Biomarkers of left ventricular function after acute myocardial infarction: sex-biased differences. (Doctoral thesis)

Cardiovascular disease is the first cause of mortality worldwide. Ischemic heart diseases among which myocardial infarction (MI), are responsible for half of these deaths. In order to cope with the loss of cardiomyocytes after MI and to attenuate the alteration of contractility, a repair process is implemented in the heart. If this repair process is dysregulated, it could lead to a maladaptive left ventricular remodeling (LVR) altering LV function and leading to heart failure. The discovery of novel biomarkers able to predict accurately the risk of LVR could lead to a better management of the patients at risk and reduce the incidence of heart failure. Many differences have been highlighted between men and women with MI, regarding the pathophysiology, the symptoms, levels of cardiac biomarkers and the process of LVR. These differences imply the discovery of novel sex-specific biomarkers for LVR prediction or the use of the known biomarkers in a sex-specific manner. The aim of this work was to discover novel biomarkers of left ventricular function (LVF) after an AMI, focusing on sex-differences.
First, we aimed to validate the association between five genes previously found to be associated with LVF in small-scale studies. A panel of three genes (LTBP4, TGFBR1 and TNXB) was able to improve the ability of a clinical model to predict LVF. Second, we observed that the cardiac biomarker NT-proBNP was not predictor of LVF in women, whereas cardiac troponin was associated with LVF in this sex-group. A third study showed the association of the gene CDKN1C with LVF post-MI in a female-specific manner.
In conclusion, our studies contribute to the discovery of novel biomarkers of LVF and draw the attention to sex differences in the clinical use of biomarkers towards the implementation of personalized medicine.
Key words: myocardial infarction – biomarker – gene - sex – left ventricular remodelling