Sex-Specific Impact of 17β-Estradiol and Testosterone Levels on Inflammation and Injury in Acute Myocardial Infarction-Preliminary Results

Abstract

Background: Estrogens play a protective role during the early stages of life. However, endogenous 17β-estradiol (E2) can accelerate atherosclerosis progression. Aim: The purpose of this study was to test for the significance of the sex-specific associations of gonadal hormones with the extent of the inflammatory response, myocardial damage, and ventricular arrhythmia risk in acute myocardial infarction (MI). Materials and Methods: Study design: single-center cohort study. Blood samples for the assessment of sex steroids (E2, total testosterone [T]), oxidized low-density lipoproteins, high-sensitivity C-reactive protein (CRP), white blood cell (WBC) counts, and cardiac enzymes were collected 48 h after the onset of symptoms (and within 6 h after PCI) from 111 patients (37% women) with acute MI. Coronary disease severity, left ventricular systolic function (LV), and indices of ventricular repolarization were assessed using coronary angiography, echocardiography, and a conventional electrocardiogram, respectively. Results: In men with acute MI, peak cardiac enzyme levels were predicted by post-percutaneous coronary intervention (PCI) E2 plasma levels, peak WBC count, and peak CRP plasma levels. T levels and the E2/T ratio were associated with post-PCI CRP in these men. For women, peak WBC count was a marker of highest testosterone, and only WBC count was a significant indicator of myocardial injury extent. The incidence of acute ventricular tachycardia detected in AMI was significantly associated with left ventricular ejection fraction and with peak WBC count (as a tendency) regardless of sex. A longer duration of cardiac repolarization prior to PCI was predicted by lower ejection fractions in men and by age, CRP, and testosterone levels in female patients. Conclusions: During acute MI, elevated endogenous estradiol levels in men and increased leukocytes in women indicate acute myocardial damage. Post-PCI plasma inflammatory markers are sex-specific confounding factors for acute endogenous E2 levels, T levels, and the E2/T ratio. LV systolic function in men and, characteristically, the acute inflammatory response and testosterone levels in women are predictors of longer ventricular repolarization and arrhythmia risk.

Keywords: 17β-estradiol; C-reactive protein; acute myocardial infarction; oxidized low-density lipoproteins; total testosterone; ventricular tachycardia.

Figure 1

Patient group; inclusion and exclusion criteria. Abbreviations: STEMI, ST elevation myocardial infarction; NSTEMI, myocardial infarction without ST elevation; UA, unstable angina; COPD, chronic obstructive pulmonary disease; RA, rheumatoid arthritis; AMI, acute myocardial infarction; oxLDL, oxidized low-density lipoprotein.

Figure 2

Correlation of E2/T with (A) WBC count, (B) troponin, and (C) ejection fraction in male patients. Abbreviations: WBC, white blood cell; E2/T, ratio of plasma 17β-estradiol to total testosterone concentrations; EF, ejection fraction.

Figure 3

Correlation of E2/T with with heart rate, (A) BMI and (B) CRP in female patients. Abbreviations: CRP, C-reactive protein; BMI, body mass index; E2/T, ratio of plasma 17β-estradiol to total testosterone concentrations.

Figure 4

Indicators of troponin T and gonadal steroid hormones in male and female patients assessed using univariable regression analysis. Abbreviations: oxLDL, oxidized low-density lipoprotein; WBC, white blood cell; CRP, C-reactive protein; EF, ejection fraction; T, total testosterone; E2/T, ratio of plasma 17β-estradiol to total testosterone concentrations.