Correspondence Circulating sex hormones, alcohol consumption and echocardiographic parameters of cardiac function in men with heart failure Viktor Čulić a,b, ⁎, Željko Bušić b , Marija Bušić b a Department of Cardiology, University Hospital Center Split, Split, Croatia b University of Split School of Medicine, Split, Croatia article info Article history: Received 11 August 2016 Received in revised form 24 August 2016 Accepted 15 September 2016 Available online 16 September 2016 Keywords: Alcohol Diastolic function Echocardiography Estradiol Heart failure Testosterone Among the multiple hormonal alterations that accompany heart fail- ure (HF) [1], lower endogenous testosterone levels are associated with poorer clinical status [2,3] and overall prognosis [4,5] in men with HF. Without affecting left ventricular ejection fraction (LVEF) [2,3,5–7], testosterone's beneficial mechanism in HF may include peripheral vaso- dilation which reduces cardiac afterload and increases cardiac output [2, 3,7], increased baroreflex sensitivity [2,3], and prevention of diastolic dysfunction (DD) [8,9]. Approximately half of all HF patients have preserved LVEF, and DD underlies their symptoms [10,11]. Women are twice as likely to have HF with preserved LVEF as men, and postmenopausal loss of estrogen protection against DD has been linked to this phenomenon [11–13]. In animal male models, estrogen protected from adverse ventricular re- modeling [14–17]. In men with HF, estrogen administration decreased pulmonary and systemic vascular resistance and improved cardiac out- put [18]. Yet, there is no clinical evidence about estrogen effects on sys- tolic and diastolic function in men. Excessive alcohol consumption is associated with alcoholic cardio- myopathy [19]. However, the beneficial effects of moderate alcohol con- sumption on cardiometabolic profile [20–24] may underlie a lower risk of incident HF [21–23]. At the same time, chronic heavy alcohol intake may lower circulating testosterone and increase estrogen levels by promoting the induction of aromatase and impairing estrogen metabo- lism in the liver [13]. Therefore, alcohol may affect the link between sex hormones and cardiovascular disease. The aim of the present study was to examine the associations of circulating sex hormones and alcohol consumption with echocardiographic parameters of systolic and dia- stolic function in men with HF. Male patients hospitalized because of HF at the Department of Cardi- ology, University Hospital Center Split-Križine between October 2012 and December 2013 were eligible for enrollment in this prospective study. The inclusion criteria were: 1) clinical presentation suggestive of HF; 2) echocardiographic finding of either LVEF ≤ 45% or DD; 3) un- changed medications for at least 1 month preceding the study. Exclu- sion criteria were: 1) any current or previous hormonal treatment or drugs noticeably inhibiting hormone production; 2) cardiac surgery, acute coronary syndrome or coronary revascularization within the 6 months preceding the study; 3) previous myocardial infarction; 4) acute or chronic illness that might influence hormonal metabolism (all endocrine disorders, infectious, autoimmune or malignant diseases; circulating CRP levels under 10 mg/L may be regarded as clinically insig- nificant [26], and to account for a low-grade systemic inflammation which accompanies HF [27], we determined a maximum of 15 mmol/ L, i.e. 50% increase, as a cutoff value for inclusion); 5) end-stage renal disease (i.e. peritoneal or hemodialysis); 6) primary liver disease or liver cirrhosis; and 7) a BMI b 18.5 kg/m 2 to adjust for possible frailty. Out of the 171 eligible patients, 67 were included in the analysis. The study complies with the Helsinki Declaration. The study protocol was approved by the Hospital Ethics Committee and all patients gave their written informed consent. For each patient, a devoted questionnaire was administered by spe- cially trained interns and medical students. The questionnaire covered questions on general and anthropometric data, presence of cardiovascu- lar risk factors and diseases, NYHA class, medications used, and quantity of consumption of specific beverage items during the past 6 months. The patients were asked about their usual daily consumption of beer, wine, and spirits as separate items. To account for the alcohol content of a specific beverage, alcohol intake was assessed separately for each beverage and then summated for total alcohol consumption. A drink was considered to contain approximately 13 g to 15 g ethanol, i.e. ap- proximately 3.5 dL (12 oz.) of beer, 1.5 dL (5 oz.) of wine, 0.5 dL (1.5 oz.) of 80-proof spirits, or 0.3 dL (1 oz.) of 100-proof spirits. All subjects twice underwent standard transthoracic echocardio- graphic examination at rest during the first 2 days of hospitalization. International Journal of Cardiology 224 (2016) 245–251 ⁎ Corresponding author at: Department of Cardiology, University Hospital Center Split- Križine, Šoltanska 1, 21000 Split-Križine, Croatia. E-mail address: viktor.culic@st.t-com.hr (V. Čulić). http://dx.doi.org/10.1016/j.ijcard.2016.09.050 0167-5273/© 2016 Elsevier Ireland Ltd. All rights reserved. Contents lists available at ScienceDirect International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard