 months later. On the basis of the presence and extent of reversible perfusion defects on exercise scintigraphy, patients were assigned to groups with no exertional ischemia (group 1, n = 20 [22%], mild to moderate ischemia (group 2, n = 45 [49%]) and severe exertional ischemia (group 3, n = 26 [29%]). RESULTS: Initial left ventricular volumes were similar, and no differences were found among the three groups in the remodeling response over the 6-month period of the study. However, patients in groups 2 and 3 with an ejection fraction < or = 40% showed significant (p < 0.01) ventricular enlargement over time, which was similar between the two groups (end-diastolic volume [mean +/- SD] from 74 +/- 13 to 80 +/- 17 ml/m2 in group 2 and from 72 +/- 11 to 81 +/- 19 ml/m2 in group 3; regional dilation from 42 +/- 16% to 52 +/- 22% in group 2 and from 38 +/- 18% to 46 +/- 27% in group 3). In contrast, ventricular dimensions did not change in group 1 patients with an ejection fraction < or = 40% as well as in patients in all three groups with an ejection fraction > 40%. CONCLUSIONS: Exercise-induced myocardial ischemia may contribute to progressive ventricular enlargement in patients with poor left ventricular function after a large anterior myocardial infarction.

Long-term physical training and left ventricular remodeling after anterior myocardial infarction: results of the Exercise in Anterior Myocardial Infarction (EAMI) trial. EAMI Study Group.

OBJECTIVES: The aim of this multicenter randomized study was to investigate whether long-term physical training would influence left ventricular remodeling after anterior myocardial infarction. BACKGROUND: Exercise is currently recommended for patients after myocardial infarction; however, the effects of long-term physical training on ventricular size and remodeling still have to be defined. METHODS: Patients with no contraindications to exercise were studied 4 to 8 weeks after anterior Q wave myocardial infarction and 6 months later by echocardiography at rest and bicycle ergometric testing. After the initial study, patients were randomly allocated to a 6-month exercise training program (n = 49) or a control group (n = 46). A computerized system was used to derive echocardiographic variables of ventricular size, function and topography. RESULTS: After 6 months, a significant (p < 0.01) increase in work capacity (from 4,596 +/- 1,246 to 5,508 +/- 1,335 kp-m) was observed only in the training group, whereas global ventricular size, regional dilation and shape distortion did not change in either the control or the training group. However, compared with patients with an ejection fraction > 40%, patients with an ejection fraction < or = 40% had more significant (p < 0.001) ventricular enlargement at entry and demonstrated further (p < 0.01) global and regional dilation after 6 months, in both the control and the training group (end-diastolic volume from 77 +/- 14 to 85 +/- 17 ml/m2 in the control group and from 74 +/- 11 to 77 +/- 15 ml/m2 in the training group; regional dilation from 46 +/- 18% to 57 +/- 21% in the control group and from 42 +/- 18% to 44 +/- 26% in the training group). Ventricular size and topography did not change in patients with an ejection fraction > 40%. CONCLUSIONS: Patients with poor left ventricular function 1 to 2 months after anterior myocardial infarction are prone to further global and regional dilation. Exercise training does not appear to influence this spontaneous deterioration. Thus, postinfarction patients without clinical complications, even those with a large anterior infarction, may benefit from long-term physical training without any additional negative effect on ventricular size and topography.

Polymorphisms in the thrombopoietin gene are associated with risk of myocardial infarction at a young age.

Five polymorphisms in the thrombopoietin (TPO) gene were identified, one in the 5' untranslated region (UTR) (C1796T), two within intron 5 (C4830A and A4877C), and two in the 3' UTR (A5713G and A6160T). The allele frequencies were determined in a group of 450 healthy middle aged men from the UK and found to be 0.46 for 1796T, 0.38 for 4830A, 0.004 for 4877C, 0.47 for 5713G and 0.07 for 6160T. Genotypes for the three common polymorphisms were determined in a group of 176 young male Swedish survivors of a myocardial infarction (MI) and 186 age-matched controls and a group of 156 young Italian survivors of an MI and 147 age and sex matched controls. In both the Swedish and the Italian studies polymorphisms were found to be associated with increased risk of MI. In the Swedish sample the frequency of 4830A was significantly higher in controls (0.40) compared with patients (0.29) (P=0.003), with an odds ratio for AA homozygotes of 0.48 (0.25-0.92; P=0.03) compared with CC homozygotes. In the Italian sample the frequency of 5713G was significantly lower in controls (0.31) compared with cases (0.40) (P=0.03), with an odds ratio for GG homozygotes of 2.29 (1.08-4.89; P=0.03) compared with AA homozygotes. These risk associations are consistent since 4830A and 5713A show strong allelic association. After adjusting for other measured risk factors the effect on risk was still significant in the Italian sample 2.39 (1.02-5.58), but not in the Swedish sample 0.46 (0.16-1.32). The observation of frequency differences between cases and controls in two independent samples strongly suggests that the TPO gene is involved as a risk factor for developing MI at a young age, but the identified polymorphisms are probably acting as markers for an unidentified functional mutation elsewhere in the gene locus.

Chlamydia pneumoniae and cytomegalovirus seropositivity, inflammatory markers, and the risk of myocardial infarction at a young age.

BACKGROUND: Pathogens causing chronic infections may promote atherosclerosis. The aim of our study was to evaluate the association of Chlamydia pneumoniae (Cp) and cytomegalovirus (CMV) infection and of inflammatory activation with premature myocardial infarction (MI). METHODS: Specific anti-Cp and anti-CMV immunoglobulin G (IgG), fibrinogen, white blood cells (WBC), and C-reactive protein (CRP) were measured in 120 post-MI patients

The E27 beta2-adrenergic receptor polymorphism reduces the risk of myocardial infarction in dyslipidemic young males.

In the present study we evaluated whether two polymorphisms of beta2-adrenergic receptors (beta2-AR) gene (R16G and Q27E) could modify the risk of myocardial infarction (MI). Using a case-control design, we analyzed the data from 125 male patients who had experienced a first episode of MI before the age of 45 years and 108 male controls matched for age. The allele frequencies for R16G and Q27E were: G16=0.56 and E27=0.36 in patients with MI and G16=0.61 and E27=0.42 in the control group. There was a trend (not statistically significant) of decreasing MI risk according to E27 or G16 alleles. Combined effect between E27 allele and history of dyslipidemia has been observed. Whereas dyslipidemia conferred a relative risk of MI of 4.8 (P<0.001) compared with normolipidemia in the entire study population, the relative risk increased to 9.0 (P<0.001) in Q27 homozygotes with dyslipidemia, and decreased to 1.8 (P=0.36) in E27 homozygotes. Our results show that the E27 allele of the beta2-adrenergic receptor has a significant protective effect on MI in dyslipidemic young male.

EAMI--exercise training in anterior myocardial infarction: an ongoing multicenter randomized study. Preliminary results on left ventricular function and remodeling. The EAMI Study Group.

To determine the effects of a 6-month exercise training program on left ventricular (LV) function and remodeling, 49 consecutive patients (pts) with first Q anterior myocardial infarction (51 +/- 8 years), in I-II NYHA class, were studied 4 to 8 weeks after the acute episode and 6 months later by 2D-ECHO and upright bicycle ergometric test. At entry, pts were randomly allocated to physical training (T = 25pts) or control (C = 24pts). Global endocardial surface area (ESA), LV volumes and EF, extent of abnormal wall motion (%WMA), of regional dilatation (%REG DIL), and the shape distortion (DIST) index were analyzed. After 6 months, a significant increase in work capacity (4,589 +/- 1,417 to 5,379 +/- 1,485 KPM/min, p less than 0.03) and in lactic anaerobic threshold (45 +/- 13 to 63 +/- 15 W, p less than 0.01) was observed only in T. Initial ESA, EDV, EF, %WMA, %REG DIL, and DIST index were similar and they did not change after 6 months in both groups. However, pts with less than 40%EF had greater (p less than 0.0001) EDV and %WMA with marked DIST index at entry and showed further (p less than 0.01) deterioration after 6 months both in C and in T (EDV, ml/m2: 68 +/- 12 to 77 +/- 18 in C, 71 +/- 12 to 74 +/- 18 in T; %REG DIL: 39 +/- 20 to 49 +/- 24 in C, 32 +/- 12 to 35 +/- 23 in T; DIST index: 0.16 +/- 0.07 to 0.21 +/- 0.09 in C, 0.2 +/- 0.07 to 0.22 +/- 0.1 in T). These variables did not change in pts with greater than 40%EF. Thus, from these preliminary data, pts with less than 40%EF at entry are prone to further global and regional LV deterioration. Physical training does not seem to increase this spontaneous deterioration.

Wear properties of a novel resin composite compared to human enamel and other restorative materials.

The purpose of this in vitro study was to compare the two-body wear resistance of human enamel, a pressable glass-ceramic (Imagine PressX), a type 3 gold alloy (Aurocast8), three resins composites currently available on the market (Enamel plus HRi, Filtek Supreme XTE, Ceram.X duo), and one recently introduced resin composite (Enamel plus HRi-Function). Resin composites were tested after simple light curing and after a further heat polymerization cycle. Ten cylindrical specimens (7 mm in diameter) were manufactured with each dental material according to standard laboratory procedures. Ten flat enamel specimens were obtained from freshly extracted human molars and included in the control group. All samples were subjected to a two-body wear test in a dual-axis chewing simulator over up to 120,000 loading cycles, against yttria stabilized tetragonal zirconia polycrystal cusps. Wear resistance was analyzed by measuring the vertical substance loss (mm) and the volume loss (mm(3)). Antagonist wear (mm) was also recorded. Data were statistically analyzed using one-way analysis of variance (ANOVA) (wear depth and volume loss) and Kruskal-Wallis one-way ANOVA on ranks (antagonist wear). Heat-cured HRi function and Aurocast8 showed similar mean values for wear depth and volumetric loss, and their results did not statistically differ in comparison with the human enamel.

Tissue factor gene polymorphisms and haplotypes and the risk of ischemic vascular events: four studies and a meta-analysis.

OBJECTIVE: The exposure of tissue factor (TF) to blood flow is the initial step in the coagulation process and plays an important role in thrombogenesis. We investigated the role of genetic polymorphisms and haplotypes of the TF gene in the risk of ischemic vascular disease. METHODS: Four hundred and twenty-two Italian patients with juvenile myocardial infarction (MI) and 434 controls, 808 US cases with MI and 1005 controls, 267 Italian cases with juvenile ischemic stroke and 209 controls and 148 German cases with juvenile ischemic stroke and 191 controls were studied. rs1361600, rs3917629 (rs3354 in the US population), rs1324214 and rs3917639 Tag single nucleotide polymorphisms were genotyped. Additionally, a meta-analysis of all previous studies on TF loci and the risk of ischemic coronary disease (ICD) was performed. RESULTS: After multivariable analysis none of the SNPs, major SNP haplotypes or haplotype-pairs showed any consistent association with MI. Pooled meta-analysis of six studies also suggested that TF polymorphisms are not associated with CHD. A significant, independent association between SNP rs1324214 (C/T) and juvenile stroke was found in Italian and German populations (OR for TT homozygotes = 0.47, 95% CI 0.24-0.92, in combined analysis). Pooled analysis also showed a significant association for haplotype H3 (OR = 0.76, 95% CI 0.57-1.00) and haplotype-pair H3-H3 (OR = 0.43, 95% CI 0.20-0.92). CONCLUSIONS: TF genetic variations were associated with the risk of ischemic stroke at young age, but did not affect ischemic coronary disease.

The anaerobic index: uses and limitations in the assessment of heart failure.

Limitation of exercise tolerance is a hallmark of heart failure. Anaerobic threshold is a quantitative, reproducible, nonmotivational, submaximal index of exercise tolerance. The pathophysiological significance and methods of determination of anaerobic threshold are matters of debate. The principal aspects of such problems are discussed in this paper.