RESUMO
BACKGROUND: Cardiovascular risk factors (CRF) have been associated with myocardial infarction (MI), while the role of genetic risk factors (GRF) remains undetermined. METHODS: Cineventriculograms of 3436 were analyzed for presence of regional function impairment as sign of MI. Genotyping for genetic polymorphism (vitamin D receptor VDR BsmI, interleukin-6 IL6-174 G/C, chemokine receptor 2 CCR2 64 V/I) was performed. CRF were assessed (hypertension, hypercholesterolemia, smoking, and diabetes mellitus). RESULTS: In patients <65 years (n=1946) genotypes (VDR BB, IL6 GC/CC, CCR2 VI/II, defined as GRF) were significantly associated with the presence of MI (BB: OR 1.38, 95%CI 1.07-1.79, p=0.016 GC/CC: 1.28, 95%CI 1.03-1.60, p=0.028 VI/II: 1.49, 95%CI 1.17-1.88, p=0.001). Combining four CRF (14% vs. 21% vs. 27% vs. 31% vs. 38%, p<0.0001) and three GRF (21% vs. 25% vs. 32% vs. 44%, p<0.0001) revealed additive effects on the prevalence of MI. The more combined CRF and GRF were present (from 0 to 7) the higher was the prevalence of MI (11% vs. 12% vs. 21% vs. 27% vs. 30% vs. 34% vs. 59%, p< 0.0001). Age was not associated with MI. In patients > or =65 years (n=1490) the combination of CRF was only weakly associated with MI, while GRF were not. In these patients age was a predictor of MI. CONCLUSION: Certain GRF might have additive but small effects on the disposition for MI before the age of 65. In older patients the tested GRF had no effect, possibly indicating a mechanism of aging rather than a purely genetic determined entity. Given the small effect of the tested genetic polymorphisms the value of testing GRF remains uncertain.
Assuntos
Predisposição Genética para Doença/genética , Infarto do Miocárdio/genética , Polimorfismo Genético/genética , Fatores Etários , Idoso , Doenças Cardiovasculares/genética , Feminino , Frequência do Gene , Genótipo , Humanos , Interleucina-6/genética , Masculino , Pessoa de Meia-Idade , Fenótipo , Receptores CCR2 , Receptores de Calcitriol/genética , Receptores de Quimiocinas/genética , Fatores de RiscoRESUMO
Inflammation is associated with atherosclerosis of coronary arteries. Chemokines have an important role in inflammation. The CCR2 chemokine receptor mediates leukocyte chemoattraction, which is involved in the pathogenesis of coronary heart disease. We prospectively studied 1960 consecutive patients aged under 65 years and referred for a first-time left ventricular catheter. Left heart catheters were analyzed by two independent cardiologists for the presence of myocardial infarction (regional wall motion abnormality) and moderate or severely reduced left ventricular function on cineventriculography and presence of coronary atherosclerosis on angiography. Genotyping for CCR2 V64I polymorphism was performed. The presence of the rare allele of the CCR2 gene was significantly associated with a higher prevalence of myocardial infarction on cinventriculography (32.0% vs. 24.2%, moderately or severely reduced left ventricular function (14.0% vs. 9.5%) and NYHA class III or IV (16.7% vs. 12.2%). The association of the CCR2 genotype with heart failure was not independent of the presence of myocardial infarction in multivariate analysis. There was no association of the CCR2 genotype with coronary atherosclerosis. The CCR2 genotype seems to predispose patients for myocardial infarction before the age of 65 years. The higher prevalence of heart failure in gene carriers with the rare alle might be a consequence of myocardial infarction. If the CCR2 genotype is associated with higher mortality in the general population must be investigated in further studies.
Assuntos
Baixo Débito Cardíaco/genética , Coração/fisiopatologia , Infarto do Miocárdio/genética , Polimorfismo Genético , Receptores de Quimiocinas/genética , Alelos , Baixo Débito Cardíaco/fisiopatologia , Angiografia Coronária , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/fisiopatologia , Ecocardiografia , Eletrocardiografia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Contração Miocárdica , Infarto do Miocárdio/fisiopatologia , Receptores CCR2 , Fatores de Risco , Função Ventricular EsquerdaRESUMO
BACKGROUND: The aim of this study was to analyze the association of polymorphisms of five candidate genes with the outcome of consecutive patients admitted to a medical ICU. MATERIALS AND METHODS: The study population was prospectively recruited. Inclusion criteria were admission to the ICU and written informed consent by the patients or their relatives. A total of 533 patients were recruited. The morbidity was assessed by SAPS II Score. Outcome data of in hospital mortality and length of ICU and hospital stay were obtained. Genotyping for genetic polymorphisms (CRP 1059, IL1B -511, CTGF -477, CCR2 64VI, IL6 -174) were performed by allele-specific fluorogenic oligonucleotide probes (TaqMan analysis). RESULTS: All of the investigated polymorphisms were not associated with an altered outcome. There was no difference in morbidity and ICU or in-hospital mortality (neither in cross tabs analysis nor in Kaplan Meier or Cox regression analysis including age, gender and diagnosis as covariates) between the different genotypes. CONCLUSIONS: Genotyping of the investigated polymorphism for risk stratification of patients admitted to ICU does not seem to be appropriated.