Should Target Organ Damage Become a Therapeutic Target?

In this issue of the Journal, Shlomai, Grassi, Grossman, and Mancia address the always "hot topic" of target organ damage in patients with hypertension in an article entitled "Assessment of Target Organ Damage in the Evaluation and Follow-Up of the Hypertensive Patients: Where Do We Stand?"The article is thoughtful and informative, considers the facts and takes away the fiction, and balances the totality of evidence to reach conclusions.It is a pleasure to offer my brief commentary from a different angle.Hypertension is a well-known cardiovascular (CV) risk factor that contributes substantially to increased morbidity and mortality.High blood pressure (BP) can cause changes in many organs in the body, such as left ventricular hypertrophy (LVH), proteinuria and renal failure, retinopathy and vascular dementia, increased carotid intima-media thickness, and even increased calcium score.These changes are collectively called "target organ damage" (TOD) and are associated with increased risk for CV complications.There are many processes involved in the pathogenesis of TOD and these include endothelial activation, platelet activation, increased thrombogenesis, changes in the reninangiotensin-aldosterone system (RAAS), and collagen turnover.Most of the changes early on affect the vasculature, cause endothelial dysfunction, vascular hypertrophy, arteriosclerosis, and atherosclerosis.For this reason, hypertension has also been called a vascular disease.Endothelial dysfunction (or endothelial activation) is characterized by 3 distinct properties: inability to vasodilate, inability to prevent adhesion of inflammatory molecules, and loss of ability to prevent protein leak.Endothelial dysfunction is associated with decreased production of nitric oxide (NO) and decreased NO bioavailability in the vessel wall 1 and has been linked to multiple CV risk factors including uncontrolled essential hypertension.2 The pioneering work of Furchgott and Zawadzki 3 first identified NO as an endothelium-derived relaxing factor that helps maintain the ability of the vessels to vasodilate.NO is generated by the action of endothelial NO synthase (eNOS).Shear stress is a key activator of eNOS in normal physiology, and this helps adapt organ perfusion to changes in cardiac output.