Assuntos
Antraciclinas/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Cardiomiopatias/induzido quimicamente , Antraciclinas/uso terapêutico , Cardiomiopatias/diagnóstico , Cardiotoxicidade , Ecocardiografia , Feminino , Humanos , Imagem Cinética por Ressonância Magnética , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Fatores de TempoRESUMO
BACKGROUND AND AIMS: Anthracyclines are highly effective chemotherapeutic agents which may cause long-term cardiac damage (chronic anthracycline cardiotoxicity) and heart failure. The pathogenesis of anthracycline cardiotoxicity remains incompletely understood and individual susceptibility difficult to predict. We sought clinical features which might contribute to improved risk assessment. METHODS: Subjects were women with early breast cancer, free of pre-existing cardiac disease. Left ventricular ejection fraction was measured using cardiovascular magnetic resonance before and >12 months after anthracycline-based chemotherapy (>3 months post-Trastuzumab). Variables associated with subclinical cardiotoxicity (defined as a fall in left ventricular ejection fraction of ≥5%) were identified by logistic regression. RESULTS: One hundred and sixty-five women (mean age 48.3 years at enrollment) completed the study 21.7 months [IQR 18.0-26.8] after starting chemotherapy. All received anthracyclines (98.8% epirubicin, cumulative dose 400 [300-450] mg/m2); 18% Trastuzumab. Baseline blood pressure was elevated (≥140/90mmHg, mean 147.3/86.1mmHg) in 18 subjects. Thirty-four subjects (20.7%) were identified with subclinical cardiotoxicity, independent predictors of which were the number of anthracycline cycles (odds ratio, OR 1.64 [1.17-2.30] per cycle), blood pressure ≥140/90mmHg (OR 5.36 [1.73-17.61]), body surface area (OR 2.08 [1.36-3.20] per standard deviation (0.16m2) increase), and Trastuzumab therapy (OR 3.35 [1.18-9.51]). The resultant predictive-model had an area under the receiver operating characteristics curve of 0.78 [0.70-0.86]. CONCLUSIONS: We found subclinical cardiotoxicity to be common even within this low risk cohort. Risk of cardiotoxicity was associated with modestly elevated baseline blood pressure-indicating that close attention should be paid to blood pressure in patients considered for anthracycline based chemotherapy. The association with higher body surface area suggests that indexing of anthracycline doses to surface area may not be appropriate for all, and points to the need for additional research in this area.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Superfície Corporal , Neoplasias da Mama , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/fisiopatologia , Cardiotoxinas/administração & dosagem , Cardiotoxinas/efeitos adversos , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Medição de Risco , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversosRESUMO
Understanding the mechanisms by which estrogens affect cardiovascular disease risk, including the role of variation in the gene for estrogen receptor alpha (ESR1), may be key to new treatment strategies. We investigated whether the CC genotype at ESR1 c.454-397T>C is associated with increased risk among men. Study of more than 7000 whites in 5 cohorts from 4 countries provided evidence that genotype CC, present in roughly 20% of individuals, is a risk factor for nonfatal acute myocardial infarction (odds ratio=1.44; P<0.0001), after adjustment for established cardiovascular risk factors. After exclusion of younger subjects from 2 cohorts, because of age interaction, the odds ratio increased (to 1.63).
Assuntos
Receptor alfa de Estrogênio/genética , Infarto do Miocárdio/etiologia , Adulto , Fatores Etários , Idoso , Estudos de Coortes , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/genética , Razão de Chances , Fatores de RiscoRESUMO
BACKGROUND AND PURPOSE: Estrogen receptor alpha (ESR1) gene variation is associated with a range of important estrogen-dependent characteristics, including responses of lipid profile and atherosclerotic severity to hormone replacement therapy, coronary heart disease risk, and migraine. The roles that reproductive steroids play in cerebrovascular pathophysiology and ischemia are an important area of investigation. Given that there is a significantly higher risk of myocardial infarction among men with the CC genotype (PP of PvuII) of c.454-397T>C (rs2234693), we asked whether this genotype is associated with a higher risk of stroke. METHODS: Relative risk of stroke by genotype was determined in 2709 participants of the Second Northwick Park Heart Study, white males with a mean baseline age 56 years and follow up 10.5 years. RESULTS: Compared with participants with the ESR1 c.454-397CT or TT genotype, those with the CC genotype had a relative risk of stroke of 1.92 (95% confidence interval, 1.06 to 3.48, P=0.03) after adjustment for age, primary care practice; additional adjustment for body mass index, serum cholesterol and triglyceride levels, hypertension, diabetes, and smoking status. Exclusion of stroke cases with coronary heart disease gave results that were essentially unchanged. CONCLUSIONS: In this study, subjects with the common ESR1 c.454-397CC genotype have a substantial increase in risk of stroke. In another publication, other ESR1 variation was associated with migraine. We thus hypothesize that estrogen receptor variation may provide a basis for the established relationship among estrogens, migraine, and stroke.