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Ventricular-arterial coupling disease as pathogenic link between subclinical heart remodelling and arterial stiffening

Boek - Dissertatie

Current heart failure (HF) guidelines place special emphasis on the early detection of people with subclinical left ventricular (LV) remodeling and dysfunction. To better understand the mechanism of LV remodeling related to cardiovascular risk factors such as hypertension and diabetes, it is important to evaluate LV function in relation to changes in loading, i.e. preload and afterload. For instance, arterial stiffening increases the vascular loading on the heart, triggering a cardiac response of hypertrophy and LV stiffening to cope with the increased systolic afterload. However, this matched increase in cardiac and arterial stiffness likely contributes to systolic and diastolic LV dysfunction as it impairs the hemodynamic stability and cardiac reserve. To date, the early signs of such ventricular-arterial coupling (VAC) mismatching and indexes of myocardial performance (work) remain insufficiently investigated in a general population. Within an epidemiological framework, this PhD dissertation addresses the contribution of increased central haemodynamics and arterial stiffening to early remodelling and dysfunction of the heart. We first explored in both cross-sectional and longitudinal analyses the relationship between subclinical LV remodelling and dysfunction and arterial stiffening in a general population. Then, we studied the clinical correlates of the area of the LV pressure-strain loop during ejection (EWD) as VAC index and explored its relation with conventional echocardiographic and central blood pressure indexes. In addition, we aimed to identify circulating biomarkers that predict changes in LV geometry and function in the community. We addressed our research objectives by analysing cardiovascular and biochemical profiles retrieved from European general population cohorts. In short, we observed from an epidemiological perspective that: i) aortic stiffening plays an important role in LV concentric remodelling; (ii) increased pulsatile load might mediate LV diastolic dysfunction, particularly in women; iii) the LV pressure-strain loop area is a promising index to evaluate the sex-dependent interplay between preload, afterload and LV performance; and that iv) a set of circulating biomarkers reflecting insulin resistance, vascular calcification and LV fibrosis and injury predicted adverse changes in LV geometry and function. Our findings justify further research to unravel the pathophysiological mechanisms mediated by systemic hypertension, arterial stiffening and insulin resistance that precede LV maladaptation. Interventions targeting these risk factors might timely prevent or delay the progression of LV maladaptation and, on the long run, clinically overt HF. The imaging and molecular biomarkers highlighted in our studies merit further validation in patient and community-based cohorts for risk stratification of HF.
Jaar van publicatie:2019
Toegankelijkheid:Open