The renin-angiotensin system, in both its circulating and local tissue roles, is intertwined with multiple other regulatory and signalling mechanisms in various tissues and organ systems. It plays a central role in the normal regulation of arterial blood pressure and in the development of hypertension, which is an immense global public health burden and a crucial modifiable risk factor in the development of cardiovascular diseases. The renin-angiotensin system plays also important roles in a range of other clinical conditions such as heart failure, kidney failure, diabetes mellitus and others. Therapeutic interventions within the renin-angiotensin system include the use of medications such as angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists, which are well established and have been invaluable as clinically effective tools during many years of practical use. Additionally, numerous other therapeutic approaches targeting components of the renin-angiotensin system have been developed or are currently in development. This chapter will discuss details of the roles of this system in the most relevant clinical conditions.

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Heart failure with reduced ejection fraction (HFrEF) is a progressive clinical syndrome defined by changes in the myocardial structure, which lead to predominant systolic myocardial function impairment, with a left ventricle ejection of fraction ≤40%. The rehospitalization burden in HFrEF patients (pts) remains very high, with poor quality of life, increased mortality and large healthcare expenditures. In this research project, we investigated the risk factors for first and repeated hospitalization in pts with HFrEF. This retrospective study included 50 adult pts with a diagnosis of HFrEF and who were within the age range of 55 to 89 years old and of both sexes. Demographic and clinical data (HFrEF etiology, renal function parameters, complete blood count, markers of nflammation, electrocardiogram, troponin I, NTproBNP, echocardiographic parameters and comorbidities data) were collected from the pts’ medical histories. Statistical analysis was performed via Fischer’s exact test, the Shapiro-Wilk test and the Spearman correlation coefficient. This study included 70% male and 30% female HFrEF pts. Males were younger in both group of pts and had a higher incidence of rehospitalization. The most important HFrEF etiologic risk factors are arterial hypertension (82%), coronary heart disease (54%), atrial fibrillation (52%) and diabetes mellitus (40%). The most important noncardiac comorbidity related with the first HFrEF hospitalization is pneumonia (P=0.03), while progression of left ventricle systolic and diastolic dysfunction is related to rehospitalization risk (left ventricle end systolic diameter, P=0.003; diastolic dysfunction degree, P=0.04). The troponin level was associated with an increased risk of rehospitalization, but this was not statistically significant at this sample size (troponin I, p=0.10). Following the first and repeated hospitalizations of HFrEF pts, comorbidities, ageing and gender difference are crucial to HFrEF development, while echocardiographic parameters and biomarkers critically affect HFrEF rehospitalization risk.

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