Subject(s)
Heart Failure/blood , Heart Failure/mortality , Lymphocyte Count/methods , Aged , Biomarkers/blood , Cohort Studies , Confidence Intervals , Databases, Factual , Female , Heart Failure/therapy , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Prognosis , Proportional Hazards Models , Retrospective Studies , Severity of Illness Index , Survival AnalysisABSTRACT
BACKGROUND: Functional variants of angiotensin-converting enzyme (ACE) gene may be associated with response to therapy in patients with heart failure (HF). OBJECTIVE: To test the hypothesis of differences in sequential echocardiographic evaluations of left ventricular ejection fraction in patients with HF on medical therapy, including ACE inhibitors in relation to insertion (I) / deletion (D) polymorphism of the ACE gene. METHODS: We studied 168 patients (mean age 43.3+/-10.1 years), 128 (76.2%) men, with HF and sequential echocardiograms. The I/D polymorphism was determined by polymerase chain reaction. Left ventricular ejection fraction (LVEF) was analyzed comparatively to genotypes. More than 90% of patients were on ACE inhibitors. RESULTS: There was a significantly greater increase in mean LVEF in patients with the D allele compared to patients with the II genotype (p=0.01) after a mean follow-up of 38.9 months. The D allele was associated with an increase of 8.8% in mean LVEF over the same period. Furthermore, there was a tendency toward a D allele "copy number" effect on the increase of mean LVEF over time: a 3.5% difference in LVEF variation between patients with the II and the ID genotypes (p = 0.03) and a 5% difference between patients with the II and DD genotypes (p=0.02). CONCLUSION: ACE gene deletion polymorphism may be operative in response to medical treatment that included ACE inhibitors in patients with HF. Further controlled studies may contribute to better understanding of genetic influences on response to therapy.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Heart Failure/genetics , Peptidyl-Dipeptidase A/genetics , Polymorphism, Genetic/genetics , Ventricular Function, Left/genetics , Adult , Analysis of Variance , Chi-Square Distribution , Female , Gene Deletion , Genotype , Heart Failure/drug therapy , Heart Failure/enzymology , Humans , Male , Middle Aged , Ventricular Function, Left/drug effects , Ventricular Function, Left/physiology , Young AdultABSTRACT
FUNDAMENTO: Variantes funcionais do gene da enzima conversora da angiotensina (ECA) podem estar associados com a resposta à terapia em portadores de insuficiência cardíaca (IC). OBJETIVO: Testar a hipótese de diferenças na avaliação ecocardiográfica seqüencial da fração de ejeção do ventrículo esquerdo de pacientes com IC em tratamento farmacológico, inclusive com inibidores da ECA, em relação ao polimorfismo de inserção (I) e deleção (D) do gene da ECA. MÉTODOS: Estudamos 168 pacientes (média de idade 43,3±10,1 anos), 128 (76,2 por cento) dos quais homens, com IC e ecocardiogramas seqüenciais. O polimorfismo I/D foi determinado por reação em cadeia da polimerase. A fração de ejeção do ventrículo esquerdo (FEVE) foi analisada comparativamente aos genótipos. Mais de 90 por cento dos pacientes estavam tomando inibidores da ECA. RESULTADOS: Houve um aumento significantemente maior na FEVE média em pacientes com o alelo D, em comparação com pacientes com genótipo II (p = 0,01) após um seguimento médio de 38,9 meses. O alelo D foi associado com aumento de 8,8 por cento na FEVE média no mesmo período. Além disso, observou-se uma tendência para um efeito do "número de cópias" do alelo D sobre o aumento da FEVE média com o tempo: uma diferença de 3,5 por cento na variação da FEVE entre os pacientes com genótipos II e ID (p = 0,03) e de 5 por cento entre os pacientes com genótipos II e DD (p = 0,02). CONCLUSÃO: O polimorfismo de deleção do gene da ECA pode estar associado com a resposta ao tratamento farmacológico com inibidores da ECA em portadores de IC. Outros estudos controlados poderão contribuir para uma melhor compreensão das influências genéticas sobre a resposta à terapia.
BACKGROUND: Functional variants of angiotensin-converting enzyme (ACE) gene may be associated with response to therapy in patients with heart failure (HF). OBJECTIVE: To test the hypothesis of differences in sequential echocardiographic evaluations of left ventricular ejection fraction in patients with HF on medical therapy, including ACE inhibitors in relation to insertion (I) / deletion (D) polymorphism of the ACE gene. METHODS: We studied 168 patients (mean age 43.3±10.1 years), 128 (76.2 percent) men, with HF and sequential echocardiograms. The I/D polymorphism was determined by polymerase chain reaction. Left ventricular ejection fraction (LVEF) was analyzed comparatively to genotypes. More than 90 percent of patients were on ACE inhibitors. RESULTS: There was a significantly greater increase in mean LVEF in patients with the D allele compared to patients with the II genotype (p=0.01) after a mean follow-up of 38.9 months. The D allele was associated with an increase of 8.8 percent in mean LVEF over the same period. Furthermore, there was a tendency toward a D allele "copy number" effect on the increase of mean LVEF over time: a 3.5 percent difference in LVEF variation between patients with the II and the ID genotypes (p = 0.03) and a 5 percent difference between patients with the II and DD genotypes (p=0.02). CONCLUSION: ACE gene deletion polymorphism may be operative in response to medical treatment that included ACE inhibitors in patients with HF. Further controlled studies may contribute to better understanding of genetic influences on response to therapy.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Young Adult , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Heart Failure/genetics , Peptidyl-Dipeptidase A/genetics , Polymorphism, Genetic/genetics , Ventricular Function, Left/genetics , Analysis of Variance , Chi-Square Distribution , Gene Deletion , Genotype , Heart Failure/drug therapy , Heart Failure/enzymology , Ventricular Function, Left/drug effects , Ventricular Function, Left/physiology , Young AdultABSTRACT
BACKGROUND: Angiotensin-converting enzyme is involved in the pathophysiology of heart failure. We hypothesized that clinical characteristics as well as survival rate in patients with heart failure of different etiologies may be modulated by functional variants DD, ID and II of the angiotensin-converting enzyme gene. METHODS: We studied 333 patients with heart failure, aged 43.3 +/- 10.5 years, 262 (78.7%) men and 71 (21.3%) women. Heart failure was ascribed to idiopathic dilated cardiomyopathy in 125 patients. Heart failure was caused by ischemic heart disease in 63 patients, Chagas' disease in 58, hypertensive heart disease in 41, alcoholic cardiomyopathy in 24, and was due to other etiologies in 22 patients. Statistical analysis was performed with the chi(2) test, Student's t-test, analysis of variance, Kaplan-Meier and Cox proportional hazards methods. RESULTS: The DD genotype was associated with increased systolic left ventricular diameter (p = 0.031). Earlier onset of symptoms was observed in patients with alcoholic cardiomyopathy and DD genotype (p = 0.033, codominant D) and in patients with hypertensive cardiomyopathy and DD genotype (p = 0.048, codominant D; p = 0.024, recessive D). Mortality was higher in patients older than 50 years with DD genotype (p = 0.007, codominant D; p = 0.002, recessive D). Variables independently associated with higher mortality in patients older than 50 years were age, diabetes mellitus, Chagas' disease etiology and DD genotype. CONCLUSIONS: These results add evidence for an association of the DD genotype of the angiotensin-converting enzyme gene with earlier onset of symptoms and decreased survival rate of selected patients with heart failure.
