Towards personalized antihypertensive therapy: innovate or denervate?

In this thesis we employed novel techniques to gain a better understanding of hypertensive disorders and improve antihypertensive treatment strategies. We discuss novel aspects in phenotyping and treatment modalities. Assessment of central hemodynamics may improve hypertensive phenotyping beyond conventional blood pressure (BP) measurements and help to understand differences in the efficacy of BP lowering medication. Further insight in the (patho)physiology of central hemodynamics, including individual differences and impact of antihypertensive medication is therefore of utmost interest. In part I we addressed central hemodynamics and some of the (patho)physiological mechanisms that are involved. We demonstrate an important role for the heart in the physiology of wave reflection and central BP augmentation. In part II, we studied individual differences in central hemodynamics and effects of pharmacotherapy. We show that ethnic differences in wave reflection are driven by body height and large artery stiffness. Furthermore we demonstrate that isolated systolic hypertension of the young is a heterogeneous condition in whom the assessment of central hemodynamics is paramount. Finally, although antihypertensive drugs may exhibit disparate effects on central versus peripheral BP, third generation beta blocker nebivolol has a comparable effect on central hemodynamics as metoprolol despite its vasodilatory properties. Part III focussed on renal sympathetic denervation (RSD), a novel treatment modality for refractory hypertension. We studied the effects of RSD on renal and cardiac sympathetic nervous activity by use of 123I-mIBG scintigraphy and illustrated this by a case report of a subject undergoing a renal auto-transplantation.